US 9,040,547 B2 · Pyrrolopyrimidine and purine derivatives

Abstract

The present invention relates to compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein Q, T, V, W, X, Y, Z, ring A, R1, R2, R3, R4, R5, R5a, R6, R7, R8, R9, R10, R11, R12, R13, R14, R15, R16, R17 and m are defined herein. There novel pyrrolopyrimidine and purine derivatives are useful in the treatment of abnormal cell growth, such as cancer, in mammals. Additional embodiments relate to pharmaceutical compositions containing the compounds and to methods of using the compounds and compositions in the treatment of abnormal cell growth in mammals.

A compound of formula (I):

wherein
X is N or CR7;
Y is absent, O, S or NR8;
Q, T, V and W are each independently C or N, provided that at least two of Q, T, V and W are N and at least one of Q, T, V and W is C, and provided that when Q and T are N, at least one of R1 and R2 is absent, and further provided that when T and V are N, at least one of R2 and R3 is absent;
R1 and R4 are each independently absent, hydrogen, cyano, difluoromethyl, trifluoromethyl, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkoxy, —N(R9)(R10), C3-C5 cycloalkyl or 4-6 membered heterocycloalkyl, wherein the C1-C6 alkyl may be optionally substituted by halogen, hydroxy, C1-C6 alkoxy or N(R11)(R12);
R2 and R3 are each independently absent, hydrogen, C1-C6 alkyl, C2-C6 alkynyl, C1-C6 alkoxy, C3-C7 cycloalkyl or 3-7 membered heterocycloalkyl, wherein the C1-C6 alkyl and C1-C6 alkoxy in R2 and R3 are each independently optionally substituted by one or more R13 groups, and further wherein the C3-C7 cycloalkyl and the 3-7 membered heterocycloalkyl in R2 and R3 are each independently optionally substituted by one or more R14 groups;
or
R1 and R2 or R2 and R3 may combine to form a C5-C7 cycloalkyl ring or a 5-7 membered heterocycloalkyl ring, wherein the C5-C7 cycloalkyl ring and the 5-7 membered heterocycloalkyl ring are each independently optionally substituted by one or more R13 groups;
ring A is absent, C3-C10 cycloalkyl, 3-10 membered heterocycloalkyl, C5-C10 aryl or 5-12 membered heteroaryl;
R5 and R5a are each independently absent, halogen, cyano, hydroxy, difluoromethyl, trifluoromethyl, C1-C3 alkyl, C1-C3 alkoxy, C3-C5 cycloalkyl or 4-6 membered heteroaryl, wherein the C1-C3 alkyl is optionally substituted by hydroxy, difluoromethyl, trifluoromethyl, C1-C3 alkoxy or C3-C5 cycloalkyl;
R6 is
Z is absent when the attachment point of R6 on ring A is a nitrogen atom, and Z is —NR17— when ring A is absent or when the attachment point of R6 on ring A is a carbon atom;
R7 is hydrogen, halogen, cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl or 4-6 membered heteroaryl, wherein the C1-C6 alkyl may be optionally substituted by hydroxy or C1-C3 alkoxy, and further wherein the 4-6 membered heteroaryl may be optionally substituted by C1-C3 alkyl;
R8 is hydrogen or C1-C3 alkyl;
R9 and R10 are each independently hydrogen or C1-C6 alkyl;
or R9 and R10 together with the nitrogen to which they are attached, may combine to form a 4-7 membered ring, when R9 and R10 are each C1-C3 alkyl, wherein the 4-7 membered ring is optionally substituted by one or more R14 groups;
R11 and R12 are each independently hydrogen or C1-C3 alkyl;
each R13 is independently halogen, cyano, hydroxy, C1-C6 alkoxy, —N(R9)(R10), —CON(R9)(R10) or 3-7 membered heterocycloalkyl, wherein the 3-7 membered heterocycloalkyl in R13 is optionally substituted by one or more R14 groups;
each R14 is independently halogen, C1-C3 alkyl, hydroxy, C1-C6 alkoxy, —NH2, —NHCH3 or N(CH3)2;
R15 and R16 are each independently hydrogen or C1-C6 alkyl, wherein the C1-C6 alkyl of one of R15 and R16 is optionally substituted by —N(R9)(R10);
R17 is hydrogen or C1-C3 alkyl;
and
m is 0, 1 or 2, provided that when ring A is absent, m is 2;
or
a pharmaceutically acceptable salt thereof.

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Pyrrolopyrimidine and purine derivatives

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Pyrrolopyrimidine and purine derivatives

Life of this patent

Abstract

Claims41