US 10,780,090 B2 · Heteroaryl compounds useful as inhibitors of SUMO activating enzyme

Abstract

Disclosed are chemical entities which are compounds of formula (I): or pharmaceutically acceptable salts thereof; wherein Y, Ra, Ra′, Rb, Rc, X1, X2, X3, Rd, Z1, and Z2 have the values described herein and stereochemical configurations depicted at asterisked positions indicate absolute stereochemistry. Chemical entities according to the disclosure can be useful as inhibitors of Sumo Activating Enzyme (SAE). Further provided are pharmaceutical compositions comprising a compound of the disclosure and methods of using the compositions in the treatment of proliferative, inflammatory, cardiovascular, and neurodegenerative diseases or disorders.

Claims16

Dependent claims

A compound chosen from:

or a pharmaceutically acceptable salt thereof;
wherein R is an amine protecting group.

A method for preparing [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate of formula I-263a or a pharmaceutically acceptable salt thereof,

the method comprising:
a) providing a Compound 1;
wherein R is an amine protecting group;
b) converting Compound 1 to [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate of formula I-263a, or a pharmaceutically acceptable salt thereof;
and
c) isolating [(1R,2S,4R)-4-{[5-({4-[(1R)-7-chloro-1,2,3,4-tetrahydroisoquinolin-1-yl]-5-methyl-2-thienyl}carbonyl)pyrimidin-4-yl]amino}-2-hydroxycyclopentyl]methyl sulfamate of formula I-263a, or a pharmaceutically acceptable salt thereof.

3 more elements

Dependencies are inferred from the claim text.

Facts

Application

16/391,534Filed 23 Apr 2019 · continuation

Priority

1 Jul 2014

Published

US 2020/0085821 A119 Mar 2020

Granted

22 Sep 2020

Term ends

Not estimatedThe source records don’t support an estimate.

Classification23 codes

A61K 31/506
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: not condensed and containing further heterocyclic rings
A61K 31/34
Having oxygen as the only ring hetero atom, e.g. fungichromin: having five-membered rings with one oxygen as the only ring hetero atom, e.g.…
A61K 31/505
Having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines: pyrimidines; Hydrogenated…
A61P 35/00
Antineoplastic agents

Family

Application62/019,756Us provisional application · filed 1 Jul 2014

Application62/185,678Us provisional application · filed 28 Jun 2015

Application14/788,675Parent of this division · filed 30 Jun 2015

Application15/488,795Parent of this division · filed 17 Apr 2017

US 9,683,003 B2Parent of this division · filed 20 Jun 2017

Application15/923,015Parent of this continuation · filed 16 Mar 2018

US 9,962,386 B2Parent of this division · filed 8 May 2018

US 2020/0085821 A1Pre-grant publication · published 19 Mar 2020

US 10,335,410 B2Parent of this continuation

Application15/923,015Parent of this division

US 2016/0009744 A1Published application

US 2017/0002032 A9Published application

US 2017/0216290 A1Published application

US 2018/0311239 A1Published application

US 10,780,090 B2This patent

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

Heteroaryl compounds useful as inhibitors of SUMO activating enzyme

Life of this patent

Heteroaryl compounds useful as inhibitors of SUMO activating enzyme

Life of this patent

Abstract

Claims16