US 11,999,721 B2
Pyrazole compounds and uses thereof
Dansu Li, Warrington, PA (US); Irit Snir-Alkalay, Mevasseret Zion (IL); Joseph P. Vacca, Telford, PA (US); Yinon Ben-Neriah, Mevasseret Zion (IL); and Avanthika Venkatachalam, Jerusalem (IL)
Assigned to Yissum Research Development Company of the Hebrew University of Jerusalem Ltd, Jerusalem (IL)
Filed by Yissum Research Development Company of the Hebrew University of Jerusalem Ltd., Jerusalem (IL)
Filed on Jul. 26, 2021, as Appl. No. 17/384,922.
Application 17/384,922 is a division of application No. 16/482,199, granted, now 11,072,599, previously published as PCT/IL2018/050100, filed on Jan. 30, 2018.
Claims priority of provisional application 62/453,192, filed on Feb. 1, 2017.
Prior Publication US 2022/0017493 A1, Jan. 20, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/4439 (2006.01); A61K 31/4155 (2006.01); A61K 31/427 (2006.01); A61K 31/506 (2006.01); A61P 29/00 (2006.01); A61P 35/00 (2006.01); C07D 401/04 (2006.01); C07D 403/04 (2006.01); C07D 403/14 (2006.01); C07D 417/04 (2006.01)
CPC C07D 403/04 (2013.01) [C07D 401/04 (2013.01); C07D 403/14 (2013.01); C07D 417/04 (2013.01)] 24 Claims
 
1. A method of treating a malignant condition in a subject in need thereof, comprising administering to the subject a compound having Formula (I), or a stereoisomer or pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein:
R1 and R2 are each independently selected from H; and straight or branched C1-C8 alkyl, straight or branched C1-C5 alkoxy, —C(O)-(straight or branched C1-C5 alkyl), phenyl, naphthyl, anthracenyl, and C3-C7 heteroaryl, each optionally substituted by at least one of halide, hydroxyl, —C(O)OR10, —OC(O)R10, —R13OR14′, —OR15′, phenyl, naphthyl, anthracenyl, C3-C7 heteroaryl, —C(O)NR11R12′, and —NR11C(O)R12′; or
R1 and R2 together with the nitrogen atom they are connected to form a 4-7 membered saturated, unsaturated, or aromatic ring that optionally comprises at least one of N, O, NH, C═O, and SO2, and is optionally substituted with at least one of straight or branched C1-C5 alkyl, phenyl, naphthyl, anthracenyl, C3-C7 heteroaryl, hydroxyl, halide, and cyano;
R3 and R4 are each independently selected from H, and straight or branched C1-C8 alkyl optionally substituted by at least one of halide, hydroxyl, C1-C5 alkoxy, phenyl, naphthyl, anthracenyl, C3-C7 heteroaryl, —C(O)OR10, —OC(O)R10, —C(O)NR11R12′, and —NR11C(O)R12′; or
R1 or R2 together with R3 and the carbon and nitrogen atoms they are each connected to form a 4-7 membered saturated, unsaturated, or aromatic ring that optionally comprises at least one of N, NH, O, C═O, and SO2, and is optionally substituted with at least one of straight or branched C1-C5 alkyl, phenyl, naphthyl, anthracenyl, C3-C7 heteroaryl, hydroxyl, and halide;
W, X, Y, and Z are each selected from CH, CR5, CR5c, NH, N, and S; provided that at least one of W, X, Y and Z is selected from NH, N, and S; and provided that, when W is N and Z is N, then X is CR5c;
n is an integer of 0 or 1;
R5 is OH, NH2, or halide; R5c is OH or NH2;
R8 is selected from H and halide; and straight or branched C1-C8 alkyl, straight or branched C2-C8 alkenyl, and straight or branched C2-C8 alkynyl, each optionally substituted by at least one halide;
R6 is selected from straight or branched C1-C8 alkyl, straight or branched C2-C8 alkenyl, straight or branched C2-C8 alkynyl, C5-C10 cycloalkyl, and saturated or unsaturated 4-6 membered heterocyclyl, each optionally substituted by at least one of straight or branched C1-C8 alkyl, C3-C7 cycloalkyl, 4-6 membered heterocyclyl, phenyl, naphthyl, anthracenyl, C3-C7 heteroaryl, halide, hydroxyl, and C1-C5 haloalkyl;
R7 is selected from straight or branched C1-C8 alkyl, straight or branched C2-C8 alkenyl, and straight or branched C2-C8 alkynyl, each independently substituted by at least one of C3-C7 cycloalkyl, 4-6 membered heterocyclyl, phenyl, naphthyl, anthracenyl, C3-C7 heteroaryl, halide, hydroxyl, and C1-C5 haloalkyl;
each R10 is independently straight or branched C1-C8 alkyl;
each R11 and R12′ is independently H, or straight or branched C1-C8 alkyl;
each R13 is independently straight or branched C1-C8 alkylene; and
each R14′ and R15′ is independently H, or straight or branched C1-C8 alkyl;
wherein each heteroaryl independently comprises at least one heteroatom selected from N, O, and S and each heterocyclyl independently comprises at least one heteroatom selected from N, O, and S, and
wherein the malignant condition is selected from multiple myeloma, myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), melanoma, breast cancer, diffuse large B cell lymphoma (DLBCL), chronic myelogenous leukemia (CML), chronic lymphocytic leukemia (CLL), prostate cancer, colorectal cancer, and head and neck cancer.