Patent EA-003604-B1 (EA)
Title: Pyrrolo[2,3]pyrimidine compositions and their use
Inventor: CASTELHANO ARLINDO L
IPC: A61P1/00
Filed: 1999-06-01
Abstract: 1. A compound of formula I: wherein R1 and R2 are each independently a hydrogen atom, substituted or unsubstituted linear (C1-C30) alkyl, substituted or unsubstituted (C3-C30) alkyl, substituted or unsubstituted (C4-C10) cycloalkyl, or substituted or unsubstituted aryl, wherein only one of R1 and R2 can be hydrogen; wherein while alkyl is (C1)alkyl, or (C2)alkyl, then any substituent of phenyl if available, is substituted, or R1 and R2 together form a substituted or unsubstituted from 4 to 10-membered heterocyclic ring; R3 is a hydrogen atom or a substituted or unsubstituted aryl; R4 is a hydrogen atom, a substituted or unsubstituted linear (C1-C30) alkyl, unsubstituted branched (C3-C30) alkyl, a substituted or unsubstituted aryl; and R5 and R6 are each independently a halogen atom, a hydrogen atom or a substituted or unsubstituted linear (C1-C30) alkyl, branched (C3-C30) alkyl or aryl; wherein any substituent, if available, is halogen, hydroxyl, linear (C1-C30) alkylcarbonyloxy, unsubstituted branched (C3-C30) alkylcarbonyloxy, arylcarbonyloxy, linear(C1-C30) alkoxycarbonyloxy, branched (C3-C30) alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylat, linear (C1-C30) alkylcarbonyl, branched (C3-C30) alkylcarbonyl, linear(C1-C30) alkoxycarbonyl, branched (C3-C30) alkoxycarbonyl, aminocarbonyl, linear (C1-C30) alkylthiocarbonyl, branched (C3-C30) alkylthiocarbonyl, linear (C1-C30) alkoxyl, branched (C3-C30) alkoxyl, phosphate, phosphonate, cyano, amino, linear (C1-C30) alkylamino, branched (C3-C30) alkylamino, linear (C1-C30) dialkylamino, branched (C3-C30) dialkylamino, arylamino, diarylamino, linear (C1-C30) alkylarylamino, branched (C3-C30) alkylarylamino, acylamino, linear (C1-C30) alkylcarbonylamino, branched (C3-C30) alkylcarbonylamino, arylcarbonylamino, carbamoyl, ureido, amidino, imino, sulphohydryl, linear (C1-C30) alkylthio, branched (C3-C30) alkylthio, arylthio, thiocarboxylat, sulphates, sulphonate, sulphamoyl, sulfonamido, nitro, trifluomethyl, azido, 4-10-membered heterocyclyl, linear (C1-C30) alkylaryl, branched (C3-C30) alkylaryl or aromatic or 5-6-membered heteroaromatic group, wherein substituent is optionally substituted by any of above mentioned substituents; and pharmaceutically acceptable salts thereof. 2. A compound according to claim 1, wherein R1 is hydrogen; R2 is substituted (C4-C10) cycloalkyl, substituted linear (C3-C30) alkyl, substituted branched (C3-C30) alkyl, or R1 and R2 together form a substituted or unsubstituted 4-10-membered heterocyclic ring; R3 is unsubstituted or substituted aryl; R4 is hydrogen; and R5 and R6 are each independently hydrogen or linear (C1-C30) alkyl, branched (C3-C30) alkyl or pharmaceutically acceptable salts thereof. 3. The compound of claim 2, wherein R2 is substituted or substituted (C4-C10) cycloalkyl. 4. The compound of claim 3, wherein R1 and R4 are hydrogen, R3 is unsubstituted or substituted phenyl, and R5 and R6 are each linear (C1-C30) alkyl or branched (C3-C30) alkyl. 5. The compound of claim 4, wherein R2 is mono-hydroxycyclopentyl. 6. The compound of claim 4, wherein R2 is mono-hydroxycyclohexyl. 7. The compound of claim 2, wherein R1 and R2 together form substituted or unsubstituted 4-10-membered heterocyclic ring. 8. The compound of claim 7, wherein said heterocyclic ring is substituted with an amine or acetamido. 9. The compound of claim 2, wherein R2 is-A-NHC (=O) B, wherein A is unsubstituted C1-C4 alkyl, and B is substituted or unsubstituted C1-C4 alkyl. 10. The compound of claim 9, wherein R1 and R4 are hydrogen, R3 is unsubstituted or substituted phenyl, and R5 and R6 are each linear (C1-C30) alkyl and branched (C3-C30) alkyl. 11. The compound of claim 2, wherein R3 is unsubstituted or substituted phenyl. 12. The compound of claim 11, wherein R5 and R6 are each linear (C1-C30) alkyl and branched (C3-C30) alkyl. 13. The compound of claim 12, wherein R3 is unsubstituted phenyl. 14. The compound of claim 12, wherein R3 is substituted phenyl. 15. The compound of claim 14, wherein R3 is phenyl, substituted with at least one substituent. 16. The compound of claim 2, wherein R3 is unsubstituted or substituted aryl, wherein aryl is heteroaryl group. 17. The compound of claim 16, wherein R5 and R6 are each linear (C1-C30) alkyl and branched (C3-C30) alkyl. 18. The compound of claim 2, wherein R5 and R6 are each hydrogen. 19. The compound of claim 2, wherein R5 and R6 are each methyl. 20. The compound of claim 2, wherein the compound is selected from group, comprising: 4-(cis-3hydroxycyclopentyl) amino-5, 6-dimethyl-2-phenyl-7H-pyrrolo [2,3d] pyrimidine. 4-(cis-3-(2aminoacetoxy) cyclopentyl) amino-5, 6-dimethyl-2-phenyl-7H-pyrrolo [2,3d] pyrimidine trifluoroacetic acid salt. 4-(2-N'- methylureapropyl) amino-5, 6-dimethyl-2-phenyl-7H-pyrrolo [2,3d] pyrimidine. 4-(2acetamidobutyl) amino-5, 6-dimethyl-2-phenyl-7H-pyrrolo [2,3d] pyrimidine. 4-(2-N'- methylureabutyl) amino-5, 6-dimethyl-2-phenyl-7H-pyrrolo [2,3d] pyrimidine. 4-(2aminocyclopropylacetamidoethyl) amino-2-phenyl-7H-pyrrolo [2,3d] pyrimidine. 21. A compound of formula II: wherein wherein X is N or CR6; R1 and R2 are each independently hydrogen, or substituted or unsubstituted linear (C1-C30) alkoxy, branched (C3-C30) alkoxy, amino(linear (C1-C30) alkyl), amino(branched (C1-C30) alkyl), (linear (C1-C30) alkyl, branched (C1-C30) alkyl or aryl, wherein only one of R1 and R2 ban be hydrogen, provided that R1 and R2 together form a substituted or unsubstituted 4-10-membered heterocyclic ring; R3 is substituted or unsubstituted aryl or heteroalkyl; R4 is hydrogen; L is hydrogen, substituted or unsubstituted linear (C1-C30) alkyl, or branched (C3-C30) alkyl; R6 is hydrogen, substituted or unsubstituted linear (C1-C30) alkyl, or branched (C3-C30) alkyl or halogen; Q is CH2, O, S, or NR7, wherein R7 is hydrogen or substituted or unsubstituted C1-C6 alkyl; and W is substituted or unsubstituted linear (C1-C30) alkyl, or branched (C3-C30) alkyl, (C4-C10) cycloalkyl, linear(C2-C30) alkynyl, branched (C3-C30) alkynyl, aryl, biaryl, heteroaryl, substituted carbonyl, substituted thiocarbonyl, or substituted sulfonyl; wherein any substituent, if available, is halogen, hydroxyl, linear (C1-C30) alkylcarbonyloxy, unsubstituted branched (C3-C30) alkylcarbonyloxy, arylcarbonyloxy, linear(C1-C30) alkoxycarbonyloxy, branched (C3-C30) alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylat, linear (C1-C30) alkylcarbonyl, branched (C3-C30) alkylcarbonyl, linear(C1-C30) alkoxycarbonyl, branched (C3-C30) alkoxycarbonyl, aminocarbonyl, linear (C1-C30) alkylthiocarbonyl, branched (C3-C30) alkylthiocarbonyl, linear (C1-C30) alkoxyl, branched (C3-C30) alkoxyl, phosphate, phosphonate, cyano, amino, linear (C1-C30) alkylamino, branched (C3-C30) alkylamino, linear (C1-C30) dialkylamino, branched (C3-C30) dialkylamino, arylamino, diarylamino, linear (C1-C30) alkylarylamino, branched (C3-C30) alkylarylamino, acylamino, linear (C1-C30) alkylcarbonylamino, branched (C3-C30) alkylcarbonylamino, arylcarbonylamino, carbamoyl, ureido, amidino, imino, sulphohydryl, linear (C1-C30) alkylthio, branched (C3-C30) alkylthio, arylthio, thiocarboxylat, sulphates, sulphonate, sulphamoyl, sulfonamido, nitro, trifluomethyl, azido, 4-10-membered heterocyclyl, linear (C1-C30) alkylaryl, branched (C3-C30) alkylaryl or aromatic or 5-6-membered heteroaromatic group, wherein substituent is optionally substituted by any of above mentioned substituents. 22. The compound of claim 21 wherein Q is CH2, O, S, or NH. 23. The compound of claim 22 wherein R4 is hydrogen, L is hydrogen or methyl and R3 is unsubstituted or substituted aryl. 24. The compound of claim 23 wherein W is substituted or unsubstituted linear (C1-C30) alkyl, or branched (C3-C30) alkyl, (C4-C10) cycloalkyl, linear(C2-C30) alkynyl, branched (C3-C30) alkynyl. 25. The compound of claim 24 wherein W is linear(C2-C30) alkynyl, branched (C3-C30) alkynyl. 26. The compound of claim 25 wherein W is substituted with one or more substituents selected from the group consisting of halogen, hydroxy, substituted or unsubstituted linear (C1-C30) alkyl, or branched (C3-C30) alkyl, (C4-C10) cycloalkyl, aryl or NHR10, wherein R10 is hydrogen, substituted or unsubstituted linear (C1-C30) alkyl, or branched (C3-C30) alkyl, (C4-C10) cycloalkyl, or aryl. 27. The compound of claim 24, wherein W is substituted or unsubstituted cyclopentyl. 28. The compound of claim 23, wherein W is -(CH2)a -C (=O) Y or (CH2)a -C (=S) Y, wherein a is 0, 1, 2 or 3, Y is aryl, linear (C1-C30) alkyl, or branched (C3-C30) alkyl, (C4-C10) cycloalkyl, heteroaryl, NHR11R12, or, provided that Q is NH, OR13, and wherein R11, R12 and R13 are each independently hydrogen, or unsubstituted or substituted linear (C1-C30) alkyl, or branched (C3-C30) alkyl, (C4-C10) cycloalkyl, aryl. 29. The compound of claim 22, wherein R3 is selected from the group consisting of substituted and unsubstituted phenyl, pyridyl, pyrimidyl, pyridazinyl, pyrazinyl, pyrrolyl, triazolyl, thioazolyl, oxazolyl, oxadiazolyl, pyrazolyl, furanyl, methylenedioxyphenyl, and thiophenyl. 30. The compound of claim 29, wherein R3 is unsubstituted phenyl. 31. The compound of claim 29, wherein R3 is phenyl with at least one substituent. 32. The compound of claim 22, wherein R1 and R2 represents together wherein n is 1 or 2, and the ring is optionally substituted with one or more groups of hydroxyl, amino, aminocarbonyl, thiole, carboxyl, halogen, CH2OH, CH2NHC (=O) -(C1-C30) linear alkyl, CH2NHC (=O) -(C3-C30) branched alkyl or CH2NHC (=O) NH- (C1-C30) linear alkyl or CH2NHC (=O) NH- (C3-C30) branched alkyl. 33. The compound of claim 32, wherein n is 1 or 2, and said ring is substituted with NHC (=O) - (C1-C30) linear alkyl or CH2NHC (=O) -(C3-C30) branched alkyl. 34. The compound of claim 22, wherein R1 is hydrogen, R2 is substituted or unsubstituted C1-C6 alkyl, R3 is substituted or unsubstituted phenyl, R4 is hydrogen, L is hydrogen or unsubstituted or substituted C1-C6 alkyl, Q