US 8,524,709 B2Granted

Kinase inhibitor compounds

AssigneeTyrogenex, Inc.

InventorsCongxin Liang, Ming Qi, Shu Gao, Zhigang Li

Life of this patent

Estimating the term…

Abstract

The invention relates to compounds, compositions comprising the compounds, and methods of using the compounds and compound compositions. The compounds, compositions, and methods described herein can be used for the therapeutic modulation of kinase-mediated processes, and treatment of disease and disease symptoms, particularly those mediated by certain kinase enzymes.

Claims17

Dependent claims

A method of treating a disease or disease symptom that is modulated by a kinase enzyme in a subject in need thereof comprising administering to the subject an effective amount of a compound of formula (I), or pharmaceutical salt thereof,

wherein
the disease or disease symptom is selected from the group consisting of renal cell carcinoma, GI stromal tumor, pancreatic neuroendocrine tumor, lung cancer, colorectal cancer, age-related macular degeneracy (AMD), glioblastoma, ovarian cancer, and hepatocellular carcinoma;
Cy is a cyclic structure that can be cycloalkyl, heterocyclic, or heteroaryl, each optionally substituted with Z1, Z2 and Z3;
R4 and R5 are each independently:
(1) hydrogen or R6, where R6, is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z1, Z2 and one or more groups Z3;
(2) —OH or —OR6;
(3) —SH or —SR6;
(4) —C(O)2H, —C(O)qR6, —C(O)NR7R8, —C(O)C(O)NR7R8, or —O—C(O)qR6, where q is 1 or 2;
(5) —SO3H, —S(O)qR6, or —S(O)qNR7R8
6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NR7R8;
(10) —Z4—N(R9)—Z6—NR10R11;
(11) —Z4—N(R12)—Z5—R6;
(12) —P(O)(OR6)2;
R1, R2, and R3 are each independently:
(1) hydrogen or R′6, where R′6, is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, heteroaryl, aralkyl, heteroarylalkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z1, Z2 and one or more groups Z3;
(2) —OH or —OR6;
(3) —SH or —SR6;
(4) —C(O)2H, —C(O)qR6, —C(O)NR7R8, —C(O)C(O)NR7R8, or —O—C(O)qR6, where q is 1 or 2;
(5) —SO3H, —S(O)qR″6, or —S(O)qNR7R8,
(a) wherein R″6 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, heteroarylalkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z1, Z2 and one or more groups Z3;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NR7R8;
(10) —Z4—N(R9) —Z5—NR10R11;
(11) —Z4—N(R12) —Z5—R6;
(12) —P(O)(OR6)2;
R7, R8, R9, R10, R11 and R12 are each independently:
(1) hydrogen or R6;
(2) R7 and R8 together with the nitrogen atom to which they are attached may be a heterocycle which is unsubstituted or substituted with Z1, Z2 and Z3;
or
(3) any two of R9, R10 and R11 together with the nitrogen atoms to which they are attached may be a 3- to 12-membered saturated or unsaturated mono-, bi-, or tri-heterocyclic ring which is unsubstituted or substituted with Z1, Z2 and Z3;
Z1, Z2 and Z3 are each independently:
(1) hydrogen or Z6, where Z6 is (i) alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
(ii) a group (i) which is itself substituted by one or more of the same or different groups (i);
or (iii) a group (i) or (ii) which is substituted by one or more of the following groups (2) to (13);
(2) —OH or —OZ16;
(3) —SH or —SZ16;
(4) —C(O)2H, C(O)qZ16, —C(O)NZ17Z18, —C(O)C(O)NZ17Z18, or —O—C(O)qZ16, where q is 1 or 2;
(5) —SO3H, —S(O)qZ16, or —S(O)qNZ17Z18;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NZ17Z18;
(10) —Z4—N(Z18) —Z5—NZ19Z20;
(11) oxo;
(12) —O—C(O)—Z16;
(13) any two of Z1, Z2, and Z3 may together be alkylene, alkenylene, aryl, heteroaryl, or heterocyclo completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached;
Z4 and Z5 are each independently
(1) a single bond;
(2) —Z11—S(O)q—Z12—;
(3) —Z11—C(O)—Z12—;
(4) —Z11—O—Z12—;
(5) —Z11—S—Z12—;
(6) —Z11—O—C(O)—Z12—;
or
(7) —Z11—C(O)—O—Z12;
Z11 and Z12 are each independently
(1) a single bond;
(2) alkylene;
(3) alkenylene;
or
(4) alkynylene;
each Z16 is independently alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl, each optionally substituted with one or more of the following groups:
(2) —OH or —OZ21;
(3) —SH or —SZ21;
(4) —C(O)2H, C(O)qZ21, —C(O)NZ17Z18, —C(O)C(O)NZ17Z18, or —O—C(O)qZ21, where q is 1 or 2;
(5) —SO3H, —S(O)qZ21, or —S(O)qNZ17Z18;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NZ17Z18;
(10) —Z4—N(Z18) —Z5—NZ19Z20;
(11) oxo;
(12) —O—C(O)—Z21;
each Z17 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z18 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z19 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z20 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z21 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z22 is independently is,
(2) —OH or —OZ21;
(3) —SH or —SZ21;
(4) —C(O)2H, C(O)qZ21, —C(O)NZ21Z21, —C(O)C(O)NZ21Z21, or —O—C(O)qZ21, where q is 1 or 2;
(5) —SO3H, —S(O)qZ21, or —S(O)qNZ21Z21;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NZ21Z21;
(10) —Z4—N(Z21) —Z5—NZ21Z21;
(11) oxo;
(12) —O—C(O)—Z21;
where Z17 and Z18, or Z19 and Z20, together with the nitrogen atom to which they are attached may be a heterocycle which is unsubstituted or substituted with 1, 2, or 3 independent Z22;
and
where any two of Z18, Z19 or Z20 together with the nitrogen atoms to which they are attached may be a 3- to 12-membered saturated or unsaturated mono-, bi-, or tri-heterocyclic ring which is unsubstituted or substituted with 1, 2, or 3 independent Z22;
provided said compound is other than a compound of formula IIa or IIb:

96 more elements

wherein
the disease or disease symptom is selected from the group consisting of renal cell carcinoma, GI stromal tumor, pancreatic neuroendocrine tumor, lung cancer, colorectal cancer, age-related macular degeneracy (AMD), glioblastoma, ovarian cancer, and hepatocellular carcinoma,
Cy is a cyclic structure that can be cycloalkyl, heterocyclic, or heteroaryl, each optionally substituted with Z1, Z2 and Z3;
R1, R2, and R3 are each independently:
(1) hydrogen or R6, where R6, is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z1, Z2 and one or more groups Z3;
(2) —OH or —OR6;
(3) —SH or —SR6;
(4) —C(O)2H, —C(O)qR6, —C(O)NR7R8, —C(O)C(O)NR7R8, or —O—C(O)qR6, where q is 1 or 2;
(5) —SO3H, —S(O)qR″6, or —S(O)qNR7R8,
(a) wherein R″6 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, heteroarylalkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z1, Z2 and one or more groups Z3;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NR7R8;
(10) —Z4—N(R9)—Z5—NR10R11;
(11) —Z4—N(R12)—Z5—R6;
(12) —P(O)(OR6)2;
Z1, Z2 and Z3 are each independently:
(1) hydrogen or Z6, where Z6 is (i) alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
(ii) a group (i) which is itself substituted by one or more of the same or different groups (i);
or (iii) a group (i) or (ii) which is substituted by one or more of the following groups (2) to (13);
(2) —OH or —OZ16;
(3) —SH or —SZ16;
(4) —C(O)2H, C(O)qZ16, —C(O)NZ17Z18, —C(O)C(O)NZ17Z18, or —O—C(O)qZ16, where q is 1 or 2;
(5) —SO3H, —S(O)qZ16, or —S(O)qNZ17Z18;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NZ17Z18;
(10) —Z4—N(Z18)—Z5—NZ19Z20;
(11) oxo;
(12) —O—C(O)—Z16;
(13) any two of Z1, Z2, and Z3 may together be alkylene, alkenylene, aryl, heteroaryl, or heterocyclo completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached;
Z4 and Z5 are each independently
(1) a single bond;
(2) —Z11—S(O)q—Z12—;
(3) —Z11—C(O)—Z12—;
(4) —Z11—O—Z12—;
(5) —Z11—S—Z12—;
(6) —Z11—O—C(O)—Z12—;
or
(7) —Z11—C(O)—O—Z12;
Z11 and Z12 are each independently
(1) a single bond;
(2) alkylene;
(3) alkenylene;
or
(4) alkynylene;
each Z16 is independently alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl, each optionally substituted with one or more of the following groups:
(2) —OH or —OZ21;
(3) —SH or —SZ21;
(4) —C(O)2H, C(O)qZ21, —C(O)NZ17Z18, —C(O)C(O)NZ17Z18, or —O—C(O)qZ21, where q is 1 or 2;
(5) —SO3H, —S(O)qZ21, or —S(O)qNZ17Z18;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NZ17Z18;
(10) —Z4—N(Z18)—Z5—NZ19Z20;
(11) oxo;
(12) —O—C(O)—Z21;
each Z17 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z18 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z19 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z20 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z21 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z22 is independently is,
(2) —OH or —OZ21;
(3) —SH or —SZ21;
(4) —C(O)2H, C(O)qZ21, —C(O)NZ21Z21, —C(O)C(O)NZ21Z21, or —O—C(O)qZ21, where q is 1 or 2;
(5) —SO3H, —S(O)qZ21, or —S(O)qNZ21Z21;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NZ21Z21;
(10) —Z4—N(Z21) —Z5—NZ21Z21;
(11) oxo;
(12) —O—C(O)—Z21;
where Z17 and Z13, or Z19 and Z20, together with the nitrogen atom to which they are attached may be a heterocycle which is unsubstituted or substituted with 1, 2, or 3 independent Z22;
and
where any two of Z18, Z19 or Z20 together with the nitrogen atoms to which they are attached may be a 3- to 12-membered saturated or unsaturated mono-, bi-, or tri-heterocyclic ring which is unsubstituted or substituted with 1, 2, or 3 independent Z22.

77 more elements

wherein
the disease or disease symptom is selected from the group consisting of renal cell carcinoma, GI stromal tumor, pancreatic neuroendocrine tumor, lung cancer, colorectal cancer, age-related macular degeneracy (AMD), glioblastoma, ovarian cancer, and hepatocellular carcinoma;
Cy is aryl optionally substituted with Z1, Z2 and Z3;
R4 and R5 are each independently:
(1) hydrogen or R6, where R6, is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z1, Z2 and one or more groups Z3;
(2) —OH or —OR6;
(3) —SH or —SR6;
(4) —C(O)2H, —C(O)qR6, —C(O)NR7R8, —C(O)C(O)NR7R8, or —O—C(O)qR6, where q is 1 or 2;
(5) —SO3H, —S(O)qR6, or —S(O)qNR7R8
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NR7R8;
(10) —Z4—N(R9) —Z5—NR10R11;
(11) —Z4—N(R12) —Z5—R6;
(12) —P(O)(OR6)2;
R1, R2, and R3 are each independently:
(1) hydrogen or R′6, where R′6, is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, heteroaryl, aralkyl, heteroarylalkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z1, Z2 and one or more (preferably, one or two) groups Z3;
(2) —OH or —OR6;
(3) —SH or —SR6;
(4) —C(O)2H, —C(O)qR6, —C(O)NR7R8, —C(O)C(O)NR7R8, or —O—C(O)qR6, where q is 1 or 2;
(5) —SO3H, —S(O)qR″16, or —S(O)qNR7R6,
(a) wherein R″6 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, heteroarylalkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z1, Z2 and one or more groups Z3;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NR7R8;
(10) —Z4—N(R9)—Z5—NR10R11;
(11) —Z4—N(R12)—Z5—R6;
(12) —P(O)(OR6)2;
R7, R8, R9, R10, R11 and R12 are each independently:
(1) hydrogen or R6;
(2) R7 and R8 together with the nitrogen atom to which they are attached may be a heterocycle which is unsubstituted or substituted with Z1, Z2 and Z3;
or
(3) any two of R9, R10 and R11 together with the nitrogen atoms to which they are attached may be a 3- to 12-membered saturated or unsaturated mono-, bi-, or tri-heterocyclic ring which is unsubstituted or substituted with Z1, Z2 and Z3;
Z1, Z2 and Z3 are each independently:
(1) hydrogen or Z6, where Z6 is (i) alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
(ii) a group (i) which is itself substituted by one or more of the same or different groups (i);
or (iii) a group (i) or (ii) which is substituted by one or more of the following groups (2) to (13);
(2) —OH or —OZ16;
(3) —SH or —SZ16;
(4) —C(O)2H, C(O)qZ16, —C(O)NZ17Z18, —C(O)C(O)NZ17Z18, or —O—C(O)qZ16, where q is 1 or 2;
(5) —SO3H, —S(O)qZ16, or —S(O)qNZ17Z18;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NZ17Z18;
(10) —Z4—N(Z18) —Z5—NZ19Z2o;
(11) oxo;
(12) —O—C(O)—Z16;
(13) any two of Z1, Z2, and Z3 may together be alkylene, alkenylene, aryl, heteroaryl, or heterocyclo completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached;
Z4 and Z5 are each independently
(1) a single bond;
(2) —Z11—S(O)q—Z12—;
(3) —Z11—C(O)—Z12—;
(4) —Z11—O—Z12—;
(5) —Z11—S—Z12—;
(6) —Z11—O—C(O)—Z12—;
or
(7) —Z11—C(O)—O—Z12;
Z11 and Z12 are each independently
(1) a single bond;
(2) alkylene;
(3) alkenylene;
or
(4) alkynylene;
each Z16 is independently alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl, each optionally substituted with one or more of the following groups:
(2) —OH or —OZ21;
(3) —SH or —SZ21;
(4) —C(O)2H, C(O)qZ21, —C(O)NZ17Z18, —C(O)C(O)NZ17Z18, or —O—C(O)qZ21, where q is 1 or 2;
(5) —SO3H, —S(O)qZ21, or —S(O)qNZ17Z18;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NZ17Z18;
(10) —Z4—N(Z18) —Z5—NZ19Z20;
(11) oxo;
(12) —O—C(O)—Z21;
each Z17 is independently alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z18 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z19 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z20 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z21 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z22 is independently is,
(2) —OH or —OZ21;
(3) —SH or —SZ21;
(4) —C(O)2H, C(O)qZ21, —C(O)NZ21Z21, —C(O)C(O)NZ21Z21, or —O—C(O)qZ21, where q is 1 or 2;
(5) —SO3H, —S(O)qZ21, or —S(O)qNZ21Z21;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NZ21Z21;
(10) —Z4—N(Z21) —Z5—NZ21Z21;
(11) oxo;
(12) —O—C(O)—Z21;
where Z17 and Z18, or Z19 and Z20, together with the nitrogen atom to which they are attached may be a heterocycle which is unsubstituted or substituted with 1, 2, or 3 independent Z22;
and
where any two of Z18, Z19 or Z20 together with the nitrogen atoms to which they are attached may be a 3- to 12-membered saturated or unsaturated mono-, bi-, or tri-heterocyclic ring which is unsubstituted or substituted with 1, 2, or 3 independent Z22;
provided said compound is other than a compound of formula IIa or IIb.

96 more elements

wherein
the disease or disease symptom is selected from the group consisting of renal cell carcinoma, GI stromal tumor, pancreatic neuroendocrine tumor, lung cancer, colorectal cancer, age-related macular degeneracy (AMD), glioblastoma, ovarian cancer, and hepatocellular carcinoma;
Cy is aryl optionally substituted with Z1, Z2 and Z3;
R1, R2, and R3 are each independently:
(1) hydrogen or R6, where R6, is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z1, Z2 and one or more (preferably, one or two) groups Z3;
(2) —OH or —OR6;
(3) —SH or —SR6;
(4) —C(O)2H, —C(O)qR6, —C(O)NR7R8, —C(O)C(O)NR7R8, or —O—C(O)qR6, where q is 1 or 2;
(5) —SO3H, —S(O)qR″6, or —S(O)qNR7R8,
(a) wherein R″6 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, heteroarylalkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z1, Z2 and one or more groups Z3;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NR7R8;
(10) —Z4—N(R9)—Z5—NR10R11;
(11) —Z4—N(R12)—Z5—R6;
(12) —P(O)(OR6)2;
Z1, Z2 and Z3 are each independently:
(1) hydrogen or Z6, where Z6 is (i) alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
(ii) a group (i) which is itself substituted by one or more of the same or different groups (i);
or (iii) a group (I) or (ii) which is substituted by one or more of the following groups (2) to (13);
(2) —OH or —OZ16;
(3) —SH or —SZ16;
(4) —C(O)2H, C(O)qZ16, —C(O)NZ17Z18, —C(O)C(O)NZ17Z18, or —O—C(O)qZ16, where q is 1 or 2;
(5) —SO3H, —S(O)qZ16, or —S(O)qNZ17Z18;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NZ17Z18;
(10) —Z4—N(Z18)—Z5—NZ19Z20;
(11) oxo;
(12) —O—C(O)—Z16;
(13) any two of Z1, Z2, and Z3 may together be alkylene, alkenylene, aryl, heteroaryl, or heterocyclo completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached;
Z4 and Z5 are each independently
(1) a single bond;
(2) —Z11—S(O)q—Z12—;
(3) —Z11—C(O)—Z12—;
(4) —Z11—O—Z12—;
(5) —Z11—S—Z12—;
(6) —Z11—O—C(O)—Z12—;
or
(7) —Z11—C(O)—O—Z12;
Z11 and Z12 are each independently
(1) a single bond;
(2) alkylene;
(3) alkenylene;
or
(4) alkynylene;
each Z16 is independently alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl, each optionally substituted with one or more of the following groups:
(2) —OH or —OZ21;
(3) —SH or —SZ21;
(4) —C(O)2H, C(O)qZ21, —C(O)NZ17Z18, —C(O)C(O)NZ17Z18, or —O—C(O)qZ21, where q is 1 or 2;
(5) —SO3H, —S(O)qZ21, or —S(O)qNZ17Z18;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NZ17Z18;
(10) —Z4—N(Z18)—Z5—NZ19Z20;
(11) oxo;
(12) —O—C(O)—Z21;
each Z17 is independently alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z18 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z19 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z20 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z21 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z22 is independently is,
(2) —OH or —OZ21;
(3) —SH or —SZ21;
(4) —C(O)2H, C(O)qZ21, —C(O)NZ21Z21, —C(O)C(O)NZ21Z21, or —O—C(O)qZ21, where q is 1 or 2;
(5) —SO3H, —S(O)qZ21, or —S(O)qNZ21Z21;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NZ21Z21;
(10) —Z4—N(Z21) —Z5—NZ21Z21;
(11) oxo;
(12) —O—C(O)—Z21;
where Z17 and Z18, or Z19 and Z20, together with the nitrogen atom to which they are attached may be a heterocycle which is unsubstituted or substituted with 1, 2, or 3 independent Z22;
and
where any two of Z18, Z19 or Z20 together with the nitrogen atoms to which they are attached may be a 3- to 12-membered saturated or unsaturated mono-, bi-, or tri-heterocyclic ring which is unsubstituted or substituted with 1, 2, or 3 independent Z22.

77 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/349,222Filed 12 Jan 2012 · continuation
Priority: 15 Sep 2006
Published: US 2012/0115866 A110 May 2012
Granted: 3 Sep 2013
Term ends: Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07D 493/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 35/00
Antineoplastic agents
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00
C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…

Family

Application60/844,902Us provisional application · filed 15 Sep 2006
PCT/US2007/020193Parent of this continuation · filed 14 Sep 2007
Application12/005,872Parent of this division · filed 28 Dec 2007
Application12/657,887Parent of this continuation · filed 28 Jan 2010
US 7,683,057 B2Parent of this division · filed 23 Mar 2010
Application13/108,598Parent of this continuation · filed 16 May 2011
US 8,039,470 B2Parent of this continuation · filed 18 Oct 2011
US 2012/0115866 A1Pre-grant publication · published 10 May 2012
Application12/657,887Parent of this division
Application12/005,872Parent of this continuation
US 2009/0076005 A1Published application
US 2010/0261665 A1Published application
US 2011/0224212 A1Published application
US 8,524,709 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

wherein
the disease or disease symptom is selected from the group consisting of renal cell carcinoma, GI stromal tumor, pancreatic neuroendocrine tumor, lung cancer, colorectal cancer, age-related macular degeneracy (AMD), glioblastoma, ovarian cancer, and hepatocellular carcinoma;
Cy is a cyclic structure that can be cycloalkyl, heterocyclic, or heteroaryl, each optionally substituted with Z1, Z2 and Z3;
R4 and R5 are each independently:
(1) hydrogen or R6, where R6, is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z1, Z2 and one or more groups Z3;
(2) —OH or —OR6;
(3) —SH or —SR6;
(4) —C(O)2H, —C(O)qR6, —C(O)NR7R8, —C(O)C(O)NR7R8, or —O—C(O)qR6, where q is 1 or 2;
(5) —SO3H, —S(O)qR6, or —S(O)qNR7R8
6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NR7R8;
(10) —Z4—N(R9)—Z6—NR10R11;
(11) —Z4—N(R12)—Z5—R6;
(12) —P(O)(OR6)2;
R1, R2, and R3 are each independently:
(1) hydrogen or R′6, where R′6, is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, heteroaryl, aralkyl, heteroarylalkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z1, Z2 and one or more groups Z3;
(2) —OH or —OR6;
(3) —SH or —SR6;
(4) —C(O)2H, —C(O)qR6, —C(O)NR7R8, —C(O)C(O)NR7R8, or —O—C(O)qR6, where q is 1 or 2;
(5) —SO3H, —S(O)qR″6, or —S(O)qNR7R8,
(a) wherein R″6 is alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, heteroarylalkyl, heterocyclo, or heterocycloalkyl, each of which is unsubstituted or substituted with Z1, Z2 and one or more groups Z3;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NR7R8;
(10) —Z4—N(R9) —Z5—NR10R11;
(11) —Z4—N(R12) —Z5—R6;
(12) —P(O)(OR6)2;
R7, R8, R9, R10, R11 and R12 are each independently:
(1) hydrogen or R6;
(2) R7 and R8 together with the nitrogen atom to which they are attached may be a heterocycle which is unsubstituted or substituted with Z1, Z2 and Z3;
or
(3) any two of R9, R10 and R11 together with the nitrogen atoms to which they are attached may be a 3- to 12-membered saturated or unsaturated mono-, bi-, or tri-heterocyclic ring which is unsubstituted or substituted with Z1, Z2 and Z3;
Z1, Z2 and Z3 are each independently:
(1) hydrogen or Z6, where Z6 is (i) alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
(ii) a group (i) which is itself substituted by one or more of the same or different groups (i);
or (iii) a group (i) or (ii) which is substituted by one or more of the following groups (2) to (13);
(2) —OH or —OZ16;
(3) —SH or —SZ16;
(4) —C(O)2H, C(O)qZ16, —C(O)NZ17Z18, —C(O)C(O)NZ17Z18, or —O—C(O)qZ16, where q is 1 or 2;
(5) —SO3H, —S(O)qZ16, or —S(O)qNZ17Z18;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NZ17Z18;
(10) —Z4—N(Z18) —Z5—NZ19Z20;
(11) oxo;
(12) —O—C(O)—Z16;
(13) any two of Z1, Z2, and Z3 may together be alkylene, alkenylene, aryl, heteroaryl, or heterocyclo completing a 3- to 8-membered saturated or unsaturated ring together with the atoms to which they are attached;
Z4 and Z5 are each independently
(1) a single bond;
(2) —Z11—S(O)q—Z12—;
(3) —Z11—C(O)—Z12—;
(4) —Z11—O—Z12—;
(5) —Z11—S—Z12—;
(6) —Z11—O—C(O)—Z12—;
or
(7) —Z11—C(O)—O—Z12;
Z11 and Z12 are each independently
(1) a single bond;
(2) alkylene;
(3) alkenylene;
or
(4) alkynylene;
each Z16 is independently alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl, each optionally substituted with one or more of the following groups:
(2) —OH or —OZ21;
(3) —SH or —SZ21;
(4) —C(O)2H, C(O)qZ21, —C(O)NZ17Z18, —C(O)C(O)NZ17Z18, or —O—C(O)qZ21, where q is 1 or 2;
(5) —SO3H, —S(O)qZ21, or —S(O)qNZ17Z18;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NZ17Z18;
(10) —Z4—N(Z18) —Z5—NZ19Z20;
(11) oxo;
(12) —O—C(O)—Z21;
each Z17 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z18 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z19 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z20 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z21 is independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl, cycloalkenylalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkylaryl, cycloalkylaryl, heterocyclo, or heterocycloalkyl;
each Z22 is independently is,
(2) —OH or —OZ21;
(3) —SH or —SZ21;
(4) —C(O)2H, C(O)qZ21, —C(O)NZ21Z21, —C(O)C(O)NZ21Z21, or —O—C(O)qZ21, where q is 1 or 2;
(5) —SO3H, —S(O)qZ21, or —S(O)qNZ21Z21;
(6) halo;
(7) cyano;
(8) nitro;
(9) —Z4—NZ21Z21;
(10) —Z4—N(Z21) —Z5—NZ21Z21;
(11) oxo;
(12) —O—C(O)—Z21;
where Z17 and Z18, or Z19 and Z20, together with the nitrogen atom to which they are attached may be a heterocycle which is unsubstituted or substituted with 1, 2, or 3 independent Z22;
and
where any two of Z18, Z19 or Z20 together with the nitrogen atoms to which they are attached may be a 3- to 12-membered saturated or unsaturated mono-, bi-, or tri-heterocyclic ring which is unsubstituted or substituted with 1, 2, or 3 independent Z22;
provided said compound is other than a compound of formula IIa or IIb:

96 more elements

Facts

Application

13/349,222Filed 12 Jan 2012 · continuation

Priority

15 Sep 2006

Published

US 2012/0115866 A110 May 2012

Granted

3 Sep 2013

Term ends

Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07D 493/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 35/00
Antineoplastic agents
A61P 43/00
Drugs for specific purposes, not provided for in groups a61p1/00-a61p41/00
C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…

Family

Application60/844,902Us provisional application · filed 15 Sep 2006

PCT/US2007/020193Parent of this continuation · filed 14 Sep 2007

Application12/005,872Parent of this division · filed 28 Dec 2007

Application12/657,887Parent of this continuation · filed 28 Jan 2010

US 7,683,057 B2Parent of this division · filed 23 Mar 2010

Application13/108,598Parent of this continuation · filed 16 May 2011

US 8,039,470 B2Parent of this continuation · filed 18 Oct 2011

US 2012/0115866 A1Pre-grant publication · published 10 May 2012

Application12/657,887Parent of this division

Application12/005,872Parent of this continuation

US 2009/0076005 A1Published application

US 2010/0261665 A1Published application

US 2011/0224212 A1Published application

US 8,524,709 B2This patent

From the US filing history. Foreign family members aren’t listed.