# US 10,766,904 B2 · Bicyclic heteroaryl derivatives as CFTR potentiators

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- Number: US 10,766,904 B2
- Document ID: US10766904B2
- Status: Granted
- Kind: B2
- Application number: 16/506,883
- Filed: 2019-07-09
- Published: 2019-10-31
- Granted: 2020-09-08
- Earliest claimed: 2016-12-16
- Assignees: Cystic Fibrosis Foundation
- Applicants: Cystic Fibrosis Foundation
- Inventors: Joseph Walter Strohbach; David Christopher Limburg; John Paul Mathias; Atli Thorarensen; John James Mousseau; Rajiah Aldrin Denny; Christoph Wolfgang Zapf; Ivan Viktorovich Efremov
- Web page: https://patentgrep.com/patent/US10766904B2

## CPC

- C07D 487/04: Ortho-condensed systems
- A61P 11/00: Drugs for disorders of the respiratory system
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention relates to 5,7-disubstituted-imidazo[5,1-f][1,2,4]triazine-4-amine derivatives, and pharmaceutically acceptable salts thereof. The compounds are potentiators of Cystic Fibrosis Transmembrane conductance Regulator (CFTR). The invention also discloses pharmaceutical compositions comprising the compounds, optionally in combination with additional therapeutic agents, and methods of potentiating, in mammals, including humans, CFTR by administration of the compounds. These compounds are useful for the treatment of cystic fibrosis (CF), asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD), constipation, Diabetes mellitus, dry eye disease, pancreatitis, rhinosinusitis, Sjögren's Syndrome, and other CFTR associated disorders.

## Claims

### Claim 1

A compound of Formula IB:
wherein Hal is selected from the group consisting of chloro, bromo, and iodo;
Y is a five membered heteroaryl comprising one to four heteroatoms each of which is independently selected from the group consisting of N, O and S(O)n; wherein the heteroaryl is optionally substituted with one to three substituents each of which is independently selected from the group consisting of halo, C1-C6 alkyl and C1-C6 haloalkyl;
Z is phenyl, optionally substituted with one to three halo;
R1a and R1b are each independently selected from the group consisting of H, OH, halo, C1-C6 alkyl optionally substituted with one to three substituents each of which is independently selected from the group consisting of halo, —OH, C1-C3 alkoxy, C3-C7 cycloalkyl and a four to seven membered heterocycloalkyl comprising one to three heteroatoms each of which is independently selected from the group consisting of N, O and S(O)n, C3-C7 cycloalkyl optionally substituted with one to three substituents each of which is independently selected from the group consisting of —OH, halo and C1-C6 alkyl, and four to seven membered heterocycloalkyl comprising one to three heteroatoms each of which is independently selected from the group consisting of N, O and S(O)n; and wherein the four to seven membered heterocycloalkyl is optionally substituted with one to three substituents each of which is independently selected from the group consisting of —OH, halo and C1-C6 alkyl; or
R1a and R1b taken together with the carbon to which they are attached form a C3-C7 cycloalkyl or a four to seven membered heterocycloalkyl comprising one to three heteroatoms each of which is independently selected from the group consisting of N, O and S(O)n; and wherein the C3-C7 cycloalkyl or four to seven membered heterocycloalkyl are optionally substituted with one to three substituents each of which is independently selected from the group consisting of —OH, halo and C1-C6 alkyl; and
wherein n at each occurrence is independently 0, 1 or 2.