Claims for Patent: 10,696,660

Summary for Patent: 10,696,660

Title:	Rho kinase inhibitors
Abstract:	The invention relates to inhibitors of ROCK1 and/or ROCK2. Also provided are methods of treating diseases and disorders involving inhibiting ROCK1 and/or ROCK2.
Inventor(s):	Poyurovsky; Masha V. (New York, NY), Kim; Ji-In (Princeton, NJ), Liu; Kevin G. (West Windsor, NJ), Zanin-Zhorov; Alexandra (Staten Island, NY)
Assignee:	Kadmon Corporation, LLC (New York, NY)
Application Number:	16/251,952
Patent Claims:	1. A method for the treatment of graft-versus-host disease (GVHD) in a human subject by orally administering a therapeutically effective amount of a compound of the formula XXXI: ##STR00221## or a pharmaceutically acceptable salt thereof, wherein: R.sup.13 and R.sup.14 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), --(C.sub.1-C.sub.6 alkyl)-NR.sup.16R.sup.17, --(C.sub.1-C.sub.6 alkyl)-C(.dbd.O)NR.sup.16R.sup.17, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.13 and R.sup.14 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, C.sub.3-C.sub.7 cycloalkyl, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; X is selected from a covalent bond, 0, NH, and C.sub.1-C.sub.6 alkyl; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; each R.sup.2 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; each R.sup.3 is independently selected from the group consisting of lower alkyl, CN, halo, hydroxy, lower alkoxy, amino, and perfluoro lower alkyl; n is selected from 0 to 4; and m is selected from 0 to 3. 2. The method according to claim 1, wherein the compound has formula XXXIV.sub.a: ##STR00222## or a pharmaceutically acceptable salt thereof, wherein: R.sup.13 and R.sup.14 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C(.dbd.O)NR.sup.16R.sup.17, aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.3-C.sub.7 cycloalkyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.13 and R.sup.14 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; R.sup.16 and R.sup.17 are independently selected from the group consisting of H, C.sub.1-C.sub.8 alkyl, C.sub.2-C.sub.8 alkenyl, C.sub.2-C.sub.8 alkynyl, --(C.sub.1-C.sub.6 alkyl)-O--(C.sub.1-C.sub.6 alkyl), aryl, aralkyl, heteroaryl, C.sub.3-C.sub.7 cycloalkyl, a three to twelve membered heterocyclic ring containing up to 3 heteroatoms, each of which may be optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl; or R.sup.16 and R.sup.17 may be taken together to form a three to twelve membered heterocyclic ring having up to 3 heteroatoms which is optionally substituted by from 1 to 3 substituents independently selected from halo, C.sub.1-C.sub.6 alkyl, C.sub.2-C.sub.6 alkenyl, C.sub.1-C.sub.6 alkoxy, oxo, hydroxy, amino, cyano and C.sub.1-C.sub.3 perfluoro alkyl. 3. The method according to claim 1, wherein the compound has of the formula: ##STR00223## or a pharmaceutically acceptable salt thereof.