US6660744B1 — Pyrazolopyrimidines as therapeutic agents

Claim 1

Independent Claim 1267 words

A compound of Formula (I) racemic-diastereomeric mixtures, optical isomers, pharmaceutically-acceptable salts or prodrugs thereof wherein: G is where Z 100 is or a group optionally substituted with R 1 selected from the group consisting of, cycloalkyl, naphthyl, tetrahydronaphthyl, benzothienyl, furanyl, thienyl, benzoxazolyl, benzothiazolyl, thiazolyl, benzofuranyl, 2,3-dihydrobenzofuranyl, indolyl, isoxazolyl, tetrahydropyranyl, tetrahydrofuranyl, piperidinyl, pyrazolyl, pyrrolyl, oxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, indolinyl, indazolyl, benzoisothiazolyl, pyrido-oxazolyl, pyrido-thiazolyl, pyrimido-oxazolyl, pyrimido-thiazolyl and benzimidazolyl; Z 110 is a covalent bond, or an optionally substituted (C 1 -C 6 ) which is optionally substituted with one or more substituents selected from the group consisting of alkyl, CN, OH, halogen, NO 2 , COOH, substituted or unsubstituted amino and substituted or unsubstituted phenyl; Z 111 is a covalent bond, an optionally substituted (C 1 -C 6 ) or an optionally substituted —(CH 2 ) n -cycloalkyl-(CH 2 ) n —; where the optionally substituted groups are optionally substituted with one or more substituents selected from the group consisting of alkyl, CN, OH, halogen, NO 2 , COOH, substituted or unsubstituted amino and substituted or unsubstituted phenyl; R a and R 1 each represent one or more substituents for each occurrence independently selected from the group consisting of hydrogen, halogen, —CN, —NO 2 , —C(O)OH, —C(O)H, —OH, —C(O)O-alkyl, substituted or unsubstituted carboxamido, tetrazolyl, trifluoromethylcarbonylamino, trifluoromethylsulfonamido, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted arylalkyl, substituted or unsubstituted alkynyl, substituted or unsubstituted amino, substituted or unsubstituted aminoalkyl, substituted or unsubstituted amido groups, substituted or unsubstituted heteroarylthio, substituted or unsubstituted arylthio, —Z 105 —C(O)N(R) 2 , —Z 105 —N(R)—C(O)—Z 200 , —Z 105 —N(R)—S(O) 2 —Z 200 , —Z 105 —N(R)—C(O)—N(R)—Z 200 , R c and CH 2 OR c ; where R c for each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, —CH 2 —NR d R e , —W—(CH 2 ) t —NR d R e , —W—(CH 2 ) t —O-alkyl, —W—(CH 2 ) t —S-alkyl, or —W—(CH 2 ) t —OH; Z 105 for each occurrence is independently a covalent bond or (C 1 -C 6 ); Z 200 for each occurrence is independently a substituted or unsubstituted (C 1 -C 6 ), substituted or unsubstituted phenyl or substituted or unsubstituted —(C 1 -C 6 )-phenyl; R d and R e for each occurrence are independently H, alkyl, alkanoyl or SO 2 -alkyl; or R d , R e and the nitrogen atom to which they are attached together form a five- or six-membered heterocyclic ring; t for each occurrence is independently an integer from 2 to 6; W for each occurrence is independently a direct bond or O, S, S(O), S(O) 2 , or NR f , wherein R f for each occurrence is independently H or alkyl; or R 1 is a substituted or unsubstituted carbocyclic or heterocyclic ring fused with ring 2; R 3 is hydrogen, hydroxy, substituted or unsubstituted alkoxy; A is -, —O—; —S—; —S(O) p —; —N(R)—; —N(C(O)OR)—; —N(C(O)R)—; —N(SO 2 R)—; —CH 2 O—; —CH 2 S—; —CH 2 N(R)—; —CH(NR)—; —CH 2 N(C(O)R))—; —CH 2 N(C(O)OR)—; —CH 2 N(SO 2 R)—; —CH(NHR)—; —CH(NHC(O)R)—; —CH(NHSO 2 R)—; —CH(NHC(O)OR)—; —CH(OC(O)R)—; —CH(OC(O)NHR)—; —CH═CH—; —C(═NOR)—; —C(O)—; —CH(OR)—; —C(O)N(R)—; —N(R)C(O)—; —N(R)S(O) p —; —OC(O)N(R)—; —N(R)—C(O)—(CH 2 ) n —N(R)—, —N(R)C(O)O—; —N(R)—(CH 2 ) n+1 —C(O)—, —S(O) p N(R)—; —O—(CR 2 ) n+1 —C(O)—, —O—(CR 2 ) n+1 —O—, —N(C(O)R)S(O) p —; —N(R)S(O) p N(R)—; —N(R)—C(O)—(CH 2 ) n —O—, —C(O)N(R)C(O)—; —S(O) p N(R)C(O)—; —OS(O) p N(R)—; —N(R)S(O) p O—; —N(R)S(O) p C(O)—; —SO p N(C(O)R)—; —N(R)SO p N(R)—; —C(O)O—; —N(R)P(OR b )O—; —N(R)P(OR b )—; —N(R)P(O)(OR b )O—; —N(R)P(O)(OR b )—; —N(C(O)R)P(OR b )O—; —N(C(O)R)P(OR b )—; —N(C(O)R)P(O)(OR b )O—, or —N(C(O)R)P(OR b )—; where R for each occurrence is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted arylalkyl or substituted or unsubstituted aryl; R b for each occurrence is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted cycloalkyl or substituted or unsubstituted aryl; p is 1 or 2; or in a phosphorus containing group, the nitrogen atom, the phosphorus atom, R and R b together form a five- or six-membered heterocyclic ring; or A is NRSO 2 and R, R a and the nitrogen atom together form a substituted or unsubstituted five or-six-membered heterocyclic ring fused to ring 1; R 2 is —Z 101 -Z 102 ; Z 101 is a covalent bond, —(C 1 -C 6 )—, —(C 1 -C 6 )— —O—, —(C 1 -C 6 )—C(O)—, —(C 1 -C 6 )— —C(O)O—, —(C 1 -C 6 )—C(O)—NH—, —(C 1 -C 6 )—C(O)—N((C 1 -C 6 ))— or a substituted or unsubstituted phenyl group; Z 102 is hydrogen; a substituted or unsubstituted alkyl group; a substituted or unsubstituted cycloalkyl group; a substituted or unsubstituted, saturated or unsaturated heterocyclic group; or a substituted or unsubstituted, saturated or unsaturated heterobicyclic group; said substituted heterocyclic and substituted heterobicyclic group having one or more substituents each independently selected from the group consisting of hydroxyl, cyano, substituted or unsubstituted alkoxy, substituted or unsubstituted sulfonamido, substituted or unsubstituted ureido, substituted or unsubstituted carboxamido, substituted or unsubstituted amino, oxo, a saturated, unsaturated or aromatic, substituted or unsubstituted heterocyclic group consisting of one or more nitrogen atoms, one or more oxygen atoms or a combination thereof wherein the nitrogen atoms are independently optionally substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl group; or R 2 is a group of the formula —B—E, wherein B is a substituted or unsubstituted cycloalkyl, substituted or unsubstituted azacycloalkyl, substituted or unsubstituted amino, substituted or unsubstituted aminoalkylsulfonyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aminoalkylcarbonyl, hydroxy substituted or unsubstituted alkylene, substituted or unsubstituted aminoalkyl, substituted or unsubstituted alkylenecarbonyl or substituted or unsubstituted aminoalkylcarbonyl group; and E is substituted or unsubstituted azacycloalkyl, substituted or unsubstituted azacycloalkylcarbonyl, substituted or unsubstituted azacycloalkylsulfonyl, substituted or unsubstituted azacycloalkylalkyl, substituted or unsubstituted heteroaryl-substituted or unsubstituted heteroarylcarbonyl, substituted or unsubstituted heteroarylsulfonyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted azacycloalkylcarbonylamino, substituted or unsubstituted heteroarylcarbonylamino s or substituted or unsubstituted aryl; a is 1 and D 1 , G 1 , J 1 , L 1 and M 1 are each independently selected from the group consisting of CR a and N, provided that at least two of D 1 , G 1 , J 1 , L 1 and M 1 are CR a ; or a is 0, and one of D 1 , G 1 , L 1 and M 1 is NR a , one of D 1 , G 1 , L 1 and M 1 is CR a and the remainder are independently selected from the group consisting of CR a and N, wherein R a is as defined above; b is 1 and D 2 , G 2 , J 2 , L 2 and M 2 are each independently selected from the group consisting of CR a and N, provided that at least two of D 2 , G 2 , J 2 , L 2 and M 2 are CR a ; or b is 0, and one of D 2 , G 2 , L 2 and M 2 is NR a , one of D 2 , G 2 , L 2 and M 2 is CR a and the remainder are independently selected from the group consisting of CR a and N, wherein R a is as defined above; and n for each occurrence is independently an integer from 0 to 6.

Claim 2

Dependent Claim 1267 words

A compound of Formula (I) racemic-diastereomeric mixtures, optical isomers, pharmaceutically-acceptable salts or prodrugs thereof wherein: G is where Z 100 is or a group optionally substituted with R 1 selected from the group consisting of, cycloalkyl, naphthyl, tetrahydronaphthyl, benzothienyl, furanyl, thienyl, benzoxazolyl, benzothiazolyl, thiazolyl, benzofuranyl, 2,3-dihydrobenzofuranyl, indolyl, isoxazolyl, tetrahydropyranyl, tetrahydrofuranyl, piperidinyl, pyrazolyl, pyrrolyl, oxazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, indolinyl, indazolyl, benzoisothiazolyl, pyrido-oxazolyl, pyrido-thiazolyl, pyrimido-oxazolyl, pyrimido-thiazolyl and benzimidazolyl; Z 110 is a covalent bond, or an optionally substituted (C 1 -C 6 ) which is optionally substituted with one or more substituents selected from the group consisting of alkyl, CN, OH, halogen, NO 2 , COOH, substituted or unsubstituted amino and substituted or unsubstituted phenyl; Z 111 is a covalent bond, an optionally substituted (C 1 -C 6 ) or an optionally substituted —(CH 2 ) n -cycloalkyl-(CH 2 ) n —; where the optionally substituted groups are optionally substituted with one or more substituents selected from the group consisting of alkyl, CN, OH, halogen, NO 2 , COOH, substituted or unsubstituted amino and substituted or unsubstituted phenyl; R a and R 1 each represent one or more substituents for each occurrence independently selected from the group consisting of hydrogen, halogen, —CN, —NO 2 , —C(O)OH, —C(O)H, —OH, —C(O)O-alkyl, substituted or unsubstituted carboxamido, tetrazolyl, trifluoromethylcarbonylamino, trifluoromethylsulfonamido, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryloxy, substituted or unsubstituted heteroaryloxy, substituted or unsubstituted arylalkyl, substituted or unsubstituted alkynyl, substituted or unsubstituted amino, substituted or unsubstituted aminoalkyl, substituted or unsubstituted amido groups, substituted or unsubstituted heteroarylthio, substituted or unsubstituted arylthio, —Z 105 —C(O)N(R) 2 , —Z 105 —N(R)—C(O)—Z 200 , —Z 105 —N(R)—S(O) 2 —Z 200 , —Z 105 —N(R)—C(O)—N(R)—Z 200 , R c and CH 2 OR c ; where R c for each occurrence is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, —CH 2 —NR d R e , —W—(CH 2 ) t —NR d R e , —W—(CH 2 ) t —O-alkyl, —W—(CH 2 ) t —S-alkyl, or —W—(CH 2 ) t —OH; Z 105 for each occurrence is independently a covalent bond or (C 1 -C 6 ); Z 200 for each occurrence is independently a substituted or unsubstituted (C 1 -C 6 ), substituted or unsubstituted phenyl or substituted or unsubstituted —(C 1 -C 6 )-phenyl; R d and R e for each occurrence are independently H, alkyl, alkanoyl or SO 2 -alkyl; or R d , R e and the nitrogen atom to which they are attached together form a five- or six-membered heterocyclic ring; t for each occurrence is independently an integer from 2 to 6; W for each occurrence is independently a direct bond or O, S, S(O), S(O) 2 , or NR f , wherein R f for each occurrence is independently H or alkyl; or R 1 is a substituted or unsubstituted carbocyclic or heterocyclic ring fused with ring 2; R 3 is hydrogen, hydroxy, substituted or unsubstituted alkoxy; A is -, —O—; —S—; —S(O) p —; —N(R)—; —N(C(O)OR)—; —N(C(O)R)—; —N(SO 2 R)—; —CH 2 O—; —CH 2 S—; —CH 2 N(R)—; —CH(NR)—; —CH 2 N(C(O)R))—; —CH 2 N(C(O)OR)—; —CH 2 N(SO 2 R)—; —CH(NHR)—; —CH(NHC(O)R)—; —CH(NHSO 2 R)—; —CH(NHC(O)OR)—; —CH(OC(O)R)—; —CH(OC(O)NHR)—; —CH═CH—; —C(═NOR)—; —C(O)—; —CH(OR)—; —C(O)N(R)—; —N(R)C(O)—; —N(R)S(O) p —; —OC(O)N(R)—; —N(R)—C(O)—(CH 2 ) n —N(R)—, —N(R)C(O)O—; —N(R)—(CH 2 ) n+1 —C(O)—, —S(O) p N(R)—; —O—(CR 2 ) n+1 —C(O)—, —O—(CR 2 ) n+1 —O—, —N(C(O)R)S(O) p —; —N(R)S(O) p N(R)—; —N(R)—C(O)—(CH 2 ) n —O—, —C(O)N(R)C(O)—; —S(O) p N(R)C(O)—; —OS(O) p N(R)—; —N(R)S(O) p O—; —N(R)S(O) p C(O)—; —SO p N(C(O)R)—; —N(R)SO p N(R)—; —C(O)O—; —N(R)P(OR b )O—; —N(R)P(OR b )—; —N(R)P(O)(OR b )O—; —N(R)P(O)(OR b )—; —N(C(O)R)P(OR b )O—; —N(C(O)R)P(OR b )—; —N(C(O)R)P(O)(OR b )O—, or —N(C(O)R)P(OR b )—; where R for each occurrence is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted arylalkyl or substituted or unsubstituted aryl; R b for each occurrence is independently H, substituted or unsubstituted alkyl, substituted or unsubstituted arylalkyl, substituted or unsubstituted cycloalkyl or substituted or unsubstituted aryl; p is 1 or 2; or in a phosphorus containing group, the nitrogen atom, the phosphorus atom, R and R b together form a five- or six-membered heterocyclic ring; or A is NRSO 2 and R, R a and the nitrogen atom together form a substituted or unsubstituted five or-six-membered heterocyclic ring fused to ring 1; R 2 is —Z 101 -Z 102 ; Z 101 is a covalent bond, —(C 1 -C 6 )—, —(C 1 -C 6 )— —O—, —(C 1 -C 6 )—C(O)—, —(C 1 -C 6 )— —C(O)O—, —(C 1 -C 6 )—C(O)—NH—, —(C 1 -C 6 )—C(O)—N((C 1 -C 6 ))— or a substituted or unsubstituted phenyl group; Z 102 is hydrogen; a substituted or unsubstituted alkyl group; a substituted or unsubstituted cycloalkyl group; a substituted or unsubstituted, saturated or unsaturated heterocyclic group; or a substituted or unsubstituted, saturated or unsaturated heterobicyclic group; said substituted heterocyclic and substituted heterobicyclic group having one or more substituents each independently selected from the group consisting of hydroxyl, cyano, substituted or unsubstituted alkoxy, substituted or unsubstituted sulfonamido, substituted or unsubstituted ureido, substituted or unsubstituted carboxamido, substituted or unsubstituted amino, oxo, a saturated, unsaturated or aromatic, substituted or unsubstituted heterocyclic group consisting of one or more nitrogen atoms, one or more oxygen atoms or a combination thereof wherein the nitrogen atoms are independently optionally substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl group; or R 2 is a group of the formula —B—E, wherein B is a substituted or unsubstituted cycloalkyl, substituted or unsubstituted azacycloalkyl, substituted or unsubstituted amino, substituted or unsubstituted aminoalkylsulfonyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted aminoalkylcarbonyl, hydroxy substituted or unsubstituted alkylene, substituted or unsubstituted aminoalkyl, substituted or unsubstituted alkylenecarbonyl or substituted or unsubstituted aminoalkylcarbonyl group; and E is substituted or unsubstituted azacycloalkyl, substituted or unsubstituted azacycloalkylcarbonyl, substituted or unsubstituted azacycloalkylsulfonyl, substituted or unsubstituted azacycloalkylalkyl, substituted or unsubstituted heteroaryl-substituted or unsubstituted heteroarylcarbonyl, substituted or unsubstituted heteroarylsulfonyl, substituted or unsubstituted heteroarylalkyl, substituted or unsubstituted azacycloalkylcarbonylamino, substituted or unsubstituted heteroarylcarbonylamino s or substituted or unsubstituted aryl; a is 1 and D 1 , G 1 , J 1 , L 1 and M 1 are each independently selected from the group consisting of CR a and N, provided that at least two of D 1 , G 1 , J 1 , L 1 and M 1 are CR a ; or a is 0, and one of D 1 , G 1 , L 1 and M 1 is NR a , one of D 1 , G 1 , L 1 and M 1 is CR a and the remainder are independently selected from the group consisting of CR a and N, wherein R a is as defined above; b is 1 and D 2 , G 2 , J 2 , L 2 and M 2 are each independently selected from the group consisting of CR a and N, provided that at least two of D 2 , G 2 , J 2 , L 2 and M 2 are CR a ; or b is 0, and one of D 2 , G 2 , L 2 and M 2 is NR a , one of D 2 , G 2 , L 2 and M 2 is CR a and the remainder are independently selected from the group consisting of CR a and N, wherein R a is as defined above; and n for each occurrence is independently an integer from 0 to 6.

Claim 3

Dependent Claim 91 words

The compound of claim 1 wherein R 3 is H; R 1 for each occurrence is independently selected from the group consisting of F, Cl, Br, I, CH 3 , NO 2 , OCF 3 , OCH 3 , CN, CO 2 CH 3 , CF 3 , —CH 2 NR d R e , t-butyl, pyridyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted benzyl, substituted or unsubstituted benzenesulfonyl, substituted or unsubstituted phenoxy, substituted or unsubstituted phenyl, substituted or unsubstituted amino, carboxyl, substituted or unsubstituted tetrazolyl, and substituted or unsubstituted styryl.

Claim 4

Dependent Claim 84 words

The compound of claim 1 wherein R 3 is H; R a for each occurrence is independently selected from the group consisting of F, Cl, Br, I, CH 3 , NO 2 , OCF 3 , OCH 3 , CN, CO 2 CH 3 , CF 3 , t-butyl, pyridyl, substituted or unsubstituted oxazolyl, substituted or unsubstituted benzyl, substituted or unsubstituted benzenesulfonyl, substituted or unsubstituted phenoxy, substituted or unsubstituted phenyl, substituted or unsubstituted amino, carboxyl, substituted or unsubstituted tetrazolyl, and substituted or unsubstituted styryl.

Claim 5

Dependent Claim 23 words

The compound of claim 1 wherein R 3 is H; R 2 is of the formula wherein n is 1, 2 or 3.

Claim 6

Dependent Claim 169 words

The compound of claim 1 wherein R 3 is H; R 2 is of the formula wherein m is 0, 1, 2 or 3 and R g is H or —(CH 2 ) p N(R 4 )R 5 , wherein p is an integer from 2 to 6 and R 4 and R 5 are each, independently, H, azabicycloalkyl or Y—Z, wherein Y is selected from the group consisting of —C(O)—, —(CH 2 ) q —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, —(CH2) q O—, —(CH 2 ) q NH—, and —(CH 2 ) q S(O) r —; wherein q is an integer from 0 to 6; and r is 0, 1 or 2; and Z is a substituted or unsubstituted moiety selected from the group consisting of alkyl, alkoxy, amino, aryl, heteroaryl and heterocycloalkyl group or R 4 , R 5 and the nitrogen atom to which they are attached together form a 3, 4, 5, 6 or 7-membered, substituted or unsubstituted heterocyclic or heterobicyclic group.

Claim 7

Dependent Claim 176 words

The compound of claim 1 wherein R 3 is H; R 2 is of the formula wherein m is 0, 1, 2 or 3 a and b are each, independently, an integer from 0 to 6; Q is —OR 6 or —NR 4 R 5 ; each R 4 and R 5 is, independently, H, azabicycloalkyl or Y—Z, wherein Y is selected from the group consisting of —C(O)—, —(CH 2 ) q —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, (CH 2 ) q O—, —(CH 2 ) q NH—, and —(CH 2 ) q S(O) r —; wherein q is an integer from 0 to 6; and r is 0, 1 or 2; and Z is a substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, amino, aryl, heteroaryl or heterocycloalkyl group or R 4 , R 5 and the nitrogen atom to which they are attached together form a 3, 4, 5, 6 or 7-membered, substituted or unsubstituted heterocyclic or heterobicyclic group; and R 6 is hydrogen or a substituted or unsubstituted alkyl group.

Claim 8

Dependent Claim 110 words

The compound of claim 1 wherein R 3 is H; R 2 is of the formula wherein n is 1, 2 or 3; and R 4 is H, azabicycloalkyl or Y—Z, wherein Y is selected from the group consisting of —C(O)—, —(CH 2 ) q —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, (CH 2 ) q O—, —(CH 2 ) q NH—, and —(CH 2 ) q S(O) r —; wherein q is an integer 0 to 6; and r is 0, 1 or 2; and Z is a substituted or unsubstituted alkyl, substituted or unsubstituted amino, aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl group.

Claim 9

Dependent Claim 282 words

The compound of claim 1 wherein R 3 is H; R 2 is of the formula wherein m is 0, 1, 2 or 3; R 5 is H, azabicycloalkyl or Y—Z, wherein Y is selected from the group consisting of a covalent bond, —C(O)—, —(CH 2 ) q —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, —(CH 2 ) q O—, —(CH 2 ) q NH—, (CH 2 ) q C(O)—, —C(O)(CH 2 ) q — and —(CH 2 ) q S(O) r —, where the alkyl portion of —(CH 2 ) q O—, —(CH 2 ) q O—, —(CH 2 ) q NH—, —(CH 2 ) q C(O)—, —C(O)(CH 2 ) q — and —(CH 2 ) q S(O) r is optionally substituted by a halogen, hydroxy or an alkyl group; wherein q is an integer from 0 to 6; and r is 0, 1 or 2; and Z is a substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl group; or Y and Z together are a natural or unnatural amino acid, which may be mono- or di-alkylated at the amine nitrogen; and R 6 represents one or more substituents each independently selected from the group consisting of hydrogen, hydroxy, oxo, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted aminocarbonyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted arylcarbonyl, substituted or unsubstituted heterocyclylcarbonyl, substituted or unsubstituted aminoalkyl and substituted or unsubstituted arylalkyl; provided that the carbon atoms adjacent to the nitrogen atom are not substituted by a hydroxy group.

Claim 10

Dependent Claim 113 words

The compound of claim 1 wherein R 3 is H; R 2 is of the formula wherein R 4 is H, substituted or unsubstituted alkyl, substituted or unsubstituted azabicycloalkyl or Y—Z, wherein Y is selected from the group consisting of —C(O)—, —(CH 2 ) q —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, —(CH 2 ) q O—, —(CH 2 ) q NH—, and —(CH 2 ) q S(O) r —; wherein q is an integer from 0 to 6, and r is 0, 1 or 2; and Z is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl.

Claim 11

Dependent Claim 158 words

The compound of claim 1 wherein R 3 is H; R 2 is of the formula wherein m is an integer from 1 to 6; and R 4 and R 5 are each, independently, H, substituted or unsubstituted azabicycloalkyl or Y—Z, wherein Y is selected from the group consisting of —C(O)—, —(CH 2 ) q —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, —(CH 2 ) q O—, —(CH 2 ) q NH—, and —(CH 2 ) q S(O) r —; wherein q is an integer from 0 to 6; and r is 0, 1 or 2; and Z is a substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl group; or R 4 , R 5 and the nitrogen atom to which they are attached together form a 3, 4, 5, 6 or 7-membered, substituted or unsubstituted heterocyclic or substituted or unsubstituted heterobicyclic group.

Claim 12

Dependent Claim 201 words

The compound of claim 1 wherein R 3 is H; R 2 is of the formula wherein n is an integer from 0 to 4; r is 0 and m is an integer from 1 to 6; or r is 1 and m is an integer from 0 to 6; Q is —OR 6 or —NR 4 R 5 ; each R 4 and R 5 is, independently, H, substituted or unsubstituted azabicycloalkyl or Y—Z, wherein Y is selected from the group consisting of —C(O)—, —(CH 2 ) q —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, —(CH 2 ) q O—, —(CH 2 ) q NH—, and —(CH 2 ) q S(O) r —; q is an integer from 0 to 6; and r is 0, 1 or 2; and Z is a substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl group; or R 4 , R 5 and the nitrogen atom to which they are attached together form a 3, 4, 5 or 6-membered, substituted or unsubstituted heterocyclic group; and R 6 is hydrogen or a substituted or unsubstituted alkyl group.

Claim 13

Dependent Claim 135 words

The compound of claim 1 wherein R 3 is H; R 2 is of the formula n is an integer from 0 to 4; m is an integer from 0 to 6; R 4 is H, substituted or unsubstituted azabicycloalkyl or Y—Z, wherein Y is selected from the group consisting of —C(O)—, —(CH 2 ) q —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, —(CH 2 ) q O—, (CH 2 ) q NH—, and —(CH 2 ) q S(O) r —; wherein q is an integer from 0 to 6; and r is 0, 1 or 2; and Z is substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl; and R 6 is hydrogen or a substituted or unsubstituted alkyl group.

Claim 14

Dependent Claim 320 words

The compound of claim 10 wherein R 4 , R 5 and the nitrogen atom together form a heterocyclic group of the formula wherein R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 and R 14 are each, independently, lower alkyl or hydrogen; or at least one pair of substituents R 7 and R 8 ; R 9 and R 10 ; R 11 and R 12 ; or R 13 and R 14 together are an oxygen atom; or at least one of R 7 and R 9 is cyano, CONHR 15 , COOR 15 , CH 2 OR 15 or CH 2 NR 15 (R 16 ), wherein R 15 and R 16 are each, independently, H, azabicycloalkyl or V—L, wherein V is selected from the group consisting of —C(O)—, —(CH 2 ) p —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, (CH 2 ) q O—, —(CH 2 ) q NH—, and —(CH 2 ) q S(O) r —; wherein p is an integer from 0 to 6, q is an integer from 0 to 6, and r is 0, 1 or 2; and L is substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl; or R 15 , R 16 and the nitrogen atom together form a 3, 4, 5, 6 or 7-membered, substituted or unsubstituted heterocyclic or a substituted or unsubstituted heterobicyclic group; X is O, S, SO, SO 2 , CH 2 , CHOR 17 or NR 17 , wherein R 17 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, —C(NH)NH 2 , —C(O)R 17 , or —C(O)OR 18 , wherein R 18 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl or substituted or unsubstituted arylalkyl; and t is 0 o 1.

Claim 15

Dependent Claim 191 words

The compound of claim 10 wherein R 4 , R 5 and the nitrogen atom together form a heterocycle of the formula wherein R 19 and R 20 are each, independently, hydrogen or lower alkyl; or R 19 and R 20 together are an oxygen atom; R 21 and R 22 are each, independently, H, substituted or unsubstituted azabicycloalkyl or V—L, wherein V is selected from the group consisting of —C(O)—, —(CH 2 ) p —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, (CH 2 ) q O—, (CH 2 ) q NH—, and —(CH 2 ) q S(O) r —; wherein p is an integer from 0 to 6, q is an integer from 0 to 6, and r is 0, 1 or 2; and L is substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl group; or R 21 , R 22 and the nitrogen atom together form a 3, 4, 5 or 6-membered, substituted or unsubstituted heterocyclic group; m is an integer from 1 to 6; and n is an integer from 0 to 6.

Claim 16

Dependent Claim 65 words

The compound of claim 10 wherein R 4 , R 5 and the nitrogen atom together form a heterocyclic group of the formula wherein m is an integer from 1 to 6; and R 23 is CH 2 OH, NRR′, C(O)NRR′ or COOR, wherein R and R′ are each, independently, hydrogen or substituted or unsubstituted alkyl, substituted or unsubstituted aryl or substituted or unsubstituted arylalkyl.

Claim 17

Dependent Claim 212 words

The compound of claim 10 wherein R 4 , R 5 and the nitrogen atom together form a heterocyclic group of the formula wherein R 24 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, carboxyl, cyano, C(O)OR 25 , CH 2 OR 25 , CH 2 NR 26 R 27 or C(O)NHR 26 , wherein R 25 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclic or substituted or unsubstituted heterocycloaryl; and R 26 and R 27 are each, independently, H, substituted or unsubstituted azabicycloalkyl or V—L, wherein V is selected from the group consisting of —C(O)—, —(CH 2 ) p —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, (CH 2 ) q O—, —(CH 2 ) q NH—, and —(CH 2 ) q S(O) r —; wherein p is an integer from 0 to 6, q is an integer from 0 to 6, and r is 0, 1 or 2; and L is substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl; or R 26 , R 27 and the nitrogen atom together form a 3, 4, 5 or 6-membered, substituted or unsubstituted heterocyclic group.

Claim 18

Dependent Claim 65 words

The compound of claim 10 wherein at least one of R 4 and R 5 is of the formula Y—Z, wherein Z is of the formula wherein T is C(O), S, SO, SO 2 , CHOR or NR, wherein R is hydrogen or a substituted or unsubstituted alkyl, substituted or unsubstituted aryl or substituted or unsubstituted arylalkyl group; and n is 0, 1 or 2.

Claim 19

Dependent Claim 87 words

The compound of claim 10 wherein at least one of R 4 and R 5 is of the formula Y—Z, wherein Z is of the formula —N(R 28 )R 29 , wherein R 28 and R 29 are each, independently, substituted or unsubstituted carboxyalkyl, substituted or unsubstituted alkoxycarbonylalkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkylcarbonyl or substituted or unsubstituted cyanoalkyl; or R 28 and R 29 , together with the nitrogen atom, form a five- or six-membered substituted or unsubstituted heterocyclic group.

Claim 20

Dependent Claim 316 words

The compound of claim 11 wherein R 4 , R 5 and the nitrogen atom together form a heterocycle of the formula wherein R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 and R 14 are each, independently, lower alkyl or hydrogen; or at least one pair of substituents R 7 and R 8 ; R 9 and R 10 ; R 11 and R 12 ; or R 13 and R 14 together are an oxygen atom; or at least one of R 7 and R 9 is cyano, CONHR 15 , COOR 15 , CH 2 OR 15 or CH 2 NR 15 (R 16 ), wherein R 15 and R 16 are each, independently, H, substituted or unsubstituted azabicycloalkyl or V—L, wherein V is selected from the group consisting of —C(O)—, —(CH 2 ) p —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, (CH 2 ) q O—, —(CH 2 ) q NH—, and —(CH 2 ) q S(O) r —; wherein p is an integer from 0 to 6, q is an integer from 0 to 6, and r is 0, 1 or 2; and L is substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl; or R 15 , R 16 and the nitrogen atom together form a 3, 4, 5, 6 or 7-membered, substituted or unsubstituted heterocyclic or heterobicyclic group; X is O, S, SO, SO 2 , CH 2 , CHOR 17 or NR 17 , wherein R 17 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, —C(NH)NH2, —C(O)R, 8 , or —C(O)OR 18 , wherein R 18 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl or substituted or unsubstituted arylalkyl; and t is 0 or 1.

Claim 21

Dependent Claim 191 words

The compound of claim 1 wherein R 4 , R 5 and the nitrogen atom together form a heterocycle of the formula wherein R 19 and R 20 are each, independently, hydrogen or lower alkyl; or R 19 and R 20 together are an oxygen atom; R 21 and R 22 are each, independently, H, substituted or unsubstituted azabicycloalkyl or V—L, wherein V is selected from the group consisting of —C(O)—, —(CH 2 ) p —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, (CH 2 ) q O—, —(CH 2 ) q NH—, and —(CH 2 ) q S(O) r —; wherein p is an integer from 0 to 6, q is an integer from 0 to 6, and r is 0, 1 or 2; and L is substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl group; or R 21 , R 22 and the nitrogen atom together form a 3, 4, 5 or 6-membered, substituted or unsubstituted heterocyclic group; m is an integer from 2 to 6; and n is an integer from 0 to 6.

Claim 22

Dependent Claim 63 words

The compound of claim 11 wherein R 4 , R 5 and the nitrogen atom together form a heterocyclic group of the formula wherein m is an integer from 1 to 6; and R 23 is CH 2 OH, NRR′, C(O)NRR′ or COOR, wherein R is hydrogen or a substituted or unsubstituted alkyl, substituted or unsubstituted aryl or substituted or unsubstituted arylalkyl group.

Claim 23

Dependent Claim 216 words

The compound of claim 11 wherein R 4 , R 5 and the nitrogen atom together form a heterocyclic group of the formula wherein R 24 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl or substituted or unsubstituted arylalkyl , carboxyl, cyano, C(O)OR 25 , CH 2 OR 25 , CH 2 NR 26 R 27 or C(O)NHR 26 , wherein R 25 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heterocyclic or substituted or unsubstituted heterocycloaryl group; and R 26 and R 27 are each, independently, H, substituted or unsubstituted azabicycloalkyl or V—L, wherein V is selected from the group consisting of —C(O)—, —(CH 2 ) p —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, (CH 2 ) q O—, —(CH 2 ) q NH—, and —(CH 2 ) q S(O) r —; wherein p is an integer from 0 to 6, q is an integer from 0 to 6, and r is 0, 1 or 2; and L is substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl group; or R 26 , R 27 and the nitrogen atom together form a 3, 4, 5 or 6-membered, substituted or unsubstituted heterocyclic group.

Claim 24

Dependent Claim 130 words

The compound of claim 11 wherein at least one of R 4 and R 5 is of the formula Y—Z, wherein Z is of the formula wherein g is 0 or 1; T is C(O), O, S, SO, SO 2 , CH 2 , CHOR 7 or NR 17 , wherein R 17 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, —C(NH)NH 2 , —C(O)R 18 , or —C(O)OR 18 , wherein R 18 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl or substituted or unsubstituted arylalkyl; and R 32 is hydrogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted aminocarbonyl, substituted or unsubstituted alkylcarbonyl or substituted or unsubstituted arylalkyl.

Claim 25

Dependent Claim 87 words

The compound of claim 11 wherein at least one of R 4 and R 5 is of the formula Y—Z, wherein Z is of the formula —N(R 28 )R 29 , wherein R 28 and R 29 are each, independently, substituted or unsubstituted carboxyalkyl, substituted or unsubstituted alkoxycarbonylalkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkylcarbonyl or substituted or unsubstituted cyanoalkyl; or R 28 and R 29 , together with the nitrogen atom, form a five- or six-membered substituted or unsubstituted heterocyclic group.

Claim 26

Dependent Claim 40 words

The compound of claim 8 wherein R 5 is Y—Z, wherein Z is of the formula N(R 30 )R 31 , wherein R 30 and R 31 are each, independently, hydrogen, alkyl, alkoxycarbonyl, alkoxyalkyl, hydroxyalkyl, aminocarbonyl, cyano, alkylcarbonyl or arylalkyl.

Claim 27

Dependent Claim 60 words

The compound of claim 8 wherein R 5 is Y—Z, wherein Z is of the formula wherein each X is, independently, CH or N; and R 32 is hydrogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted aminocarbonyl, substituted or unsubstituted alkylcarbonyl or substituted or unsubstituted arylalkyl group.

Claim 28

Dependent Claim 123 words

The compound of claim 8 wherein R 5 is Y—Z, wherein Z is of the formula wherein g is 0 or 1; T is O, S, SO, SO 2 , CH 2 , CHOR 17 or NR 17 , wherein R 17 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, C(O)NH 2 , —C(NH)NH 2 , —C(O)R 17 , or —C(O)OR 18 , wherein R 18 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl or substituted or unsubstituted arylalkyl; and R 32 is hydrogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted aminocarbonyl, substituted or unsubstituted alkylcarbonyl or substituted or unsubstituted arylalkyl group.

Claim 29

Dependent Claim 59 words

The compound of claim 8 wherein R 5 is Y—Z, wherein Z is of the formula wherein g is 0, 1 or 2; and R 32 is hydrogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted aminocarbonyl, substituted or unsubstituted alkylcarbonyl or substituted or unsubstituted arylalkyl group.

Claim 30

Dependent Claim 115 words

The compound of claim 8 wherein R 5 is Y—Z, wherein Z is of the formula wherein T is C(O), O, S, SO, SO 2 , CH 2 , CHOR 17 or NR 17 , wherein R 17 is hydrogen, substituted or unsubstituted alkyl, aryl, arylalkyl, —C(NH)NH 2 , —C(O)R 18 , or —C(O)OR 18 , wherein R 18 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl or substituted or unsubstituted arylalkyl; g is 0 or 1; and R 32 is hydrogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted aminocarbonyl, substituted or unsubstituted alkylcarbonyl or substituted or unsubstituted arylalkyl group.

Claim 31

Dependent Claim 87 words

The compound of claim 8 wherein R 5 is Y—Z, wherein Z is of the formula wherein R 32 is hydrogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted hydroxyalkyl, substituted or unsubstituted aminocarbonyl, alkylcarbonyl, substituted or unsubstituted thioalkoxy or substituted or unsubstituted arylalkyl; and R 33 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkoxycarbonyl, substituted or unsubstituted alkoxyalkyl, substituted or unsubstituted aminocarbonyl, perhaloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkylcarbonyl or substituted or unsubstituted arylalkyl.

Claim 32

Dependent Claim 366 words

The compound of claim 1 wherein R 3 is H; R 2 is of the formula wherein m is 0 or 1; R 34 , R 35 , R 36 , R 37 , R 38 , R 39 , R 40 and R 41 are each, independently, methyl or hydrogen; or at least one pair of substituents R 34 and R 35 ; R 36 and R 37 ; R 38 and R 39 ; or R 40 and R 41 together are an oxygen atom; and R 42 is H, substituted or unsubstituted azabicycloalkyl or Y—Z, wherein Y is selected from the group consisting of —C(O)—, —(CH 2 ) p —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, (CH 2 ) q O—, —(CH 2 ) q NH—, and —(CH 2 ) q S(O) r —; wherein p is an integer from 0 to 6, q is an integer from 0 to 6, and r is 0, 1 or 2; and Z is substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl group; or R 42 is of the formula wherein u is 0 or 1; R 43 , R 44 , R 45 , R 46 , R 47 , R 48 , R 49 and R 50 are each, independently, methyl or hydrogen; or at least one pair of substituents R 43 and R 44 ; R 45 and R 46 ; R 47 and R 48 ; or R 49 and R 50 together are an oxygen atom; and R 51 is H, substituted or unsubstituted azabicycloalkyl or V—L, wherein V is selected from the group consisting of —C(O)—, —(CH 2 ) p —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, (CH 2 ) q O, —(CH 2 ) q NH—, and —(CH 2 ) q S(O) r —; wherein p is an integer from 0 to 6, q is an integer from 0 to 6, and r is 0, 1 or 2; and L is substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl.

Claim 33

Dependent Claim 375 words

The compound of claim 1 wherein R 3 is H; R 2 is of the formula wherein h, i, j, k and l are independently 0 or 1; R 52 , R 53 , R 54 , R 55 , R 56 , R57, R 58 , R 59 , R g and R h are each, independently, methyl or hydrogen; or at least one pair of substituents R 52 and R 53 ; R 54 and R 55 ; R 56 and R 57 ; or R 58 and R 59 together are an oxygen atom; and R 60 is H, substituted or unsubstituted azabicycloalkyl or Y—Z, wherein Y is selected from the group consisting of —C(O)—, —(CH 2 ) p —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, —(CH 2 ) q O—, (CH 2 ) q NH—, and —(CH 2 ) q S(O) r —; wherein p is an integer from 0 to 6, q is an integer from 0 to 6, and r is 0, 1 or 2; and Z is substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl; or R 60 is of the formula wherein v is 0 or 1; R 61 , R 62 , R 63 , R 64 , R 65 , R 66 , R 67 and R 68 are each, independently, lower alkyl or hydrogen; or at least one pair of substituents R 61 and R 62 ; R 63 and R 64 ; R65 and R 66 ; and R 67 and R 68 together are an oxygen atom; and R 69 is H, substituted or unsubstituted azabicycloalkyl or V—l, wherein V is selected from the group consisting of —C(O)—, —(CH 2 ) p —, —S(O) 2 —, —C(O)O—, —SO 2 NH—, —CONH—, (CH 2 ) q O—, —(CH 2 ) q NH—, and ≦(CH 2 ) q S(O) r —; wherein p is an integer from 0 to 6, q is an integer from 0 to 6, and r is 0, 1 or 2; and L is substituted or unsubstituted alkyl, substituted or unsubstituted amino, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocycloalkyl.

Claim 34

Dependent Claim 36 words

A method of inhibiting one or more protein kinase activity in a patient comprising administering a therapeutically effective amount of a compound of claim 1 or a physiologically acceptable salt, or prodrug thereof to said patient.

Claim 35

Dependent Claim 35 words

The method of claim 33 wherein said protein kinase is selected from the group consisting of KDR, FGFR-1, PDGFRβ, PDGFRα, IGF-1R, c-Met, Flt-1, Flt-4, TIE-2, TIE-1, Lck, Src, fyn, Lyn, Blk, hck, fgr and yes.

Claim 36

Dependent Claim 31 words

A method of affecting angiogenesis in a patient comprising administering a therapeutically effective amount of a compound of claim 1 or a physiologically acceptable salt, or prodrug thereof to said patient.

Claim 37

Dependent Claim 19 words

The method of claim 33 wherein the protein kinase is a protein serine/threonine kinase or a protein tyrosine kinase.

Claim 38

Dependent Claim 34 words

A method of treating one or more ulcers in a patient comprising administering a therapeutically effective amount of a compound of claim 1 or a physiologically acceptable salt, or prodrug thereof to said patient.

Claim 39

Dependent Claim 37 words

The method of claim 37 wherein the ulcer or ulcers are caused by a bacterial or fungal infection; or the ulcer or ulcers are Mooren ulcers; or the ulcer or ulcers are a symptom of ulcerative colitis.

Claim 40

Dependent Claim 120 words

A method of treating a condition in a patient comprising administering a therapeutically effective amount of a compound of claim 1 or a physiologically acceptable salt, prodrug or biologically active metabolites thereof to said patient, wherein said condition is Crow-Fukase (POEMS) syndrome, a diabetic condition, sickle cell anaemia, systemic lupus, glomerulonephritis, synovitis, inflammatory bowel disease, Crohn's disease, glomerulonephritis, rheumatoid arthritis, osteoarthritis, multiple sclerosis, graft rejection, Lyme disease, sepsis, von Hippel Lindau disease, pemphigoid, psoriasis, Paget's disease, polycystic kidney disease, fibrosis, sarcoidosis, cirrhosis, thyroiditis, hyperviscosity syndrome, Osler-Weber-Rendu disease, chronic occlusive pulmonary disease, asthma or edema following burns, trauma, radiation, hypoxia, ischemia, ovarian hyperstimulation syndrome, preeclampsia, menometrorrhagia, endometriosis, or infection by Herpes simplex, Herpes Zoster, human immunodeficiency virus, parapoxvirus, protozoa or toxoplasmosis.

Claim 41

Dependent Claim 40 words

The method of claim 39 wherein the ocular condition is ocular or macular edema, ocular neovascular disease, scleritis, radial keratotomy, uveitis, vitritis, myopia, optic pits, chronic retinal detachment, post-laser treatment complications, conjunctivitis, Stargardt's disease, Eales disease, retinopathy or macular degeneration.

Claim 42

Dependent Claim 20 words

The method of claim 39 wherein the cardiovascular condition is atherosclerosis, restenosis, ischemia/reperfusion injury, vascular occlusion or carotid obstructive disease.

Claim 43

Dependent Claim 36 words

The method of claim 39 wherein the cancer is a solid tumor, a sarcoma, fibrosarcoma, osteoma, melanoma, retinoblastoma, a rhabdomyosarcoma, glioblastoma, neuroblastoma, teratocarcinoma, an hematopoietic malignancy, Kaposi's sarcoma, Hodgkin's disease, lymphoma, myeloma, leukemia or malignant ascites.

Claim 44

Dependent Claim 18 words

The method of claim 39 wherein the diabetic condition is insulin-dependent diabetes mellitus glaucoma, diabetic retinopathy or microangiopathy.

Claim 45

Dependent Claim 35 words

A method of decreasing fertility in a patient, said method comprising the step of administering to the patient an effective amount of a compound of claim 1 or a physiologically acceptable salt, or prodrug thereof.

Claim 46

Dependent Claim 11 words

The method of claim 34 wherein the protein kinase is Tie-2.

Claim 47

Dependent Claim 27 words

The method of claim 35 wherein the compound of Formula I, or physiologically acceptable salt, or prodrug thereof, is administered in combination with a pro-angiogenic growth factor.

Claim 48

Dependent Claim 30 words

The method of claim 46 wherein the pro-angiogenic growth factor is selected from the group consisiting of VEGF, VEGF-B, VEGF-C, VEGF-D, VEGF-E, HGF, FGF-1, FGF-2, derivatives thereof and antiiodotypic antibodies.

Claim 49

Dependent Claim 21 words

The method of claim 35 wherein the patient is suffering from anemia, ischemia, infarct, transplant rejection, a wound, gangrene or necrosis.

Claim 50

Dependent Claim 34 words

The method of claim 33 wherein the protein kinase activity is involved in T cell activation, B cell activation, mast cell degranulation, monocyte activation, the potentiation of an inflammatory response or a combination thereof.

Claim 51

Dependent Claim 86 words

A compound according to claim 1 , wherein R 3 is H; R 2 is —Z 101 -Z 102 where Z 101 is a covalent bond, —(C 1 -C 6 )—, —(C 1 -C 6 )—O—, —(C 1 -C 6 )—C(O)—, —(C 1 -C 6 )—C(O)O—, —(C 1 -C 6 )—C(O)—NH—, —(C 1 -C 6 )—C(O)—N((C 1 -C 6 ))— or a substituted phenyl group; and Z 102 is hydrogen, a substituted or unsubstituted alkyl group or a substituted or unsubstituted, saturated or unsaturated heterocyclic group.

Claim 52

Dependent Claim 62 words

A compound according to claim 50 , wherein Z 101 is selected from the group consisting of —CH 2 —C(O)O—, —CH 2 —C(O)—, —CH 2 —C(O)—NH—, —CH 2 —C(O)—N(Me)—, —CH(Me)—C(O)O—, —(CH 2 ) 3 —C(O)O—, —CH(Me)—C(O)—NH— and —(CH 2 ) 3 —C(O)—NH—; Z 102 is selected from the group consisting of hydrogen, methyl, ethyl, N,N-dimethylaminoethyl, N,N-diethylaminoethyl, 2-phenyl-2-hydroxyethyl, morpholino, piperazinyl, N-methylpiperazinyl and 2-hydroxymethylpyrrolidinyl.

Claim 53

Dependent Claim 25 words

A compound according to claim 51 , wherein G is where Z 100 is a substituted or unsubstituted benzoxazolyl or a substituted or unsubstituted benzthiazolyl.

Claim 54

Dependent Claim 29 words

A compound according to claim 8 , 9 , 10 or 51 , wherein G is where there is only one R a and it is H or F.

Claim 55

Dependent Claim 22 words

A compound according to claim 50 , wherein Z 101 is a covalent bond; and Z 102 is an optionally substituted pyridyl.

Claim 56

Dependent Claim 10 words

A compound according to claim 54 , wherein G is

Claim 57

Dependent Claim 19 words

A compound according to claim 1 , wherein R 3 is H; R 2 is cyclopentyl; and G is

Claim 58

Dependent Claim 57 words

A compound according to claim 56 , wherein Z 110 is hydrogen; A is O; and Z 100 is optionally substituted phenyl, furanyl or thienyl, where Z 100 is optionally substituted with one or more substituents each independently selected from the group consisting of F, COOH, NO 2 , OMe, —COOMe, OCF 3 and CF 3 .

Claim 59

Dependent Claim 77 words

A compound according to claim 56 , wherein Z 110 is hydrogen; A is —O—, —O—(CR 2 ) n —C(O)— or —O—(CR 2 ) n —O—; n for each occurrence is 0 to 3; Z 100 is an optionally substituted group selected from the group consisting of cyclohexyl, phenyl, tetrahydropyranyl, tetrahydrofuranyl, isoxazolyl and piperidinyl; where Z 100 is optionally substituted with one or more substituents selected from the group consisting of alkyl, alkoxy, halo, hydroxy and alkoxycarbonyl.

Claim 60

Dependent Claim 24 words

A compound according to claim 56 , wherein R 2 is an optionally substituted group selected from the group consisting of cyclobutyl and cyclohexyl.

Claim 61

Dependent Claim 30 words

A compound according to claim 59 , wherein R 2 is optionally substituted with one or more substituents selected from the group consisting of hydroxy, alkyl, hydroxyalkyl, carboxyalkyl and phenylalkoxyalkyl.

Claim 62

Dependent Claim 11 words

A compound according to claim 60 , wherein G is 4-phenoxyphenyl.

Claim 63

Dependent Claim 31 words

A compound according to claim 6 wherein m is 2; a is 0; R 6 is H; b is 1 or 2; and R 4 and R 5 are each hydrogen.

Claim 64

Dependent Claim 108 words

A compound according to claim 8 , wherein m is 0, 1 or 2; R 6 is hydrogen; R 5 is H or Y—Z; where Y is a covalent bond, —C(O)—, —(CH 2 ) q O—, —(CH 2 ) q —, —(CH 2 ) q C(O)— or —C(O)(CH 2 ) q —, where the alkyl portion of —(CH 2 ) q O—, —(CH 2 ) q —, —(CH 2 ) q C(O)— and —C(O)(CH 2 ) q — is optionally substituted by a halogen, hydroxy or an alkyl group; and Z is hydrogen, alkyl, optionally substituted alkyl, alkoxyalkyl, optionally substituted heterocycloalkyl, optionally substituted heteroaryl, or optionally substituted amino.

Claim 65

Dependent Claim 47 words

A compound according to claim 63 , wherein Z is hydrogen, methyl, ethyl, hydroxymethyl, methoxyethyl, N-methylpiperidinyl, (t-butoxycarbonyl)(hydroxy)-piperidinyl, hydroxypiperidinyl, (hydroxymethyl)piperdinyl, (hydroxy)(methyl)-piperidinyl, morpholino, (methoxyethyl)piperizinyl, methylpiperizinyl, 4-piperidinylpiperidinyl, imidazolyl, methylimidazolyl, N-methylamino, N,N-dimethylamino, N-isopropylamino, N,N-diethylamino, 2,3-dihydroxypropylamino, 2-hydroxyethylamino, 3-hydroxypropylamino, methoxyethylamino, ethoxycarbonylmethylamino, phenylmethylamino, N-methyl-N-methoxyamino, furanylmethylamino, piperidinylethylamino, N-(2-N,N-dimethylaminoethyl)-N-methylamino, 2-N,N-dimethylaminoethylamino, N-methyl-N-(N-methylpiperidin-4-yl)amino, 2-morpholino-ethylamino, 3-morpholino-propylamino, 3-imidazolylpropylamino, or 3-(2-oxopyrrolidinyl)propylamino.

Claim 66

Dependent Claim 29 words

A compound according to claim 8 , wherein m is 2; R 5 is Y—Z; Y is —C(O)—; and Z is where n is 0, 1, 2 or 3.

Claim 67

Dependent Claim 134 words

A compound according to claim 9 , wherein R 4 is hydrogen or methyl; G is A is selected from the group consisting of O, —N(R)— and —N(R)C(O)—; Z 111 is —(CH 2 ) n -cycloalkyl-(CH 2 ) n —; R is hydrogen or alkyl; n is 0 to 5; R a is one or more substituents each independently selected from the group consisting of H, OH, F, Cl, methyl and methoxy; and R 1 is one or more substituents each independently selected from the group consisting of H, CN, F, CF 3 , OCF 3 , methyl, methoxy and an optionally substituted amino group; where said amino group is optionally substituted with one or two groups each independently selected from the group consisting of alkyl, alkoxyalkyl, phenyl, substituted phenyl, and optionally substituted heteroaryl.

Claim 68

Dependent Claim 14 words

A compound according to claim 66 , wherein R 1 is 4-methylphenylthio or 2-pyridinylthio.

Claim 69

Dependent Claim 24 words

A compound according to claim 9 , wherein G is where Z 100 is selected from the group consisting of benzo[b]thiophene, furanyl and thiophene.

Claim 70

Dependent Claim 27 words

A compound according to claim 9 , wherein R a is alkoxy; A is —NH—C(O)—; and there is a covalent bond between A and Z 100 .

Claim 71

Dependent Claim 113 words

A compound according to claims 1 , 8 or 9 , wherein G is A is selected from the group consisting of —N(R)—C(O)—N(R)—, —(CH 2 ) n —N(R)C(O)N(R)—, —N(R)— and —N(R)—SO 2 —; R is hydrogen or alkyl; Z 100 is pyridinyl, thiazolyl, furanyl, benzofuranyl or oxazolyl; X is S, O or NR 1 where R 1 for each occurrence is independently H or Me; R a is one or more substituents each independently selected from the group consisting of H and F; and R 1 is one or more substituents each independently selected from the group consisting of H, F, Cl, Br, NO 2 , CF 3 , alkyl, alkoxy and alkoxycarbonyl.

Claim 72

Dependent Claim 41 words

A compound according to claim 70 , wherein R 4 is methyl; m is 1, 2 or 3; R 5 is Y—Z, where Y is —C(O)O—, —C(O)— or —C(O)—(CH 2 ) p —; and Z is aminoalkyl, N-alkylamino, N,N-dialkylamino or hydroxyalkylaminoalkyl.

Claim 73

Dependent Claim 42 words

A compound according to claim 9 , wherein R 4 is methyl; G is where n is 0 to 3; Z 100 is an optionally substituted group selected from the group consisting of indolyl, indenyl, methylindenyl, methylindolyl, dimethylaminophenyl, phenyl, cyclohexyl and benzofuranyl.

Claim 74

Dependent Claim 161 words

A compound according to claim 9 , wherein G is Z 100 is an optionally substituted group selected from the group consisting of phenyl, imidazolyl, indolyl, furanyl, benzofuranyl and 2,3-dihydrobenzofuranyl; where Z 100 is optionally substituted with one or more substituents each independently selected from the group consisting of F, Cl, CN, optionally substituted alkyl, —O— (optionally substituted alkyl), —COOH, —Z 105 —C(O)N(R) 2 , —Z 105 —N(R)—C(O)—Z 200 , —Z 105 —N(R)—S(O) 2 —Z 200 , and —Z 105 —N(R)—C(O)—N(R)—Z 200 ; Z 105 is a covalent bond or (C 1 -C 6 ); Z 200 is an optionally substituted group selected from group consisting of (C 1 -C 6 ), phenyl and —(C 1 -C 6 )-phenyl; Z 110 and Z 111 are each independently a covalent bond or (C 1 -C 3 ) group optionally substituted with alkyl, hydroxy, COOH, CN or phenyl; and A is O, —N(R)—C(O)—N(R)—, —N(R)—C(O)—O—, —N(R)— or —N(R)—C(O)—, where R is H or alkyl.

Claim 75

Dependent Claim 12 words

A compound according to claim 73 , wherein R 4 is methyl.

Claim 76

Dependent Claim 32 words

A compound according to claim 8 , 9 or 10 , wherein G is where Z 100 is an optionally substituted group selected from the group consisting of benzoxazolyl, benzothiazolyl and benzimidazolyl.

Claim 77

Dependent Claim 53 words

A compound according to claim 75 , wherein R 4 is methyl; A is —NH—; there is only one R a and it is H or F; and Z 100 is optionally substituted with one or more substituents each independently selected from the group consisting of alkyl, halo, CF 3 , and alkoxy.

Claim 78

Dependent Claim 98 words

A compound according to claim 9 , wherein G is Z 100 is an optionally substituted group selected from the group consisting of phenyl, pyrrolyl, pyridyl, benzimidazolyl, naphthyl and where Z 100 is optionally substituted with one or more substituents each independently selected from the group consisting of F, Cl, Br, NO 2 , amino, N-alkylamino, N,N-dialkylamino, CN, optionally substituted alkyl, —O-(optionally substituted alkyl) and phenyl; Z 110 and Z 111 for each occurrence is independently (C 0 -C 3 ) optionally substituted with optionally substituted phenyl; and A is —N(R)—C(O)—N(R)—, —N(R)—S(O) 2 —, —N(R)—C(O)—, —N(R)— or —N(R)—C(O)—O—.

Claim 79

Dependent Claim 23 words

A compound according to claim 77 , wherein R 4 is methyl and there is only one R a and it is F.

Claim 80

Dependent Claim 104 words

A compound according to claim 9 or 64 , wherein G is Z 100 is an optionally substituted group selected from the group consisting of phenyl, isoxazolyl, tetrahydronaphthyl, furanyl, benzofuranyl, pyridyl and indolyl; where Z 100 is optionally substituted with one or more substituents each independently selected from the group consisting of F, CN,N0 2 , —C(O)H, —CONH 2 , —NHSO 2 CF 3 , optionally substituted alkyl, optionally substituted heteroaryl and —O-(optionally substituted alkyl); Z 110 and Z 111 are each independently optionally substituted (C 0 -C 3 ); and A is O, —N(R)—C(O)—(CH 2 ) n —N(R)—, —C(O)—N(R)—, —N(R)—C(O)—O—, —N(R)—C(O)— or —N(R)—.

Claim 81

Dependent Claim 27 words

A compound according to claim 79 , wherein R 4 is methyl; R a is H or methoxy; and Z 110 and Z 111 are each unsubstituted.

Claim 82

Dependent Claim 28 words

A compound according to claim 9 , wherein G is where R is H or lower alkyl and n is for each occurrence is independently 1 to 6.

Claim 83

Dependent Claim 10 words

A compound according to claim 81 , wherein G is

Claim 84

Dependent Claim 15 words

A compound according to claim 82 , wherein Z 100 is substituted or unsubstituted phenyl.

Claim 85

Dependent Claim 32 words

A compound according to claim 8 , 9 or 10 , wherein G is where Z 100 is an optionally substituted group selected from the group consisting of benzoxazolyl, benzothiazolyl and benzimidazolyl.

Claim 86

Dependent Claim 29 words

A compound according to claim 11 wherein n is 2; R 6 is H; m is 1; r is 1; and R 4 and R 5 are each hydrogen.

Claim 87

Dependent Claim 12 words

A compound according to claim 66 or 85 wherein G is 4-phenoxyphenyl.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	2006-12-08	2007-06-09	2007-12-09	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2010-12-08	2011-06-09	2011-12-09	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2014-12-08	2015-06-09	2015-12-09	$7700.00	Window Closed / Lapsed

Pyrazolopyrimidines as therapeutic agents

Abstract

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