Pyrrolopyrimidines as therapeutic agents

• US 20030153752A1
• Filed: 03/29/2000
• Published: 08/14/2003
• Est. Priority Date: 09/18/1998
• Status: Active Grant

• Current Assignee: Abbvie Deutschland GmbH & Company KG (Abbvie Incorporated)
• Original Assignee: Abbott GmbH & Company KG (Abbott Laboratories Incorporated)
• Inventors: Johnston, David N., Calderwood, David, Munschauer, Rainer, Hirst, Gavin C., Rafferty, Paul, Arnold, Lee D.
• Granted Patent: US 6,713,474 B2
• Time in Patent Office: Days
• US Class Current: 544/117
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07F 9/6561 containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
• CPC Class Codes: C07F 9/65842 Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring

Abstract

Chemical compounds having structural formula I

and physiologically acceptable salts and metabolites thereof, are inhibitors of serine/threonine and tyrosine kinase activity. Several of the kinases, whose activity is inhibited by these chemical compounds, are involved in immunologic, hyperproliferative, or angiogenic processes. Thus, these chemical compounds can ameliorate disease states where angiogenesis or endothelial cell hyperproliferation is a factor. These compounds can be used to treat cancer and hyper proliferative disorders, rheumatiod arthritis, disorders of the immune system, trasplant refections and imflammatory disorders.

Claims

1. A compound represented by the following structural formula:

2. The compound of claim 1, wherein R₃ is selected from the group consisting of a substituted or unsubstituted phenyl, a substituted or unsubstituted naphthyl, a substituted or unsubstituted pyridyl, a substituted or unsubstituted thienyl, a substituted or unsubstituted benzotriazole, a substituted or unsubstituted tetrahydropyranyl, a substituted or unsubstituted tetrahydrofuranyl, a substituted or unsubstituted dioxane, a substituted or unsubstituted dioxolane, a substituted or unsubstituted quinoline, a substituted or unsubstituted thiazole, substituted or unsubstituted isoxazole, substituted or unsubstituted cyclopentyl, a substituted or unsubstituted benzofuran, substituted or unsubstituted benzothiophene, substituted or unsubstituted benzisoxazole, substituted or unsubstituted benzisothiazole, substituted or unsubstituted benzothiazole, substituted or unsubstituted benzoxazole, substituted or unsubstituted benzoxazole, substituted or unsubstituted benzimidazole, substituted or unsubstituted benzoxadiazole, substituted or unsubstituted benzothiadiazole, substituted or unsubstituted isoquinoline, substituted or unsubstituted quinoxaline, substituted or unsubstituted indole and substituted or unsubstituted pyrazole.

3. The compound of claim 2 wherein R₃ 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, —

NR_fR_g, alkynyl, —

C(O)NR_fR_g, R_c and CH₂OR_c;

R_f, R_g 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

R_f and R_g are each, independently, —

H, a substituted or unsubstituted aliphatic group, or a substituted or unsubstituted aromatic group; and

R_c is hydrogen, or substituted or unsubstituted alkyl or substituted or unsubstituted aryl, —

W—

(CH₂)_t—

NR_dR_e, —

W—

(CH₂)_t—

O-alkyl,, —

W—

(CH₂)_t—

S-alkyl, —

W—

(CH₂)_t—

OH;

or —

W—

(CH₂)_t—

OR_f,

t is an integer from 0 to 6;

W is a bond or —

O—

, —

S—

, —

S(O)—

, —

S(O)₂—

, or —

NR_k—

;

R_k is —

H or alkyl; and

R_d, R_e and the nitrogen atom to which they are attached together form a 3, 4, 5, 6 or 7-membered substituted or unsubstituted heterocycloalkyl or substituted or unsubstituted heterobicyclic group;

or

R_d and R_e 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, COOR_i, or substituted or unsubstituted alkyl; and

p1 R_i is a substituted or unsubstituted aliphatic group or a substituted or unsubstituted aromatic group.

4. The compound of claim 3, wherein R₃ is a substituted or unsubstituted phenyl or phenyl fused to a five- or six-membered heterocyclic group.

5. The compound of claim 4 wherein R₃ is selected from the group consisting of

6. The compound of claim 5 wherein ring A is a 1,4-phenylene group substituted with methoxy or fluoro.

7. The compound of claim 1, wherein ring A is selected from the group consisting of a substituted or unsubstituted phenyl, a substituted or unsubstituted naphthyl, a substituted or unsubstituted pyridyl, and a substituted or unsubstituted indole.

8. The compound of claim 7 wherein ring A is substituted with one or more substituent selected from the group consisting of —

F, —

Cl, —

Br, —

I, —

OH, —

CH₃, —

NO₂, —

OCF₃, —

OCH₃, —

CN, —

CO₂CH₃, —

CF₃, —

CH₂OH, —

CH₂NMe₂, —

CH₂NHMe, CH₂NH₂, t-butyl, pyridyl, methylenedioxy;

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, —

NR_fR_g, alkynyl, —

C(O)NR_fR_g, R_c and CH₂OR_c,

R_f, R_g 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

R_f and R_g are each, independently, —

H, a substituted or unsubstituted aliphatic group or a substituted or unsubstituted aromatic group; and

R_c is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted aryl, —

W—

(CH₂)_t—

NR_dR_e, —

W—

(CH₂)_t—

O-alkyl,, —

W—

(CH₂)_t—

S-alkyl, —

W—

(CH₂)_t—

OH;

or —

W—

(CH₂)_t—

OR_f;

t is an integer from 0 to 6;

W is a bond or —

O—

, —

S—

, —

S(O)—

, —

S(O)₂—

, or —

NR_k—

;

R_k is —

H or alkyl; and

R_d, R_e 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;

or

R_d and R_e 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, COOR_i, or a substituted or unsubstituted alkyl; and

R₁ is a substituted or unsubstituted aliphatic group or a substituted or unsubstituted aromatic group.

9. The compound of claim 8, wherein ring A is a substituted or unsubstituted phenyl.

10. The compound of claim 9 wherein ring A is a substituted or unsubstituted 1,4-phenylene group.

11. The compound of claim 1 wherein R₁ is of the formula

12. The compound of claim 1 wherein R₁ is of the formula

13. The compound of claim 1 wherein R₁ is of the formula

14. The compound of claim 13 wherein m is 2;

s is 0; and

R₇₇ is —

OH.

15. The compound of claim 14 wherein R₁ is selected from the group consisting of:

16. The compound of claim 1 wherein R₁ is of the formula

17. The compound of claim 1 wherein R₁ is of the formula

18. The compound of claim 17 wherein Z₂ is of the formula N(R₃₅)R₃₆, wherein R₃₅ and R₃₆ are each, independently, hydrogen, alkyl, alkoxycarbonyl, alkoxyalkyl, hydroxyalkyl, aminocarbonyl, cyano, alkylcarbonyl or aralkyl.

19. The compound of claim 17 wherein Z₂ is of the formula

20. The compound of claim 17 wherein Z₂ is of the formula

21. The compound of claim 17 wherein Z₂ is of the formula

22. The compound of claim 17 wherein Z₂ is of the formula

23. The compound of claim 17 wherein Z₂ is of the formula

24. The compound of claim 1 wherein R₁ is of the formula

25. A compound of claim 24 wherein R₁₀ is methyl;

ring A is

26. The compound of claim 1 wherein R₁ is of the formula

27. The compound of claim 26 wherein R₈, R₉ and the nitrogen atom together form a heterocycloalkyl group;

of the formula

28. The compound of claim 26 wherein R₈, R₉ and the nitrogen atom together form a heterocycloalkyl of the formula

29. The compound of claim 26 wherein R₈, R₉ and the nitrogen atom together form a heterocycloalkyl group;

of the formula

30. The compound of claim 26 wherein R₈, R₉ and the nitrogen atom together form a heteroaromatic group of the formula

31. The compound of claim 26 wherein at least one of R₈ and R₉ is of the formula Y₃—

D, wherein D is of the formula

32. The compound of claim 26 wherein at least one of R₈ and R₉ is of the formula Y₃—

N(R₃₁)R₃₂, wherein;

Y₃ is selected from the group consisting of —

C(O)—

, —

(CH₂)_t—

, —

S(O)₂—

, —

C(O)O—

, —

SO₂NH—

, —

CONH—

, (CH₂)_tO—

, —

(CH₂)_tNH—

, —

(CH₂)_tS—

, —

(CH₂)_tS(O)—

, and —

(CH₂)_tS(O)₂—

;

t is an interger from 0 to 6;

R₃₁ and R₃₂ are each, independently, substituted or unsubstituted carboxyalkyl, a substituted or unsubstituted alkoxycarbonylalkyl, a substituted or unsubstituted hydroxyalkyl, a substituted or unsubstituted alkylsulfonyl, a substituted or unsubstituted alkylcarbonyl or a substituted or unsubstituted cyanoalkyl;

or R₃₁ and R₃₂, together with the nitrogen atom, form a five- or six-membered heterocycloalkyl group, a substituted or unsubstituted heteroaromatic or a substituted or unsubstituted heterobicycloalkyl.

33. The compound of claim 1 wherein R₁ is of the formula

34. The compound of claim 33 wherein R₈, R₉ and the nitrogen atom together form a heterocycloalkyl of the formula

35. The compound of claim 33 wherein R₈, R₉ and the nitrogen atom together form a heterocycloalkyl of the formula

36. The compound of claim 33 wherein R₈, R₉and the nitrogen atom together form a heterocycloalkyl group of the formula

37. The compound of claim 33 wherein R₈, R₉ and the nitrogen atom together form a heteroaromatic group of the formula

38. The compound of claim 33 wherein at least one of R₈ and R₉ is of the formula Y₃—

D, wherein D is of the formula

39. The compound of claim 33 wherein at least one of R₈ and R₉ is of the formula Y₃—

N(R₃₁)R₃₂, wherein;

Y₃ is selected from the group consisting of —

C(O)—

, —

(CH₂)_s—

, —

S(O)₂—

, —

C(O)O—

, —

SO₂NH—

, —

CONH—

, (CH₂)_sO—

, —

(CH₂)_sNH—

, —

(CH₂)_sS—

, —

(CH₂)_sS(O)—

, and —

(CH₂)_sS(O)₂—

;

s is an integer from 0 to 6;

R₃₁ and R₃₂ are each, independently, substituted or unsubstituted carboxyalkyl, a substituted or unsubstituted alkoxycarbonylalkyl, a substituted or unsubstituted hydroxyalkyl, a substituted or unsubstituted alkylsulfonyl, a substituted or unsubstituted alkylcarbonyl or a substituted or unsubstituted cyanoalkyl;

or R₃₁ and R₃₂, together with the nitrogen atom, form a five- or six-membered heterocycloalkyl group, a substituted or unsubstituted heteroaromatic or a substitutituted or unsubstituted heterobicycloalkyl.

40. The compound of claim 1 wherein R₁ is of the formula

41. The compound of claim 1 wherein R₁ is of the formula

42. The compound of claim 1 wherein R₁ is of the formula

43. The compound of claim 1, wherein R₂ is —

H.

44. The compound of claim 1, wherein L is —

O—

, —

NHSO₂R—

, —

NC(O)O—

, or NHC(O)—

.

45. The compound of claim 1 wherein R₁ is of the formula

46. The compound of claim 45 wherein R₁ is selected from the group consisting of

47. The compound of claim 1 wherein G is selected from the group consisting of a direct bond;

—

(CH₂)_j—

, wherein j is 1 or 2;

trans —

CH═

CH—

;

-cycloC₃H₄—

; and

CH₂O—

48. The compound of claim 13 wherein m is 2.

49. The compound of claim 48 wherein S is 0 and R₇₇ is hydrogen.

50. The compound of claim 49 wherein the —

(CH₂)_t—

NR₈R₉ group is

51. The compound of claim 49 wherein L is —

O—

, j is 0 or 1 and R₃ is phenyl.

52. The compound of claim 48 wherein

L is —

CH₂NHC(O)—

;

—

CH₂NHC(O)NH—

;

—

CH₂NHC(O)O—

;

—

CH₂C(O)NH—

;

—

CH₂NHS(O)₂—

;

—

NHC(O)—

;

—

NHC(O)NH—

;

—

NHC(O)O—

;

—

C(O)NH—

;

or —

NS(O)₂—

;

A is 1,4-phenylene or 1,4-phenylene substituted with one or more methoxy groups or fluorine atoms;

R₃ is phenyl or phenyl substituted with one or more substituents selected from the group consisting of chloro, cyano, bromo, fluoro, trifluoromethoxy, methoxy, methylenedioxy, methyl, amino, dimethylamino and nitro;

R₂ is hydrogen; and

G is a direct bond or —

(CH₂)_j—

, wherein j is 0 to 4.

53. The compound of claim 24 wherein R₁₀ is methyl, isopropyl or methoxyethyl.

54. A compound of claim 24, 26, 27, 28, 29, 30, 31, 45 or 47 wherein ring A is

56. A method of inhibiting protein kinase activity comprising administering a compound of claim 1 or a physiogically acceptable salt, prodrug or biologically active metabolites thereof.

57. The method of claim 56 wherein said protein kinase is selected from the group consisting of KDR, FGFR-1, PDGFRβ

, PDGFRα

, IGF-1R, c-Met, Flt-1, TIE-2, Lck, Src, fyn, Lyn, Blk, and yes.

58. The method of claim 56 wherein the activity of said protein kinase affects hyperproliferative disorders.

59. The method of claim 56 wherein the activity of said protein kinase affects angiogenesis, vascular permeability, immune response or inflammation.

60. A method of treating a patient having a condition which is mediated by protein kinase activity, said method comprising the step of administering to the patient a therapeutically effective amount of a compound of Formula I as defined in claim 1 or a physiologically acceptable salt, prodrug or biologically active metabolite thereof.

61. The method of claim 60 wherein said protein kinase is selected from the group consisting of KDR, Flt-1, PDGFRβ

, PDGFRα

, IGF-1R, c-Met, TIE-2, Lck, Src, fyn, Lyn, Blk, and yes.

62. The method of claim 60 wherein the condition mediated by protein kinase activity is a hyperproliferative disorder.

63. The method of claim 60 wherein the activity of said protein kinase affects angiogensis, vascular permeability, an immulogic response or an inflammatory response.

64. The method of claim 60 wherein the protein kinase is a protein serine/threonine kinase or a protein tyrosine kinase.

65. The method of claim 60 wherein the condition mediated by protein kinase activity is one or more ulcers.

66. The method of claim 65 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.

67. The method of claim 60 wherein the condition mediated by protein kinase activity is Lyme disease, sepsis or infection by Herpes simplex, Herpes Zoster, human immunodeficiency virus, parapoxvirus, protozoa or toxoplasmosis.

68. The method of claim 60 wherein the condition mediated by protein kinase activity is von Hippel Lindau disease, pemphigoid, psoriasis, Paget'"'"'s disease or polycystic kidney disease.

69. The method of claim 60 wherein the condition mediated by protein kinase activity is fibrosis, sarcoidosis, cirrhosis, thyroiditis, hyperviscosity syndrome, Osler-Weber-Rendu disease, chronic occlusive pulmonary disease, asthma, exudtaes, ascites, pleural effusions, pulmonary edema, cerebral edema or edema following burns, trauma, radiation, stroke, hypoxia or ischemia.

70. The method of claim 60 wherein the condition mediated by protein kinase activity is ovarian hyperstimulation syndrome, preeclampsia, menometrorrhagia, or endometriosis.

71. The method of claim 60 wherein the condition mediated by protein kinase activity is chronic inflammation, systemic lupus, glomerulonephritis, synovitis, inflammatory bowel disease, Crohn'"'"'s disease, glomerulonephritis, rheumatoid arthritis and osteoarthritis, multiple sclerosis or graft rejection.

72. The method of claim 60 wherein the condition mediated by protein kinase activity is sickle cell anaemia.

73. The method of claim 60 wherein the condition mediated by protein kinase activity is an ocular condition.

74. The method of claim 73 wherein the ocular condition is ocular or macular edema, ocular neovasular disease, sclertis, radial keratotomy, uveitis, vitritis, myopia, optic pits, chronic retinal detachment, post-laser treatment complications, conjunctivitis, Stargardt'"'"'s disease, Eales disease, retinopathy or macular degeneration.

75. The method of claim 60 wherein the condition mediated by protein kinase activity is a cardiovascular condition.

76. The method of claim 75 wherein the condition mediated by protein kinase activity is atherosclerosis, restenosis, ischemia/reperfusion injury, vascular occulsion, venous malformation or carotid obstructive disease.

77. The method of claim 60 wherein the condition mediated by protein kinase activity is cancer.

78. The method of claim 77 wherein the cancer is a solid tumor, a sarcoma, fibrosarcoma, osteoma, melanoma, retinoblastoma, a rhabdomyosarcoma, glioblastoma, neuroblastoma, teratocarcinoma, an hematopoietic malignancy and malignant ascites.

79. The method of claim 78 wherein the cancer is Kaposi'"'"'s sarcoma, Hodgkin'"'"'s disease, lymphoma, myeloma or leukemia.

80. The method of claim 60 wherein the condition mediated by protein kinase activity is Crow-Fukase (POEMS) syndrome or a diabetic condition.

81. The method of claim 80 wherein the diabetic condition is insulin-dependent diabetes mellitus glaucoma, diabetic retinopathy or microangiopathy.

82. The method of claim 60 wherein the compound of Formula I or a physiologically acceptable salt, prodrug or biologically active metabolite thereof is administered in an amount effective to promote angiogenesis or vasculogenesis.

83. The method of claim 82 wherein the protein kinase is Tie-2.

84. The method of claim 82 wherein the compound of Formula I, or physiologically acceptable salt, prodrug or biologically active metabolite thereof, is administered in combination with a pro-angiogenic growth factor.

85. The method of claim 84 wherein the pro-angiogenic growth factor is selected from the group consisting of VEGF, VEGF-B, VEGF-C, VEGF-D, VEGF-E, HGF, FGF-1, FGF-2, derivatives thereof and antiiodotypic antibodies.

86. The method of claim 82 wherein the protein kinase-mediated condition is anemia, ischemia, infarct, transplant rejection, a wound, gangrene or necrosis.

87. The method of claim 60 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.

55. A compound selected from the group consisting of:

Cis-5-(4-phenoxyphenyl)-7-(4-pyrrolidinocyclohex-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine,

Trans-5-(4-phenoxyphenyl)-7-(4-pyrrolidinocyclohex-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine,

Cis-5-(4-phenoxyphenyl)-7-(4-piperidinocyclohex-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine hydrochloride,

Trans-5-(4-phenoxyphenyl)-7-(4-piperidinocyclohex-1-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine,

Trans-7-(4-dimethylaminocyclohexyl)-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine,

Cis-7-(4-dimethylaminocyclohexyl)-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine,

5-(4-phenoxyphenyl)-7-(4-piperidyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine dihydrochlorid,

5-(4-phenoxyphenyl)-7-(3-pyrrolidinyl)-7H-pyrrolo[2,3-d]pyrimidin-4-ylamine dihydrochloride,

Cis-7-[4-(4-isopropylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,

Trans-7-[4-(4-isopropylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,

Cis-7-{4-[4-(2-methoxyethyl)piperazino]cyclohexyl}-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,

Trans-7-{4-[4-(2-methoxyethyl)piperazino]cyclohexyl}-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,

Cis-7-[-4-(4-ethylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,

trans-7-[4-(4-ethylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,

Cis-7-[4-(4-isopropylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine tris maleate,

Trans-7-[4-(4-isopropylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine tris maleate,

Cis-7-{4-[4-(2-methoxyethyl)piperazino]cyclohexyl}-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine tris maleate,

Trans-7-{4-[4-(2-methoxyethyl)piperazino]cyclohexyl}-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine tris maleate,

Cis-7-(4-{[3-(1H-1-imidazolyl)propyl]amino}cyclohexyl)-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine trimaleate salt,

Trans-7-(4-{[3-(1H-1-imidazolyl)propyl]amino}cyclohexyl)-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine dimaleate salt,

Cis-7-[4-(dimethylamino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine dimaleate salt,

Trans-5-(4-phenoxyphenyl)-7-(4-piperidinocyclohexyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine dimaleate salt,

Trans-5-(4-phenoxyphenyl)-7-(4-tetrahydro-1H-1-pyrrolylcyclohexyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine dimaleate salt,

Cis-5-(4-phenoxyphenyl)-7-(4-piperazinocyclohexyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine trimaleate salt,

Trans-5-(4-phenoxyphenyl)-7-(4-piperazinocyclohexyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine trimaleate salt,

7-[3-(4-methylpiperazino)cyclopentyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine tri-maleate,

Trans-7-[3-(4-methylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine,

Trans-7-[3-(4-methylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine tri-maleate,

trans-7-[3-(4-methylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine tri-hydrochloride,

cis-7-[3-(4-methylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine tri-maleate salt,

cis-7-[3-(4-methylpiperazino)cyclohexyl]-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine tri-hydrochloride,

Trans-5-(2-methyl-4-phenoxyphenyl)-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine trimaleate,

Cis-benzyl N-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}2-methoxyphenyl)carbamate tri-maleate,

Trans-benzyl N-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-methoxyphenyl)carbamate tri-maleate,

Trans-N1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-methoxyphenyl)benzamide,

Trans-N1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-methoxyphenyl)benzamide tri-maleate,

Cis-N1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-methoxyphenyl)-3-phenylpropanamide,

Trans-N1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-methoxyphenyl)-3-phenylpropanamide,

cis-N1-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl-2-methoxyphenyl)-3-phenylpropanamide trimaleate salt,

trans-N1-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl-2-methoxyphenyl)-3-phenylpropanamide tri-maleate,

cis-2-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]-d]pyrimidin-5-ylphenoxy)-6-[(3-methoxypropyl)amino]benzonitrile tri-maleate,

trans-2-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-ylphenoxy)-6-[(3-methoxypropyl)amino]benzonitrile tri-maleate,

is-2-amino-6-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-ylphenoxy)benzonitrile tri-maleate,

trans-2-amino-6-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-ylphenoxy)benzonitrile tri-maleate,

cis-2-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-ylphenoxy)-6-[(4-methylphenyl)sulfanyl]benzonitrile tri-maleate,

trans-2-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-ylphenoxy)-6-[(4-methylphenyl)sulfanyl]benzonitrile tri-maleate,

cis-2-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-ylphenoxy)-6-(2-pyridylsulfanyl)benzonitrile tri-maleate,

trans-2-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-ylphenoxy)-6-(2-pyridylsulfanyl)benzonitrile tri-maleate,

cis-5-(2-methyl-4-phenoxyphenyl)-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine tri-maleate,

trans-5-(2-methyl-4-phenoxyphenyl)-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine tri-maleate,

cis-N1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-4-fluoro-1-benzenesulfonamide tri-maleate,

trans-N1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-4-fluoro-1-benzenesulfonamide tri-maleate,

N1-4-[4-amino-7-(1-benzyl-4-piperidyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-fluorophenyl-4-fluoro-1-benzenesulfonamide,

N1-4-[4-amino-7-(1-benzyl-4-piperidyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-fluorophenyl-2,3-dichloro-1-benzenesulfonamide,

N1-4-[4-amino-7-(4-piperidyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-fluorophenyl-4-fluoro-1-benzenesulfonamide,

N1-4-[4-amino-7-(1-formyl-4-piperidyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-2-fluorophenyl-4-fluoro-1-benzenesulfonamide,

N1-[4-(4-amino-7-1-[(1-methyl-1H-4-imidazolyl)sulfonyl]-4-piperidyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl]-4-fluoro-1-benzenesulfonamide dimaleate,

N1-[4-(4-amino-7-1-[(1,2-dimethyl-1H-4-imidazolyl)sulfonyl]-4-piperidyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl]-4-fluoro-1-benzenesulfonamide,

N1-[4-(4-amino-7-1-[(1,3-dimethyl-1H-5-pyrazolyl)carbonyl]-4-piperidyl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-fluorophenyl]-4-fluoro-1-benzenesulfonamide,

N1-(4-{4-amino-7-[1-(2-pyridylcarbonyl)-4-piperidyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-4-fluoro-1-benzenesulfonamide,

N1-4-(4-amino-7-{4-[1-(1-methylpiperid-4-yl)piperidyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl})-2-fluorophenyl-4-fluoro-1-benzenesulfonamide tri-maleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl }-2-fluorophenyl)-2-(trifluoromethoxy)-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-5-chloro-2-thiophenesulfonamide benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-chloro-4-fluoro-1-benzenesulfonamide benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,3-dichloro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-chloro-4-fluoro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl-2-fluorophenyl)-2,5-difluoro-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,6-difluoro-1-benzenesulfonamide trimaleate,

Trans-N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,1,3-benzothiadiazole-4-sulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,3,4-trifluoro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-nitro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-fluoro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,4,6-trichloro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,6-dichloro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-chloro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-3-fluoro-1-benzenesulfonamide dimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-5-chloro-2-thiophenesulfonamide dimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-4-bromo-2,6-difluoro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-3-chloro-4-fluoro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl-2-iodo-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-(trifluoromethoxy)-l1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,3-dichloro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-chloro-6-methyl-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-chloro-4-cyano-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,3,4-trifluoro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-3,4-difluoro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-4-bromo-2-fluoro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-5-bromo-2-thiophenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,4-dichloro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,3,4-trichloro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-3-bromo-5-chloro-2-thiophenesulfonamide trimaleate,

cis-N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,1,3-benzothiadiazole-4-sulfonamide trimaleate,

cis-N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,1,3-benzoxadiazole-4-sulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,5-dichloro-1-thiophenesulfonamide trimaleate,

cis-N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-(7-chloro-2,1,3-benzoxadiazole)-4-sulfonamide trimaleate,

cis-N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-(7-methyl-2,1,3-benzothiadiazole)-4-sulfonamide trimaleate,

cis-N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-(5-methyl-2,1,3-benzothiadiazole)-4-sulfonamide trimaleate,

cis-N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-(5-chloro-2,1,3-benzothiadiazole)-4-sulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-3-chloro-2-methyl-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-bromo-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,5-dibromo-3,6-difluoro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,3-dichloro-1-benzenesulfonamide trimaleate,

cis-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-(2-nitrophenyl)methanesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-nitro-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-fluoro-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,4,6-trichloro-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,6-dichloro-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-chloro-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-3-fluoro-1-benzenesulfonamide dimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-4-bromo-2,5-difluoro-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-3-chloro-4-fluoro-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl-2-iodo-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,3-dichloro-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-chloro-6-methyl-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-chloro-4-cyano-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-3,4-difluoro-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-4-bromo-2-fluoro-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-5-bromo-2-thiophenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,4-dichloro-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,3,4-trichloro-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-3-bromo-5-chloro-2-thiophenesulfonamide trimaleate,

Trans-N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,1,3-benzoxadiazole-4-sulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,5-dichloro-1-thiophenesulfonamide trimaleate,

Trans-N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-(7-chloro-2,1,3-benzoxadiazole)-4-sulfonamide trimaleate,

Trans-N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-(7-methyl-2,1,3-benzothiadiazole)-4-sulfonamide trimaleate,

Trans-N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-(5-methyl-2,1,3-benzothiadiazole)-4-sulfonamide trimaleate,

Trans-N-4-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-(5-chloro-2,1,3-benzothiadiazole)-4-sulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-3-chloro-2-methyl-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2-bromo-1-benzenesulfonamide trimaleate,

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-2,5-dibromo-3,6-difluoro-1-benzenesulfonamide trimaleate, or

Trans-N-1-(4-{4-amino-7-[4-(4-methylpiperazino)cyclohexyl]-7H-pyrrolo[2,3-d]pyrimidin-5-yl}-2-fluorophenyl)-(2-nitrophenyl)methanesulfonamide trimaleate.

88. 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 Formula I as defined in claim I or a physiologically acceptable salt, prodrug or biologically active metabolite thereof.