	US 7,514,564 B2
	Substituted amine derivatives and methods of use
Guoqing Chen, Thousand Oaks, Calif. (US); Jeffrey Adams, Thousand Oaks, Calif. (US); Jean Bemis, Arlington, Mass. (US); Lucian Di Pietro, Gloucester, Mass. (US); Celia Dominguez, Thousand Oaks, Calif. (US); Daniel Elbaum, Newton, Mass. (US); Julie Germain, Somerville, Mass. (US); Qi Huang, Moorpark, Calif. (US); Joseph L. Kim, Wayland, Mass. (US); Xiaohu Ouyang, Flushing, N.Y. (US); Vinod F. Patel, Acton, Mass. (US); Leon M. Smith, Somerset, N.J. (US); Andrew Tasker, Simi Valley, Calif. (US); Ning Xi, Thousand Oaks, Calif. (US); Shimin Xu, Newbury Park, Calif. (US); Chester Chenguang Yuan, Newbury Park, Calif. (US); Michael Croghan, Ventura, Calif. (US); and Tae-Seong Kim, Thousand Oaks, Calif. (US)
Assigned to Amgen Inc., Thousand Oaks, Calif. (US)
Filed on May 02, 2006, as Appl. No. 11/417,329.
Application 11/417329 is a division of application No. 10/046622, filed on Jan. 10, 2002, granted, now 7,105,682.
Claims priority of provisional application 60/261882, filed on Jan. 12, 2001.
Claims priority of provisional application 60/323808, filed on Sep. 19, 2001.
Prior Publication US 2006/0194848 A1, Aug. 31, 2006
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 211/94 (2006.01); C07D 211/98 (2006.01); A61K 31/44 (2006.01)

U.S. Cl. 546—304 [546/290; 546/296; 546/297; 546/300; 546/301; 546/302; 546/303; 546/312; 514/345; 514/349; 514/352]

15 Claims

1. A method of therapeutic treatment of cancer in a subject, said method comprising administering an effective amount of a compound of Formula I

wherein each of A¹and A²is C;

wherein ring A is pyridyl

wherein X is

wherein Z is oxygen or sulfur;

wherein R is Substituted or unsubstituted fused 9-14-membered bicyclic or tricyclic heterocyclyl;

wherein substituted R is substituted with one or more substituents independently selected from halo, —OR³, —SR³, —SO₂R³, —CO₂R³, —CONR³R³, —COR³, —NR³R³, —SO₂NR³R³, —NR³C(O)OR³, —NR³C(O)R³, cycloalkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted phenyl, nitro, alkylaminoalkoxyalkoxy, cyano, alkylaminoalkoxy, lower alkyl substituted with R², lower alkenyl substituted with R², and lower alkynyl substituted with R²;

wherein R¹is selected from

a) substituted or unsubstituted 6-10 membered aryl,

b) substituted or unsubstituted 4-6 membered heterocyclyl,

c) substituted or unsubstituted 9-14 membered bicyclic or tricyclic heterocyclyl,

d) cycloalkyl, and

e) cycloalkenyl,

wherein substituted R¹is substituted with one or more substituents independently selected from halo, —OR³, —SR³, —CO₂R³, —CONR³R³, —COR³, —NR³R³, —NH(C₁-C₄alkylenylR¹⁴), —SO₂R³, —SO₂NR³R³, —NR³C(O)OR³, —NR³C(O)R³, optionally substituted cycloalkyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted phenyl, halosulfonyl, cyano, alkylaminoalkoxy, alkylaminoalkoxyalkoxy, nitro, lower alkyl substituted with R², lower alkenyl substituted with R², and lower alkynyl substituted with R²;

wherein R²is one or more substituents independently selected from H, halo, —OR³, oxo, —SR³, —CO₂R³, —COR³, —CONR³R³, —NR³R³, —SO₂NR³R³, —NR³C(O)0R³, —NR³C(O)R³, cycloalkyl, optionally substituted phenylalkylenyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted heteroarylalkylenyl, optionally substituted phenyl, lower alkyl, cyano, lower hydroxyalkyl, lower carboxyalkyl, nitro, lower alkenyl, lower alkynyl, lower aminoalkyl, lower alkylaminoalkyl and lower haloalkyl;

wherein R³is selected from H, lower alkyl, optionally substituted phenyl, optionally substituted 4-6 membered heterocyclyl, optionally substituted C₃-C₆-cycloalkyl, optionally substituted phenylalkyl, optionally substituted 4-6 membered heterocyclylalkyl, optionally substituted C₃-C₆cycloalkylalkyl, and lower haloalkyl;

wherein R⁴is selected from a direct bond, C_2-4-alkylenyl, C_2-4-alkenylenyl and C_2-4-alkynylenyl, where one of the CH₂groups may be replaced with an oxygen atom or an —NH—, wherein R⁴is optionally substituted with hydroxy;

wherein R⁵is selected from H, lower alkyl, optionally substituted phenyl and optionally substituted lower aralkyl;

wherein R^5ais selected from H, lower alkyl, optionally substituted phenyl and lower aralkyl;

wherein R¹⁴is selected from H, optionally substituted phenyl, optionally substituted 4-6 membered heterocyclyl and optionally substituted C₃-C₆cycloalkyl;

and pharmaceutically acceptable salts thereof.