	US 12,150,934 B2
	Methods of using substituted pyrazole and pyrazole compounds and for treatment of hyperproliferative diseases
Arshad M. Siddiqui, Newton, MA (US); Stephane Ciblat, Montreal (CA); Lea Constantineau-Forget, Montreal (CA); Chantal Grand-Maitre, Boisbriand (CA); Xiangyu Guo, Montreal (CA); Sanjay Srivastava, Pierrefonds (CA); Gerald W. Shipps, Boston, MA (US); Alan B. Cooper, Kenilworth, NJ (US); Vibha Oza, Acton, MA (US); Matthew W. Kostura, Hillsborough, NC (US); Michael Luther, Andover, MA (US); and Jedd Levine, Litchfield, CT (US)
Assigned to Bantam Pharmaceutical, LLC, New York, NY (US)
Appl. No. 16/465,137
Filed by Bantam Pharmaceutical, LLC, New York, NY (US)
PCT Filed Nov. 29, 2017, PCT No. PCT/US2017/063772 § 371(c)(1), (2) Date May 29, 2019, PCT Pub. No. WO2018/102452, PCT Pub. Date Jun. 7, 2018.
Claims priority of provisional application 62/428,274, filed on Nov. 30, 2016.
Prior Publication US 2020/0069656 A1, Mar. 5, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/427 (2006.01); A61K 31/4155 (2006.01); A61K 31/437 (2006.01); A61K 31/4439 (2006.01); A61K 31/454 (2006.01); A61K 31/506 (2006.01); A61K 31/519 (2006.01); A61K 31/5377 (2006.01); A61P 35/00 (2006.01)

CPC A61K 31/427 (2013.01) [A61K 31/437 (2013.01); A61K 31/4439 (2013.01); A61K 31/454 (2013.01); A61K 31/506 (2013.01); A61K 31/519 (2013.01); A61K 31/5377 (2013.01); A61P 35/00 (2018.01)]

31 Claims

1. A method for treating a hematopoietic cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound having the structural formula

wherein

L¹is —S—, —S(O)— or —S(O)₂—;

R¹is unsubstituted or fluorinated C₁-C₈alkyl, unsubstituted or fluorinated C₁-C₈alkenyl and unsubstituted or fluorinated C₁-C₈alkynyl;

L²is a bond;

Q is —COOH;

L³is a bond;

R³is phenyl or monocyclic heteroaryl optionally substituted with 1-5 R^3E,

in which

each R^3Eis independently selected from oxo, optionally-substituted C_1-4alkyl, C₁-C₄fluoroalkyl, halogen, —CN, SF₅, —N₃, —C(O)R^3F, —SR^3F, —S(O)_1-2R^3F, —OR^3F, —NR^3GR^3F, —C(O)R^3F, —C(O)NR^3GR^3F, —NR^3GC(O)R^3F, —C(S)NR^3GR^3F, —NR^3GC(S)R^3F, —C(O)OR^3F, —OC(O)R^3F, —C(O)SR^3F, —SC(O)R^3F, —C(S)OR^3F, —OC(S)R^3F, —C(S)SR^3F, —SC(S)R^3F, —S(O)_1-2OR^3F, —OS(O)_1-2R^3F, —S(O)_1-2NR^3GR^3F, —NR^3GS(O)_1-2R^3F;

each R^3Fis independently selected from H, C₁-C₃alkyl and C₁-C₃fluoroalkyl and

each R^3Gis independently selected from H and C₁-C₃alkyl, C₁-C₃fluoroalkyl;

L⁴is a bond;

R⁴is selected from the group consisting of unsubstituted or fluorinated C₁-C₈alkyl, unsubstituted or fluorinated C₁-C₈alkenyl and unsubstituted or fluorinated C₁-C₈alkynyl,

L⁵is a bond;

R⁵is phenyl or monocyclic heteroaryl each optionally substituted with 1-5 R^5E,

in which

each R^5Eis independently selected from oxo, optionally-substituted C₁-C₄alkyl, C₁-C₄fluoroalkyl, halogen, —CN, —SF₅, —N₃, —C(O)R^5F, —SR^5F, —S(O)_1-2R^5F, —OR^5F, —NR^5GR^5F, —C(O)R^5F, —C(O)NR^5GR^5F, —NR^5GC(O)R^5F, —C(S)NR^5GR^5F, —NR^1GC(S)R^5F, —C(O)OR^5F, —OC(O)R^5F, —C(O)SR^5F, —SC(O)R^5F, —C(S)OR^5F, —OC(S)R^5F, —C(S)SR^5F, —SC(S)R^5F, —S(O)_1-2OR^5F, —OS(O)_1-2R^5F, —S(O)_1-2NR^5GR^5Fand —NR^5GS(O)_1-2R^5F;

each R^5Fis independently selected from H, C₁-C₃alkyl and C₁-C₃fluoroalkyl and

each R^5Gis independently selected from H and C₁-C₃alkyl;

wherein

each optionally substituted alkyl, alkenyl and alkynyl is unsubstituted, fluorinated or substituted with one or two hydroxyl groups;

each cycloalkyl has 3-10 ring carbons and is unsaturated or partially unsaturated, and optionally includes one or two fused cycloalkyl rings, each fused ring having 3-8 ring members;

each heterocycloalkyl has 3-10 ring members and 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur and is unsaturated or partially unsaturated, and optionally includes one or two fused cycloalkyl rings, each having 3-8 ring members;

each heteroaryl is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur or a 8-10 membered bicyclic heteroaryl having 1-5 heteroatoms independently selected from nitrogen, oxygen or sulfur, and optionally includes one or two fused cycloalkyl or heterocycloalkyl rings, each fused cycloalkyl or heterocycloalkyl ring having 4-8 ring members,

the compound being optionally in the form of a pharmaceutically acceptable salt or N-oxide, or a solvate or hydrate.