US 11,866,442 B2
Bifunctional compounds for degrading BTK via ubiquitin proteosome pathway
Daniel W. Robbins, San Francisco, CA (US); Arthur T. Sands, San Francisco, CA (US); Joel McIntosh, San Francisco, CA (US); Jeffrey Mihalic, San Francisco, CA (US); Jeffrey Wu, San Francisco, CA (US); Daisuke Kato, San Francisco, CA (US); Dahlia Weiss, San Francisco, CA (US); and Ge Peng, San Francisco, CA (US)
Assigned to NURIX THERAPEUTICS, INC., San Francisco, CA (US)
Filed by NURIX THERAPEUTICS, INC., San Francisco, CA (US)
Filed on Jul. 28, 2022, as Appl. No. 17/876,433.
Application 17/876,433 is a continuation of application No. 15/734,774, granted, now 11,479,556, previously published as PCT/US2019/056112, filed on Oct. 14, 2019.
Claims priority of provisional application 62/901,984, filed on Sep. 18, 2019.
Claims priority of provisional application 62/887,812, filed on Aug. 16, 2019.
Claims priority of provisional application 62/836,398, filed on Apr. 19, 2019.
Claims priority of provisional application 62/767,819, filed on Nov. 15, 2018.
Claims priority of provisional application 62/745,786, filed on Oct. 15, 2018.
Prior Publication US 2023/0029378 A1, Jan. 26, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 487/10 (2006.01); C07D 413/14 (2006.01); C07D 491/107 (2006.01); C07D 498/10 (2006.01); C07D 471/10 (2006.01); C07D 401/14 (2006.01); C07D 417/14 (2006.01); C07D 487/04 (2006.01)
CPC C07D 487/10 (2013.01) [C07D 401/14 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07D 471/10 (2013.01); C07D 487/04 (2013.01); C07D 491/107 (2013.01); C07D 498/10 (2013.01)] 37 Claims
 
1. A compound of Formula (A)

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
W is N;
D is a bond;
Ring A is phenyl, optionally and independently substituted with up to 3 substituents selected from halo, —CN, —COOH, NH2, and optionally substituted C1-6 alkyl;
Ring B is a

OG Complex Work Unit Chemistry
wherein R10 is

OG Complex Work Unit Chemistry
L is —X1—X2—X3—X4—X5—;
X1 is a bond, —C(O)—, —C(O)—N(R)—, —N(R)—C(O)—, —(O—CH2—CH2)m—, —O(C6H4)—, —(O—CH2—CH2—CH2)m—, —C1-5 alkyl-, 7-12 membered spiro or fused bicyclic heterocycloalkyl having 1-3 heteroatoms independently selected from N, O, or S, or 4-6 membered monocyclic heterocycloalkyl having 1-2 heteroatoms independently selected from N, O, or S, wherein each of the monocyclic and bicyclic heterocycloalkyl of X1 is optionally substituted with —CH3;
X2 is a bond, —(O—CH2—CH2)n—, —(CH2—CH2—O)n—, —N(R)—C(O)—, —N(R)—, —C(O)—, —C(O)—N(R)—, —C1-5 alkyl-, 4-6 membered monocyclic cycloalkyl, or 4-6 membered monocyclic heterocycloalkyl having 1-2 heteroatoms independently selected from N, O, or S;
X3 is a bond, —C1-8 alkyl-,

OG Complex Work Unit Chemistry
4-6 membered cycloalkyl, —N(R)—, —N(R)—C(O)—, —(O—CH2—CH2)p—, —(CH2—CH2—O)p—, 4-6 membered heterocycloalkyl having 1-2 heteroatoms independently selected from N, O, or S wherein the heterocycloalkyl is optionally substituted with —CH3;
X4 is a bond, —CH2—CH2—N(R)—, —N(R)—, —C1-4 alkyl-, —(O—CH2—CH2—CH2)m—, a 5-6 membered saturated, partially unsaturated, or fully unsaturated carbocycle, or a 5-6 membered saturated, partially unsaturated, or fully unsaturated heterocycle having 1-3 heteroatoms independently selected from N, O, or S;
X5 is a bond, —C1-4 alkyl-, —N(R)—, —O—, —C(O)—, or —C(O)—N(R)—;
each R is independently —H or —C1-3 alkyl; and
each of m, n, and p is independently an integer from 1 to 3; and
Y is

OG Complex Work Unit Chemistry