# US 8,772,312 B2 · Heterocyclic compounds as CRTH2 receptor antagonists

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 8,772,312 B2
- Document ID: US8772312B2
- Status: Granted
- Kind: B2
- Application number: 12/681,356
- Filed: 2008-10-09
- Published: 2010-09-02
- Granted: 2014-07-08
- Earliest claimed: 2007-10-10
- Assignees: Cspc Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd.; Centaurus Biopharma Co., Ltd.
- Applicants: Wei W. Yuan
- Inventors: Wei W. Yuan
- Web page: https://patentgrep.com/patent/US8772312B2

## CPC

- C07D 471/14: Ortho-condensed systems
- A61P 5/00: Drugs for disorders of the endocrine system
- A61P 5/24: of the sex hormones
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/08: Vasodilators for multiple indications
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/02: Nasal agents, e.g. decongestants
- A61P 11/06: Antiasthmatics
- A61P 15/00: Drugs for genital or sexual disorders (for disorders of sex hormones A61P5/24); Contraceptives
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/10: for osteoporosis
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/06: Antimigraine agents
- A61P 27/06: Antiglaucoma agents or miotics
- A61P 27/10: for accommodation disorders, e.g. myopia
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 37/06: Immunosuppressants, e.g. drugs for graft rejection
- A61P 37/08: Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

This application relates to a compound of Formula ! (or a pharmaceutically acceptable salt thereof) as defined herein, pharmaceutical compositions thereof, and its use as an antagonist of receptor CRTH2, as well as a process for its preparation and intermediates therefor.

## Claims

### Claim 1

A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
A is N and B, C, and D are independently selected from CH and C(R1);
m is an integer from 1 to 4;
n is an integer from 0 to 4;
R1 is halogen;
R2 and R3 are hydrogen;
R4 is selected from H, C1-6 alkyl;
Ar is aryl optionally substituted with one or more halogen atoms;
X is —C(Ra)(Rb)—, wherein Ra and Rb are H;
Y is —S(O)2—.

### Claim 2 (depends on 1)

The compound, or salt thereof, of claim 1 wherein n and m are 1.

### Claim 3 (depends on 1)

The compound or salt thereof of claim 1 wherein n is 2 and m is 1.

### Claim 4 (depends on 1)

The compound or salt thereof of claim 1 wherein n is 2 and m is 1, R2 and R3 are H, and R4 is methyl.

### Claim 5 (depends on 1)

The compound or salt thereof of claim 1 wherein Ar is phenyl or substituted phenyl.

### Claim 6 (depends on 1)

The compound or salt thereof of claim 1 wherein n is 2, m is 1, X is —CH2—, R2 and R3 are H, R4 is methyl, Ar is phenyl or substituted phenyl, and A is N.

### Claim 7 (depends on 1)

The compound or salt thereof of claim 1 wherein n is 2, m is 1, X is —CH2—, R2 and R3 are H, R4 is Me, Ar is phenyl or substituted phenyl, and B is N.

### Claim 8 (depends on 1)

The compound or salt thereof of claim 1 wherein n is 2, m is 1, X is —CH2—, R2 and R3 are H , R4 is methyl, Ar is phenyl or substituted phenyl, and C is N.

### Claim 9 (depends on 1)

The compound or salt thereof of claim 1 wherein n is 2 and m is 1, X is —CH2—, R2 and R3 are H , R4 is methyl, Ar is phenyl or substituted phenyl, and D is N.

### Claim 10 (depends on 1)

The compound of claim 1 comprising (±)-{2-chloro-8-[(4-fluoro-benzenesulfonyl)-methyl-amino]-6,7,8,9-tetrahydro-pyrido[3,2-b]indolizin-5-yl}-acetic acid.

### Claim 11 (depends on 10)

The more active enantiomer of claim 10 which is the fast eluting on Chiralcel OJ-RH column when eluted with 0.05% TFA in Methanol.

### Claim 12 (depends on 1)

The compound of claim 1 comprising (±)-{8-[(4-fluoro-benzenesulfonyl)-methyl-amino]-6,7,8,9-tetrahydro-pyrido[3,2-b]indolizin-5-yl}-acetic acid.

### Claim 13 (depends on 12)

The more active enantiomer of claim 12 which is the fast eluting on Chiralcel OJ-RH column when eluted with 0.05% TFA in Methanol.

### Claim 14 (depends on 1)

A pharmaceutical composition having the properties of CRTH2 receptor antagonists, comprising a pharmaceutically acceptable carrier, diluent, or excipient, and a compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1.

### Claim 15 (depends on 1)

A method of inhibiting PGD2 binding in a mammal by administering an inhibitory effective amount of a compound of Formula I or a pharmaceutically acceptable salt thereof according to claim 1.