[4-(5-aminomethyl-2-fluoro-phenyl)-piperidin-1-yl]-[7-flouro-1-(2-methoxy-ethyl)-4-trifluorom as an inhibitor of mast cell tryptase

• US 8,217,178 B2
• Filed: 02/16/2011
• Issued: 07/10/2012
• Est. Priority Date: 08/22/2008
• Status: Active Grant

• Current Assignee: Sanofi
• Original Assignee: Sanofi
• Inventors: Choy, Nakyen, Choi-Sledeski, Yong Mi, Poli, Gregory Bernard, Shay, John J. Jr., Shum, Patrick Wai-Kwok, Sledeski, Adam W.
• Primary Examiner(s): Andres, Janet
• Assistant Examiner(s): REESE, HEIDI L
• Application Number:
  US13/028,745
• Publication Number:
  US 20110201647A1
• Time in Patent Office: 510 Days
• Field of Search: None
• US Class Current: 546/201
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 11/08 Bronchodilators
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 27/14 Decongestants or antiallergics
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 401/06 : linked by a carbon chain containing only aliphatic carbon atoms

Abstract

The present invention is directed to an indole benzylamine compound of formula I:

useful as an inhibitor of tryptase. In addition, the present invention is directed to the use of the compound for treating a patient suffering from, or subject to, a physiological condition in need of amelioration by inhibition of tryptase, comprising administering to the patient of a therapeutically effective amount of the compound, and to a pharmaceutical composition comprising a pharmaceutically effective amount of the compound of formula I, and a pharmaceutically acceptable carrier.

Claims

1. A compound of formula I:

2. The compound of claim 1 as a pharmaceutically acceptable salt selected from:

hydrochloride, fumarate, besylate, tosylate, sulfate, citrate, methanesulfonate, tartrate, phosphate, glutamate and benzoate.

3. The compound according to claim 2, wherein the salt is benzoate.

4. A crystalline form A of the compound according to claim 3, wherein the crystalline form has XRPD peaks at at least five of the following 2 theta angles:

7.75;

10.13;

17.03;

17.16;

18.39;

21.33; and

21.88.

5. A crystalline form of the compound according to claim 3, wherein the crystalline form melts at 162 degrees Celsius.

6. A method for treating a patient suffering from a physiological condition selected from the group consisting of inflammatory disease, a disease of joint cartilage destruction, inflammatory bowel disease, asthma, interstitial lung disease, fibrosis, chronic obstructive pulmonary disease, pulmonary fibrosis, myocardial fibrosis, and neurofibroma, comprising administering to the patient a therapeutically effective amount of the compound according to claim 1.

7. The method of claim 6, wherein the physiological condition is COPD.

8. An intermediate compound having a formula selected from the group consisting of:

9. A compound having the formula: