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US 9,012,462 B2Granted
Phosphorous derivatives as kinase inhibitors
AssigneeARIAD Pharmaceuticals, Inc.
InventorsYihan Wang, Wei-Sheng Huang, Shuangying Liu, William C. Shakespeare, R. Mathew Thomas, Jiwei Qi, Feng Li, Xiaotian Zhu, Anna Kohlman, David C. Dalgarno, Jan Antoinette C. Romero, Dong Zou
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Abstract
The invention features compounds of the general formula (I) in which the variable groups are as defined herein, and to their preparation and use.
Claims72
A compound of the formula:
- wherein
- X1 is NRb1 or CRb;
- X3 is NRd1 or CRd;
- X4 is NRe1 or CRe;
- Ring A and Ring E are each an independently selected aryl or heteroaryl ring, the heteroaryl ring being a 5- or 6-membered ring containing 1 to 4 heteroatoms selected from N, O and S(O)r;
- each Ra, Rb, Rd, Re, and Rg is independently halo, —CN, —NO2, —R1, —OR2, —O—NR1R2, —NR1R2, —NR1—NR1R2, —NR1—OR2, —C(O)YR2, —OC(O)YR2, —NR1C(O)YR2, —SC(O)YR2, —NR1C(═S)YR2, —OC(═S)YR2, —C(═S)YR2, —YC(═NR1)YR2, —YC(═N—OR1)YR2, —YC(═N—NR1R2)YR2, —YP(═O)(YR3)(YR3), —Si(R3a)3, —NR1SO2R2, —S(O)1R2, —SO2NR1R2 or —NR1SO2NR1R2;
- provided that at least one of Ra and Rg is or includes —P(═O)(R3)2 or a ring system containing —P(═O)(R3)— as a ring member;
- and Rb1, Rd1 and Re1 are absent;
- or alternatively two adjacent substituents selected from Rd, Rd1, Re, and Re1, or two adjacent Ra form, with the atoms to which they are attached, a fused, 5-, 6- or 7-membered saturated, partially saturated or unsaturated ring, which contains 0-4 heteroatoms selected from N, O and S(O)r and which may bear up to four substituents;
- L is O or NH;
- r is 0, 1 or 2;
- s is 1, 2, 3, 4 or 5;
- p is 1, 2, 3 or 4;
- each Y is independently a bond, —O—, —S— or —NR1—;
- each R1 and R2 is independently H or an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, heterocyclic or heteroaryl;
- each R3 is independently an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, heterocyclic or heteroaryl, or two adjacent R3 combine to form a ring system including a phosphorous atom;
- each R3a is independently an alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroalkyl, heterocyclic, or heteroaryl;
- alternatively, each NR1R2 may be a 5-, 6- or 7-membered saturated, partially saturated or unsaturated ring, which can be optionally substituted and which contains 0-2 additional heteroatoms selected from N, O and S(O)r;
- and
- each of the foregoing alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, cycloalkynyl, aryl, heteroaryl and heterocyclic is optionally substituted,
- or a pharmaceutically acceptable salt thereof.
18 more elements
Dependencies are inferred from the claim text.