US 2008/0287410 A1 · PYRIMIDINE DERIVATIVES USEFUL AS INHIBITORS OF PKC-THETA

Abstract

Disclosed are novel compounds of formula (I): wherein X, Y, R1, R2 and R3 are as defined herein, which are useful as inhibitors of PKC-theta and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC-theta, including immunological disorders and type II diabetes. This invention also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

Claims14

Dependent claims

-11. (canceled)

A method of treating a disease or disorder that is that is mediated or sustained through the activity of inhibiting PKC-theta in a patient comprising administering to said patient a therapeutically effect amount of a compound of the following formula (I):

wherein:
X is C1-6 alkyl wherein one or two of the methylene units can be replaced by an oxygen or sulfur atom, and wherein the C1-6alkyl group is optionally and independently substituted with:
(A) oxo,
(B) C1-6alkyl which is optionally substituted with one or more of the following groups:
(i) hydroxyl,
(ii) C1-3alkyloxy,
(iii) halogen,
(C) C1-6alkyloxy,
(D) C1-6alkylthio,
(E) aryl
(F) —COR6, wherein R6 is:
(i) C1-6alkyl,
(ii) C1-6alkyloxy,
(iii) —NR7R8, wherein R7 and R8 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) aryl,
(d) heteroaryl,
(iv) —OH,
(G) halogen,
(H) —NR9R10, wherein R9 and R10 are each independently selected from:
(i) hydrogen,
(ii) C1-6alkyl,
(iii) C1-6alkylcarbonyl,
(iv) C1-6alkylsulfonyl,
(v) aryl,
(vi) heteroaryl;
Y is —NH—, —O— or —S—;
R1 is:
(A) aryl or heteroaryl, each optionally and independently substituted with one or more of the following groups:
(i) C1-6alkyl, which is optionally substituted one or more of the following:
(a) halogen,
(b) NH2
(ii) C1-6alkoxy, which is optionally substituted with halogen,
(iii) C1-6alkylthio, which is optionally substituted with halogen,
(iv) C1-6alkylsulfonyl,
(v) cyano,
(vi) halogen,
(vii) hydroxyl,
(viii) nitro,
(ix) —COR11, wherein R1 is:
(a) C1-6alkyl,
(b) C1-6alkyloxy,
(c) —OH,
(d) —NR12R13, wherein R12 and R13 are each independently selected from:
(I) hydrogen,
(II) C1-6alkyl,
(III) aryl,
(IV) heteroaryl,
(x) —NR14R15, wherein R14 and R15 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) C1-6alkylcarbonyl,
(d) C1-6alkylsulfonyl,
or wherein R14 and R15 together constitute an alkylene bridge which together with the nitrogen atom between them forms a five to seven-membered ring,
(xi) arylthio, arylsulfonyl or aryloxy, each optionally and independently substituted with one or more of the following groups:
(a) C1-6alkyl,
(b) C1-6alkoxy,
(c) C1-6alkylthio,
(d) C1-6alkylsulfonyl,
(e) cyano,
(f) halogen,
(g) nitro,
(h) —NR16R17, wherein R16 and R17 are each independently selected from:
(I) hydrogen,
(II) C1-6alkyl,
(III) C1-6alkylcarbonyl,
(IV) C1-6alkylsulfonyl,
(B) C3-6cycloalkyl which is optionally and independently substituted with one or more of the following groups:
(i) C1-6alkyl, which is optionally substituted with halogen,
(ii) C1-6alkoxy, which is optionally substituted with halogen,
(iii) C1-6alkylthio, which is optionally substituted with halogen,
(iv) C1-6alkylsulfonyl,
(v) halogen,
(vi) hydroxyl,
(vii) —NR18R19, wherein R18 and R19 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) C1-6alkylcarbonyl,
(d) C1-6alkylsulfonyl,
(viii) —COR20, wherein R20 is:
(a) C1-6alkyl,
(b) C1-6alkyloxy,
(c) —OH,
(d) —NR21R22, wherein R21 and R22 are each independently selected from:
(I) hydrogen,
(II) C1-6alkyl,
(C) —COR23, wherein R23 is:
(i) C1-6alkyloxy,
(ii) —NR24R25, wherein R24 and R25 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
or wherein R24 and R25 together constitute an alkylene bridge which together with the nitrogen atom between them forms a four to six-membered ring, wherein one of the methylene groups is optionally replaced by an oxygen, sulfur or NH group, and which ring is optionally and independently substituted with one or more of the following groups:
(a) C1-6alkyloxy,
(b) C1-6alkyl, which is optionally substituted with halogen,
(c) hydroxyl,
(d) halogen,
(e) —COR26, wherein R26 is:
(I) C1-6alkyloxy,
(II) —NR27R28, wherein R27 and R28 are each independently selected from:
a. hydrogen,
b. C1-6alkyl,
c. aryl,
d. heteroaryl,
(D) is:
which is optionally substituted with halogen;
(E) is selected from the following:
R2 is selected from the following groups:
(A) CF3,
(B) cyano,
(C) halogen,
(D) nitro,
(E) C1-6alkylalkynyl,
(F) arylalkynyl which is optionally substituted with one or more of the following groups:
(i) halogen,
(ii) C1-6alkyl, which is optionally substituted with halogen,
R3 is selected from the following groups:
R4 and R5 are each independently selected from:
(A) hydrogen,
(B) C1-6alkyl, optionally and independently substituted with one or more of the following groups:
(i) oxo,
(ii) C3-6cycloalkyl,
(iii) C1-6alkyloxy,
(iv) C1-6alkylthio,
(v) —COR29, wherein R29 is:
(a) C1-6alkyl,
(b) C1-6alkyloxy,
(c) —OH,
(vi) —CONR30R31, wherein R30 and R31 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) aryl,
(d) heteroaryl,
(vii) halogen,
(viii) hydroxyl,
(ix) —NR32R33, wherein R32 and R33 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) C1-6alkylcarbonyl,
(d) C1-6alkylsulfonyl,
(e) aryl,
(f) heteroaryl,
(x) aryl or heteroaryl, each optionally and independently substituted with one or more of the following groups:
(a) C1-6alkyl, which is optionally substituted with halogen,
(b) C1-6alkoxy, which is optionally substituted with halogen,
(c) C1-6alkylthio, which is optionally substituted with halogen,
(d) C1-6alkylsulfonyl,
(e) cyano,
(f) halogen,
(g) nitro,
(h) —NR34R35, wherein R34 and R35 are each independently selected from:
(I) hydrogen,
(II) C1-6alkyl,
(III) C1-6alkylcarbonyl,
(IV) C1-6alkylsulfonyl,
(i) —COR36, wherein R36 is:
(I) C1-6alkyl,
(II) C1-6alkyloxy,
(III) —OH,
(j) —CONR37R38, wherein R37 and R38 are each independently selected from:
(I) hydrogen,
(II) C1-6alkyl,
(III) aryl,
(IV) heteroaryl,
(C) C1-6alkylsulfonyl,
(D) arylsulfonyl,
(E) aryl-C1-6alkylsulfonyl,
(F) heteroarylsulfonyl,
(G) C1-6alkylcarbonyl,
(H) arylcarbonyl,
(I) aryl-C1-6alkylcarbonyl,
(J) heteroarylcarbonyl,
(K) C1-6alkylaminocarbonyl, or
(L) heteroaryl,
or wherein R4 and R5 together constitute an alkylene bridge which together with the nitrogen atom between them forms a four- to seven-membered ring, wherein one of the methylene groups is optionally replaced by an oxygen, sulfur or NH group, and which ring is optionally and independently substituted with one or more of the following groups:
(A) C1-6alkyl, which is optionally substituted with halogen,
(B) C1-6alkoxy, which is optionally substituted with halogen,
(C) C1-6alkylthio, which is optionally substituted with halogen,
(D) C1-6alkylsulfonyl,
(E) halogen,
(F) —NR39R40, wherein R39 and R40 are each independently selected from:
(i) hydrogen,
(ii) C1-6alkyl,
(iii) C1-6alkylcarbonyl,
(iv) C1-6alkylsulfonyl,
(v) arylcarbonyl,
(vi) arylsulfonyl
(vii) heteroarylcarbonyl,
(viii) heteroarylsulfonyl,
(G) —COR41, wherein R1 is:
(i) C1-6alkyl,
(ii) C1-6alkyloxy,
(iii) —NR42R43, wherein R42 and R43 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) aryl,
(d) heteroaryl,
(iv) hydroxyl,
(H) —OR44, wherein R44 is selected from:
(i) hydrogen,
(ii) C1-6alkylcarbonyl,
(iii) C1-6alkylsulfonyl
(I) oxo,
or wherein NR4R5 constitutes a 5-membered heteroaryl ring containing a total of 2 nitrogen hetero atoms in the ring;
or a tautomer or pharmaceutically acceptable salt thereof or a corresponding compound having at least one amine group protected by an amino-protecting group.

202 more elements

A method of treating a disease or disorder associated with the activation of T cells in a patient comprising administering to said patient a therapeutically effective amount of a compound of the following formula (I):

wherein:
X is C1-6 alkyl wherein one or two of the methylene units can be replaced by an oxygen or sulfur atom, and wherein the C1-6alkyl group is optionally and independently substituted with:
(A) oxo,
(B) C1-6alkyl which is optionally substituted with one or more of the following groups:
(i) hydroxyl,
(ii) C1-3alkyloxy,
(iii) halogen,
(C) C1-6alkyloxy,
(D) C1-6alkylthio,
(E) aryl
(F) —COR6, wherein R6 is:
(i) C1-6alkyl,
(ii) C1-6alkyloxy,
(iii) —NR7R8, wherein R7 and R8 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) aryl,
(d) heteroaryl,
(iv) —OH,
(G) halogen,
(H) —NR9R10, wherein R9 and R10 are each independently selected from:
(i) hydrogen,
(ii) C1-6alkyl,
(iii) C1-6alkylcarbonyl,
(iv) C1-6alkylsulfonyl,
(v) aryl,
(vi) heteroaryl;
Y is —NH—, —O— or —S—;
R1 is:
(A) aryl or heteroaryl, each optionally and independently substituted with one or more of the following groups:
(i) C1-6alkyl, which is optionally substituted one or more of the following:
(a) halogen,
(b) NH2
(ii) C1-6alkoxy, which is optionally substituted with halogen,
(iii) C1-6alkylthio, which is optionally substituted with halogen,
(iv) C1-6alkylsulfonyl,
(v) cyano,
(vi) halogen,
(vii) hydroxyl,
(viii) nitro,
(ix) —COR11, wherein R11 is:
(a) C1-6alkyl,
(b) C1-6alkyloxy,
(c) —OH,
(d) —NR12R13, wherein R12 and R13 are each independently selected from:
(I) hydrogen,
(II) C1-6alkyl,
(III) aryl,
(IV) heteroaryl,
(x) —NR14R15, wherein R14 and R15 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) C1-6alkylcarbonyl,
(d) C1-6alkylsulfonyl,
or wherein R14 and R15 together constitute an alkylene bridge which together with the nitrogen atom between them forms a five to seven-membered ring,
(xi) arylthio, arylsulfonyl or aryloxy, each optionally and independently substituted with one or more of the following groups:
(a) C1-6alkyl,
(b) C1-6alkoxy,
(c) C1-6alkylthio,
(d) C1-6alkylsulfonyl,
(e) cyano,
(f) halogen,
(g) nitro,
(h) —NR16R17, wherein R16 and R17 are each independently selected from:
(I) hydrogen,
(II) C1-6alkyl,
(III) C1-6alkylcarbonyl,
(IV) C1-6alkylsulfonyl,
(B) C3-6cycloalkyl which is optionally and independently substituted with one or more of the following groups:
(i) C1-6alkyl, which is optionally substituted with halogen,
(ii) C1-6alkoxy, which is optionally substituted with halogen,
(iii) C1-6alkylthio, which is optionally substituted with halogen,
(iv) C1-6alkylsulfonyl,
(v) halogen,
(vi) hydroxyl,
(vii) —NR18R19, wherein R18 and R19 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) C1-6alkylcarbonyl,
(d) C1-6alkylsulfonyl,
(viii) —COR20, wherein R20 is:
(a) C1-6alkyl,
(b) C1-6alkyloxy,
(c) —OH,
(d) —NR21R22, wherein R21 and R22 are each independently selected from:
(I) hydrogen,
(II) C1-6alkyl,
(C) —COR23, wherein R23 is:
(i) C1-6alkyloxy,
(ii) —NR24R25, wherein R24 and R25 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
or wherein R24 and R25 together constitute an alkylene bridge which together with the nitrogen atom between them forms a four to six-membered ring, wherein one of the methylene groups is optionally replaced by an oxygen, sulfur or NH group, and which ring is optionally and independently substituted with one or more of the following groups:
(a) C1-6alkyloxy,
(b) C1-6alkyl, which is optionally substituted with halogen,
(c) hydroxyl,
(d) halogen,
(e) —COR26, wherein R26 is:
(I) C1-6alkyloxy,
(II) —NR27R28, wherein R27 and R28 are each independently selected from:
a. hydrogen,
b. C1-6alkyl,
c. aryl,
d. heteroaryl,
(D) is:
which is optionally substituted with halogen;
(E) is selected from the following:
R2 is selected from the following groups:
(A) CF3,
(B) cyano,
(C) halogen,
(D) nitro,
(E) C1-6alkylalkynyl,
(F) arylalkynyl which is optionally substituted with one or more of the following groups:
(i) halogen,
(ii) C1-6alkyl, which is optionally substituted with halogen,
R3 is selected from the following groups:
R4 and R5 are each independently selected from:
(A) hydrogen,
(B) C1-6alkyl, optionally and independently substituted with one or more of the following groups:
(i) oxo,
(ii) C3-6cycloalkyl,
(iii) C1-6alkyloxy,
(iv) C1-6alkylthio,
(v) —COR29, wherein R29 is:
(a) C1-6alkyl,
(b) C1-6alkyloxy,
(c) —OH,
(vi) —CONR30R31, wherein R30 and R31 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) aryl,
(d) heteroaryl,
(vii) halogen,
(viii) hydroxyl,
(ix) —NR32R33, wherein R32 and R33 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) C1-6alkylcarbonyl,
(d) C1-6alkylsulfonyl,
(e) aryl,
(f) heteroaryl,
(x) aryl or heteroaryl, each optionally and independently substituted with one or more of the following groups:
(a) C1-6alkyl, which is optionally substituted with halogen,
(b) C1-6alkoxy, which is optionally substituted with halogen,
(c) C1-6alkylthio, which is optionally substituted with halogen,
(d) C1-6alkylsulfonyl,
(e) cyano,
(f) halogen,
(g) nitro,
(h) —NR34R35, wherein R34 and R35 are each independently selected from:
(I) hydrogen,
(II) C1-6alkyl,
(III) C1-6alkylcarbonyl,
(IV) C1-6alkylsulfonyl,
(i) —COR36, wherein R36 is:
(I) C1-6alkyl,
(II) C1-6alkyloxy,
(III) —OH,
(j) —CONR37R38, wherein R37 and R38 are each independently selected from:
(I) hydrogen,
(II) C1-6alkyl,
(III) aryl,
(IV) heteroaryl,
(C) C1-6alkylsulfonyl,
(D) arylsulfonyl,
(E) aryl-C1-6alkylsulfonyl,
(F) heteroarylsulfonyl,
(G) C1-6alkylcarbonyl,
(H) arylcarbonyl,
(I) aryl-C1-6alkylcarbonyl,
(J) heteroarylcarbonyl,
(K) C1-6alkylaminocarbonyl, or
(L) heteroaryl,
or wherein R4 and R5 together constitute an alkylene bridge which together with the nitrogen atom between them forms a four- to seven-membered ring, wherein one of the methylene groups is optionally replaced by an oxygen, sulfur or NH group, and which ring is optionally and independently substituted with one or more of the following groups:
(A) C1-6alkyl, which is optionally substituted with halogen,
(B) C1-6alkoxy, which is optionally substituted with halogen,
(C) C1-6alkylthio, which is optionally substituted with halogen,
(D) C1-6alkylsulfonyl,
(E) halogen,
(F) —NR39R40, wherein R39 and R40 are each independently selected from:
(i) hydrogen,
(ii) C1-6alkyl,
(iii) C1-6alkylcarbonyl,
(iv) C1-6alkylsulfonyl,
(v) arylcarbonyl,
(vi) arylsulfonyl
(vii) heteroarylcarbonyl,
(viii) heteroarylsulfonyl,
(G) —COR41, wherein R41 is:
(i) C1-6alkyl,
(ii) C1-6alkyloxy,
(iii) —NR42R43, wherein R42 and R43 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) aryl,
(d) heteroaryl,
(iv) hydroxyl,
(H) —OR44, wherein R44 is selected from:
(i) hydrogen,
(ii) C1-6alkylcarbonyl,
(iii) C1-6alkylsulfonyl
(I) oxo,
or wherein NR4R5 constitutes a 5-membered heteroaryl ring containing a total of 2 nitrogen hetero atoms in the ring;
or a tautomer or pharmaceutically acceptable salt thereof or a corresponding compound having at least one amine group protected by an amino-protecting group.

202 more elements

A method of treating an immunological disorder in a patient comprising administering to said patient a therapeutically effective amount of a compound of the following formula (I):

wherein:
X is C1-6 alkyl wherein one or two of the methylene units can be replaced by an oxygen or sulfur atom, and wherein the C1-6alkyl group is optionally and independently substituted with:
(A) oxo,
(B) C1-6alkyl which is optionally substituted with one or more of the following groups:
(i) hydroxyl,
(ii) C1-3alkyloxy,
(iii) halogen,
(C) C1-6alkyloxy,
(D) C1-6alkylthio,
(E) aryl
(F) —COR6, wherein R6 is:
(i) C1-6alkyl,
(ii) C1-6alkyloxy,
(iii) —NR7R8, wherein R7 and R8 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) aryl,
(d) heteroaryl,
(iv) —OH,
(G) halogen,
(H)—NR9R10, wherein R9 and R10 are each independently selected from:
(i) hydrogen,
(ii) C1-6alkyl,
(iii) C1-6alkylcarbonyl,
(iv) C1-6alkylsulfonyl,
(v) aryl,
(vi) heteroaryl;
Y is —NH—, —O— or —S—;
R1 is:
(A) aryl or heteroaryl, each optionally and independently substituted with one or more of the following groups:
(i) C1-6alkyl, which is optionally substituted one or more of the following:
(a) halogen,
(b) NH2
(ii) C1-6alkoxy, which is optionally substituted with halogen,
(iii) C1-6alkylthio, which is optionally substituted with halogen,
(iv) C1-6alkylsulfonyl,
(v) cyano,
(vi) halogen,
(vii) hydroxyl,
(viii) nitro,
(ix) —COR11, wherein R11 is:
(a) C1-6alkyl,
(b) C1-6alkyloxy,
(c) —OH,
(d) —NR12R13, wherein R12 and R13 are each independently selected from:
(I) hydrogen,
(II) C1-6alkyl,
(III) aryl,
(IV) heteroaryl,
(x) —NR14R15, wherein R14 and R15 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) C1-6alkylcarbonyl,
(d) C1-6alkylsulfonyl,
or wherein R14 and R15 together constitute an alkylene bridge which together with the nitrogen atom between them forms a five to seven-membered ring,
(xi) arylthio, arylsulfonyl or aryloxy, each optionally and independently substituted with one or more of the following groups:
(a) C1-6alkyl,
(b) C1-6alkoxy,
(c) C1-6alkylthio,
(d) C1-6alkylsulfonyl,
(e) cyano,
(f) halogen,
(g) nitro,
(h) —NR16R17, wherein R16 and R17 are each independently selected from:
(I) hydrogen,
(II) C1-6alkyl,
(III) C1-6alkylcarbonyl,
(IV) C1-6alkylsulfonyl,
(B) C3-6cycloalkyl which is optionally and independently substituted with one or more of the following groups:
(i) C1-6alkyl, which is optionally substituted with halogen,
(ii) C1-6alkoxy, which is optionally substituted with halogen,
(iii) C1-6alkylthio, which is optionally substituted with halogen,
(iv) C1-6alkylsulfonyl,
(v) halogen,
(vi) hydroxyl,
(vii) —NR18R19, wherein R18 and R19 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) C1-6alkylcarbonyl,
(d) C1-6alkylsulfonyl,
(viii) —COR20, wherein R20 is:
(a) C1-6alkyl,
(b) C1-6alkyloxy,
(c) —OH,
(d) —NR21R22, wherein R21 and R22 are each independently selected from:
(I) hydrogen,
(II) C1-6alkyl,
(C) —COR23, wherein R23 is:
(i) C1-6alkyloxy,
(ii) —NR24R25, wherein R24 and R25 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
or wherein R24 and R25 together constitute an alkylene bridge which together with the nitrogen atom between them forms a four to six-membered ring, wherein one of the methylene groups is optionally replaced by an oxygen, sulfur or NH group, and which ring is optionally and independently substituted with one or more of the following groups:
(a) C1-6alkyloxy,
(b) C1-6alkyl, which is optionally substituted with halogen,
(c) hydroxyl,
(d) halogen,
(e) —COR26, wherein R26 is:
(I) C1-6alkyloxy,
(II) —NR27R28, wherein R27 and R28 are each independently selected from:
a. hydrogen,
b. C1-6alkyl,
c. aryl,
d. heteroaryl,
(D) is
which is optionally substituted with halogen;
(E) is selected from the following:
R2 is selected from the following groups:
(A) CF3,
(B) cyano,
(C) halogen,
(D) nitro,
(E) C1-6alkylalkynyl,
(F) arylalkynyl which is optionally substituted with one or more of the following groups:
(i) halogen,
(ii) C1-6alkyl, which is optionally substituted with halogen,
R3 is selected from the following groups:
R4 and R5 are each independently selected from:
(A) hydrogen,
(B) C1-6alkyl, optionally and independently substituted with one or more of the following groups:
(i) oxo,
(ii) C3-6cycloalkyl,
(iii) C1-6alkyloxy,
(iv) C1-6alkylthio,
(v) —COR29, wherein R29 is:
(a) C1-6alkyl,
(b) C1-6alkyloxy,
(c) —OH,
(vi) —CONR30R31, wherein R30 and R31 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) aryl,
(d) heteroaryl,
(vii) halogen,
(viii) hydroxyl,
(ix) —NR32R33, wherein R32 and R33 are each independently selected from:
(a) hydrogen,
(b) C1-6alkyl,
(c) C1-6alkylcarbonyl,
(d) C1-6alkylsulfonyl,
(e) aryl,
(f) heteroaryl,
(x) aryl or heteroaryl, each optionally and independently substituted with one or more of the following groups:
(a) C1-6alkyl, which is optionally substituted with halogen,
(b) C1-6alkoxy, which is optionally substituted with halogen,
(c) C1-6alkylthio, which is optionally substituted with halogen,
(d) C1-6alkylsulfonyl,
(e) cyano,
(f) halogen,
(g) nitro,
(h) —NR34R35, wherein R34 and R35 are each independently selected from:
(I) hydrogen,
(II) C1-6alkyl,
(III) C1-6alkylcarbonyl,
(IV) C1-6alkylsulfonyl,
(i) —COR36, wherein R36 is:
(I) C1-6alkyl,
(II) C1-6alkyloxy,
(III) —OH,
(j) —CONR37R38, wherein R37 and R38 are each independently selected from:
(I) hydrogen,
(II) C1-6alkyl,
(III) aryl,
(IV) heteroaryl,
(C) C1-6alkylsulfonyl,
(D) arylsulfonyl,
(E) aryl-C1-6alkylsulfonyl,
(F) heteroarylsulfonyl,
(G) C1-6alkylcarbonyl,
(H) arylcarbonyl,
(I) aryl-C1-6alkylcarbonyl,
(J) heteroarylcarbonyl,
(K) C1-6alkylaminocarbonyl, or
(L) heteroaryl,
or wherein R4 and R5 together constitute an alkylene bridge which together with the nitrogen atom between them forms a four- to seven-membered ring, wherein one of the methylene groups is optionally replaced by an oxygen, sulfur or NH group, and which ring is optionally and independently substituted with one or more of the following groups:
(A) C1-6alkyl, which is optionally substituted with halogen,
(B) C1-6alkoxy, which is optionally substituted with halogen,
(C) C1-6alkylthio, which is optionally substituted with halogen,
(D) C1-6alkylsulfonyl,
(E) halogen,
(F) —NR39R40, wherein R39 and R40 are each independently selected from:
(i) hydrogen,
(ii) C1-6alkyl,
(iii) C1-6alkylcarbonyl,
(iv) C1-6alkylsulfonyl,
(v) arylcarbonyl,
(vi) arylsulfonyl,
(vii) heteroarylcarbonyl,
(viii) heteroarylsulfonyl,
(G) —COR41, wherein R1 is:
(i) C1-6alkyl,
(ii) C1-6alkyloxy,
(iii) —NR42R43, wherein R42 and R43 are each independently selected from:
hydrogen,
(a) C1-6alkyl,
(b) aryl,
(c) heteroaryl,
(iv) hydroxyl,
(H) —OR44, wherein R44 is selected from:
(i) hydrogen,
(ii) C1-6alkylcarbonyl,
(iii) C1-6alkylsulfonyl
(I) oxo,
or wherein NR4R5 constitutes a 5-membered heteroaryl ring containing a total of 2 nitrogen hetero atoms in the ring;
or a tautomer or pharmaceutically acceptable salt thereof or a corresponding compound having at least one amine group protected by an amino-protecting group.

202 more elements

Dependencies are inferred from the claim text.

Pyrimidine derivatives useful as inhibitors of pkc-theta

Life of this patent

Pyrimidine derivatives useful as inhibitors of pkc-theta

Life of this patent

Abstract

Claims14