| US 7,595,399 B2 | ||
| Tyrosine derivatives | ||
| David Y. Jackson, San Bruno, Calif. (US); Frederick C. Sailes, Stone Mountain, Ga. (US); and Daniel P. Sutherlin, San Carlos, Calif. (US) | ||
| Assigned to Genentech, Inc., South San Francisco, Calif. (US) | ||
| Filed on Feb. 04, 2004, as Appl. No. 10/772,678. | ||
| Application 10/772678 is a continuation of application No. 10/198328, filed on Jul. 16, 2002, abandoned. | ||
| Application 10/198328 is a continuation of application No. 09/669779, filed on Sep. 25, 2000, granted, now 6,469,047. | ||
| Claims priority of provisional application 60/156062, filed on Sep. 24, 1999. | ||
| Prior Publication US 2004/0158076 A1, Aug. 12, 2004 | ||
| Int. Cl. C07D 211/06 (2006.01); C07D 295/027 (2006.01); C07D 217/12 (2006.01) | ||
| U.S. Cl. 544—162 [544/398; 546/16; 546/149; 546/194; 564/155] | 20 Claims |
1. A compound of the formula I:
![]() Z is H or lower alkyl;
A has the structure:
![]() q is 0-3;
R1, R2, R3, R4, R5 and R6 independently are hydrogen, alkyl, amino, alkylamino, dialkylamino, nitro, urea, cyano, thio, alkylthio, hydroxy, alkoxy,
alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylamino, aryloxycarbonylamino, alkylsulfinyl, sulfonyl, alkylsulfonyl, aralkylsulfonyl,
arylsulfonyl, heteroarylsulfonyl, alkanoyl, alkanoylamino, cycloalkanoylamino, aryl, arylalkyl, halogen, or alkylphosphonyl,
and R1, R2, R3, R4 and R5 are substituted with 0-3 substituents selected from the group consisting of hydroxy, carboxyl, lower alkoxycarbonyl, lower
alkyl, nitro, oxo, cyano, carbocyclyl, heterocyclyl, heteroaryl, lower alkylthio, lower alkoxy, lower alkylamino, lower alkanoylamino,
lower alkylsulfinyl, lower sulfonyl, lower alkylsulfonyl, lower alkanoyl, aryl, aroyl, heterocyclylcarbonyl, halogen and lower
alkylphosphonyl; or two of R1 to R5 together form a carbocycle or heterocyclic ring; provided that R1 or R5 is not hydrogen;
Y is H, OH, alkoxy, alkoxyalkoxy, aryloxy, alkylaminoalkoxy, dialkylaminoalkoxy, alkylamino, arylamino, heterocyclyl or heteroarylalkyl,
where each of the forgoing may be substituted or unsubstituted;
X1 is C(O)NRaRb wherein Ra and Rb, individually, is hydrogen or alkyl, alkoxy, aryl, heterocyclyl, heteroaryl, substituted with
0-4 substituents selected from the group consisting of halogen, hydroxy, amino, carboxyl, nitro, cyano, heterocylyl, heteroaryl,
aryl, aroyl, aryloxy, aralkyl, aralkyloxy, aryloxycarbonyl, aralkyloxycarbonyl, alkylenedioxy, lower alkoxycarbonyl, lower
alkyl, lower alkenyl, lower alkynyl, lower alkylthio, lower alkoxy, lower alkylamino, lower alkylsulfinyl, lower sulfonyl,
lower alkylsulfonyl, lower alkanoyl, lower alkylphosphonyl, aminosulfonyl lower alkyl, hydroxy lower alkyl, alkylsulfinyl
lower alkyl, alkylsulfonyl lower alkyl, alkylthio lower alkyl, heteroarylthio lower alkyl, heteroaryloxy lower alkyl, heteroarylamino
lower alkyl, halo lower alkyl, and alkoxy lower alkyl; wherein said heterocyclyl, heteroaryl, aryl, aroyl, aryloxy, aralkyl,
aralkyloxy, aryloxycarbonyl and aralkyloxycarbonyl substituent is optionally substituted with halogen, hydroxyl, amino, carboxyl,
nitro, cyano, alkyl and alkoxy; and wherein Ra and Rb together with the nitrogen to which they are attached form a heterocyclyl
or heteroaryl group substituted with 0-5 substituents R or Rd; wherein Rd has the structure
![]() R is hydrogen or alkyl, alkoxy, aryl, heterocyclyl or heteroaryl, substituted with 0-4 substituents selected from the group
consisting of halogen, hydroxy, amino, carboxyl, nitro, cyano, heterocylyl, heteroaryl, aryl, aroyl, aryloxy, aralkyl, aralkyloxy,
aryloxycarbonyl, aralkyloxycarbonyl, alkylenedioxy, lower alkoxycarbonyl, lower alkyl, lower alkenyl, lower alkynyl, lower
alkylthio, lower alkoxy, lower alkylamino, lower alkylsulfinyl, lower sulfonyl, lower alkylsulfonyl, lower alkanoyl, lower
alkylphosphonyl, aminosulfonyl lower alkyl, hydroxy lower alkyl, alkylsulfinyl lower alkyl, alkylsulfonyl lower alkyl, alkylthio
lower alkyl, heteroarylthio lower alkyl, heteroaryloxy lower alkyl, heteroarylamino lower alkyl, halo lower alkyl, and alkoxy
lower alkyl; wherein said heterocyclyl, heteroaryl, aryl, aroyl, aryloxy, aralkyl, aralkyloxy, aryloxycarbonyl and aralkyloxycarbonyl
substituent is optionally substituted with halogen, hydroxyl, amino, carboxyl, nitro, cyano, alkyl and alkoxy;
X2 and X3 are each independently hydrogen, halogen, hydroxy, amino, carboxyl, nitro, cyano, or substituted or unsubstituted alkyl, aryl,
heterocylyl, heteroaryl, aryl, aroyl, aryloxy, alkylenedioxy, lower alkyl carbonylamino, lower alkenyl carbonylamino, aryl
carbonylamino, arylalkyl carbonylamino, lower alkoxy carbonylamino, lower alkylamino carbonylamino, arylamino carbonylamino,
lower alkoxycarbonyl, lower alkyl, lower alkenyl, lower alkynyl, lower alkylthio, lower alkoxy, lower alkylamino, lower alkylsulfinyl,
lower sulfonyl, lower alkylsulfonyl, lower alkanoyl, lower alkylphosphonyl, aminosulfonyl lower alkyl, hydroxy lower alkyl,
alkylsulfinyl lower alkyl, alkylsulfonyl lower alkyl, alkylthio lower alkyl, heteroarylthio lower alkyl, heteroaryloxy lower
alkyl, heteroarylamino lower alkyl, halo lower alkyl, alkoxy lower alkyl; and wherein X1 and X2 or X3 may be bonded together to form a heterocylic or heteroaryl ring(s); or
X3 and Z together form a heterobicyclic ring;or a pharmaceutically acceptable salt thereof.
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