4-AMINOPYRROLOPYRIMIDINES AS KINASE INHIBITORS
First Claim
3-1. The compound of claim 3, wherein R3 is a substituted or unsubstituted phenyl threnyl, benzoxadiazolyl, or benzothiadiazolyl.
3 Assignments
0 Petitions
Accused Products
Abstract
Chemical compounds having structural formula I
and physiologically acceptable salts thereof, are inhibitors of serine/threonine and tyrosine kinase activity. Several of the kinases whose activity is inhibited by these compounds are involved in immunologic, hyperpro;iferative or angiogenic processes. Thus, these compounds can ameliorate disase states where angiogenesis or endothelial cell hyperproliferaton is a factor. These compounds can be used to treat cancer, hyperproliferative disorders, rheumatoid artheritis, disorders of the immune system, transplant rejection, and inflammatory disorders.
165 Citations
44 Claims
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3-1. The compound of claim 3, wherein R3 is a substituted or unsubstituted phenyl threnyl, benzoxadiazolyl, or benzothiadiazolyl.
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5. The compound of claim 5 wherein ring A is substituted with one or more substituent selected from the group consisting of F, Cl, Br, I, CH3, NO2, OCF3, OCH3, CN, CO2CH3, CF3, 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, styryl, —
- S-(substituted or unsubstituted aryl), —
S-(substituted or unsubstituted heteroaryl), substituted or unsubstituted heteroaryl, substituted or unsubstituted heterocycloalkyl, alkynyl, —
C(O)NRfRg, Rc and CH2ORc;
Rf, Rg and the nitrogen atom together form a 3, 4, 5, 6 or 7-membered, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterobicycloalkyl or a substituted or unsubstituted heteroaromatic;
or Rf and Rg are each, independently, —
H, a substituted or unsubstituted aliphatic group or a substituted or unsubstuituted aromatic group; and
Rc is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, —
W—
(CH2)t—
NRdRe, —
W—
(CH2)t—
O-alkyl, —
W—
(CH2)t—
S-alkyl, or —
W—
(CH2)t—
OH;
t is an integer from 0 to 6;
W is a bond or —
O—
, —
S—
, —
S(O)—
, —
S(O)2—
, or —
NRk—
;
Rk is —
H or alkyl; and
Rd, Re and the nitrogen atom to which they are attached together form a 3, 4, 5, 6 or 7-membered substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted heterobicycloalkyl or a substituted or unsubstituted heteroaromatic;
orRd and Re are each, independently, —
H, alkyl, alkanoyl or -K-D;
K is —
S(O)2—
, —
C(O)—
, —
C(O)NH—
, —
C(O)2—
, or a direct bond;
D is a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted aralkyl, a substituted or unsubstituted heteroaromatic group, a substituted or unsubstituted heteroaralkyl, a substituted or unsubstituted cycloalkyl, a substituted or unsubstituted heterocycloalkyl, a substituted or unsubstituted amino, a substituted or unsubstituted aminoalkyl, a substituted or unsubstituted aminocycloalkyl, COORi, or a substituted or unsubstituted alkyl; and
Ri is a substituted or unsubstituted aliphatic group or a substituted or unsubstituted aromatic group.
- S-(substituted or unsubstituted aryl), —
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6. The compound of claim 6, wherein ring A is a substituted or unsubstituted phenyl.
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9. A compound selected from the group consisting of
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2-(trifluoromethoxy)-1-benzenesulfonamide; -
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-chlorophenyl)-2-chloro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-chlorophenyl)-2-fluoro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2-chloro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-chlorophenyl)-3-fluoro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-chlorophenyl)-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-nitrophenyl)-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-chlorophenyl)-3-(trifluoromethyl)-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-chlorophenyl)-4-chloro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-chlorophenyl)-2-cyano-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2-nitro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2,6-difluoro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methoxyphenyl)-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2,3,4-trifluoro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-4-bromo-2-fluoro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2,5-difluoro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-3,4-difluoro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2-bromo-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2,6-dichloro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2,4,6-trichloro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2,4-dichloro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2-chloro-4-fluoro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2,4-difluoro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2-iodo-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2,3-dichloro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-4-bromo-2,5-difluoro-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2-chloro-4-cyano-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2-chloro-6-methyl-1-benzenesulfonamide;
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-3-chloro-2-methyl-1-benzenesulfonamide;
N2-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-4,5-dibromo-2-thiophenesulfonamide, N2-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-5-bromo-2-thiophenesulfonamide, N2-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-3-bromo-5-chloro-2-thiophenesulfonamide, N3-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2,5-dichloro-3-thiophenesulfonamide, N4-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2, 1,3-benzothiadiazole-4-sulfonamide, N4-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2, 1,3-benzoxadiazole-4-sulfonamide, N4-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-7-chloro-2,1,3-benzoxadiazole-4-sulfonamide, N4-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-7-methyl-2, 1,3-benzothiadiazole-4-sulfonamide, N4-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-5-methyl-2,1,3-benzothiadiazole-4-sulfonamide, N4-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-5-chloro-2,1,3-benzothiadiazole-4-sulfonamide, N-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-(2-nitrophenyl)methanesulfonamide; and
N1-(4-(4-amino-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl)-2,5-dibromo-3,6-difluoro-1-benzenesulfonamide;
and pharmaceutically acceptable salts thereof.
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44-2. The method of claim 16 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.
Specification