Sulphonamido-substituted bridged bicycloalkyl derivatives
View Patent ↗A class of compounds is disclosed, comprising sulphonamido-substituted bridged bicycloalkyl structures. The compounds are inhibitors of gamma-secretase, and hence are useful in the treatment of and/or prevention of Alzheimer's disease.
1. A compound of formula II:
wherein:
w is 1 or 2; and
A 1 represents —CH 2 CH 2 CH 2 CH 2 —, —CH 2 CH═CHCH 2 — or —CH 2 CXYCH 2 —;
X represents halogen, R 9 , —OR 9 , —SR 9 , —S(O) t R 10 where t is 1 or 2, —OSO 2 R 9 , —N(R 9 ) 2 , —COR 9 , CO 2 R 9 , —OCOR 10 , —OCO 2 R 10 , —CON(R 9 ) 2 , —SO 2 N(R 9 ) 2 , —OSO 2 N(R 9 ) 2 , —NR 9 COR 10 , —NR 9 CO 2 R 10 or —NR 9 SO 2 R 10 ;
Y represents H or C 1-6 alkyl;
or X and Y together represent ═O, ═S, ═N—OR 11 or ═CHR 11 ;
R 1 represents H, C 1-4 alkyl, or C 2-4 alkenyl;
R 2 represents H;
R 3 represents C 1-16 alkyl, C 3-10 cycloalkyl, C 2-16 alkenyl, C 2-16 alkynyl, C 6-10 arylC 1-6 alkyl, heteroarylC 1-6 alkyl, C 6-10 arylC 2-6 alkenyl, heteroarylC 2-6 alkenyl, C 6-10 aryl, bi(C 6-10 aryl), heteroaryl, bi(heteroaryl) or heterocyclyl; wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups represented by R 3 or forming part of a group represented by R 3 optionally bear up to 3 substituents independently selected from halogen, CN, NO 2 , —OR 7 , —SR 7 , —S(O) t R 8 where t is 1 or 2, —N(R 7 ) 2 , —COR 7 , —CO 2 R 7 , —OCOR 8 , —CON(R 7 ) 2 , —NR 7 COR 8 , —C 1-6 alkylNR 7 COR 8 , —NR 7 CO 2 R 8 and —NR 7 SO 2 R 8 ; and the aryl, heteroaryl and heterocyclic groups represented by R 3 or forming part of a group represented by R 3 optionally bear up to 5 substituents independently selected from R 8 , halogen, CN, NO 2 , —OR 7 , —SR 7 , —S(O) t R 8 where t is 1 or 2, —N(R 7 ) 2 , —COR 7 , —CO 2 R 7 , —OCOR 8 , —CON(R 7 ) 2 , —NR 7 COR 8 , —C 1-6 alkylNR 7 COR 8 , —NR 7 CO 2 R 8 and —NR 7 SO 2 R 8 ;
R 7 represents H or R 8 ; or two R 7 groups together with a nitrogen atom to which they are mutually attached may complete a pyrrolidine, piperidine, piperazine or morpholine ring;
R 8 represents C 1-10 alkyl, perfluoroC 1-6 alkyl, C 3-10 cycloalkyl, C 3-6 cycloalkylC 1-6 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, Ar or —C 1-6 alkylAr;
R 9 represents H or R 10 ; or two R 9 groups together with a nitrogen atom to which they are mutually attached may complete a pyrrolidine, piperidine, piperazine or morpholine ring which is optionally substituted by R 12 , —COR 12 or —SO 2 R 12 ;
R 10 represents C 1-10 alkyl, perfluoroC 1-6 alkyl, C 3-10 cycloalkyl, C 3-6 cycloalkylC 1-6 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 6-10 aryl, heteroaryl, heterocyclyl, C 6-10 arylC 1-6 alkyl, heteroarylC 1-6 alkyl, C 6-10 arylC 2-6 alkenyl, or heteroarylC 2-10 alkenyl, wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups optionally bear one substituent selected from halogen, CF 3 , NO 2 , CN, —OR 11 , —SR 11 , —SO 2 R 12 , —COR 11 , —CO 2 R 11 , —CON(R 11 ) 2 , —OCOR 12 , —N(R 11 ) 2 and —NR 11 COR 12 ; and the aryl, heteroaryl and heterocyclic groups optionally bear up to 3 substituents independently selected from halogen, NO 2 , CN, R 12 , —OR 11 , —SR 11 , —SO 2 R 12 , —COR 11 , —CO 2 R 11 , —CON(R 11 ) 2 , —OCOR 12 , —N(R 11 ) 2 and —NR 11 COR 12 ;
R 11 represents H, C 1-6 alkyl, perfluoroC 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ar, —C 1-6 alkylAr or ArOC 1-6 alkyl;
R 12 represents C 1-6 alkyl, perfluoroC 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ar, —C 1-6 alkylAr or ArOC 1-6 alkyl; or two R 12 groups together with a nitrogen atom to which they are mutually attached may complete a heterocyclic ring system selected from the group consisting of pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, 2,5-diazabicyclo[2.2.1]heptane and 2-aza-5-oxabicyclo[2.2.1]heptane, said ring system bearing 0-2 substituents selected from halogen, CN, NO 2 , C 1-6 alkyl, perfluoroC 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ar, —C 1-6 alkylAr or ArOC 1-6 alkyl, OR 11 , NHR 11 , and COR 11 ;
Z 2 completes an imidazole ring;
X represents halogen, R 9 , —OR 9 , —SR 9 , —S(O) t R 10 where t is 1 or 2, —OSO 2 R 9 , —N(R 9 ) 2 , —COR 9 , —CO 2 R 9 , —OCOR 10 , —OCO 2 R 10 , —CON(R 9 ) 2 , —SO 2 N(R 9 ) 2 , —OSO 2 N(R 9 ) 2 , —NR 9 COR 10 , —NR 9 CO 2 R 10 or —NR 9 SO 2 R 10 ;
Y represents H or C 1-6 alkyl;
or X and Y together represent ═O, ═S, ═N—OR 11 or ═CHR 11 ;
R 1 represents H, C 1-4 alkyl, or C 2-4 alkenyl;
R 2 represents H;
R 3 represents C 1-16 alkyl, C 3-10 cycloalkyl, C 2-16 alkenyl, C 2-16 alkynyl, C 6-10 arylC 1-6 alkyl, heteroarylC 1-6 alkyl, C 6-10 arylC 2-6 alkenyl, heteroarylC 2-6 alkenyl, C 6-10 aryl, bi(C 6-10 aryl), heteroaryl, bi(heteroaryl) or heterocyclyl; wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups represented by R 3 or forming part of a group represented by R 3 optionally bear up to 3 substituents independently selected from halogen, CN, NO 2 , —OR 7 , —SR 7 , —S(O) t R 8 where t is 1 or 2, —N(R 7 ) 2 , —COR 7 , —CO 2 R 7 , —OCOR 8 , —CON(R 7 ) 2 , —NR 7 COR 8 , —C 1-6 alkylNR 7 COR 8 , —NR 7 CO 2 R 8 and —NR 7 SO 2 R 8 ; and the aryl, heteroaryl and heterocyclic groups represented by R 3 or forming part of a group represented by R 3 optionally bear up to 5 substituents independently selected from R 8 , halogen, CN, NO 2 , —OR 7 , —SR 7 , —S(O) t R 8 where t is 1 or 2, —N(R 7 ) 2 , —COR 7 , —CO 2 R 7 , —CON(R 7 ) 2 , —NR 7 COR 8 , —C 1-6 alkylNR 7 COR 8 , —NR 7 CO 2 R 8 and —NR 7 SO 2 R 8 ;
R 7 H or R 8 ; or two R 7 groups together with a nitrogen atom to which they are mutually attached may complete a pyrrolidine, piperidine, piperazine or morpholine ring;
R 8 represents C 1-10 alkyl, perfluoroC 1-6 alkyl, C 3-10 cycloalkyl, C 3-6 cycloalkylC 1-6 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, Ar or —C 1-6 alkylAr;
R 9 H or R 10 ; or two R 9 groups together with a nitrogen atom to which they are mutually attached may complete a pyrrolidine, piperidine, piperazine or morpholine ring which is optionally substituted by R 12 , —COR 12 or —SO 2 R 12 ;
R 10 represents C 1-10 alkyl, perfluoroC 1-6 alkyl, C 3-10 cycloalkyl, C 3-6 cycloalkylC 1-6 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 6-10 aryl, heteroaryl, heterocyclyl, C 6-10 arylC 1-6 alkyl, heteroarylC 1-6 alkyl, C 6-10 arylC 2-6 alknyl, or heteroarylC 2-6 alkenyl, wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups optionally bear one substituent selected from halogen, CF 3 , NO 2 , CN, —OR 11 , —SR 11 , —SO 2 R 12 , —COR 11 , —CO 2 R 11 , —CON(R 11 ) 2 , —OCOR 12 , —N(R 11 ) 2 and —NR 11 COR 12 ; and the aryl, heteroaryl and heterocyclic groups optionally bear up to 3 substituents independently selected from halogen, NO 2 , CN, R 12 , —OR 11 , —SR 11 , —SO 2 R 12 , —COR 11 , —CO 2 R 11 , —CON(R 11 ) 2 , —OCOR 12 , —N(R 11 ) 2 and —NR 11 COR 12 ;
R 11 represents H, C 1-6 alkyl, perfluoroC 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ar, —C 1-6 alkylAr or ArOC 1-6 alkyl;
Ar represents phenyl or heteroaryl either of which optionally bears up to 3 substituents independently selected from halogen, CF 3 , NO 2 , CN, OCF 3 , C 1-6 alkyl and C 1-6 alkoxy;
“heterocyclyl” at every occurrence thereof means a cyclic or polycyclic system of up to 10 ring atoms selected from C, N, O and S, wherein none of the constituent rings is aromatic and wherein at least one ring atom is other than C; and
“heteroaryl” at every occurrence thereof means a cyclic or polycyclic system of up to 10 ring atoms selected from C, N, O and S, wherein at least one of the constituent rings is aromatic and wherein at least one ring atom is other than C;
or a pharmaceutically acceptable salt thereof.
2. A compound according to claim 1 wherein w is 1; R 1 and R 2 are both H; Y is H or together with X represents ═O, ═N—OR 11 or ═CH 2 ; and X is selected from H, C 1-6 alkyl, —CO 2 R 9 , —OCOR 10 , —OCO 2 R 10 , —OSO 2 R 9 , and —CON(R 9 ) 2 , or together with Y represents ═O, ═N—OR 11 or ═CH 2 .
3. A compound of formula IIA:
wherein:
w is 1 or 2; and
A 2 represents —CH 2 —NR 13 —CXY—CH 2 — or
R 12 represents C 1-6 alkyl, perfluoroC 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ar, —C 1-6 alkylAr or ArOC 1-6 alkyl; or two R 12 groups together with a nitrogen atom to which they are mutually attached may complete a heterocyclic ring system selected from the group consisting of pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, 2,5-diazabicyclo[2.2.1 ]heptane and 2-aza-5-oxabicyclo[2.2.1]heptane, said ring system bearing 0-2 substituents selected from halogen, CN, NO 2 , C 1-6 alkyl, perfluoroC 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ar, —C 1-6 alkylAr or ArOC 1-6 alkyl, OR 11 , NHR 11 , and COR 11 ;
R 13 represents R 9 , —COR 10 , —CO 2 R 10 , —SO 2 R 10 , —CON(R 9 ) 2 or —SO 2 N(R 9 ) 2 ;
Ar represents phenyl or heteroaryl either of which optionally bears up to 3 substituents independently selected from halogen, CF 3 , NO 2 , CN, OCF 3 , C 1-6 alkyl and C 1-6 alkoxy;
“heterocyclyl” at every occurrence thereof means a cyclic or polycyclic system of up to 10 ring atoms selected from C, N, O and S, wherein none of the constituent rings is aromatic and wherein at least one ring atom is other than C; and
“heteroaryl” at every occurrence thereof means a cyclic or polycyclic system of up to 10 ring atoms selected from C, N, O and S, wherein at least one of the constituent rings is aromatic and wherein at least one ring atom is other than C;
or a pharmaceutically acceptable salt thereof.
4. A compound of formula III:
wherein w is 1 or 2;
Z completes an aromatic ring;
R 1 represents H, C 1-4 alkyl, or C 2-4 alkenyl;
R 2 represents H;
R 3 represents C 1-16 alkyl, C 3-10 cycloalkyl, C 2-16 alkenyl, C 2-16 alkynyl, C 6-10 arylC 1-6 alkyl, heteroarylC 1-6 alkyl, C 6-10 arylC 2-6 alkenyl, heteroarylC 2-6 alkenyl, C 6-10 aryl, bi(C 6-10 aryl), heteroaryl, bi(heteroaryl) or heterocyclyl; wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups represented by R 3 or forming part of a group represented by R 3 optionally bear up to 3 substituents independently selected from halogen, CN, NO 2 , —OR 7 , —SR 7 , —S(O) t R 8 where t is 1 or 2, —N(R 7 ) 2 , —COR 7 , —CO 2 R 7 , —OCOR 8 , —CON(R 7 ) 2 , —NR 7 COR 8 , —C 1-6 alkylNR 7 COR 8 , —NR 7 CO 2 R 8 and —NR 7 SO 2 R 8 ; and the aryl, heteroaryl and heterocyclic groups representented by R 3 or forming part of a group represented by R 3 optionally bear up to 5 substituents independently selected from R 8 , halogen, CN, NO 2 , —OR 7 , —SR 7 , —S(O) t R 8 where t is 1 or 2, —N(R 7 ) 2 , —COR 7 , —CO 2 R 7 , —OCOR 8 , —CON(R 7 ) 2 , —NR 7 COR 8 , —C 1-6 alkylNR 7 COR 8 , —NR 7 CO 2 R 8 and —NR 7 SO 2 R 8 , wherein the R 3 heteroaryl group is a cyclic or polycyclic system of up to 10 ring atoms selected from C, N, O and S, wherein at least one of the constituent rings is aromatic and wherein at least one ring atom is other than C;
R 4 , R 5 and R 6 independently represent R 9 , halogen, CN, NO 2 , —OR 9 , —SR 9 , —S(O) t R 10 where t is 1 or 2, —N(R 9 ) 2 , —COR 9 , —CO 2 R 9 , —OCOR 10 , —CON(R 9 ) 2 , —SO 2 N(R 9 ) 2 , —NR 9 COR 10 , —NR 9 CO 2 R 10 , —NR 9 SO 2 R 10 , —CH═CHCH 2 N(R 16 ) 2 , —CH 2 OR 10 , —CH 2 N(R 16 ) 2 , —NHCOCH 2 OR 10 or —NHCOCH 2 N(R 16 ) 2 ;
R 7 represents H or R 8 ; or two R 7 groups together with a nitrogen atom to which they are mutually attached may complete a pyrrolidine, piperidine, piperazine or morpholine ring;
R 8 represents C 1-10 alkyl, perfluoroC 1-6 alkyl, C 3-10 cycloalkyl, C 3-6 cycloalkylC 1-6 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, Ar or —C 1-6 alkylAr;
R 9 represents H or R 10 ; or two R 9 groups together with a nitrogen atom to which they are mutually attached may complete a pyrrolidine, piperidine, piperazine or morpholine ring which is optionally substituted by R 12 , —COR 12 or —SO 2 R 12 ;
R 10 represents C 1-10 alkyl, perfluoroC 1-6 alkyl, C 3-10 cycloalkyl, C 3-6 cycloalkylC 1-6 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 6-10 aryl, heteroaryl, heterocyclyl, C 6-10 arylC 1-6 alkyl, heteroarylC 1-6 alkyl, C 6-10 arylC 2-6 alkenyl, or heteroarylC 2-6 alkenyl, wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups optionally bear one substituent selected from halogen, CF 3 , NO 2 , CN, —OR 11 , —SR 11 , —SO 2 R 12 , —COR 11 , —CO 2 R 11 , —CON(R 11 ) 2 , —OCOR 12 , —N(R 11 ) 2 and —NR 11 COR 12 ; and the aryl, heteroaryl and heterocyclic groups optionally bear up to 3 substituents independently selected from halogen, NO 2 , CN, R 12 , —OR 11 , —SR 11 , —SO 2 R 12 , —COR 11 , —CO 2 R 11 , —CON(R 11 ) 2 , —OCOR 12 , —N(R 11 ) 2 and —NR 11 COR 12 , wherein the R 10 heteroaryl group is selected from the group consisting of pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, 1,2,4-triazine, 1,3,5-triazine, 1,2,3,4-tetrahydroisoquinoline, imidazor[2,1-b]thiazole and benzo[1,4]dioxin;
R 11 represents H, C 1-6 alkyl, perfluoroC 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ar, —C 1-6 alkylAr or ArOC 1-6 alkyl;
R 12 represents C 1-6 alkyl, perfluoroC 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ar, —C 1-6 alkylAr or ArOC 1-6 alkyl; or two R 12 groups together with a nitrogen atom to which they are mutually attached may complete a heterocyclic ring system selected from the group consisting of pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, 2,5-diazabicyclo[2.2.1]heptane and 2-aza-5-oxabicyclo[2.2.1]heptane, said ring system bearing 0-2 substituents selected from halogen, CN, NO 2 , C 1-6 alkyl, perfluoroC 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ar, —C 1-6 alkylAr or ArOC 1-6 alkyl, OR 11 , NHR 11 , and COR 11 ;
each R 16 independently represents H or R 10 , or two R 16 groups together with the nitrogen to which they are mutually attached complete a mono- or bicyclic heterocyclic ring system of 5-10 ring atoms selected from C, N, O and S, said ring system optionally having an additional aryl or heteroaryl ring fused thereto, said heterocyclic system and/or additional fused ring bearing 0-3 substituents independently selected from halogen, NO 2 , CN, R 12 , —OR 11 , —SR 11 , —SO 2 R 12 , —COR 11 , —CO 2 R 11 , —CON(R 11 ) 2 , —OCOR 12 , —N(R 11 ) 2 and —NR 11 COR 12 ;
Ar represents phenyl or heteroaryl either of which optionally bears up to 3 substituents independently selected from halogen, CF 3 , NO 2 , CN, OCF 3 , C 1-6 alkyl and C 1-6 alkoxy;
“heterocyclyl” at every occurrence thereof means a cyclic or polycyclic system of up to 10 ring atoms selected from C, N, O and S, wherein none of the constituent rings is aromatic and wherein at least one ring atom is other than C; and
or a pharmaceutically acceptable salt thereof.
5. A compound according to claim 4 of formula IV:
or a pharmaceutically acceptable salt thereof.
6. A compound according to claim 5 of formula V:
wherein R 4a represents —N(R 9 ) 2 , —NR 9 COR 10 or —NR 9 CO 2 R 10 ;
or a pharmaceutically acceptable salt thereof.
7. A compound according to claim 5 of formula VA:
wherein R 4b represents C 2-6 alkenyl (which is optionally substituted by halogen, CN, OR 11 , —CO 2 R 11 , —COR 11 or —CON(R 11 ) 2 ), C 6-10 arylC 2-6 alkenyl, heteroarylC 2-6 alkenyl, —CH═CHCH 2 N(R 16 ) 2 , —OR 10 , —CH 2 OR 9 , —NHCOCH 2 OR 10 or —NHCOCH 2 N(R 16 ) 2 ;
or a pharmaceutically acceptable salt thereof.
8. A compound according to claim 7 wherein R 4b represents —CH═CH 2 , —CH═CHCN, —CH═CH—CH 2 OR 11 , —CH═CH—CO—Ar, —CH═CH—CO 2 R 11 , —CH═CHAr, —CH═CHCH 2 N(R 16 ) 2 , —OCH 2 Ar, —OCH 2 CH 2 OR 12 , —OCH 2 CON(R 12 ) 2 , —OCH 2 CH 2 N(R 12 ) 2 , —CH 2 OR 9 , —NHCOCH 2 OR 10 or —NHCOCH 2 N(R 16 ) 2 .
9. A compound of formula IIIC:
wherein
X represents halogen, R 9 , —OR 9 , —SR 9 , —S(O) t R 10 where t is 1 or 2, —OSO 2 R 9 , —N(R 9 ) 2 , —COR 9 , —CO 2 R 9 , —OCOR 10 , —OCO 2 R 10 , —CON(R 9 ) 2 , —SO 2 N(R 9 ) 2 , —OSO 2 N(R 9 ) 2 , —NR 9 COR 10 , —NR 9 CO 2 R 10 or —NR 9 SO 2 R 10 ;
Y represents H or C 1-6 alkyl;
or X and Y together represent ═O, ═S, ═N—OR 11 or ═CHR 11 ;
R 1 represents H, C 1-4 alkyl, or C 2-4 alkenyl;
R 2 represents H;
R 3 represents C 1-16 alkyl, C 3-10 cycloalkyl, C 2-16 alkenyl, C 2-16 alkynyl, C 6-10 arylC 1-6 alkyl, heteroarylC 1-6 alkyl, C 6-10 arylC 2-6 alkenyl, heteroarylC 2-6 alkenyl, C 6-10 aryl, bi(C 6-10 aryl), heteroaryl, bi(heteroaryl) or heterocyclyl; wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups represented by R 3 or forming part of a group represented by R 3 optionally bear up to 3 substituents independently selected from halogen, CN, NO 2 , —OR 7 , —SR 7 , —S(O) t R 8 where t is 1 or 2, —N(R 7 ) 2 , —COR 7 , —CO 2 R 7 , —OCOR 8 , —CON(R 7 ) 2 , —NR 7 COR 8 , —C 1-6 alkylNR 7 COR 8 , —NR 7 CO 2 R 8 and —NR 7 SO 2 R 8 ; and the aryl, heteroaryl and heterocyclic groups represented by R 3 or forming part of a group represented by R 3 optionally bear up to 5 substituents independently selected from R 8 , halogen, CN, NO 2 , —OR 7 , —SR 7 , —S(O) t R 8 where t is 1 or 2, —N(R 7 ) 2 , —COR 7 , —CO 2 R 7 , —OCOR 8 , —CON(R 7 ) 2 , —NR 7 COR 8 , —C 1-6 alkylNR 7 COR 8 , —NR 7 CO 2 R 8 and —NR 7 SO 2 R 8 , wherein the R 3 heteroaryl group is a cyclic or polycyclic system of up to 10 ring atoms selected from C, N, O and S, wherein at least one of the constituent rings is aromatic and wherein at least one ring atom is other than C;
R 4 represents halogen, CN, NO 2 , —OR 9 , —SR 9 , —S(O) t R 10 where t is 1 or 2, —N(R 9 ) 2 , —COR 9 , —CO 2 R 9 , OCOR 10 , —CON(R 9 ) 2 , —SO 2 N(R 9 ) 2 , —NR 9 COR 10 , —NR 9 CO 2 R 10 , —NR 9 SO 2 R 10 , —CH═CHCH 2 N(R 16 ) 2 , —CH 2 OR 10 , —CH 2 N(R 16 ) 2 , —NHCOCH 2 OR 10 , or —NHCOCH 2 N(R 16 ) 2 ;
R 7 represents H or R 8 ; or two R 7 groups together with a nitrogen atom to which they are mutually attached may complete a pyrrolidine, piperidine, piperazine or morpholine ring;
R 8 represents C 1-10 alkyl, perfluoroC 1-6 alkyl, C 3-10 cycloalkyl, C 3-6 cycloalkylC 1-6 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, Ar or —C 1-6 alkylAr;
R 9 H or R 10 ; or two R 9 groups together with a nitrogen atom to which they are mutually attached may complete a pyrrolidine, piperidine, piperazine or morpholine ring which is optionally substituted by R 12 , —COR 12 or —SO 2 R 12 ;
R 10 represents C 1-10 alkyl, perfluoroC 1-6 alkyl, C 3-10 cycloalkyl, C 3-6 cycloalkylC 1-6 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 6-10 aryl, heteroaryl, heterocyclyl, C 6-10 arylC 1-6 alkyl, heteroarylC 1-6 alkyl, C 6-10 arylC 2-6 alkenyl, or heteroarylC 2-6 alkenyl, wherein the alkyl, cycloalkyl, alkenyl and alkynyl groups optionally bear one substituent selected from halogen, CF 3 , NO 2 , CN, —OR 11 , —SR 11 , —SO 2 R 12 , —COR 11 , —CO 2 R 11 , —CON(R 11 ) 2 , —OCOR 12 , —N(R 11 ) 2 and —NR 11 COR 12 ; and the aryl, heteroaryl and heterocyclic groups optionally bear up to 3 substituents independently selected from halogen, NO 2 , CN, R 12 , —OR 11 , —SR 11 , —SO 2 R 12 , —COR 11 , —CO 2 R 11 , —CON(R 11 ) 2 , —OCOR 12 , —N(R 11 ) 2 and —NR 11 COR 12 , wherein the R 10 heteroaryl group is selected from the group consisting of pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, pyrrolyl, furyl, thienyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, 1,2,4-triazine, 1,3,5-triazine, 1,2,3,4-tetrahydroisoquinoline, imidazo[2,1-b]thiazole and benzo[1,4]dioxin;
R 11 represents H, C 1-6 alkyl, perfluoroC 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ar, —C 1-6 alkylAr or ArOC 1-6 alkyl;
R 12 represents C 1-6 alkyl, perfluoroC 1-6 alkyl, C 3-7 cycloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, Ar, —C 1-6 alkylAr or ArOC 1-6 alkyl; or two R 12 groups together with a nitrogen atom to which they are mutually attached may complete a heterocyclic ring system selected from the group consisting of pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, 2,5-diazabicyclo[2.2.1]heptane and 2-aza-5-oxabicyclo[2.2.1]heptane, said ring system bearing 0-2 substituents selected from halogen, CN, NO 2 , C 1-6 alkyl, perfluoroC 1-6 alkyl, C 3-7 cycloalkly, C 2-6 alkenyl, C 2-6 alkynyl, Ar, —C 1-6 alkylAr or ArOC 1-6 alkyl, OR 11 , NHR 11 , and COR 11
R 13 represents R 9 , —COR 10 , —CO 2 R 10 , —SO 2 R 10 , —CON(R 9 ) 2 or —SO 2 N(R 9 ) 2 ;
each R 16 independently represents H or R 10 , or two R 16 groups together with the nitrogen to which they are mutually attached complete a mono- or bicyclic heterocyclic ring system of 5-10 ring atoms selected from C, N, O and S, said ring system optionally having an additional aryl or heteroaryl ring fused thereto, said heterocyclic system and/or additional fused ring bearing 0-3 substituents independently selected from halogen, NO 2 , CN, R 12 , —OR 11 , —SR 11 , —SO 2 R 12 , —COR 11 , —CO 2 R 11 , —CON(R 11 ) 2 , —OCOR 12 , —N(R 11 ) 2 and —NR 11 COR 12 ;
V represents CR 4 or N;
W represents CH or N;
a is 0 or 1;
b is 0; and
w is 1 or 2;
or a pharmaceutically acceptable salt thereof.
10. A compound according to claim 5 wherein:
w is 1;
R 1 is H;
R 3 is selected from n-propyl, n-butyl, phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,4-difluorophenyl, 4-chlorophenyl, 2-thienyl, 5-chloro-2-thienyl, 5-bromo-2-thienyl, 3-pyridyl, 6-chloro-2-pyridyl and 5-isothiazolyl; and
R 4 is selected from pyridine-2-carboxamido, phenoxyacetamido, 4-chlorophenoxyacetamido, 2,4-dichlorophenoxyacetamido, 4-fluorophenoxyacetimido, morpholin-4-ylacetamido, pyrrolidin-1-ylacetamido, piperidin-1-ylacetamido, 4-phenylpiperazin-1-ylacetamido, 4-(4-fluorophenyl)piperazin-1-ylacetamido, 2-(4-fluorophenoxy)ethoxy, 2-(morpholin-4-yl)ethoxy, 2-(morpholin-4-yl)ethylamino, 2-(4-fluorophenoxy)ethylamino, 2-(4-chlorophenoxy)ethylamino, 3-(4-fluorophenoxy)propenyl, 3-(imidazol-1-yl)propenyl, 3-(morpholin-4-yl)propenyl, 5-(pyridin-2-yl)-1,2,4-oxadiazol-3-yl, 5-(pyridin-3-yl)-1,2,4-oxadiazol-3-yl, 5-(pyridin-4-yl)-1,2,4-oxadiazol-3-yl, 3-(2-aza-5-oxabicyclo[2.2.1]hept-2-yl)propenyl, 2-(2-aza-5-oxabicyclo[2.2.1]hept-2-yl)ethoxy, 3-(4-fluoropiperidin-1-yl)propenyl, 2-(4-fluoropiperidin-1-yl)ethoxy, 3-(4-trifluoromethylpiperidin-1-yl)propenyl and 2-(4-trifluoromethylpiperidin-1-yl)ethoxy.