US 6,982,265 B1 | ||
Pyrrolotriazine inhibitors of kinases | ||
John T. Hunt, Princeton, N.J. (US); Rajeev S. Bhide, Langhorne, Pa. (US); Robert Michael Borzilleri, New Hope, Pa. (US); and Ligang Qian, Hopewell, N.J. (US) | ||
Assigned to Bristol Myers Squibb Company, Princeton, N.J. (US) | ||
Filed on May 18, 2000, as Appl. No. 9/573,829. | ||
Claims priority of provisional application 60/135265, filed on May 21, 1999. | ||
Claims priority of provisional application 60/193727, filed on Mar. 31, 2000. | ||
This patent is subject to a terminal disclaimer. | ||
Int. Cl. C07D 487/04 (2006.01); A61K 31/153 (2006.01); A61P 35/00 (2006.01); A61P 27/02 (2006.01); A61P 29/00 (2006.01) |
U.S. Cl. 514—243 | 9 Claims |
1. A compound of formula I ![]() its enantiomers, diastereomers, and pharmaceutically acceptable salts, prodrugs and solvates thereof, wherein X and Y are independently O, OCO, S, SO SO2, CO, CO2, NR10, NR11CO, NR12CONR13, NR14CO2, NR15SO2, NR15SO2, NR16SO2NR17, SO2NR18, CONR19, halogen, nitro, cyano, or X or Y are absent;
Z is O, S, N, or CR20;
R1 is hydrogen, CH3, OH, OCH3, SH, SCH3, OCOR21, SOR22, SO2R23, SO2NR24R25, CO2R26, CONR27R28, NH2, NR29SO2NR30R31, NR32SO2R33, NR34COR35, NR36CO2R37, NR38CONR39R40, halogen, nitro, or cyano;
R2 and R3 are independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted
aryl, heterocyclo, substituted heterocyclo, aralkyl, substituted aralkyl, heterocycloalkyl or substituted heterocycloalkyl,
or when X is halo, nitro or cyano R2 is absent or when Y is halo, nitro or cyano R3 is absent;
R4 is alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, aralkyl, substituted aralkyl;
R5 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, aralkyl, or substituted
aralkyl;
or R4 and R5 may together form an optionally substituted monocyclic 5–7 membered saturated or unsaturated carbocyclic or heterocyclic ring,
or an optionally substituted bicyclic 7–11 membered saturated or unsaturated heterocyclic ring, except that when Z is O or
S, R5 is absent;
R6 is hydrogen, alkyl, substituted alkyl, substituted aryl, heterocyclo, substituted heterocyclo, NR7R8, OR9 or halogen;
R7 is selected from the group consisting of hydrogen, C2–C20 alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, and substituted heterocyclo,
R8, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R21, R24, R25, R26, R27, R28, R29, R30, R31, R32, R34, R35, R36, R38, R39 and R40 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo,
and substituted heterocyclo,
R22, R23, R33 and R37 are independently selected from the group consisting of alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, and
substituted heterocyclo; and
R20 is selected from the group consisting of hydrogen, lower alkyl and substituted alkyl, or R20 is absent if the carbon to which it is attached is part of an unsaturated aryl or heteroaryl ring;
with the provisos that:
a. R2 may not be hydrogen if X is SO, SO2, NR13CO2, or NR14SO2,
b. R3 may not be hydrogen if Y is SO, SO2, NR13 CO2, or NR14SO2.
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