IP Library › Granted Patent US 7,230,139

Granted Patent B2

US 7,230,139 · App. 10/865,262 · Granted Jun 12, 2007

Diterpenoid compounds, compositions thereof and their use as anti-cancer or anti-fungal agents

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Quick Facts

Patent No.: US 7,230,139
App. No.: 10/865,262
Granted: Jun 12, 2007
Kind: B2

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Abstract

The present invention relates to Diterpenoid Compounds, compositions comprising an effective amount of a Diterpenoid Compound, and methods useful for treating or preventing cancer or a neoplastic disorder comprising administering an effective amount of a Diterpenoid Compound. The compounds, compositions, and methods of the invention are also useful for inhibiting the growth of a cancer cell or neoplastic cell, or for inducing apoptosis in a cancer or neoplastic cell. The compounds, compositions, and methods of the invention are further useful for treating or preventing a fungal infection. The compounds, compositions, and methods of the invention are also useful for inhibiting the growth of a fungus.

Claims (360)

1. A compound having the Formula (Ia):

or a pharmaceutically acceptable salts thereof, wherein:

Q 1 and Q 2 are independently ═O, ═S, ═NOR, ═NR, ═N—NHR, or ═N—N(R) 2 where R is —H, —C 1 –C 10 alkyl, or -aryl;

Q 3 is —O—, —S—, or —N(H)—;

R 1 and R 2 are independently —H, -halogen, -amino, —C 1 –C 10 alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (hydroxy)alkyl, —C 1 –C 10 (amino)alkyl, —C 1 –C 10 (halo)alkyl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, (C 3 –C 7 ) cycloalkyl, -aryl, C 1 –C 10 (aryl)alkyl, or three- to seven-membered non-aromatic heterocycle, or R 1 , R 2 and the carbon atom to which they are both attached are taken together to form a (C 3 –C 7 ) cycloalkyl group or a three- to seven-membered non-aromatic heterocycle;

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

each R 3 , R 4 , R 5 and R 6 is independently —H, —OH, -halogen, —CN, —NH 2 , —NO 2 , —COOH, —C(O)NH 2 , —SH, —S(O)NH 2 , —S(O) 2 NH 2 , —C 1 –C 10 (oxy)alkyl, —C 1 –C 10 alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (hydroxy)alkyl, —C 1 –C 10 (amino)alkyl, —C 1 –C 10 (halo)alkyl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, —(C 3 –C 7 ) cycloalkyl, -aryl, —C 1 –C 10 (aryl)alkyl, three- to seven-membered non-aromatic heterocycle, five- to seven-membered aromatic heterocycle, —CH 2 OR 11 , —OCH 2 OR 11 , —OC(O)R 11 , —C(O)R 11 , —OC(O)OR 11 , —OC(O)NR 11 , —C(O)OR 11 , —C(O)NR 11 , —OP(O)(OR 11 ) 2 , —SR 11 , —S(O) 2 NHR 11 , —SOR 11 , —S(O) 2 R 11 , —NHC(O)R 11 , —NHSOR 11 , NHS(O) 2 R 11 , —OPO(OR 15 ) 2 , —O-arylPO(OR 15 ) 2 , or —O-alkylarylPO(OR 15 ) 2 wherein R 15 is H, —C 1 –C 10 alkyl, C 7 –C 12 arylalkyl, C 1 –C 10 aminoalkyl, C 1 –C 10 haloalkyl, C 1 –C 10 hydroxyalkyl, C 1 –C 10 alkoxy;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

R 8 and R 9 are each independently —H, -halogen, —CN, —NH 2 , —NO 2 , —COOH, —C(O)NH 2 , —SH, —S(O)NH 2 , —S(O) 2 NH 2 , —C 1 –C 10 (oxy)alkyl, —C 1 –C 10 alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (hydroxy)alkyl, —C 1 –C 10 (amino)alkyl, —C 1 –C 10 (halo)alkyl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, —(C 3 –C 7 ) cycloalkyl, -aryl, —C 1 –C 10 (aryl)alkyl, three- to seven-membered non-aromatic heterocycle, five- to seven-membered aromatic heterocycle, —CH 2 OR 11 , —OCR 11 , —OC(O)R 11 , —C(O)R 11 , —OC(O)OR 11 , —OC(O)NR 11 , —C(O)OR 11 , —C(O)NR 11 , —OP(O)(OR 11 ) 2 , —SR 11 , —SOR 11 , —S(O) 2 R 11 , —S(O) 2 NHR 11 , —NHSR 11 , —NHSOR 11 , or —NHS(O) 2 R 11 ;

R 8 is also —S(CH 2 ) n amino acid, —S(CH 2 ) n peptide, wherein n=0 to 4, wherein the amino acid is connected to the compound through its alpha carbon atom, and wherein the peptide is connected to the compound through the alpha carbon atom of one of its amino acids;

R 10 is —H, —C 1 –C 10 alkyl, —C 3 –C 7 cycloalkyl, —C(O)C 1 –C 10 alkyl, —C 1 –C 10 (oxy)alkyl, —C(O)NH 2 , —C(O)NHR 12 , —C(O)N(R 12 ) 2 , P(O)(OR 13 ) 2 , or -aryl, wherein R 10 is not P(O)(OR 13 ) 2 if Q 3 is —N(H)— or —S—;

R 11 is —H, —C 1 –C 10 alkyl, —(C 3 –C 7 ) cycloalkyl, —C 1 –C 10 (halo)alkyl, -aryl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, —C 1 –C 10 (aryl)alkyl, —C 2 –C 10 (aryl)alkenyl, —C 2 –C 10 (aryl)alkynyl, —C 1 –C 10 (hydroxy)alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (amino)alkyl,

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl;

each halogen is independently —F, —Cl, —Br or —I; and

R 13 is H, C 1 –C 10 alkyl, aryl, or benzyl;

with the proviso that the compound of Formula (Ia) is not:

10-Hydroxy-6-methoxy-1,1,4a,7-tetramethyl-1H,4aH-phenanthrene-2,9-dione; or

10-Hydroxy-7-hydroxymethyl-6-methoxy-1,1,4a-trimethyl-1H,4aH-phenanthrene-2,9-dione, or a pharmaceutically acceptable salt thereof; and

with the further proviso that if (i) D is C—OH; (ii) Q 1 is ═O; (iii) Q 2 is ═O; (iv) A is CH; and (v) E is CR 7 then R 4 is not —CH 3 .

2. A compound having the Formula (Ib):

and pharmaceutically acceptable salts thereof, wherein:

a dashed line indicates that the bond between the atoms that are connected by the dashed line can be a single bond or a double bond;

the ring with positions A, B, D, and E is not aromatic;

Q 1 and Q 2 are independently ═O, ═S, ═NOR, ═NR, ═N—NHR, or ═N—N(R) 2 where R is —H, —C 1 –C 10 alkyl, or -aryl;

Q 3 is —O—, —S—, or —N(H)—;

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

each R 3 , R 4 , R 5 and R 6 is independently —H, ═O, —OH, -halogen, —CN, —NH 2 , —NO 2 , —COOH, —C(O)NH 2 , —SH, —S(O)NH 2 , —S(O) 2 NH 2 , —C 1 –C 10 (oxy)alkyl, —C 1 –C 10 alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (hydroxy)alkyl, —C 1 –C 10 (amino)alkyl, —C 1 –C 10 (halo)alkyl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, —(C 3 –C 7 ) cycloalkyl, -aryl, —C 1 –C 10 (aryl)alkyl, three- to seven-membered non-aromatic heterocycle, five- to seven-membered aromatic heterocycle, —CH 2 OR 11 , —OCH 2 OR 11 , —OC(O)R 11 , —C(O)R 11 , —OC(O)OR 11 , —OC(O)NR 11 , —C(O)OR 11 , —C(O)NR 11 , —OP(O)(OR 11 ) 2 , —SR 11 , —S(O) 2 NHR 11 , —SOR 11 , —S(O) 2 R 11 , —NHC(O)R 11 , —NHSOR 11 , NHS(O) 2 R 11 , —OPO(OR 15 ) 2 , —O-arylPO(OR 15 ) 2 , or —O-alkylarylPO(OR 15 ) 2 wherein R 15 is H, —C 1 –C 10 alkyl, C 7 –C 12 arylalkyl, C 1 –C 10 aminoalkyl, C 1 –C 10 haloalkyl, C 1 –C 10 hydroxyalkyl, C 1 –C 10 alkoxy;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl; and

each halogen is independently —F, —Cl, —Br or —I.

R 13 is H, C 1 –C 10 alkyl, aryl, or benzyl.

3. A compound having the Formula (Ic):

and pharmaceutically acceptable salts thereof, wherein:

a dashed line indicates that the bond between the atoms that are connected by the dashed line can be a single bond or a double bond;

Q 1 is ═O, ═S, ═NOR, ═NR, ═N—NHR, or ═N—N(R) 2 where R is —H, —C 1 –C 10 alkyl, or -aryl;

Q 3 is at each occurance independently —O—, —S—, or —N(H)—;

R 1 and R 2 are independently —H, -halogen, -amino, —C 1 –C 10 alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (hydroxy)alkyl, C 1 –C 10 (amino)alkyl, —C 1 –C 10 (halo)alkyl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, (C 3 –C 7 ) cycloalkyl, -aryl, C 1 –C 10 (aryl)alkyl, or three- to seven-membered non-aromatic heterocycle, or R 1 , R 2 and the carbon atom to which they are both attached are taken together to form a (C 3 –C 7 ) cycloalkyl group or a three- to seven-membered non-aromatic heterocycle;

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

R 10 is at each occurance independently —H, —C 1 –C 10 alkyl, —C 3 –C 7 cycloalkyl, —C(O)C 1 –C 10 alkyl, —C 1 –C 10 (oxy)alkyl, —C(O)NH 2 , —C(O)NHR 12 , —C(O)N(R 12 ) 2 , P(O)(OR 13 ) 2 , or -aryl, wherein R 10 is not P(O)(OR 13 ) 2 if Q 3 is —N(H)— or —S—;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl; and

each halogen is independently —F, —Cl, —Br or —I.

R 13 is H, C 1 –C 10 alkyl, aryl, or benzyl.

4. A compound having the Formula (IIa):

or a pharmaceutically acceptable salt thereof, wherein:

Q 1 and Q 2 are independently ═O, ═S, ═NOR, ═NR, ═N—NHR, or ═N—N(R) 2 , where R is —H, —C 1 –C 10 alkyl, or -aryl;

Q 3 is —O—, —S—, or —N(H)—;

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

each R 3 , R 4 , R 5 and R 6 is independently —H, —OH, -halogen, —CN, —NH 2 , —NO 2 , —COOH, —C(O)NH 2 , —SH, —S(O)NH 2 , —S(O) 2 NH 2 , —C 1 –C 10 (oxy)alkyl, —C 1 –C 10 alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (hydroxy)alkyl, —C 1 –C 10 (amino)alkyl, —C 1 –C 10 (halo)alkyl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, —(C 3 –C 7 ) cycloalkyl, -aryl, —C 1 –C 10 (aryl)alkyl, three- to seven-membered non-aromatic heterocycle, five- to seven-membered aromatic heterocycle, —CH 2 OR 11 , —OCH 2 OR 11 , —OC(O)R 11 , —C(O)R 11 , —OC(O)OR 11 , —OC(O)NR 11 , —C(O)OR 11 , —C(O)NR 11 , —OP(O)(OR 11 ) 2 , —SR 11 , —S(O) 2 NHR 11 , —SOR 11 , —S(O) 2 R 11 , —NHC(O)R 11 , —NHSOR 11 , NHS(O) 2 R 11 —OPO(OR 15 ) 2 , —O-arylPO(OR 15 ) 2 , or —O-alkylarylPO(OR 15 ) 2 wherein R 15 is H, —C 1 –C 10 alkyl, C 7 –C 12 arylalkyl, C 1 –C 10 aminoalkyl, C 1 –C 10 haloalkyl, C 1 –C 10 hydroxyalkyl, C 1 –C 10 alkoxy;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl;

each halogen is independently —F, —Cl, —Br or —I; and

R 13 is H, C 1 –C 10 alkyl, aryl, or benzyl;

with the proviso that (a) if (i) D is C—OH, (ii) Q 1 is ═O, (iii) Q 2 is ═O, (iv) A is CH, and (v) E is CR 7 then R 4 is not —CH 3 ; and (b) if (i) E is C—OH, (ii) Q 1 is ═O, (iii) Q 2 is ═O, (iv) R 10 is H, (v) B is CR 4 , (vi) D is CR 5 , (vii) R 7 is CH 3 , and (viii) Q 3 is —O— then A is not C—OH.

5. A compound having the Formula (IIb):

or a pharmaceutically acceptable salt thereof, wherein:

a dashed line indicates that the bond between the atoms that are connected by the dashed line can be a single bond or a double bond;

the ring with positions A, B, D, and E is not aromatic;

Q 1 and Q 2 are independently ═O, ═S, ═NOR, ═NR, ═N—NHR, or ═N—N(R) 2 , where R is —H, —C 1 –C 10 alkyl, or -aryl;

Q 3 is —O—, —S—, or —N(H)—;

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl;

each halogen is independently —F, —Cl, —Br or —I; and

R 13 is H, C 1 –C 10 alkyl, aryl, or benzyl.

6. A compound having the Formula (IIc):

or a pharmaceutically acceptable salt thereof, wherein:

a dashed line indicates that the bond between the atoms that are connected by the dashed line can be a single bond or a double bond;

Q 1 is ═O, ═S, ═NOR, ═NR, ═N—NHR, or ═N—N(R) 2 , where R is —H, —C 1 –C 10 alkyl, or -aryl;

Q 3 is at each occurance independently —O—, —S—, or —N(H)—;

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl;

each halogen is independently —F, —Cl, —Br or —I; and

R 13 is H, C 1 –C 10 alkyl, aryl, or benzyl.

7. A compound having the Formula (IIIa):

or a pharmaceutically acceptable salt thereof, wherein:

Q 1 , Q 2 and Q 3 are independently ═O, ═S, ═NOR, ═NR, ═N—NHR, or ═N—N(R) 2 , where R is —H, —C 1 –C 10 alkyl, or -aryl;

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

R 8 and R 9 are each independently —H, -halogen, —CN, —NH 2 , —NO 2 , —COOH, —C(O)NH 2 , —SH, —S(O)NH 2 , —S(O) 2 NH 2 , —C 1 –C 10 (oxy)alkyl, —C 1 –C 10 alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (hydroxy)alkyl, —C 1 –C 10 (amino)alkyl, C 1 –C 10 (halo)alkyl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, —(C 3 –C 7 ) cycloalkyl, -aryl, —C 1 –C 10 (aryl)alkyl, three- to seven-membered non-aromatic heterocycle, five- to seven-membered aromatic heterocycle, —CH 2 OR 11 , —OCR 11 , —OC(O)R 11 , —C(O)R 11 , —OC(O)OR 11 , —OC(O)NR 11 , —C(O)OR 11 , —C(O)NR 11 , —OP(O)(OR 11 ) 2 , —SR 11 , —SOR 11 , —S(O) 2 R 11 , —S(O) 2 NHR 11 , —NHSR 11 , —NHSOR 11 , or —NHS(O) 2 R 11 ;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl; and

each halogen is independently —F, —Cl, —Br or —I.

8. A compound having the Formula (IIIb):

or a pharmaceutically acceptable salt thereof, wherein:

a dashed line indicates that the bond between the atoms that are connected by the dashed line can be a single bond or a double bond;

the ring with positions A, B, D, and E is not aromatic;

Q 1 , Q 2 and Q 3 are independently ═O, ═S, ═NOR, ═NR, ═N—NHR, or ═N—N(R) 2 , where R is —H, —C 1 –C 10 alkyl, or -aryl;

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

each R 3 , R 4 , R 5 and R 6 is independently —H, —OH, ═O, -halogen, —CN, —NH 2 , —NO 2 , —COOH, —C(O)NH 2 , —SH, —S(O)NH 2 , —S(O) 2 NH 2 , —C 1 –C 10 (oxy)alkyl, —C 1 –C 10 alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (hydroxy)alkyl, —C 1 –C 10 (amino)alkyl, C 1 –C 10 (halo)alkyl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, —(C 3 –C 7 ) cycloalkyl, -aryl, —C 1 –C 10 (aryl)alkyl, three- to seven-membered non-aromatic heterocycle, five- to seven-membered aromatic heterocycle, —CH 2 OR 11 , —OCH 2 OR 11 , —OC(O)R 11 , —C(O)R 11 , —OC(O)OR 11 , —OC(O)NR 11 , —C(O)OR 11 , —C(O)NR 11 , —OP(O)(OR 11 ) 2 , —SR 11 , —S(O) 2 NHR 11 , —SOR 11 , —S(O) 2 R 11 , —NHC(O)R 11 , —NHSOR 11 , NHS(O) 2 R 11 , —OPO(OR 15 ) 2 , —O-arylPO(OR 15 ) 2 , or —O-alkylarylPO(OR 15 ) 2 wherein R 15 is H, —C 1 –C 10 alkyl, C 7 –C 12 arylalkyl, C 1 –C 10 aminoalkyl, C 1 –C 10 haloalkyl, C 1 –C 10 hydroxyalkyl, C 1 –C 10 alkoxy;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl; and

each halogen is independently —F, —Cl, —Br or —I.

9. A compound having the Formula (IVa):

or a pharmaceutically acceptable salt thereof, wherein:

Q 1 , Q 2 and Q 3 are independently ═O, ═S, ═NOR, ═NR, ═N—NHR, or ═N—N(R) 2 , where R is —H, —C 1 –C 10 alkyl, or -aryl;

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl;

R 14 is —H, —OH, or halogen; and

each halogen is independently —F, —Cl, —Br or —I.

10. A compound having the Formula (IVb):

or a pharmaceutically acceptable salt thereof, wherein:

a dashed line indicates that the bond between the atoms that are connected by the dashed line can be a single bond or a double bond;

the ring with positions A, B, D, and E is not aromatic;

Q 1 , Q 2 and Q 3 are independently ═O, ═S, ═NOR, ═NR, ═N—NHR, or ═N—N(R) 2 , where R is —H, —C 1 –C 10 alkyl, or -aryl;

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

each R 3 , R 4 , R 5 and R 6 is independently —H, —OH, ═O, -halogen, —CN, —NH 2 , —NO 2 , —COOH, —C(O)NH 2 , —SH, —S(O)NH 2 , —S(O) 2 NH 2 , —C 1 –C 10 (oxy)alkyl, —C 1 –C 10 alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (hydroxy)alkyl, C 1 –C 10 (amino)alkyl, —C 1 –C 10 (halo)alkyl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, —(C 3 –C 7 ) cycloalkyl, -aryl, —C 1 –C 10 (aryl)alkyl, three- to seven-membered non-aromatic heterocycle, five- to seven-membered aromatic heterocycle, —CH 2 OR 11 , —OCH 2 OR 11 , —OC(O)R 11 , —C(O)R 11 , —OC(O)OR 11 , —OC(O)NR 11 , —C(O)OR 11 , —C(O)NR 11 , —OP(O)(OR 11 ) 2 , —SR 11 , —S(O) 2 NHR 11 , —SOR 11 , —S(O) 2 R 11 , —NHC(O)R 11 , —NHSOR 11 , NHS(O) 2 R 11 , —OPO(OR 15 ) 2 , —O-arylPO(OR 15 ) 2 , or —O-alkylarylPO(OR 15 ) 2 wherein R 15 is H, —C 1 –C 10 alkyl, C 7 –C 12 arylalkyl, C 1 –C 10 aminoalkyl, C 1 –C 10 haloalkyl, C 1 –C 10 hydroxyalkyl, C 1 –C 10 alkoxy;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

R 8 and R 9 are each independently —H, -halogen, —CN, —NH 2 , —NO 2 , —COOH, —C(O)NH 2 , —SH, —S(O)NH 2 , —S(O) 2 NH 2 , —C 1 –C 10 (oxy)alkyl, —C 1 –C 10 alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (hydroxy)alkyl, —C 1 –C 10 (amino)alkyl, —C 1 –C 10 (halo)alkyl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, —(C 3 –C 7 ) cycloalkyl, -aryl, —C 1 –C 10 (aryl)alkyl, three- to seven-membered non-aromatic heterocycle, five- to seven-membered aromatic heterocycle, —CH 2 OR 11 , —OCR 11 , —OC(O)R 11 , —C(O)R 11 , —OC(O)OR 11 , —OC(O)NR 11 , —C(O)OR 11 , —C(O)NR 11 , —OP(O)(OR 11 ) 2 , SR 11 , —SOR 11 , —S(O) 2 R 11 , —S(O) 2 NHR 11 , —NHSR 11 , —NHSOR 11 , or —NHS(O) 2 R 11 ;

R 11 , is —H, —C 1 –C 10 alkyl, —(C 3 –C 7 ) cycloalkyl, —C 1 –C 10 (halo)alkyl, -aryl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, —C 1 –C 10 (aryl)alkyl, —C 2 –C 10 (aryl)alkenyl, —C 2 –C 10 (aryl)alkynyl, —C 1 –C 10 (hydroxy)alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (amino)alkyl,

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl;

R 14 is —H, —OH, or halogen; and

each halogen is independently —F, —Cl, —Br or —I.

11. A compound having the Formula (Va):

or a pharmaceutically acceptable salt thereof, wherein:

Q 1 , Q 2 and Q 3 are independently ═O, ═S, ═NR, ═NOR, ═N—NHR, or ═N—N(R) 2 where R is —H, —C 1 –C 10 alkyl, or -aryl;

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

R 8 and R 9 are each independently —H, -halogen, —CN, —NH 2 , —NO 2 , —COOH, —C(O)NH 2 , —SH, —S(O)NH 2 , —S(O) 2 NH 2 , —C 1 –C 10 (oxy)alkyl, —C 1 –C 10 alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (hydroxy)alkyl, C 1 –C 10 (amino)alkyl, —C 1 –C 10 (halo)alkyl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, —(C 3 –C 7 ) cycloalkyl, -aryl, —C 1 –C 10 (aryl)alkyl, three- to seven-membered non-aromatic heterocycle, five- to seven-membered aromatic heterocycle, —CH 2 OR 11 , —OCR 11 , —OC(O)R 11 , —C(O)R 11 , —OC(O)OR 11 , —OC(O)NR 11 , —C(O)OR 11 , —C(O)NR 11 , —OP(O)(OR 11 ) 2 , —SR 11 , —SOR 11 , —S(O) 2 R 11 , —S(O) 2 NHR 11 , —NHSR 11 , —NHSOR 11 , or —NHS(O) 2 R 11 ;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl;

R 14 is —H, —OH, or halogen; and

each halogen is independently —F, —Cl, —Br or —I.

12. A compound having the Formula (Vb):

or a pharmaceutically acceptable salt thereof, wherein:

a dashed line indicates that the bond between the atoms that are connected by the dashed line can be a single bond or a double bond;

the ring with positions A, B, D, and E is not aromatic;

Q 1 , Q 2 and Q 3 are independently ═O, ═S, ═NR, ═NOR, ═N—NHR, or ═N—N(R) 2 where R is —H, —C 1 –C 10 alkyl, or -aryl;

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

each R 3 , R 4 , R 5 and R 6 is independently —H, —OH, ═O, -halogen, —CN, —NH 2 , —NO 2 , —COOH, —C(O)NH 2 , —SH, —S(O)NH 2 , —S(O) 2 NH 2 , —C 1 –C 10 (oxy)alkyl, —C 1 –C 10 alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (hydroxy)alkyl, —C 1 –C 10 (amino)alkyl, —C 1 –C 10 (halo)alkyl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, —(C 3 –C 7 ) cycloalkyl, -aryl, —C 1 –C 10 (aryl)alkyl, three- to seven-membered non-aromatic heterocycle, five- to seven-membered aromatic heterocycle, —CH 2 OR 11 , —OCH 2 OR 11 , —OC(O)R 11 , —C(O)R 11 , —OC(O)OR 11 , —OC(O)NR 11 , —C(O)OR 11 , —C(O)NR 11 , —OP(O)(OR 11 ) 2 , —SR 11 , —S(O) 2 NHR 11 , —SOR 11 , —S(O) 2 R 11 , —NHC(O)R 11 , —NHSOR 11 , NHS(O) 2 R 11 , —OPO(OR 15 ) 2 , —O-arylPO(OR 15 ) 2 , or —O-alkylarylPO(OR 15 ) 2 wherein R 15 is H, —C 1 –C 10 alkyl, C 7 –C 12 arylalkyl, C 1 –C 10 aminoalkyl, C 1 –C 10 haloalkyl, C 1 –C 10 hydroxyalkyl, C 1 –C 10 alkoxy;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl;

R 14 is —H, —OH, or halogen; and

each halogen is independently —F, —Cl, —Br or —I.

13. A compound having the Formula (VIa):

or a pharmaceutically acceptable salt thereof, wherein:

Q 1 is CHOH, CH2, CHOR, where R is C 1 –C 10 alkyl, aryl, —CH 2 OR 11 , —C(O)R 11 , —C(O)OR 11 , —C(O)OR 11 , —C(O)NR 11 , —P(O)(OR 11 )2

Q 2 is ═O, ═S, ═NR, ═NOR, ═N—NHR, or ═N—N(R) 2 where R is —H, —C 1 –C 10 alkyl, or -aryl;

Q 3 is —O—, —S—, or —N(H)—;

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl;

R 13 is H, C 1 –C 10 alkyl, aryl, or benzyl; and

each halogen is independently —F, —Cl, —Br or —I.

14. A compound having the Formula (VIb):

or a pharmaceutically acceptable salt thereof, wherein:

a dashed line indicates that the bond between the atoms that are connected by the dashed line can be a single bond or a double bond;

the ring with positions A, B, D, and E is not aromatic;

Q 1 is CHOH, CH2, CHOR, where R is C 1 –C 10 alkyl, aryl, —CH 2 OR 11 , —C(O)R 11 , —C(O)OR 11 , —C(O)OR 11 , —C(O)NR 11 , —P(O)(OR 11 ) 2

Q 2 is ═O, ═S, ═NR, ═NOR, ═N—NHR, or ═N—N(R) 2 where R is —H, —C 1 –C 10 alkyl, or -aryl;

Q 3 is —O—, —S—, or —N(H)—;

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

each R 3 , R 4 , R 5 and R 6 is independently —H, —OH, ═O, -halogen, —CN, —NH 2 , —NO 2 , —COOH, —C(O)NH 2 , —SH, —S(O)NH 2 , —S(O) 2 NH 2 , —C 1 –C 10 (oxy)alkyl, —C 1 –C 10 alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (hydroxy)alkyl, —C 1 –C 10 (amino)alkyl, —C 1 –C 10 (halo)alkyl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, —(C 3 –C 7 ) cycloalkyl, -aryl, —C 1 –C 10 (aryl)alkyl, three- to seven-membered non-aromatic heterocycle, five- to seven-membered aromatic heterocycle, —CH 2 OR 11 , —OCH 2 OR 11 , —OC(O)R 11 , —C(O)R 11 , —OC(O)OR 11 , —OC(O)NR 11 , —C(O)OR 11 , —C(O)NR 11 , —OP(O)(OR 11 ) 2 , —SR 11 , —S(O) 2 NHR 11 , —SOR 11 , —S(O) 2 R 11 , —NHC(O)R 11 , —NHSOR 11 , NHS(O) 2 R 11 , —OPO(OR 15 ) 2 , —O-arylPO(OR 15 ) 2 , or —O-alkylarylPO(OR 15 ) 2 wherein R 15 is H, —C 1 –C 10 alkyl, C 7 –C 12 arylalkyl, C 1 –C 10 aminoalkyl, C 1 –C 10 haloalkyl, C 1 –C 10 hydroxyalkyl, C 1 –C 10 alkoxy;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl;

R 13 is H, C 1 –C 10 alkyl, aryl, or benzyl; and

each halogen is independently —F, —Cl, —Br or —I.

15. A compound having the Formula (VIIa):

or a pharmaceutically acceptable salt thereof; wherein

Q 1 and Q 2 are independently ═O, ═S, ═NR, ═NOR, ═N—NHR, or ═N—N(R) 2 where R is —H, —C 1 –C 10 alkyl, or -aryl;

Q 3 is CHOH, CH2, CHOR where R is C 1 –C 10 alkyl, aryl, —CH 2 OR 11 , —C(O)R 11 , —C(O)OR 11 , —C(O)OR 11 , —C(O)NR 11 , or —P(O)(OR 11 ) 2

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

each R 3 , R 4 , R 5 and Rr is independently —H, —OH, -halogen, —CN, —NH 2 , —NO 2 , —COOH, —C(O)NH 2 , —SH, —S(O)NH 2 , —S(O) 2 NH 2 , —C 1 –C 10 (oxy)alkyl, —C 1 –C 10 alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (hydroxy)alkyl, —C 1 –C 10 (amino)alkyl, —C 1 –C 10 (halo)alkyl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, —(C 3 –C 7 ) cycloalkyl, -aryl, —C 1 –C 10 (aryl)alkyl, three- to seven-membered non-aromatic heterocycle, five- to seven-membered aromatic heterocycle, —CH 2 OR 11 , —OCH 2 OR 11 , —OC(O)R 11 , —C(O)R 11 , —OC(O)OR 11 , —OC(O)NR 11 , —C(O)OR 11 , —C(O)NR 11 , —OP(O)(OR 11 ) 2 , —SR 11 , —S(O) 2 NHR 11 , —SOR 11 , —S(O) 2 R 11 , —NHC(O)R 11 , —NHSOR 11 , NHS(O) 2 R 11 , —OPO(OR 15 ) 2 , —O-arylPO(OR 15 ) 2 , or —O-alkylarylPO(OR 15 ) 2 wherein R 15 is H, —C 1 –C 10 alkyl, C 7 –C 12 arylalkyl, C 1 –C 10 aminoalkyl, C 1 –C 10 haloalkyl, C 1 –C 10 hydroxyalkyl, C 1 –C 10 alkoxy;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl;

R 14 is —H, —OH, or halogen; and

each halogen is independently —F, —Cl, —Br or —I;

with the proviso that (a) if (i) D is C—OH, (ii) Q 1 is ═O, (iii) Q 2 is ═O, (iv) A is CH, and (v) E is CR 7 then R 4 is not —CH 3 ; and (b) if (i) B is C—CH 3 , (ii) Q 1 is ═O, (iii) Q 2 is ═O, (iv) R 1 is CH 3 , (v) R 2 is CH 3 , (vi) R 7 is methyl, (vii) D is CH, and (viii) E is CH then R 3 is not ethyl.

16. A compound having the Formula (VIIb):

or pharmaceutically acceptable salts thereof, wherein,

a dashed line indicates that the bond between the atoms that are connected by the dashed line can be a single bond or a double bond;

the ring with positions A, B, D, and E is not aromatic;

Q 1 and Q 2 are independently ═O, ═S, ═NR, ═NOR, ═N—NHR, or ═N—N(R) 2 where R is —H, —C 1 –C 10 alkyl, or -aryl;

Q 3 is CHOH, CH2, CHOR where R is C 1 –C 10 alkyl, aryl, —CH 2 OR 11 , —C(O)R 11 , —C(O)OR 11 , —C(O)OR 11 , —C(O)NR 11 , or —P(O)(OR 11 ) 2

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

each R 3 , R 4 , R 5 and R 6 is independently —H, —OH, ═O, -halogen, —CN, —NH 2 , —NO 2 , —COOH, —C(O)NH 2 , —SH, —S(O)NH 2 , —S(O) 2 NH 2 , —C 1 –C 10 (oxy)alkyl, —C 1 –C 10 alkyl, —C 1 –C 10 alkoxy, —C 1 –C 10 (hydroxy)alkyl, —C 1 –C 10 (amino)alkyl, —C 1 –C 10 (halo)alkyl, —C 2 –C 10 alkenyl, —C 2 –C 10 alkynyl, —(C 3 –C 7 ) cycloalkyl, -aryl, —C 1 –C 10 (aryl)alkyl, three- to seven-membered non-aromatic heterocycle, five- to seven-membered aromatic heterocycle, —CH 2 OR 11 , —OCH 2 OR 11 , —OC(O)R 11 , —C(O)R 11 , —OC(O)OR 11 , —OC(O)NR 11 , —C(O)OR 11 , —C(O)NR 11 , —OP(O)(OR 11 ) 2 , —SR 11 , —S(O) 2 NHR 11 , —SOR 11 , —S(O) 2 R 11 , —NHC(O)R 11 , —NHSOR 11 , NHS(O) 2 R 11 , —OPO(OR 15 ) 2 , —O-arylPO(OR 15 ) 2 , or —O-alkylarylPO(OR 15 ) 2 wherein R 15 is H, —C 1 –C 10 alkyl, C 7 –C 12 arylalkyl, C 1 –C 10 aminoalkyl, C 1 –C 10 haloalkyl, C 1 –C 10 hydroxyalkyl, C 1 –C 10 alkoxy;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl;

R 14 is —H, —OH, or halogen; and

each halogen is independently —F, —Cl, —Br or —I.

17. The compound of claim 1 , wherein the compound has the structure:

or a pharmaceutically acceptable salt thereof.

18. The compound of claim 4 , wherein the compound has the structure:

or a pharmaceutically acceptable salt thereof.

19. The compound of claim 11 , wherein the compound has the structure:

or a pharmaceutically acceptable salt thereof.

20. The compound of claim 13 , wherein the compound has the structure:

or a pharmaceutically acceptable salt thereof.

21. A compound having the structure:

or a pharmaceutically acceptable salt thereof.

22. A pharmaceutical composition comprising (i) an effective amount of the compound or of the pharmaceutically acceptable salt of claim 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , or 21 ; and (ii) a pharmaceutically acceptable carrier.

23. A pharmaceutical composition comprising (i) an effective amount of a compound; and (ii) a pharmaceutically acceptable carrier, wherein the compound is a compound of the Formula (Ia):

or pharmaceutically acceptable salts thereof, wherein:

Q 1 and Q 2 are independently ═O, ═S, ═NOR, ═NR, ═N—NHR, or ═N—N(R) 2 where R is —H, —C 1 –C 10 alkyl, or -aryl;

Q 3 is —O—, —S—, or —N(H)—;

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl;

each halogen is independently —F, —Cl, —Br or —I; and

R 13 is H, C 1 –C 10 alkyl, aryl, or benzyl.

24. A pharmaceutical composition comprising (i) an effective amount of a compound; and (ii) a pharmaceutically acceptable carrier, wherein the compound is a compound of the Formula (IIa):

or a pharmaceutically acceptable salt thereof, wherein:

Q 1 and Q 2 are independently ═O, ═S, ═NOR, ═NR, ═N—NHR, or ═N—N(R) 2 , where R is —H, —C 1 –C 10 alkyl, or -aryl;

Q 3 is —O—, —S—, or —N(H)—;

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl;

each halogen is independently —F, —Cl, —Br or —I; and

R 13 is H, C 1 –C 10 alkyl, aryl, or benzyl.

25. A pharmaceutical composition comprising (i) an effective amount of a compound; and (ii) a pharmaceutically acceptable carrier, wherein the compound is a compound of the Formula (VIIa):

or a pharmaceutically acceptable salt thereof; wherein

Q 1 and Q 2 are independently ═O, ═S, ═NR, ═NOR, ═N—NHR, or ═N—N(R) 2 where R is —H, —C 1 –C 10 alkyl, or -aryl;

Q 3 is CHOH, CH2, CHOR where R is C 1 –C 10 alkyl, aryl, —CH 2 OR 11 , —C(O)R 11 , —C(O)OR 11 , —C(O)OR 11 , —C(O)NR 11 , or —P(O)(OR 11 ) 2

A is CR 3 ; B is CR 4 ; D is CR 5 ; E is CR 6 ;

R 7 is —H, —C 1 –C 10 alkyl, or —C 1 –C 10 alkoxy;

a —(C 3 –C 7 ) cycloalkyl unsubstituted or substituted with one or more —C 1 –C 10 alkyl,

a three- to seven-membered non-aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, or

a three- to seven-membered aromatic heterocycle unsubstituted or substituted with one or more —C 1 –C 10 alkyl, —C 2 –C 10 alkenyl, or —C 2 –C 10 alkynyl;

R 12 is C 1 –C 10 alkyl;

R 14 is —H, —OH, or halogen; and

each halogen is independently —F, —Cl, —Br or —I.

Assignments (6)

RELEASE OF SECURITY INTEREST Recorded Jun 5, 2012

From: INVESTISSEMENT QUEBEC

To: GEMIN X PHARMACEUTICALS CANADA INC.

Reel/Frame 028320/0312 →

SECURITY AGREEMENT Recorded Sep 5, 2006

From: GEMIN X BIOTECHNOLOGIES INC.

To: INVESTISSEMENT QUEBEC

Reel/Frame 018275/0714 →