US 9,808,447 B2
Inhibitors of Rho associated protein kinases (ROCK) and methods of use
Ernst Schonbrunn, Tampa, FL (US); Rongshi Li, Omaha, NE (US); and Said M. Sebti, Tampa, FL (US)
Assigned to H. Lee Moffitt Cancer Center and Research Institute, Inc., Tampa, FL (US)
Filed by H. Lee Moffitt Cancer Center and Research Institute, Inc., Tampa, FL (US)
Filed on Aug. 8, 2016, as Appl. No. 15/231,124.
Application 15/231,124 is a continuation of application No. 14/374,445, granted, now 9,409,868, previously published as PCT/US2013/022965, filed on Jan. 24, 2013.
Claims priority of provisional application 61/590,283, filed on Jan. 24, 2012.
Claims priority of provisional application 61/590,573, filed on Jan. 25, 2012.
Prior Publication US 2017/0049760 A1, Feb. 23, 2017
Int. Cl. A61K 31/4418 (2006.01); A61K 31/416 (2006.01); A61K 31/4409 (2006.01); A61K 31/4439 (2006.01); A61K 31/551 (2006.01); C07D 231/56 (2006.01); C07D 213/40 (2006.01); A61K 45/06 (2006.01); A61N 5/10 (2006.01); C07D 213/36 (2006.01)
CPC A61K 31/4418 (2013.01) [A61K 31/416 (2013.01); A61K 31/4409 (2013.01); A61K 31/4439 (2013.01); A61K 31/551 (2013.01); A61K 45/06 (2013.01); A61N 5/10 (2013.01); C07D 213/36 (2013.01); C07D 213/40 (2013.01); C07D 231/56 (2013.01)] 21 Claims
 
1. A method of reducing or inhibiting tumor growth in a subject with breast cancer, comprising: administering to the subject an effective amount of a composition comprising a compound having the chemical structure shown in Formula IV

OG Complex Work Unit Drawing
wherein
R is H, alkyl, acetyl, or heteroalkyl;
R1 is H, alkyl, acetyl, or heteroalkyl;
R8 and R9 are, independently of one another, H, —OH, acetyl, —C(O)NH2, alkyl, cycloalkyl, hereterocycloalkyl, aryl, or heteroaryl, wherein any one of the alkyl, cycloalkyl, hereterocycloalkyl, aryl, or heteroaryl groups is optionally substituted with one or more of —OH, —NO2, —NH2, —NR6R7, carbonyl, alkoxy, alkyl, —OCX3, —OCHX2, —OCH2X, or halogen, or both R8 together form a carbonyl; and
R10 is cycloalkyl, aryl, or heteroaryl, any of which is optionally substituted with one or more of —OH, —C(O)NH2, —C(O)CH3, —NO2, —NH2, —NR6R7, carbonyl, alkyl, alkoxy, alkylalkoxy, alkoxylalkoxy, halogenated alkoxyl, cycloalkyl, heterocycloalkyl, heteroarylcarbonyl, aryl, heteroaryl, —OCX3, —OCHX2, —OCH2X, —OSO2CH3, or -tosyl;
R6 and R7 are, independently, H, alkyl, —SO2CH3, —C(O)CH3, or —C(O)NH2;
X is independently H or halogen; and
n is 2 or 3,
or a pharmaceutically acceptable salt thereof.