US 11,999,715 B2Granted

ASK1 inhibiting agents

AssigneeBiogen MA Inc.

InventorsFelix Gonzalez Lopez de Turiso, Zhili Xin, Martin Himmelbauer, John H. Jones

Life of this patent

Estimating the term…

Abstract

Provided are compounds of Formula (I): Formula (I), including compounds of Formulas (II), (III), (IV), (V) and (VI), wherein X, R1, R2, R3, R4 and n are as defined herein, and pharmaceutically acceptable salts thereof, and methods for their use and production. These compounds can be useful, e.g., in the treatment of disorders responsive to the inhibition of apoptosis signal-regulating kinase 1 (ASK1).

Claims20

Dependent claims

A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
X is CH or N;
n is 1 or 2;
R1 in each occurrence is independently selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, halo, —CN, —C(O)R1a, —C(O)OR1a, —C(O)N(R1a)2, —N(R1a)2, —N(R1a)C(O)R1a, —N(R1a)C(O)OR1a, —N(R1a)C(O)N(R1a)2, —N(R1a)S(O)2R1a, —OR1a, —OC(O)R1a, —OC(O)N(R1a)2, —SR1a, —S(O)R1a, —S(O)2R1a, —S(O)N(R1a)2, and —S(O)2N(R1a)2, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R10;
R1a in each occurrence is independently selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl in each occurrence are optionally and independently substituted with one or more R10;
R10 in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, halo, —CN, —C(O)R10a, —C(O)OR10a, —C(O)N(R10a)2, —N(R10a)2, —N(R10a)C(O)R10a, —N(R10a)C(O)OR10a, —N(R10a)C(O)N(R10a)2, —N(R10a)S(O)2R10a, —OR10a, —OC(O)R10a, —OC(O)N(R10a)2, —SR10a, —S(O)R10a, —S(O)2R10a, —S(O)N(R10a)2, and —S(O)2N(R10a)2, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl in each occurrence are optionally and independently substituted with one or more substituents independently selected from halo, —CN, —C(O)R10a, —C(O)OR10a, —C(O)N(R10a)2, —N(R10a)2, —N(R10a)C(O)R10a, —N(R10a)C(O)OR10a, —N(R10a)C(O)N(R10a)2, —N(R10a)S(O)2R10a, —OR10a, —OC(O)R10a, —OC(O)N(R10a)2, —SR10a, —S(O)R10a, —S(O)2R10a, —S(O)N(R10a)2, and —S(O)2N(R10a)2;
R10a in each occurrence is independently selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl;
R2 is selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R20;
R20 in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, halo, —CN, —C(O)R20a, —C(O)OR20a, —C(O)N(R20a)2, —N(R20a)2, —N(R20a)C(O)R20a, —N(R20a)C(O)OR20a, —N(R20a)C(O)N(R20a)2, —N(R20a)S(O)2R20a, —OR20a, —OC(O)R20a, —OC(O)N(R20a)2, —SR20a, —S(O)R20a, —S(O)2R20a, —S(O)N(R20a)2, and —S(O)2N(R20a)2, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl in each occurrence are optionally and independently substituted with one or more substituents independently selected from halo, —CN, —C(O)R20a, —C(O)OR20a, —C(O)N(R20a)2, —N(R2)2, —N(R20a)C(O)R20a, —N(R20a)C(O)OR20a, —N(R20a)C(O)N(R20a)2, —N(R20a)S(O)2R20a, —OR20a, —OC(O)R20a, —OC(O)N(R20a)2, —SR20a, —S(O)R20a, —S(O)2R20a, —S(O)N(R20a)2, and —S(O)2N(R20a)2;
R20a in each occurrence is independently selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl;
R3 is selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R30;
R30 in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, halo, —CN, —C(O)R30a, —C(O)OR30a, —C(O)N(R30a)2, —N(R30a)2, —N(R30a)C(O)R30a, —N(R30a)C(O)OR30a, —N(R30a)C(O)N(R30a)2, —N(R30a)S(O)2R30a, —OR30a, —OC(O)R30a, —OC(O)N(R30a)2, —SR30a, —S(O)R30a, —S(O)2R30a, —S(O)N(R30a)2, and —S(O)2N(R30a)2, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl in each occurrence are optionally and independently substituted with one or more substituents independently selected from halo, —CN, —C(O)R30a, —C(O)OR30a, —C(O)N(R30a)2, —N(R30a)2, —N(R30a)C(O)R30a, —N(R30a)C(O)OR30a, —N(R30a)C(O)N(R30a)2, —N(R30a)S(O)2R30a, —OR30a, —OC(O)R30a, —OC(O)N(R30a)2, —SR30a, —S(O)R30a, —S(O)2R30a, —S(O)N(R30a)2, and —S(O)2N(R30a)2;
R30a in each occurrence is independently selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein said carbocyclyl, and heterocyclyl are each optionally substituted with C1-4alkyl or halo;
and
R4 is H or C1-6alkyl.

12 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/267,631Filed 13 Aug 2019 · us provisional application
Priority: 14 Aug 2018
Published: US 2021/0317103 A114 Oct 2021
Granted: 4 Jun 2024
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
A61P 3/00
Drugs for disorders of the metabolism
A61P 9/00
Drugs for disorders of the cardiovascular system

Family

Application62/718,622Us provisional application · filed 14 Aug 2018
US 2021/0317103 A1Pre-grant publication · published 14 Oct 2021
US 11,999,715 B2This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
X is CH or N;
n is 1 or 2;
R1 in each occurrence is independently selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, halo, —CN, —C(O)R1a, —C(O)OR1a, —C(O)N(R1a)2, —N(R1a)2, —N(R1a)C(O)R1a, —N(R1a)C(O)OR1a, —N(R1a)C(O)N(R1a)2, —N(R1a)S(O)2R1a, —OR1a, —OC(O)R1a, —OC(O)N(R1a)2, —SR1a, —S(O)R1a, —S(O)2R1a, —S(O)N(R1a)2, and —S(O)2N(R1a)2, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R10;
R1a in each occurrence is independently selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl in each occurrence are optionally and independently substituted with one or more R10;
R10 in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, halo, —CN, —C(O)R10a, —C(O)OR10a, —C(O)N(R10a)2, —N(R10a)2, —N(R10a)C(O)R10a, —N(R10a)C(O)OR10a, —N(R10a)C(O)N(R10a)2, —N(R10a)S(O)2R10a, —OR10a, —OC(O)R10a, —OC(O)N(R10a)2, —SR10a, —S(O)R10a, —S(O)2R10a, —S(O)N(R10a)2, and —S(O)2N(R10a)2, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl in each occurrence are optionally and independently substituted with one or more substituents independently selected from halo, —CN, —C(O)R10a, —C(O)OR10a, —C(O)N(R10a)2, —N(R10a)2, —N(R10a)C(O)R10a, —N(R10a)C(O)OR10a, —N(R10a)C(O)N(R10a)2, —N(R10a)S(O)2R10a, —OR10a, —OC(O)R10a, —OC(O)N(R10a)2, —SR10a, —S(O)R10a, —S(O)2R10a, —S(O)N(R10a)2, and —S(O)2N(R10a)2;
R10a in each occurrence is independently selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl;
R2 is selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally and independently substituted with one or more R20;
R20 in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, halo, —CN, —C(O)R20a, —C(O)OR20a, —C(O)N(R20a)2, —N(R20a)2, —N(R20a)C(O)R20a, —N(R20a)C(O)OR20a, —N(R20a)C(O)N(R20a)2, —N(R20a)S(O)2R20a, —OR20a, —OC(O)R20a, —OC(O)N(R20a)2, —SR20a, —S(O)R20a, —S(O)2R20a, —S(O)N(R20a)2, and —S(O)2N(R20a)2, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl in each occurrence are optionally and independently substituted with one or more substituents independently selected from halo, —CN, —C(O)R20a, —C(O)OR20a, —C(O)N(R20a)2, —N(R2)2, —N(R20a)C(O)R20a, —N(R20a)C(O)OR20a, —N(R20a)C(O)N(R20a)2, —N(R20a)S(O)2R20a, —OR20a, —OC(O)R20a, —OC(O)N(R20a)2, —SR20a, —S(O)R20a, —S(O)2R20a, —S(O)N(R20a)2, and —S(O)2N(R20a)2;
R20a in each occurrence is independently selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl;
R3 is selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl are optionally substituted with one or more R30;
R30 in each occurrence is independently selected from C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, heterocyclyl, halo, —CN, —C(O)R30a, —C(O)OR30a, —C(O)N(R30a)2, —N(R30a)2, —N(R30a)C(O)R30a, —N(R30a)C(O)OR30a, —N(R30a)C(O)N(R30a)2, —N(R30a)S(O)2R30a, —OR30a, —OC(O)R30a, —OC(O)N(R30a)2, —SR30a, —S(O)R30a, —S(O)2R30a, —S(O)N(R30a)2, and —S(O)2N(R30a)2, wherein said C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl in each occurrence are optionally and independently substituted with one or more substituents independently selected from halo, —CN, —C(O)R30a, —C(O)OR30a, —C(O)N(R30a)2, —N(R30a)2, —N(R30a)C(O)R30a, —N(R30a)C(O)OR30a, —N(R30a)C(O)N(R30a)2, —N(R30a)S(O)2R30a, —OR30a, —OC(O)R30a, —OC(O)N(R30a)2, —SR30a, —S(O)R30a, —S(O)2R30a, —S(O)N(R30a)2, and —S(O)2N(R30a)2;
R30a in each occurrence is independently selected from H, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, carbocyclyl, and heterocyclyl, wherein said carbocyclyl, and heterocyclyl are each optionally substituted with C1-4alkyl or halo;
and
R4 is H or C1-6alkyl.

12 more elements

Facts

Application

17/267,631Filed 13 Aug 2019 · us provisional application

Priority

14 Aug 2018

Published

US 2021/0317103 A114 Oct 2021

Granted

4 Jun 2024

Term ends

Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 401/14
Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a…:…
A61P 3/00
Drugs for disorders of the metabolism
A61P 9/00
Drugs for disorders of the cardiovascular system