IP Library › Granted Patent US 7,217,702

Granted Patent B2

US 7,217,702 · App. 11/097,251 · Granted May 15, 2007

Selective antagonists of A2A adenosine receptors

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Quick Facts

Patent No.: US 7,217,702
App. No.: 11/097,251
Granted: May 15, 2007
Kind: B2

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Abstract

Selective antagonists of A 2A adenosine receptors like those of formula I are provided, wherein Y forms a ring. The novel A 2A blockers are useful for the treatment of Parkinsons disease and other diseases.

Claims (1764)

1. A compound of the formula I:

wherein:

R 1 and R 2 are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , (C 1 –C 8 )alkyl, aryl and aryl(C 1 –C 8 )alkyl, wherein R 1 and R 2 are optionally substituted with 1 to 4 substituents of R a , wherein the alkyl is optionally interrupted by 1–4 heteroatoms selected from —O—, —S—, —SO—, —S(O) 2 — or amino (—NR a —), or where R 1 and R 2 are independently absent, with the proviso that R a is not SH or halogen when the R 1 or R 2 to which R a is bound is halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 or —SCH 3 ;

R 3 is selected from the group consisting of hydrogen, halo, —OR a , SR a , (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, heterocycle, hetrocycle(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, and R a S(═O) 2 —; or if the ring formed from the group CR 3 R 4 R 5 is aryl or heteroaryl or partially unsaturated, then R 3 can be absent;

R 4 and R 5 together with the atoms to which they are attached form a saturated or partially unsaturated, mono-, bi- or tricyclic or aromatic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR a —) in the ring, wherein any ring comprising R 4 and R 5 is optionally further substituted with from 1 to 14 R 6 groups; wherein each R 6 is independently selected from the group consisting of halo, —OR a , —SR a , substituted or unsubstituted (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, heterocycle, hetrocyclyl(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , and R a S(═O)— or two R 6 groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R 6 groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring;

R 7 and R 8 are each independently hydrogen, (C 1 –C 8 )alkyl, (C 3 –C 8 )cycloalkyl, aryl aryl(C 1 –C 8 )alkylene, heteroaryl, heteroaryl(C 1 –C 8 )alkylene; or wherein R 7 and R 8 together with the nitrogen atom to which they attach form a heterocycle or heteroaromatic ring;

R 9 and R 10 are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , (C 1 –C 8 )alkyl, aryl and aryl(C 1 –C 8 )alkyl, wherein R 9 and R 10 are optionally substituted with 1 to 4 substituents of R a , wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, —SO—, —S(O) 2 — or amino (—NR a —), or where R 9 and R 10 are independently absent, with the proviso that R a is not SH or halogen in the case where the R 9 or R 10 to which R a is bound is halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 or —SCH 3 ;

Y is —CR 3 R 4 R 5 or NR 4 R 5 ;

Z is selected from the group consisting of halogen, vinyl, allyl, 1-propenyl, isopropenyl, ethynyl, 1-propynyl, 2-propynyl, 1,3-bytadienyl, penta-1,3-dienyl, penta-1,4-dienyl, hexa-1,3-dienyl, hexa-1,3,5-trienyl, (C 3 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, (C 6 –C 20 )polycyclyl, heterocyclyl, cycloalkyl(C 1 –C 8 )alkyl, bicycloalkyl(C 6 –C 12 )alkyl, heterocyclyl(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —NR a R b , —SR a , cyano, nitro, trifluoromethyl, trifluoromethoxy, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)NR a —, R a R b NC(═O)—, R a C(═O)NR b —, R a R b NC(═O)NR b —, R a R b NC(═S)NR b —, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, —OS(O 2 )R a , —OS(═O)OR a , —OS(O 2 )OR a and —O(SO 2 )NR a R b ;

R a and R b are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , propargyl, cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3 , —OS(O 2 )OCH 3 , (C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, (C 3 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, cycloalkyl(C 1 –C 8 )alkyl, bicycloalkyl(C 6 –C 12 )alkyl, heteroaryl and heteroaryl(C 1 –C 8 )alkyl, wherein the alkyl and cycloalkyl are optionally interrupted with 1–4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — and amino (—NR c —); and wherein the alkyl, cycloalkyl, aryl and heteroaryl are optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of —OR c , —NR c R c , SR c , cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3 and —OS(O 2 )OCH 3 , provided that the point of attachment of R a or R b is not a heteroatom when it is attached to another heteroatom;

R c is selected from the group consisting of hydrogen and (C 1 –C 8 )alkyl; and

m is 0 to 8; n is 0, 1, 2 or 3, provided that when m is 0, Z is not halogen, cyano, or nitro or is not attached via a heteroatom, and when n is 0, Y is not —NR 4 R 5 ; or

a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

2. A compound of the formula II:

wherein:

R 1 and R 2 are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , (C 1 –C 8 )alkyl, aryl and aryl(C 1 –C 8 )alkyl, wherein R 1 and R 2 are optionally substituted with 1 to 4 substituents of R a , wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, —SO—, —S(O) 2 — or amino (—NR a —), or where R 1 and R 2 are independently absent, with the proviso that R a is not thio or halogen when the R 1 or R 2 to which R a is bound is halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 or —SCH 3 ;

R 3 is selected from the group consisting of hydrogen, halo, —OR a , —SR a , (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, heterocycle, hetrocycle(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, R a S(═O) 2 —, or if the ring formed from the group CR 3 R 4 R 5 is aryl or heteroaryl or partially unsaturated, then R 3 can be absent;

R 4 and R 5 together with the atoms to which they are attached form a saturated or partially unsaturated, mono-, bi- or tricyclic, or aromatic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR c —) in the ring, wherein any ring comprising R 4 and R 5 is optionally further substituted with from 1 to 14 R 6 groups; wherein each R 6 is independently selected from the group consisting of hydrogen, halo, —OR a , —SR a , substituted or unsubstituted (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, heterocycle, hetrocyclyl(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, or two R 6 groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R 6 groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring;

R 7 and R 8 are each independently hydrogen, (C 1 –C 8 )alkyl, (C 3 –C 8 )cycloalkyl, aryl or aryl(C 1 –C 8 )alkylene, heteroaryl, heteroaryl(C 1 –C 8 )alkylene-; or wherein R 7 and R 8 together with the nitrogen atom to which they attach form a heterocycle or heteroaromatic ring;

R 9 and R 10 are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , (C 1 –C 8 )alkyl, aryl and aryl(C 1 –C 8 )alkyl, wherein R 9 and R 10 are optionally substituted with 1 to 4 substituents of R a , wherein the alkyl is optionally interrupted by 1 to 4 heteroatoms selected from —O—, —S—, —SO—, —S(O) 2 — or amino (—NR a —), or where R 9 and R 10 are independently absent, with the proviso that R a is not SH or halogen in the case where R 9 and R 10 to which R a is bound is halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 and —SCH 3 ;

L is a linker selected from the group consisting of —(C 1 –C 3 )alkyl-C≡C—, —C≡C—(C 1 –C 3 )alkyl-, —(CH 2 ) 1-3 —CH═CH—, —CH═CH—(CH 2 ) 1-3 —, —(CH 2 ) 1-2 —CH═CH—CH 2 — and —CH 2 —CH═CH—(CH 2 ) 1-2 —;

Y is —CR 3 R 4 R 5 or NR 4 R 5 ;

R a and R b are each independently selected from the group consisting of hydrogen, halogen, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 , —SCH 3 , propargyl, cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3 , —OS(O 2 )OCH 3 , (C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, (C 3 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, cycloalkyl(C 1 –C 8 )alkyl, bicycloalkyl(C 6 –C 12 )alkyl, heteroaryl and heteroaryl(C 1 –C 8 )alkyl, wherein the alkyl and cycloalkyl are optionally interrupted with 1 to 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — and amino (—NR c —); and wherein the alkyl, cycloalkyl, aryl and heteroaryl are optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of —OR c , —NR c R c , SR c , cyano, —OS(O 2 )H, —OS(O 2 )OH, —OS(O 2 )CH 3 and —OS(O 2 )OCH 3 , provided that the point of attachment of R a or R b is not a heteroatom when it is attached to another heteroatom;

R c is selected from the group consisting of hydrogen and (C 1 –C 8 )alkyl; and

m is 0 to 8; n is 0, 1, 2 or 3 provided that when m is 0, Z is not halogen, cyano, nitro or is not attached via or a heteroatom; or

a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

3. The compound of claim 1 , wherein (CR 1 R 2 ) m together is selected from the group consisting of methylene, ethylene, propylene, butylene, pentylene, hexylene, heptylene, octylene, iso-propylene, iso-butylene, sec-butylene and tert-butylene.

4. The compound of claim 1 , wherein (CR 1 R 2 ) m together is selected from the group consisting of methylene, ethylene, propylene and iso-propylene.

5. A compound of the formula I:

wherein:

(CR 1 R 2 ) m -Z together is selected from the group consisting of —CH 2 CH═CH 2 , —CH 2 C≡CH, —CH 2 C≡CCH 3 or —CH 2 CH 2 C≡CH;

Y is —CR 3 R 4 R 5 or NR 4 R 5 ;

R 3 is selected from the group consisting of hydrogen, halo, —OR a , SR a , (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, heterocycle, hetrocycle(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, R a S(═O) 2 —; or if the ring formed from the group CR 3 R 4 R 5 is aryl or heteroaryl or partially unsaturated, then R 3 can be absent;

R 4 and R 5 together with the atoms to which they are attached form a saturated or partially unsaturated, mono-, bi- or tricyclic or aromatic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR a —) in the ring, wherein any ring comprising R 4 and R 5 is optionally further substituted with from 1 to 14 R 6 groups; wherein each R 6 is independently selected from the group consisting of halo, —OR a , —SR a , substituted or unsubstituted (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, heterocycle, hetrocyclyl(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)— or two R 6 groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R 6 groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring;

R c is selected from the group consisting of hydrogen and (C 1 –C 8 )alkyl; and

n is 0, 1, 2 or 3; or

a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

6. The compound of claim 1 , wherein (CR 1 R 2 ) m -Z together is —CH 2 C≡CH.

7. The compound of claim 1 , wherein R 1 and R 2 are hydrogen or are absent, m is 2 to 8 and the group (CR 1 R 2 ) m optionally comprises 1 to 4 alkenyl or alkynyl conjugated or unconjugated groups.

8. The compound of claim 1 , wherein m is 1 to 8 and Z is selected from the group consisting of —NH 2 , —SH, —NR a R b , —SR a and cyano.

9. The compound of claim 1 , wherein Z is an aryl, (C 3 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, or (C 6 –C 20 )polycyclyl, wherein the ring atoms are optionally interrupted by 1 to 8 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — and amino (—NR a —).

10. A compound of the formula I:

wherein:

Z is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl ring optionally substituted with 1 to 4 substituents of R a ;

Y is —CR 3 R 4 R 5 or NR 4 R 5 ;

R 3 is selected from the group consisting of hydrogen, halo, —OR a , SR a , (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, heterocycle, hetrocycle(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, R a S(═O) 2 —; or if the ring formed from the group CR 3 R 4 R 5 is aryl or heteroaryl or partially unsaturated, then R 3 can be absent;

R 4 and R 5 together with the atoms to which they are attached form a saturated or partially unsaturated, mono-, bi- or tricyclic or aromatic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR a —) in the ring, wherein any ring comprising R 4 and R 5 is optionally further substituted with from 1 to 14 R 6 groups; wherein each R 6 is independently selected from the group consisting of halo, —OR a , —SR a , substituted or unsubstituted (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, heterocycle, hetrocyclyl(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)— or two R 6 groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R 6 groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring;

R 7 and R 8 are each independently hydrogen, (C 1 –C 8 )alkyl, (C 3 –C 8 )cycloalkyl, aryl or aryl(C 1 –C 8 )alkylene, heteroaryl, heteroaryl(C 1 –C 8 )alkylene; or wherein R 7 and R 8 together with the nitrogen atom to which they attach form a heterocycle or heteroaromatic ring;

R c is selected from the group consisting of hydrogen and (C 1 –C 8 )alkyl; and

m is 0 to 8; n is 0, 1, 2 or 3, provided that when n is 0, Y is not —NR 4 R 5 ; or

a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

11. The compound of claim 10 , wherein Z is selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, where m is 0 or 1.

12. The compound of claim 10 , wherein Z is cyclopentyl and where m is 0.

13. The compound of claim 10 , wherein Z is cyclobutyl, m is 1 and R 1 and R 2 are hydrogen.

14. A compound of formula I:

wherein Y is selected from the group consisting of

wherein Y optionally comprises 1, 2 or 3 double bonds; each carbon in the ring is optionally replaced by or interrupted by 1 to 6 heteroatoms selected from —O—, —S—, —SO—, —S(O) 2 —, or amino (—NR a —), and is optionally further substituted with from 1 to 10 R 6 groups, provided that the Y or Z ring is not attached at a bridgehead carbon atom or at a trisubstituted carbon atom;

R 6 is independently selected from the group consisting of halo, —OR a , —SR a , substituted or unsubstituted (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, heterocycle, hetrocyclyl(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)— or two R 6 groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R 6 groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring;

R c is selected from the group consisting of hydrogen and (C 1 –C 8 )alkyl; and

m is 0 to 8; n is 0, 1, 2 or 3, provided that when m is 0, Z is not halogen, cyano, or nitro or attached via a heteroatom; or

a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

15. A compound of formula I:

wherein R 1 and R 2 are hydrogen, m is 0, 1, 2 or 3 and Z is the moiety derived from the ring selected from the group consisting of furan, dihydro-furan, thiophene, pyrrole, 2H-pyrrole, 2-pyrroline, 3-pyrroline, pyrrolidine, 1,3-dioxolane, oxazole, thiazole, imidazole, dihydro-imidazole, 2-imidazoline, imidazolidine, pyrazole, 2-pyrazoline, pyrazolidine, isoxazole, isothiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,3-triazole, 1,2,4-triazole, 1,3,4-thiadiazole, 2H-pyran, 1H-tetrazole, 4H-pyran, pyridine, dihydro-pyridine, tetrahydro-pyridine, piperidine, 1,4-dioxane, morpholine, 1,4-dithiane, thiomorpholine, pyridazine, pyrimidine, dihydro-pyrimidine, tetrahydro-pyrimidine, hexahydro-pyrimidine, pyrazine, dihydro-pyrazine, tetrahydro-pyrazine, piperazine, 1,3,5-triazine and 1,3,5-trithiane, wherein each Z group is optionally substituted with from 1 to 10 R a groups;

Y is —CR 3 R 4 R 5 or NR 4 R 5 ;

R 3 is selected from the group consisting of hydrogen, halo, —OR a , SR a , (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, heterocycle, hetrocycle(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, R a S(═O) 2 —; or if the ring formed from the group CR 3 R 4 R 5 is aryl or heteroaryl or partially unsaturated, then R 3 can be absent;

R 4 and R 5 together with the atoms to which they are attached form a saturated or partially unsaturated, mono-, bi- or tricyclic or aromatic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR a —) in the ring, wherein any ring comprising R 4 and R 5 is optionally further substituted with from 1 to 14 R 6 groups; wherein each R 6 is independently selected from the group consisting of halo, —OR a , —SR a , substituted or unsubstituted (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, heterocycle, hetrocyclyl(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)— or two R 6 groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R 6 groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring;

R c is selected from the group consisting of hydrogen and (C 1 –C 8 )alkyl; and

m is 0 to 8; n is 0, 1, 2 or 3, provided that when n is 0, Z is not attached via a heteroatom, and when n is 0, Y is not —NR 4 R 5 ; or

a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

16. The compound of claim 15 , wherein R 1 and R 2 are hydrogen, m is 0 or 1, and Z is the moiety derived from the ring selected from the group consisting of furan, thiophene, pyrrole, 2H-pyrrole, oxazole, thiazole, imidazole, pyrazole, isoxazole, isothiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,3-triazole, 1,2,4-triazole, 1,3,4-thiadiazole and 1H-tetrazole, wherein each Z group is optionally substituted with from 1 to 3 R a groups selected from the group consisting of methyl, ethyl, propyl, iso-propyl, —NH 2 , —OH, —SH, —NHCH 3 , —N(CH 3 ) 2 , —OCH 3 and —SCH 3 .

17. The compound of claim 1 , wherein Z is selected from the group consisting of —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)NR a —, R a R b N—, R a R b NC(═O)—, R a C(═O)NR b —, R a R b NC(═O)NR b —, R a R b NC(═S)NR b —, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, R a S(O 2 )—, —OS(═O)OR a , —OS(O 2 )OR a and —OS(O 2 )NR a R b , wherein m is 1 to 8.

18. The compound of claim 17 , wherein Z is selected from the group consisting of —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)NR a —, R a R b N—, R a R b NC(═O)—, R a C(═O)NR b —, R a R b NC(═O)NR b —, R a R b NC(═S)NR b —, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, R a S(═O) 2 —, —OS(O 2 )R a , —OS(═O)OR a , —OS(O 2 )OR a and —O(SO 2 )NR a R b , and wherein (R 1 R 2 ) m together is selected from the group consisting of —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 —, —CH═CHCH 2 —, —CH 2 CH═CH—, —CH═CHCH 2 CH 2 —, —CH 2 CH═CHCH 2 —, —CH 2 CH 2 CH═CH—, —C≡CCH 2 —, —CH 2 C≡C—, —C≡CCH 2 CH 2 —, —CH 2 C≡CCH 2 — and —CH 2 CH 2 C≡C—.

19. The compound of claim 17 , wherein Z is —CO 2 R a , R a C(═O)—, R a R b N—, R a OC(═S)—, R a C(═S)—, R a S(═O)—, R a S(═O) 2 —, —OS(O 2 )R a , —OS(═O)OR a , —OS(O 2 )OR a , or —OS(O 2 )NR a R b , and wherein (CR 1 R 2 ) m together is selected from the group consisting of —CH 2 —, —CH 2 CH 2 —, —CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 CH 2 —, —CH 2 CH 2 CH 2 CH 2 CH 2 CH 2 —, —CH═CHCH 2 —, —CH 2 CH═CH—, —CH═CHCH 2 CH 2 —, —CH 2 CH═CHCH 2 —, —CH 2 CH 2 CH═CH—, —C≡CCH 2 —, —CH 2 C≡C—, —C≡CCH 2 CH 2 —, —CH 2 C≡CCH 2 — and —CH 2 CH 2 C≡C—.

20. The compound of claim 1 , wherein each R 9 is independently selected from the group consisting of hydrogen, halo, —OR a , —SR a , (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, heterocyclyl, hetrocyclyl(C 1 –C 8 )alkylene-, aryl, aryl(C 1 –C 8 )alkylene-, heteroaryl, heteroaryl(C 1 –C 8 )alkylene-, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, R a S(═O) 2 —.

21. The compound of claim 1 , wherein R 3 is selected from the group consisting of hydrogen, halo, —OR a , —SR a , cyano, nitro, trifluoromethyl, trifluoromethoxy, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S), SSR a , R a S(═O)—, and R a S(═O) 2 —; or if the ring formed from the group CR 3 R 4 R 5 is aryl or heteroaryl or partially unsaturated then R 3 can be absent.

22. The compound of claim 1 , wherein R 3 is selected from the group consisting of hydrogen, OH, OCH 3 , OAc, NH 2 , NHCH 3 , N(CH 3 ) 2 and NHAc.

23. The compound of claim 22 , wherein R 3 is hydrogen or OH.

24. The compound of claim 1 , wherein R 4 and R 5 together with the atom to which they are attached form a saturated or partially unsaturated, mono-, bi- or tricyclic ring, or aromatic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR a —) in the ring, wherein any ring comprising R 4 and R 5 is optionally further substituted with from 1 to 14 R 6 groups; wherein each R 6 is independently selected from the group consisting of halo, —OR a , —SR a , (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 1 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, heterocycle, hetrocyclyl(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, or two R 6 groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R 6 groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring.

25. The compound of claim 24 , wherein the ring comprising R 4 and R 5 and the atom to which they are attached is selected from the group consisting of cyclopentane, cyclohexane, piperidine, dihydro-pyridine, tetrahydro-pyridine, pyridine, piperazine, decaline, tetrahydro-pyrazine, dihydro-pyrazine, pyrazine, dihydro-pyrimidine, tetrahydro-pyrimidine, hexahydro-pyrimidine, pyrazine, imidazole, dihydro-imidazole, imidazolidine, pyrazole, dihydro-pyrazole, pyrazolidine, norbornane and adamantane, each unsubstituted or substituted.

26. The compound of claim 25 , wherein the ring comprising R 4 and R 5 and the atom to which they are attached is selected from the group consisting of cyclohexane, piperidine, piperazine, norbornane, adamantane, each unsubstituted or substituted.

27. The compound of claim 1 , wherein each R 6 is independently selected from the group consisting of substituted or unsubstituted (C 1 –C 8 )alkyl, —OR a , —CO 2 R a , R a C(═O)—, R a C(═O)O—, R a R b N—, R a R b NC(═O)— and aryl, provided that when the ring comprising R 4 and R 5 contains a ring heteroatom that is O or S, the ring heteroatom that is O or S is not substituted with R 6 .

28. The compound of claim 1 , wherein each R 6 is independently selected from the group consisting of OH, OCH 3 , methyl, ethyl, t-butyl, —CO 2 R a , —CONR a R b , OAc, NH 2 , NHCH 3 , N(CH 3 ) 2 , NHEt and N(Et) 2 , provided that when the ring comprising R 4 and R 5 contains a ring heteroatom that is O or S, the ring heteroatom that is O or S is not substituted with R 6 .

29. The compound of claim 28 , wherein each R 6 is independently selected from the group consisting of methyl, ethyl, —CO 2 R a , —CONR a R b and OAc, provided that when the ring comprising R 4 and R 5 contains a heteroatom, the heteroatom is not substituted with OAc.

30. The compound of claim 1 , wherein number of R 6 groups substituted on the R 4 R 5 ring is from 1 to 4.

31. A compound of formula I:

wherein R 7 and R 8 are each independently selected from the group consisting of hydrogen, (C 1 –C 8 )alkyl-, aryl(C 1 –C 8 )alkylene-, mono- or bicyclic-, aromatic or nonaromatic ring having 3, 4, 5, 6, 7, 8, 9 or 10 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR a —) in the ring, and each is optionally substituted with from 1, 2, 3 or 4 R a groups;

Y is —CR 3 R 4 R 5 or NR 4 R 5 ;

R 4 and R 5 together with the atoms to which they are attached form a saturated or partially unsaturated, mono-, bi- or tricyclic or aromatic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR a —) in the ring, wherein any ring comprising R 4 and R 5 is optionally further substituted with from 1 to 14 R 6 groups; wherein each R 6 is independently selected from the group consisting of halo, —OR a , —SR a , substituted or unsubstituted (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, heterocycle, hetrocyclyl(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)— or two R 6 groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R 6 groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring;

R c is selected from the group consisting of hydrogen and (C 1 –C 8 )alkyl; and

m is 0 to 8; n is 0, 1, 2 or 3, provided that when m is 0, Z is not halogen, cyano, or nitro or is not attached via a heteroatom, and when n is 0, Y is not —NR 4 R 5 ; or

a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

32. The compound of claim 31 , wherein R 7 is selected from the group consisting of hydrogen, methyl, ethyl, propyl, butyl, 3-pentyl, iso-propyl, iso-butyl, sec-butyl, tert-butyl, phenyl and benzyl.

33. The compound of claim 32 , wherein R 7 is hydrogen, methyl, 3-pentyl or sec-butyl.

34. The compound of claim 1 , wherein —NR 7 R 8 is selected from the group consisting of amino, methylamino, dimethylamino, ethylamino, 3-pentylamino, (diphenylethyl)-amino, (pyridylmethyl)-amino, diethylamino and benzylamino.

35. The compound of claim 34 , wherein —NR 7 R 8 is selected from the group consisting of amino, methylamino, dimethylamino, ethylamino, diethylamino, 3-pentylamino and benzylamino.

36. The compound of claim 35 , wherein —NR 7 R 8 is amino.

37. The compound of claim 31 , wherein R 7 is selected from the group consisting of benzyl, phenethyl, phenylpropyl and each is optionally substituted with from 1, 2 or 3 substituents of R a .

38. The compound of claim 37 , wherein R 7 is selected from the group consisting of benzyl, phenethyl, phenylpropyl and each is optionally substituted with from 1, 2 or 3 substituents of R a selected from the group consisting of methyl, ethyl, propyl, and methoxy.

39. The compound of claim 38 , wherein R 7 is benzyl and R a is methoxy.

40. The compound of claim 1 , wherein R 9 is independently selected from the group consisting of hydrogen, fluoro, —OH, —CH 2 OH, —OCH 3 , —NH 2 , —NHCH 3 , and —N(CH 3 ) 2 .

41. The compound of claim 40 , wherein R 9 is independently hydrogen or OH.

42. The compound of claim 1 , wherein each R 10 is independently selected from the group consisting of hydrogen, fluoro, (C 1 –C 8 )alkyl, aryl, and aryl(C 1 –C 8 )alkylene-.

43. The compound of claim 42 , wherein R 10 is independently selected from the group consisting of hydrogen, (C 1 –C 8 )alkyl, and benzyl.

44. The compound of claim 43 , wherein R 10 is hydrogen.

45. The compound of claim 1 , wherein R a and R b are each independently selected from the group consisting of hydrogen, (C 1 –C 4 )alkyl, aryl and aryl(C 1 –C 8 )alkylene.

46. The compound of claim 45 , wherein R a and R b are each independently selected from the group consisting of hydrogen, methyl, ethyl, phenyl and benzyl.

47. The compound of claim 45 , wherein R a is (C 1 –C 8 )alkyl.

48. The compound of claim 47 , wherein R a is selected from the group consisting of methyl, ethyl, propyl and butyl.

49. The compound of claim 1 , wherein Y is —CR 3 R 4 R 5 or NR 4 R 5 , and is selected from the group consisting of:

wherein q is 0, 1, 2, 3 or 4; R 3 is selected from the group consisting of hydrogen, halo, —OR a , —SR a , (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, heterocycle, hetrocycle(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, R a S(═O) 2 —; and each R 6 is independently selected from the group consisting of halo, —OR a , —SR a , substituted or unsubstituted (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 1 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, heterocycle, hetrocyclyl(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , and R a S(═O)—, provided that R 6 is not halogen or a heteroatom when R 6 is attached to a heteroatom.

50. The compound of claim 1 , wherein Y is —CR 3 R 4 R 5 or NR 4 R 5 and is selected from the group consisting of:

wherein R 3 is selected from the group consisting of hydrogen, halo, —OR a , —SR a , (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, heterocycle, hetrocycle(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b ), R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, and R a S(═O) 2 —; and each R 6 is independently selected from the group consisting of halo, —OR a , —SR a , substituted or unsubstituted (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, heterocycle, hetrocyclyl(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , and R a S(═O)—.

51. The compound of claim 1 , wherein the ring formed by R a R b together with the atom to which they are attached is selected from: 2-methylcyclohexan-1-yl, 2,2-dimethylcyclohexan-1-yl, 2-ethylcyclohexan-1-yl, 2,2-diethylcyclohexan-1-yl, 2-tert-butylcyclohexan-1-yl, 2-phenylcyclohexan-1-yl, 3-methylcyclohexan-1-yl, 3-ethylcyclohexan-1-yl, 3,3-dimethylcyclohexan-1-yl, 4-methylcyclohexan-1-yl, 4-ethylcyclohexan-1-yl, 4,4-dimethylcyclohexan-1-yl, 4-tert-butylcyclohexan-1-yl, 4-phenylcyclohexan-1-yl, 3,3,5,5-tetramethylcyclohexan-1-yl, 2,4-dimethylcyclopentan-1-yl, 4-(carboxyl)cyclohexan-1-yl, 4-(carboxymethyl)cyclohexan-1-yl and 4-(carboxyethyl)cyclohexan-1-yl.

52. The compound of claim 1 , wherein the ring formed by R a R b together with the atom to which they are attached is selected from: piperidin-4-yl, 1-carboxypiperiden-4-yl, 1-(methoxycarbonyl)piperidin-4-yl, 1-(ethoxycarbonyl)piperidin-4-yl, 1-(n-propoxycarbonyl)piperidin-4-yl, 1-(2,2-dimethylpropoxycarbonyl)piperidin-4-yl, piperidin-1-yl, 4-carboxypiperiden-1-yl, 4-(methoxycarbonyl)piperidine-1-yl, 4-(ethoxycarbonyl)piperidine-1-yl, 4-(n-propoxy)piperidine-1-yl, 4-(2,2-dimethylpropoxycarbonyl)piperidine-1-yl, piperidin-3-yl, 1-carboxypiperidene-3-yl, 1-(methoxycarbonyl)piperidine-3-yl, 1-(ethoxycarbonyl)piperidine-3-yl, 1-(n-propoxycarbonyl)piperidine-3-yl, 1-(2,2-dimethylpropoxycarbonyl)piperidine-3-yl, 3-carboxypiperidene-1-yl, 3-(methoxycarbonyl)piperidine-1-yl, 3-(ethoxycarbonyl)piperidine-1-yl, 3-(n-propoxycarbonyl)piperidine-1-yl, 3-(2,2-dimethylpropoxycarbonyl)piperidine-1-yl, piperazin-1-yl, 1-caboxypiperazin-4-yl, 1-(methoxycarbonyl)piperazin-4-yl, 1-(ethoxycarbonyl)piperazin-4-yl and 1-(n-propoxycarbonyl)piperazin-4-yl.

53. The compound of claim 1 , wherein the ring formed by R a R b together with the atom to which they are attached is selected from: 2-methylcyclohexan-1-yl, 2,2-dimethylcyclohexan-1-yl, 2-ethylcyclohexan-1-yl, 2,2-diethylcyclohexan-1-yl, 2-tert-butylcyclohexan-1-yl, 2-phenylcyclohexan-1-yl, 3-methylcyclohexan-1-yl, 3-ethylcyclohexan-1-yl, 3,3-dimethylcyclohexan-1-yl, 4-methylcyclohexan-1-yl, 4-ethylcyclohexan-1-yl, 4,4-dimethylcyclohexan-1-yl, 4-tert-butylcyclohexan-1-yl, 4-phenylcyclohexan-1-yl, 3,3,5,5-tetramethylcyclohexan-1-yl, 2,4-dimethylcyclopentan-1-yl, 4-(carboxyl)cyclohexan-1-yl, 4-(carboxymethyl)cyclohexan-1-yl, 4-(carboxyethyl)cyclohexan-1-yl, piperidin-4-yl, 1-(methoxycarbonyl)piperidin-4-yl, 1-(2,2-dimethylpropoxycarbonyl)piperidin-4-yl, piperidin-1-yl, 4-(methoxycarbonyl)piperidine-1-yl, 4-(2,2-dimethylpropoxycarbonyl)piperidine-1-yl, piperidin-3-yl, 1-(methoxycarbonyl)piperidine-3-yl, 1-(2,2-dimethylpropoxycarbonyl)piperidine-3-yl, 3-(methoxycarbonyl)piperidine-1-yl and 3-(2,2-dimethylpropoxycarbonyl)piperidine-1-yl.

54. The compound of claim 2 , wherein Z is an aryl, (C 3 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, or (C 3 –C 20 )polycyclyl, wherein the ring atoms are optionally interrupted by 1–8 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — and amino (—NR a —).

55. A compound of formula II:

wherein R 1 and R 2 are hydrogen, m is 0, 1, 2 or 3 and Z is selected from the group consisting of furan, dihydro-furan, thiophene, pyrrole, 2H-pyrrole, 2-pyrroline, 3-pyrroline, pyrrolidine, 1,3-dioxolane, oxazole, thiazole, imidazole, dihydro-imidazole, 2-imidazoline, imidazolidine, pyrazole, 2-pyrazoline, pyrazolidine, isoxazole, isothiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,3-triazole, 1,2,4-triazole, 1,3,4-thiadiazole, 2H-pyran, 1H-tetrazole, 4H-pyran, pyridine, dihydro-pyridine, tetrahydro-pyridine, piperidine, 1,4-dioxane, morpholine, 1,4-dithiane, thiomorpholine, pyridazine, pyrimidine, dihydro-pyrimidine, tetrahydro-pyrimidine, hexahydro-pyrimidine, pyrazine, dihydro-pyrazine, tetrahydro-pyrazine, piperazine, 1,3,5-triazine and 1,3,5-trithiane, wherein each Z group is optionally substituted with from 1 to 10 R a groups;

Y is —CR 3 R 4 R 5 or NR 4 R 5 ;

R c is selected from the group consisting of hydrogen and (C 1 –C 8 )alkyl; and

m is 0 to 8; n is 0, 1, 2 or 3, provided that when n is 0, Z is not attached via a heteroatom, and when n is 0, Y is not —NR 4 R 5 ; or

a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

56. A compound selected from the group:

9-Cyclopropylmethyl-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}adenine (1);

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-propargyladenine (2);

9-Cyclopentyl-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}adenine (3);

9-Cyanomethyl-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}adenine (4);

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-(4-methoxybenzyl)adenine (5);

9-(3,4-Dichlorobenzyl)-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}adenine (6);

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-(4-trifluoromethylbenzyl)adenine (7);

9-(3,5-Dimethyl-isoxazol-4-ylmethyl)-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}adenine (8);

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-[2-(trifluoromethylphenyl)thiazol-4-ylmethyl]adenine (9);

2-{2-[Hydroxy-adamantan-2-yl]ethyn-1-yl}-9-(3-(thiophen-2-yl)prop-2-ynyl)adenine (10);

9-Cyclopropylmethyl-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-(3-pentyl)adenine (14);

9-Cyclopentyl-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-(3-pentyl)adenine (15);

9-Allyl-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-(3-pentyl)adenine (16);

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-(3-pentyl)-9-(propargyl)adenine (17);

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-(3-pentyl)-9-(pent-4-ynyl)adenine (18);

9-(2-Chloroethyl)-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-(3-pentyl)adenine (21);

9-([1,3]-Dioxolan-2-ylmethyl)-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-(3-pentyl)adenine (22);

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-(3-pentyl)-9-(tetrahydro-pyran-2-ylmethyl)adenine (23);

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-(3-pentyl)-9-(isopropylcarboxylate)adenine (24);

9-(Acetic acid ethyl ester)-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-(3-pentyl)adenine (25);

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-(2-oxo-oxazolidin-5-ylmethyl)-N6-(3-pentyl)adenine (26);

9-Benzyl-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-(3-pentyl)adenine (27);

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-(3-pentyl)-9-(pyridin-3-ylmethyl)adenine (28);

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-(4-nitrobenzyl)-N6-(3-pentyl)adenine (29);

9-(3,5-Dimethyl-isoxazol-4-ylmethyl)-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-(3-pentyl)adenine (30);

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-(2-methyl-thiazol-5-ylmethyl)-N6-(3-pentyl)adenine (31);

N6-[(S)-(+)-sec-Butyl]-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-propargyl-adenine (32);

N6-[(s)-(+)-sec-Butyl]-9-(3,5-dimethyl-isoxazol-4-ylmethyl)-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}adenine (33);

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-[(s)-(−)-alpha-napthalen-1-yl-ethyl]-9-(propargyl)adenine (35);

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-(3-methoxybenzyl)-9-(propargyl)adenine (36);

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-(propargyl)-N6-(pyridin-2-ylmethyl)adenine (37);

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-[(methyl)(2-phenethyl)]-9-(propargyl)adenine (38);

9-Cyclopropylmethyl-2-{2-[hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (45);

9-Cyclobutylmethyl-2-{2-[hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (46);

9-Cyclopentylmethyl-2-{2-[hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (47);

9-Cyclohexylmethyl-2-{2-[hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (48);

9-Cyclobutyl-2-{2-[hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (49);

9-Cyclopentyl-2-{2-[hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (50);

2-{2-[Hydroxy-adamantan-2-yl]ethyn-1-yl}-9-propargyl-adenine (51);

2-{2-[Hydroxy-norbornan-2-yl]ethyn-1-yl}-9-propargyladenine;

9-(But-3-ynyl)-2-{2-[hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (62); and

2-{3-[1-(Methoxycarbanoyl)piperidin-4-yl]propyn-1-yl}-9-propargyladenine (63); or

a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

57. A compound selected from the group in Tables 1 to 7, or a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof wherein c-Pentyl is cyclopentyl and Me is methyl:

TABLE 1

R 7 , R 8 = H

Compound

(CR 1 R 2 ) m -Z

R 6

NC100

Propargyl

CH 2 OH

NC101

c-Pentyl

CH 2 OH

NC102

Propargyl

CO 2 H

NC103

c-Pentyl

CO 2 H

NC104

Propargyl

CO 2 Me

NC105

c-Pentyl

CO 2 Me

NC106

Propargyl

CH 2 OAc

NC107

c-Pentyl

CH 2 OAc

NC108

Propargyl

CH 2 N(CH 3 ) 2

NC109

c-Pentyl

CH 2 N(CH 3 ) 2

NC110

Propargyl

COOCH 2 CH 2 NHBoc

NC111

c-Pentyl

COOCH 2 CH 2 NHBoc

NC112

Propargyl

COOCH 2 CH 2 NH 2

NC113

c-Pentyl

COOCH 2 CH 2 NH 2

NC114

Propargyl

CONHCH 2 CH 3

NC115

c-Pentyl

CONHCH 2 CH 3

NC116

Propargyl

CONH 2

NC117

c-Pentyl

CONH 2

NC118

Propargyl

CONHMe

NC119

c-Pentyl

CONHMe

NC120

Propargyl

Me, cis CO 2 Me

NC121

c-Pentyl

Me, cis CO 2 Me

NC122

Propargyl

Me, trans CO 2 Me

NC123

c-Pentyl

Me, trans CO 2 Me

NC124

Propargyl

CH 2 CH 3

NC125

c-Pentyl

CH 2 CH 3

NC128

Propargyl

COCH 3

NC129

c-Pentyl

COCH 3

NC130

Propargyl

CHCH 3 (OH)

NC131

c-Pentyl

CHCH 3 (OH)

TABLE 2

R 7 , R 8 = H

Compound

(CR 1 R 2 ) m -Z

R 6

NC134

Propargyl

CO 2 tBu

NC135

c-Pentyl

CO 2 tBu

NC136

Propargyl

CO 2 Et

NC137

c-Pentyl

CO 2 Et

NC138

Propargyl

CO 2 iBu

NC139

c-Pentyl

CO 2 iBu

NC140

Propargyl

CO 2 iPr

NC141

c-Pentyl

CO 2 iPr

Propargyl

COMe

NC142

c-Pentyl

COMe

NC143

Propargyl

COC(CH 3 ) 3

NC144

c-Pentyl

COC(CH 3 ) 3

NC145

Propargyl

COCH 2 (CH 3 ) 3

NC146

c-Pentyl

COCH 2 (CH 3 ) 3

NC147

Propargyl

C(O)N(CH 3 ) 2

NC148

c-Pentyl

C(O)N(CH 3 ) 2

NC149

Propargyl

C(O)N(CH 3 )Et

NC150

c-Pentyl

C(O)N(CH 3 )Et

NC142

Propargyl

C(O)N(CH 3 )iPr

NC143

c-Pentyl

C(O)N(CH 3 )iPr

NC144

Propargyl

C(O)N(CH 3 )iBu

NC145

c-Pentyl

C(O)N(CH 3 )iBu

NC146

Propargyl

C(O)NH(CH 3 )

NC147

c-Pentyl

C(O)NH(CH 3 )

NC148

Propargyl

C(O)NH(Et)

NC149

c-Pentyl

C(O)NH(Et)

NC150

Propargyl

C(O)NH(iPr)

NC142

c-Pentyl

C(O)NH(iPr)

NC143

Propargyl

C(O)NH(iBu)

NC144

c-Pentyl

C(O)NH(iBu)

TABLE 3

R 7 , R 8 = H

Compound

(CR 1 R 2 ) m -Z

R 6

NC153

Propargyl

2-CH 3

NC154

c-Pentyl

2-CH 3

NC155

Propargyl

2-C(CH 3 ) 3

NC156

c-Pentyl

2-C(CH 3 ) 3

NC157

Propargyl

2-C 6 H 5

NC158

c-Pentyl

2-C 6 H 5

Propargyl

3-CH 3

c-Pentyl

3-CH 3

NC159

Propargyl

3-(CH 3 ) 2

NC160

c-Pentyl

3-(CH 3 ) 2

NC161

Propargyl

3-CH 2 CH 3

NC162

c-Pentyl

3-CH 2 CH 3

NC163

Propargyl

3-(CH 3 ) 2 , 5-(CH 3 ) 2

NC164

c-Pentyl

3-(CH 3 ) 2 , 5-(CH 3 ) 2

NC165

Propargyl

4-CH 3

NC166

c-Pentyl

4-CH 3

NC167

Propargyl

4-C 2 H 5

NC168

c-Pentyl

4-C 2 H 5

NC169

Propargyl

4-C(CH 3 ) 3

NC170

c-Pentyl

4-C(CH 3 ) 3

NC171

Propargyl

4-C 6 H 5

NC172

c-Pentyl

4-C 6 H 5

TABLE 4

R 7 , R 8 = H

Compound

(CR 1 R 2 ) m -Z

R 6

NC175

Propargyl

cyclohexyl

NC176

c-Pentyl

cyclohexyl

NC177

Propargyl

CO 2 Et

NC178

c-Pentyl

CO 2 Et

NC179

Propargyl

CO 2 tBu

NC180

c-Pentyl

CO 2 tBu

NC181

Propargyl

COMe

NC182

c-Pentyl

COMe

NC183

Propargyl

CO 2 iBu

NC184

c-Pentyl

CO 2 iBu

NC185

Propargyl

2-Pyrimidinyl

NC186

c-Pentyl

2-Pyrimidinyl

NC187

Propargyl

COC(CH 3 ) 3

NC188

c-Pentyl

COC(CH 3 ) 3

NC189

Propargyl

COMe

NC190

c-Pentyl

COMe

NC191

Propargyl

COCH 2 (CH 3 ) 3

NC192

c-Pentyl

COCH 2 (CH 3 ) 3

NC193

Propargyl

COCH 3

NC194

c-Pentyl

COCH 3

NC195

Propargyl

C(O)N(CH 3 ) 2

NC196

c-Pentyl

C(O)N(CH 3 ) 2

NC197

Propargyl

C(O)N(CH 3 )Et

NC198

c-Pentyl

C(O)N(CH 3 )Et

NC199

Propargyl

C(O)N(CH 3 )iPr

NC200

c-Pentyl

C(O)N(CH 3 )iPr

NC201

Propargyl

C(O)N(CH 3 )iBu

NC202

c-Pentyl

C(O)N(CH 3 )iBu

NC203

Propargyl

C(O)NH(CH 3 )

NC204

c-Pentyl

C(O)NH(CH 3 )

NC205

Propargyl

C(O)NH(Et)

NC206

c-Pentyl

C(O)NH(Et)

NC207

Propargyl

C(O)NH(iPr)

NC208

c-Pentyl

C(O)NH(iPr)

NC209

Propargyl

C(O)NH(iBu)

NC210

c-Pentyl

C(O)NH(iBu)

TABLE 5

R 7 , R 8 = H

Compound

(CR 1 R 2 ) m -Z

R 6

NC211

Propargyl

CH 2 OH

NC212

c-Pentyl

CH 2 OH

NC213

Propargyl

CO 2 H

NC214

c-Pentyl

CO 2 H

NC215

Propargyl

CO 2 Me

NC216

c-Pentyl

CO 2 Me

NC217

Propargyl

CO 2 Et

NC218

c-Pentyl

CO 2 Et

NC219

Propargyl

CH 2 OAc

NC220

c-Pentyl

CH 2 OAc

NC221

Propargyl

CH 2 N(CH 3 ) 2

NC222

c-Pentyl

CH 2 N(CH 3 ) 2

NC223

Propargyl

COOCH 2 CH 2 NHBoc

NC224

c-Pentyl

COOCH 2 CH 2 NHBoc

NC225

Propargyl

COOCH 2 CH 2 NH 2

NC226

c-Pentyl

COOCH 2 CH 2 NH 2

NC227

Propargyl

CONHCH 2 CH 3

NC228

c-Pentyl

CONHCH 2 CH 3

NC229

Propargyl

CONH 2

NC230

c-Pentyl

CONH 2

NC231

Propargyl

CONHMe

NC232

c-Pentyl

CONHMe

NC233

Propargyl

CH 2 CH 3

NC234

c-Pentyl

CH 2 CH 3

NC235

Propargyl

COCH 3

NC236

c-Pentyl

COCH 3

NC237

Propargyl

CHCH 3 (OH)

NG238

c-Pentyl

CHCH 3 (OH)

TABLE 6

R 7 , R 8 = H

Compound

(CR 1 R 2 ) m -Z

R 6

NC239

Propargyl

CH 2 OH

NC240

c-Pentyl

CH 2 OH

NC241

Propargyl

CO 2 H

NC242

c-Pentyl

CO 2 H

NC243

Propargyl

CO 2 Me

NC244

c-Pentyl

CO 2 Me

NC245

Propargyl

CH 2 OAc

NC246

c-Pentyl

CH 2 OAc

NC247

Propargyl

CH 2 N(CH 3 ) 2

NC248

c-Pentyl

CH 2 N(CH 3 ) 2

NC249

Propargyl

COOCH 2 CH 2 NHBoc

NC250

c-Pentyl

COOCH 2 CH 2 NHBoc

NC251

Propargyl

COOCH 2 CH 2 NH 2

NC252

c-Pentyl

COOCH 2 CH 2 NH 2

NC253

Propargyl

CONHCH 2 CH 3

NC254

c-Pentyl

CONHCH 2 CH 3

NC255

Propargyl

CONH 2

NC256

c-Pentyl

CONH 2

NC257

Propargyl

CONHMe

NC258

c-Pentyl

CONHMe

NC259

Propargyl

CH 2 CH 3

NC260

c-Pentyl

CH 2 CH 3

NC261

Propargyl

COCH 3

NC262

c-Pentyl

COCH 3

NC263

Propargyl

CHCH 3 (OH)

NC264

c-Pentyl

CHCH 3 (OH)

TABLE 7

R 7 , R 8 = H

Compound

(CR 1 R 2 ) m -Z

W′

R 6

NC265

Propargyl

CO 2 Me

NC266

c-Pentyl

CO 2 Me

NC267

Propargyl

CO 2 Me

NC268

c-Pentyl

CO 2 Me

NC269

Propargyl

CO 2 Me

NC270

c-Pentyl

CO 2 Me

NC271

Propargyl

CO 2 Me

NC272

c-Pentyl

CO 2 Me

NC273

Propargyl

CH 2 OH

NC274

c-Pentyl

CH 2 OH

NC275

Propargyl

CH 2 OH

NC276

c-Pentyl

CH 2 OH

NC277

Propargyl

CH 2 OH

NC278

c-Pentyl

CH 2 OH

NC279

Propargyl

CH 2 OH

NC280

c-Pentyl

CH 2 OH

NC281

Propargyl

CO 2 H

NC282

c-Pentyl

CO 2 H

NC283

Propargyl

CO 2 H

NC284

c-Pentyl

CO 2 H

NC285

Propargyl

CO 2 H

NC286

c-Pentyl

CO 2 H

NC287

Propargyl

CO 2 H

NC288

c-Pentyl

CO 2 H

NC289

Propargyl

CH 2 OAc

NC290

c-Pentyl

CH 2 OAc

NC291

Propargyl

CH 2 OAc

NC292

c-Pentyl

CH 2 OAc

NC293

Propargyl

CH 2 OAc

NC294

c-Pentyl

CH 2 OAc

NC295

Propargyl

CH 2 OAc

NC296

c-Pentyl

CH 2 OAc

NC297

Propargyl

CONH 2

NC298

c-Pentyl

CONH 2

NC299

Propargyl

CONH 2

NC300

c-Pentyl

CONH 2

NC301

Propargyl

CONH 2

NC302

c-Pentyl

CONH 2

NC303

Propargyl

CONH 2

NC304

c-Pentyl

CONH 2

NC305

Propargyl

CONHMe

NC306

c-Pentyl

CONHMe

NC307

Propargyl

CONHMe

NC308

c-Pentyl

CONHMe

NC309

Propargyl

CONHMe

NC310

c-Pentyl

CONHMe

NC311

Propargyl

CONHMe

NC312

c-Pentyl

CONHMe

NC313

Propargyl

CO 2 tBu

NC314

c-Pentyl

CO 2 tBu

NC315

Propargyl

CO 2 tBu

NC316

c-Pentyl

CO 2 tBu

NC317

Propargyl

CO 2 tBu

NC318

c-Pentyl

CO 2 tBu

NC319

Propargyl

CO 2 tBu

NC320

c-Pentyl

CO 2 tBu

NC321

Propargyl

CO 2 Et

NC322

c-Pentyl

CO 2 Et

NC323

Propargyl

CO 2 Et

NC324

c-Pentyl

CO 2 Et

NC325

Propargyl

CO 2 Et

NC326

c-Pentyl

CO 2 Et

NC327

Propargyl

CO 2 Et

NC328

c-Pentyl

CO 2 Et

NC329

Propargyl

CO 2 iBu

NC330

c-Pentyl

CO 2 iBu

NC331

Propargyl

CO 2 iBu

NC332

c-Pentyl

CO 2 iBu

NC333

Propargyl

CO 2 iBu

NC334

c-Pentyl

CO 2 iBu

NC335

Propargyl

CO 2 iBu

NC336

c-Pentyl

CO 2 iBu

NC337

Propargyl

CO 2 iPr

NC338

c-Pentyl

CO 2 iPr

NC339

Propargyl

CO 2 iPr

NC340

c-Pentyl

CO 2 iPr

NC341

Propargyl

CO 2 iPr

NC342

c-Pentyl

CO 2 iPr

NC343

Propargyl

CO 2 iPr

NC344

c-Pentyl

CO 2 iPr

NC345

Propargyl

COMe

NC346

c-Pentyl

COMe

NC347

Propargyl

COMe

NC348

c-Pentyl

COMe

NC349

Propargyl

COMe

NC350

c-Pentyl

COMe

NC351

Propargyl

COMe

NC352

c-Pentyl

COMe

NC353

Propargyl

COC(CH 3 ) 3

NC354

c-Pentyl

COC(CH 3 ) 3

NC355

Propargyl

COC(CH 3 ) 3

NC356

c-Pentyl

COC(CH 3 ) 3

NC357

Propargyl

COC(CH 3 ) 3

NC358

c-Pentyl

COC(CH 3 ) 3

NC359

Propargyl

COC(CH 3 ) 3

NC360

c-Pentyl

COC(CH 3 ) 3

NC361

Propargyl

COCH 2 (CH 3 ) 3

NC362

c-Pentyl

COCH 2 (CH 3 ) 3

NC363

Propargyl

COCH 2 (CH 3 ) 3

NC364

c-Pentyl

COCH 2 (CH 3 ) 3

NC365

Propargyl

COCH 2 (CH 3 ) 3

NC366

c-Pentyl

COCH 2 (CH 3 ) 3

NC367

Propargyl

COCH 2 (CH 3 ) 3

NC368

c-Pentyl

COCH 2 (CH 3 ) 3

NC369

Propargyl

C(O)N(CH 3 ) 2

NC370

c-Pentyl

C(O)N(CH 3 ) 2

NC371

Propargyl

C(O)N(CH 3 ) 2

NC372

c-Pentyl

C(O)N(CH 3 ) 2

NC373

Propargyl

C(O)N(CH 3 ) 2

NC374

c-Pentyl

C(O)N(CH 3 ) 2

NC375

Propargyl

C(O)N(CH 3 ) 2

NC376

c-Pentyl

C(O)N(CH 3 ) 2

NC377

Propargyl

C(O)N(CH 3 )Et

NC378

c-Pentyl

C(O)N(CH 3 )Et

NC379

Propargyl

C(O)N(CH 3 )Et

NC380

c-Pentyl

C(O)N(CH 3 )Et

NC381

Propargyl

C(O)N(CH 3 )Et

NC382

c-Pentyl

C(O)N(CH 3 )Et

NC383

Propargyl

C(O)N(CH 3 )Et

NC384

c-Pentyl

C(O)N(CH 3 )Et

NC385

Propargyl

C(O)N(CH 3 )iPr

NC386

c-Pentyl

C(O)N(CH 3 )iPr

NC387

Propargyl

C(O)N(CH 3 )iPr

NC388

c-Pentyl

C(O)N(CH 3 )iPr

NC389

Propargyl

C(O)N(CH 3 )iPr

NC390

c-Pentyl

C(O)N(CH 3 )iPr

NC391

Propargyl

C(O)N(CH 3 )iPr

NC392

c-Pentyl

C(O)N(CH 3 )iPr

NC393

Propargyl

C(O)N(CH 3 )iBu

NC394

c-Pentyl

C(O)N(CH 3 )iBu

NC395

Propargyl

C(O)N(CH 3 )iBu

NC396

c-Pentyl

C(O)N(CH 3 )iBu

NC397

Propargyl

C(O)N(CH 3 )iBu

NC398

c-Pentyl

C(O)N(CH 3 )iBu

NC399

Propargyl

C(O)N(CH 3 )iBu

NC400

c-Pentyl

C(O)N(CH 3 )iBu

NC401

Propargyl

C(O)NH(Et)

NC402

c-Pentyl

C(O)NH(Et)

NC403

Propargyl

C(O)NH(Et)

NC404

c-Pentyl

C(O)NH(Et)

NC405

Propargyl

C(O)NH(Et)

NC406

c-Pentyl

C(O)NH(Et)

NC407

Propargyl

C(O)NH(Et)

NC408

c-Pentyl

C(O)NH(Et)

NC409

Propargyl

C(O)NH(iPr)

NC410

c-Pentyl

C(O)NH(iPr)

NC411

Propargyl

C(O)NH(iPr)

NC412

c-Pentyl

C(O)NH(iPr)

NC413

Propargyl

C(O)NH(iPr)

NC414

c-Pentyl

C(O)NH(iPr)

NC415

Propargyl

C(O)NH(iPr)

NC416

c-Pentyl

C(O)NH(iPr)

NC417

Propargyl

C(O)NH(iBu)

NC418

c-Pentyl

C(O)NH(iBu)

NC419

Propargyl

C(O)NH(iBu)

NC420

c-Pentyl

C(O)NH(iBu)

NC421

Propargyl

C(O)NH(iBu)

NC422

c-Pentyl

C(O)NH(iBu)

NC423

Propargyl

C(O)NH(iBu)

NC424

c-Pentyl

C(O)NH(iBu)

NC425

Propargyl

CH 2 OCOCH 3

NC426

c-Pentyl

CH 2 OCOCH 3

NC427

Propargyl

CH 2 OCOCH 3

NC428

c-Pentyl

CH 2 OCOCH 3

NC429

Propargyl

CH 2 OCOCH 3

NC430

c-Pentyl

CH 2 OCOCH 3

NC431

Propargyl

CH 2 OCOCH 3

NC432

c-Pentyl

CH 2 OCOCH 3

NC433

Propargyl

CH 2 OCOEt

NC434

c-Pentyl

CH 2 OCOEt

NC435

Propargyl

CH 2 OCOEt

NC436

c-Pentyl

CH 2 OCOEt

NC437

Propargyl

CH 2 OCOEt

NC438

c-Pentyl

CH 2 OCOEt

NC439

Propargyl

CH 2 OCOEt

NC440

c-Pentyl

CH 2 OCOEt

NC441

Propargyl

CH 2 OCOiPr

NC442

c-Pentyl

CH 2 OCOiPr

NC443

Propargyl

CH 2 OCOiPr

NC444

c-Pentyl

CH 2 OCOiPr

NC445

Propargyl

CH 2 OCOiPr

NC446

c-Pentyl

CH 2 OCOiPr

NC447

Propargyl

CH 2 OCOiPr

NC448

c-Pentyl

CH 2 OCOiPr

NC449

Propargyl

CH 2 OCOiBu

NC450

c-Pentyl

CH 2 OCOiBu

NC451

Propargyl

CH 2 OCOiBu

NC452

c-Pentyl

CH 2 OCOiBu

NC453

Propargyl

CH 2 OCOiBu

NC454

c-Pentyl

CH 2 OCOiBu

NC455

Propargyl

CH 2 OCOiBu

NC456

c-Pentyl

CH 2 OCOiBu

58. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , and a pharmaceutically acceptable excipient.

59. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, in the form of a single stereoisomer or mixture of stereoisomers thereof.

60. A method for stimulating motor activity without dyskinesia in a mammal, comprising administering a therapeutically effective amount of an A 2A anatagonist compound of claim 1 to the mammal in need of such treatment.

61. The method of claim 60 , wherein the mammal suffers from a disorder selected from Huntington's disease, catalepsy, Parkinson's disease, and narcolepsy.

62. The method of claim 60 wherein the mammal suffers from a disorder selected from progressive supernuclear palsy, Huntington's disease, multiple system atrophy, corticobasal degeneration, Wilsons disease, Hallervorden-Spatz disease, progressive pallidal atrophy, Dopa-responsive dystonia-Parkinsonism, spasticity or other disoders of the basal ganglia which result in dyskinesias.

63. A compound of formula I:

wherein R 1 and R 2 are hydrogen, m is 0, 1, 2 or 3 and Z is the moiety derived from the ring selected from the group consisting of furan, dihydro-furan, tetrahydrofuran, thiophene, pyrrole, 2H-pyrrole, 2-pyrroline, 3-pyrroline, pyrrolidine, 1,3-dioxolane, oxazole, thiazole, imidazole, dihydro-imidazole, 2-imidazoline, imidazolidine, pyrazole, 2-pyrazoline, pyrazolidine, isoxazole, isothiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,3-triazole, 1,2,4-triazole, 1,3,4-thiadiazole, 2H-pyran, 1H-tetrazole, 4H-pyran, pyridine, dihydro-pyridine, tetrahydro-pyridine, piperidine, 1,4-dioxane, morpholine, 1,4-dithiane, thiomorpholine, pyridazine, pyrimidine, dihydro-pyrimidine, tetrahydro-pyrimidine, hexahydro-pyrimidine, pyrazine, dihydro-pyrazine, tetrahydro-pyrazine, piperazine, 1,3,5-triazine and 1,3,5-trithiane, wherein each Z group is optionally substituted with from 1 R a group;

Y is —CR 3 R 4 R 5 or NR 4 R 5 ;

R 3 is selected from the group consisting of hydrogen, halo, —OR a , SR a , (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, heterocycle, hetrocycle(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)—, R a S(═O) 2 —; or if the ring formed from the group CR 3 R 4 R 5 is aryl or heteroaryl or partially unsaturated, then R 3 can be absent;

R 4 and R 5 together with the atoms to which they are attached form a saturated or partially unsaturated, mono-, bi- or tricyclic or aromatic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR a —) in the ring, wherein any ring comprising R 4 and R 5 is optionally further substituted with from 1 to 14 R 6 groups; wherein each R 6 is independently selected from the group consisting of halo, —OR a , —SR a , substituted or unsubstituted (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, heterocycle, hetrocyclyl(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)— or two R 6 groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R 6 groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring;

R c is selected from the group consisting of hydrogen and (C 1 –C 8 )alkyl; and

n is 0, 1, 2 or 3, provided that when m is 0, Z is not attached via a heteroatom, and when n is 0, Y is not —NR 4 R 5 ; or

a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

64. A compound of formula II:

wherein R 1 and R 2 are hydrogen, m is 0, 1, 2 or 3 and Z is selected from the group consisting of furan, dihydro-furan, tetrahydrofuran, thiophene, pyrrole, 2H-pyrrole, 2-pyrroline, 3-pyrroline, pyrrolidine, 1,3-dioxolane, oxazole, thiazole, imidazole, dihydro-imidazole, 2-imidazoline, imidazolidine, pyrazole, 2-pyrazoline, pyrazolidine, isoxazole, isothiazole, 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,2,3-triazole, 1,2,4-triazole, 1,3,4-thiadiazole, 2H-pyran, 1H-tetrazole, 4H-pyran, pyridine, dihydro-pyridine, tetrahydro-pyridine, piperidine, 1,4-dioxane, morpholine, 1,4-dithiane, thiomorpholine, pyridazine, pyrimidine, dihydro-pyrimidine, tetrahydro-pyrimidine, hexahydro-pyrimidine, pyrazine, dihydro-pyrazine, tetrahydro-pyrazine, piperazine, 1,3,5-triazine and 1,3,5-trithiane, wherein each Z group is optionally substituted with 1 R a group;

Y is —CR 3 R 4 R 5 or NR 4 R 5 ;

R 4 and R 5 together with the atoms to which they are attached form a saturated or partially unsaturated, mono-, bi- or tricyclic or aromatic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11 or 12 ring atoms, wherein the ring atoms are optionally interrupted by 1, 2, 3 or 4 heteroatoms selected from the group consisting of —O—, —S—, —SO—, —S(O) 2 — or amine (—NR a —) in the ring, wherein any ring comprising R 4 and R 5 is optionally further substituted with from 1 to 14 R 6 groups; wherein each R 6 is independently selected from the group consisting of halo, —OR a , —SR a , substituted or unsubstituted (C 1 –C 8 )alkyl, cyano, nitro, trifluoromethyl, trifluoromethoxy, (C 3 –C 8 )cycloalkyl, (C 6 –C 12 )bicycloalkyl, heterocycle, hetrocyclyl(C 1 –C 8 )alkyl, aryl, aryl(C 1 –C 8 )alkyl, heteroaryl, heteroaryl(C 1 –C 8 )alkyl, —CO 2 R a , R a C(═O)O—, R a C(═O)—, —OCO 2 R a , R a R b NC(═O)O—, R b OC(═O)N(R a )—, R a R b N—, R a R b NC(═O)—, R a C(═O)N(R b )—, R a R b NC(═O)N(R b )—, R a R b NC(═S)N(R b )—, R a OC(═S)—, R a C(═S)—, —SSR a , R a S(═O)— or two R 6 groups and the atom to which they are attached combined to form C═O or C═S, or wherein two R 6 groups together with the atom or atoms to which they are attached can form a carbocyclic or heterocyclic ring;

R c is selected from the group consisting of hydrogen and (C 1 –C 8 )alkyl; and

m is 0 to 8; n is 0, 1, 2 or 3, provided that when n is 0, Z is not attached via a heteroatom, and when n is 0, Y is not —NR 4 R 5 ; or

a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

65. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 2 , and a pharmaceutically acceptable excipient.

66. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 5 , and a pharmaceutically acceptable excipient.

67. A method for stimulating motor activity without dyskinesia in a mammal, comprising administering a therapeutically effective amount of an A 2A anatagonist compound of claim 2 to the mammal in need of such treatment.

68. A method for stimulating motor activity without dyskinesia in a mammal, comprising administering a therapeutically effective amount of an A 2A anatagonist compound of claim 5 to the mammal in need of such treatment.

69. A compound according to claim 56 , wherein the compound is:

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-propargyladenine (2) or a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

70. A compound according to claim 56 , wherein the compound is:

9-Cyclopentyl-2-{2-[1(S)-hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}adenine (3) or a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

71. A compound according to claim 56 , wherein the compound is:

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-N6-(3-methoxybenzyl)-9-(propargyl)adenine (36) or a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

72. A compound according to claim 56 , wherein the compound is:

2-{2-[1(S)-Hydroxy-3(R)-methyl-1-cyclohexyl]ethyn-1-yl}-9-(propargyl)-N6-(pyridin-2-ylmethyl)adenine (37) or a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

73. A compound according to claim 56 , wherein the compound is:

9-Cyclobutylmethyl-2-{2-[hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (46) or a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

74. A compound according to claim 56 , wherein the compound is:

9-Cyclopentyl-2-{2-[hydroxy-adamantan-2-yl]ethyn-1-yl}adenine (50) or a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

75. A compound according to claim 56 , wherein the compound is:

2-{2-[Hydroxy-adamantan-2-yl]ethyn-1-yl}-9-propargyl-adenine (51) or a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

76. A compound according to claim 56 , wherein the compound is: 2-{2-[Hydroxy-norbornan-2-yl]ethyn-1-yl}-9-propargyladenine or a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

77. A compound according to claim 56 , wherein the compound is:

2-{3-[1-(Methoxycarbanoyl)piperidin-4-yl]propyn-1-yl}-9-propargyladenine (63) or a pharmaceutically acceptable salt thereof, optionally in the form of a single stereoisomer or mixture of stereoisomers thereof.

78. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 69 , and a pharmaceutically acceptable excipient.

79. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 70 , and a pharmaceutically acceptable excipient.

80. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 71 , and a pharmaceutically acceptable excipient.

81. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 72 , and a pharmaceutically acceptable excipient.

82. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 73 , and a pharmaceutically acceptable excipient.

83. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 74 , and a pharmaceutically acceptable excipient.

84. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 75 , and a pharmaceutically acceptable excipient.

85. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 76 , and a pharmaceutically acceptable excipient.

86. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 77 , and a pharmaceutically acceptable excipient.

Assignments (6)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 9, 2013

From: DOGWOOD PHARMACEUTICALS, INC.

To: ADENOSINE THERAPEUTICS, LLC

Reel/Frame 029785/0460 →

MERGER Recorded Jan 25, 2013

From: TROVIS PHARMACEUTICALS HOLDINGS, INC.

To: CLINICAL DATA, INC.

Reel/Frame 029694/0831 →

MERGER Recorded Jan 24, 2013

From: TROVIS PHARMACEUTICALS LLC

To: TROVIS PHARMACEUTICALS HOLDINGS, INC.