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US 2017/0320853 A1Published application
Uracil derivatives as axl and c-met kinase inhibitors
AssigneeIgnyta, Inc.
InventorsReddeppa Reddy DANDU, Robert L. HUDKINS, Kurt A. JOSEF, Catherine P. PROUTY, Rabindranath TRIPATHY
Life of this patent
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Abstract
The present invention provides compounds of Formula I or pharmaceutically acceptable salt forms thereof, wherein Ra, Rb, Rc, Rd, D, W, R1a, R1b, R1c,Y, R3, X, E and G are as defined herein, methods of treatment and uses thereof.
Claims6
(canceled)
A compound of the formula:
- wherein G is chosen from H, C1-6alkyl optionally substituted by 1-6 R19, C2-6alkenyl optionally substituted by 1-6 R19, C2-6alkynyl optionally substituted by 1-6 R19, C6-11aryl optionally substituted by 1-6 R19, C3-11cycloalkyl optionally substituted by 1-6 R19, 3-15 membered heterocyclyl optionally substituted by 1-6 R19, 5-15 membered heteroaryl optionally substituted by 1-6 R19, —C(═O)R20, —C(═O)OR20, —C(═O)NR22R23, —S(═O)2R20, and —S(═O)2NR22R23;
- R19 at each occurrence is independently chosen from C1-6alkyl optionally substituted by 1-6 R39, C2-6alkenyl optionally substituted by 1-6 R39, C2-6alkynyl optionally substituted by 1-6 R39, C6-11aryl optionally substituted by 1-6 R39, C3-11cycloalkyl optionally substituted by 1-6 R39, 3-15 membered heterocyclyl optionally substituted by 1-6 R39, 5-15 membered heteroaryl optionally substituted by 1-6 R39, halogen, —CN, —C(═O)R30, —C(═O)OR30, —C(═O)NR32R33, —NO2, —NR32R33, —NR34C(═O)R30, —NR34C(═O)OR31, —NR34C(═O)NR32R33, —NR34S(═O)2R31, —NR34S(═O)2NR32R33, —OR30, ═O, —OC(═O)R30, —OC(═O)NR32R33, —OC(═O)OR30, —S(═O)nR30, and —S(═O)2NR32R33;
- R20 at each occurrence is independently chosen from H, C1-6alkyl optionally substituted by 1-6 R49, C2-6alkenyl optionally substituted by 1-6 R49, C2-6alkynyl optionally substituted by 1-6 R49, C6-11aryl optionally substituted by 1-6 R49, C3-11cycloalkyl optionally substituted by 1-6 R49, 3-15 membered heterocyclyl optionally substituted by 1-6 R49, and 5-15 membered heteroaryl optionally substituted by 1-6 R49;
- R22, R23, R32 and R33 at each occurrence is independently chosen from H, C1-6alkyl optionally substituted by 1-6 R59, C2-6alkenyl optionally substituted by 1-6 R59, C2-6alkynyl optionally substituted by 1-6 R59, C6-11aryl optionally substituted by 1-6 R59, C3-11cycloalkyl optionally substituted by 1-6 R59, 3-15 membered heterocyclyl optionally substituted by 1-6 R59, and 5-15 membered heteroaryl optionally substituted by 1-6 R59;
- or any R22 and R23 and/or R32 and R33 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocyclyl optionally substituted by 1-6 R69 or a 5-15 membered heteroaryl optionally substituted by 1-6 R69;
- R30, R31, and R34 at each occurrence is independently chosen from H, C1-6alkyl optionally substituted by 1-6 R49, C2-6alkenyl optionally substituted by 1-6 R49, C2-6alkynyl optionally substituted by 1-6 R49, C6-11aryl optionally substituted by 1-6 R49, C3-11cycloalkyl optionally substituted by 1-6 R49, 3-15 membered heterocyclyl optionally substituted by 1-6 R49, and 5-15 membered heteroaryl optionally substituted by 1-6 R49;
- R39 and R49 at each occurrence is independently chosen from C1-6alkyl optionally substituted by 1-6 R79, C2-6alkenyl optionally substituted by 1-6 R79, C2-6alkynyl optionally substituted by 1-6 R79, C6-11aryl optionally substituted by 1-6 R79, C3-11cycloalkyl optionally substituted by 1-6 R79, 3-15 membered heterocyclyl optionally substituted by 1-6 R79, 5-15 membered heteroaryl optionally substituted by 1-6 R79, halogen, —CN, —C(═O)R70, —C(═O)OR70, —C(═O)NR72R73, —NO2, —NR72R73, —NR74C(═O)R70, —NR74C(═O)OR71, —NR74C(═O)NR72R73, —NR74S(═O)2R71, —NR74S(═O)2NR72R73, —OR70, ═O, —OC(═O)R70, —OC(═O)NR72R73, —S(═O)nR70, and —S(═O)2NR72R73;
- R59 and R69 at each occurrence is independently chosen from C1-6alkyl optionally substituted by 1-6 R79, C2-6alkenyl optionally substituted by 1-6 R79, C2-6alkynyl optionally substituted by 1-6 R79, C6-11aryl optionally substituted by 1-6 R79, C3-11 cycloalkyl optionally substituted by 1-6 R79, 3-15 membered heterocyclyl optionally substituted by 1-6 R79, 5-15 membered heteroaryl optionally substituted by 1-6 R79, halogen, —CN, —C(═O)R70, —C(═O)OR70, —C(═O)NR72R73, —NO2, —NR72R73, —NR74C(═O)R70, —NR74C(═O)OR71, —NR74C(═O)NR72R73, —NR74S(═O)2R71, —NR74S(═O)2NR72R73, —OR70, ═O, —OC(═O)R70, —OC(═O)NR72R73, —S(═O)nR70, and —S(═O)2NR72R73;
- R70, R71, R72, R73, and R74 at each occurrence is independently chosen from H, C1-6alkyl and C1-6-haloalkyl;
- R79 at each occurrence is independently chosen from C1-6alkyl, C1-6-haloalkyl, benzyl, halogen, —CN, —C(═O)(C1-6alkyl), —C(═O)O(C1-6alkyl), —C(═O)N(C1-6alkyl)2, —C(═O)OH, —C(═O)NH2, —C(═O)NHC1-6alkyl, —NO2, —NH2, —NHC1-6alkyl, —N(C1-6alkyl)2, —NHC(═O)C1-6alkyl, —NHS(═O)2C1-6alkyl, —OH, —OC1-6alkyl, ═O, —OC(═O)C1-6alkyl, —OS(═O)2C1-6alkyl, —S(═O)2C1-6alkyl, and —S(═O)2N(C1-6alkyl)2;
- and
- n at each occurrence is independently chosen from 0, 1, and 2.
9 more elements
A compound of the formula:
- wherein G is chosen from H, C1-6alkyl optionally substituted by 1-6 R19, C2-6alkenyl optionally substituted by 1-6 R19, C2-6alkynyl optionally substituted by 1-6 R19, C6-11aryl optionally substituted by 1-6 R19, C3-11cycloalkyl optionally substituted by 1-6 R19, 3-15 membered heterocyclyl optionally substituted by 1-6 R19, 5-15 membered heteroaryl optionally substituted by 1-6 R19, —C(═O)R20, —C(═O)OR20, —C(═O)NR22R23, —S(═O)2R20, and —S(═O)2NR22R33;
- R19 at each occurrence is independently chosen from C1-6alkyl optionally substituted by 1-6 R39, C2-6alkenyl optionally substituted by 1-6 R39, C2-6alkynyl optionally substituted by 1-6 R39, C6-11aryl optionally substituted by 1-6 R39, C3-11cycloalkyl optionally substituted by 1-6 R39, 3-15 membered heterocyclyl optionally substituted by 1-6 R39, 5-15 membered heteroaryl optionally substituted by 1-6 R39, halogen, —CN, —C(═O)R30, —C(═O)OR30, —C(═O)NR32R33, —NO2, —NR32R33, —NR34C(═O)R30, —NR34C(═O)OR31, —NR34C(═O)NR32R33, —NR34S(═O)2R31, —NR34S(═O)2NR32R33, —OR30, ═O, —OC(═O)R30, —OC(═O)NR32R33, —OC(═O)OR30, —S(═O)nR30, and —S(═O)2NR32R33;
- R20 at each occurrence is independently chosen from H, C1-6alkyl optionally substituted by 1-6 R49, C2-6alkenyl optionally substituted by 1-6 R49, C2-6alkynyl optionally substituted by 1-6 R49, C6-11aryl optionally substituted by 1-6 R49, C3-11cycloalkyl optionally substituted by 1-6 R49, 3-15 membered heterocyclyl optionally substituted by 1-6 R49, and 5-15 membered heteroaryl optionally substituted by 1-6 R49;
- R22, R23, R32 and R33 at each occurrence is independently chosen from H, C1-6alkyl optionally substituted by 1-6 R59, C2-6alkenyl optionally substituted by 1-6 R59, C2-6alkynyl optionally substituted by 1-6 R59, C6-11aryl optionally substituted by 1-6 R59, C3-11cycloalkyl optionally substituted by 1-6 R59, 3-15 membered heterocyclyl optionally substituted by 1-6 R59, and 5-15 membered heteroaryl optionally substituted by 1-6 R59;
- or any R22 and R23 and/or R32 and R33 may form, together with the nitrogen atom to which they are attached, a 3-15 membered heterocyclyl optionally substituted by 1-6 R69 or a 5-15 membered heteroaryl optionally substituted by 1-6 R69;
- R30, R31, and R34 at each occurrence is independently chosen from H, C1-6alkyl optionally substituted by 1-6 R49, C2-6alkenyl optionally substituted by 1-6 R49, C2-6alkynyl optionally substituted by 1-6 R49, C6-11aryl optionally substituted by 1-6 R49, C3-11cycloalkyl optionally substituted by 1-6 R49, 3-15 membered heterocyclyl optionally substituted by 1-6 R49, and 5-15 membered heteroaryl optionally substituted by 1-6 R49;
- R39 and R49 at each occurrence is independently chosen from C1-6alkyl optionally substituted by 1-6 R79, C2-6alkenyl optionally substituted by 1-6 R79, C2-6alkynyl optionally substituted by 1-6 R79, C6-11aryl optionally substituted by 1-6 R79, C3-11cycloalkyl optionally substituted by 1-6 R79, 3-15 membered heterocyclyl optionally substituted by 1-6 R79, 5-15 membered heteroaryl optionally substituted by 1-6 R79, halogen, —CN, —C(═O)R70, —C(═O)OR70, —C(═O)NR72R73, —NO2, —NR72R73, —NR74C(═O)R70, —NR74C(═O)OR71, —NR74C(═O)NR72R73, —NR74S(═O)2R71, NR74S(═O)2NR72R73, —OR70, ═O, —OC(═O)R70, —OC(═O)NR72R73, —S(═O)nR70, and —S(═O)2NR72R73;
- R59 and R69 at each occurrence is independently chosen from C1-6alkyl optionally substituted by 1-6 R79, C2-6alkenyl optionally substituted by 1-6 R79, C2-6alkynyl optionally substituted by 1-6 R79, C6-11aryl optionally substituted by 1-6 R79, C3-11cycloalkyl optionally substituted by 1-6 R79, 3-15 membered heterocyclyl optionally substituted by 1-6 R79, 5-15 membered heteroaryl optionally substituted by 1-6 R79, halogen, —CN, —C(═O)R70, —C(═O)OR70, —C(═O)NR72R73, —NO2, —NR72R73, —NR74C(═O)R70, —NR74C(═O)OR71, —NR74C(═O)NR72R73, —NR74S(═O)2R71, NR74S(═O)2NR72R73, —OR70, ═O, —OC(═O)R70, —OC(═O)NR72R73, —S(═O)nR70, and —S(═O)2NR72R73;
- R70, R71, R72, R73, and R74 at each occurrence is independently chosen from H, C1-6alkyl and C1-6-haloalkyl;
- R79 at each occurrence is independently chosen from C1-6alkyl, C1-6-haloalkyl, benzyl, halogen, —CN, —C(═O)(C1-6alkyl), —C(═O)O(C1-6alkyl), —C(═O)N(C1-6alkyl)2, —C(═O)OH, —C(═O)NH2, —C(═O)NHC1-6alkyl, —NO2, —NH2, —NHC1-6alkyl, —N(C1-6alkyl)2, —NHC(═O)C1-6alkyl, —NHS(═O)2C1-6alkyl, —OH, —OC1-6alkyl, ═O, —OC(═O)C1-6alkyl, —OS(═O)2C1-6alkyl, —S(═O)2C1-6alkyl, and —S(═O)2N(C1-6alkyl)2;
- and
- n at each occurrence is independently chosen from 0, 1, and 2.
9 more elements
Dependencies are inferred from the claim text.