	US 12,486,274 B2
	Substituted pyrazolo-pyrimidines and uses thereof
Mark D. Rosen, South San Francisco, CA (US); Robert A. Galemmo, Jr., San Francisco, CA (US); Weiling Liang, South San Francisco, CA (US); Brian Kopec, South San Francisco, CA (US); Irene Y. Choi-Muckerheide, Pacifica, CA (US); and Jane Rhodes, South San Francisco, CA (US)
Assigned to Verge Analytics, Inc., South San Francisco, CA (US)
Appl. No. 17/792,304
Filed by Verge Analytics, Inc., South San Francisco, CA (US)
PCT Filed Jan. 12, 2021, PCT No. PCT/US2021/013077 § 371(c)(1), (2) Date Jul. 12, 2022, PCT Pub. No. WO2021/146192, PCT Pub. Date Jul. 22, 2021.
Claims priority of provisional application 63/074,388, filed on Sep. 3, 2020.
Claims priority of provisional application 62/960,412, filed on Jan. 13, 2020.
Prior Publication US 2023/0133203 A1, May 4, 2023
Int. Cl. C07D 487/04 (2006.01); A61P 25/28 (2006.01)

CPC C07D 487/04 (2013.01) [A61P 25/28 (2018.01); C07B 2200/05 (2013.01)]

29 Claims

1. A compound of Formula (I):

wherein:

X is N or CH, Y is N or CR^aprovided that when X is N, then Y is CR^a, when Y is N, then X is CH;

one of R^aand R^lis H, and the other is phenyl or heteroaryl, each optionally substituted with one, two, or three R^dsubstituents;

wherein each R^dsubstituent is independently C_1-4alkyl, C_1-4alkenyl, C_1-4alkynyl, —O—C_1-4alkyl, halo, cyano, nitro, azido, halo-C_1-4alkyl, —O—C_1-4-haloalkyl, —NR^gR^h, —NR^gC(═O)R^h, —NR^gC(═O)NR^gR^h, —NR^gC(═O)OR^h, ═NOR^g, —NR^gS(═O)_1-2R^h, —NR^gS(═O)_1-2NR^gR^h, ═NSO₂R^g, —C(═O)R^g, —C(═O)OR^g, —OC(═O)OR^g, —OC(═O)R^g, —C(═O)NR^gR^h, —OC(═O)NR^gR^h, —OR^g, —SR^g, —S(═O)R^g, —S(═O)₂R^g, —OS(═O)_1-2R^g, —S(═O)_1-2OR^g, —S(═O)_1-2NR^gR^h, phenyl, —C_1-4alkyl-phenyl, monocyclic cycloalkyl, —C_1-4alkyl-cycloalkyl, monocyclic heterocycloalkyl, or monocyclic heteroaryl;

wherein each phenyl, monocyclic cycloalkyl, monocyclic heterocycloalkyl, or monocyclic heteroaryl of R^dis optionally substituted with one, two, or three substituents R^e;

wherein each R^esubstituent is independently C_1-4alkyl, C_1-4alkenyl, C_1-4alkynyl, halo, cyano, nitro, azido, —OH, halo-C_1-4alkyl, —O—C_1-4alkyl, or —O—C_1-4-haloalkyl;

R^gand R^hare each independently H or C_1-4alkyl;

or R^gand R^htaken together with the atom to which they are attached form a monocyclic cycloalkyl or heterocycloalkyl, optionally substituted with C_1-4alkyl;

wherein each of R²and R³is H or is a C_1-4alkyl, cycloalkyl, C_1-4alkylcycloalkyl, heterocyclyl, heterocycloalkyl, or R²and R³taken together with the nitrogen to which they are attached form a heterocyclyl, optionally substituted with one, two, or three R^jsubstituents;

wherein each R^jsubstituent is independently C_1-4alkyl, oxo, —OH, —NR^kR^l, halo, halo-C_1-4alkyl,

—O—C_1-4alkyl, or —O—C_1-4-haloalkyl;

where R^kand R^lare each independently H or C_1-4alkyl;

R⁴is —C(O)NR^xR^y, or is a phenyl or heteroaryl, each optionally substituted with one, two, or three R^zsubstituents;

wherein R^xis H or C_1-4alkyl and R^yis H, C_1-4alkyl, —O—C_1-4alkyl, —SO₂—C_1-4alkyl, C_1-4alkyl-SO₂—R^r, monocyclic cycloalkyl, —C_1-4alkyl(monocyclic cycloalkyl), monocyclic heterocyclyl, —O-monocyclic heterocyclyl, or monocyclic heterocycloalkyl, each optionally substituted with one, two, or three R^gsubstituents;

or R^xand R^ytaken together with the nitrogen to which they are attached form a heterocyclyl or a monocyclic heterocycloalkyl, optionally substituted with C_1-4alkyl;

wherein each R^ris C_1-4alkyl or —NR^pR^q; and

each R^zsubstituent is independently C_1-4alkyl, halo, —OH, or —OC_1-4alkyl, C_1-4alkylNR^mRⁿ, C(O)NHC_1-4alkyl-NR^mRⁿ, or —NR^mRⁿ;

wherein R^mand Rⁿare each independently H, C_1-4alkyl, or C_1-4alkylNR^pR^q, or R^mand Rⁿtaken together with the nitrogen to which they are attached form a heterocyclyl, or a monocyclic heterocycloalkyl, optionally substituted with one or two R^gsubstituents;

wherein each R^osubstituent is independently C_1-4alkyl, —OH, —OC_1-4alkyl, halo, cyano, or —NR^pR^q;

wherein R^pand R^qare each independently H or C_1-4alkyl, or R^pand R^qtaken together with the nitrogen to which they are attached form a heterocyclyl; and

R⁵is H, C_1-4alkyl, halo, —OH, or —OC_1-4alkyl;

or a pharmaceutically acceptable salt thereof.