Derivatives of 4-aminopiperidine and their use as a medicament

• US 7,393,861 B2
• Filed: 05/04/2005
• Issued: 07/01/2008
• Est. Priority Date: 12/14/1999
• Status: Expired due to Term

• Current Assignee: Ipsen Pharma Sas (Ipsen Sa)
• Original Assignee: Societe de Conseils de Recherches et d'Applications Scientifiques
• Inventors: Moinet, Christophe, Gonzalez, Jérôme, Thurieau, Christophe
• Primary Examiner(s): Saeed; Kamal A.
• Application Number:
  US11/122,293
• Publication Number:
  US 20050239796A1
• Time in Patent Office: 1,154 Days
• Field of Search: 514/320, 546/186, 546/197
• US Class Current: 514/320
• 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 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• 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 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/02 : of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
• CPC Class Codes: A61P 5/04 : for decreasing, blocking or antagonising the activity of the hypothalamic hormones
• CPC Class Codes: A61P 5/08 : for decreasing, blocking or antagonising the activity of the anterior pituitary hormones
• CPC Class Codes: A61P 5/16 : for decreasing, blocking or antagonising the activity of the thyroid hormones
• CPC Class Codes: A61P 5/46 : for decreasing, blocking or antagonising the activity of glucocorticosteroids
• CPC Class Codes: A61P 5/48 : of the pancreatic hormones
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 211/58 : attached in position 4
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 : containing three or more hetero rings
• CPC Class Codes: C07D 405/14 : containing three or more hetero rings
• CPC Class Codes: C07D 409/14 : containing three or more hetero rings
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings

Abstract

A subject of the present application is new derivatives of 4-aminopiperidines of formula

in which R₁, R₂ and R₃ represent various radical, and their preparation processes by synthetic methods in parallel in liquid and solid phase. These products having a good affinity with certain sub-types of somatostatin receptors, they are particularly useful for treating the pathological states or diseases in which one (or more) somatostatin receptors are involved.

Claims

1. A compound of the formula

2. A compound of claim 1 wherein R₁ is —

(CH₂)_m-Z₁₂ wherein

Z₁₂ is selected from the group consisting of naphthyl, bis-phenyl, substituted by oxy or phenyl, optionally substituted by at least one member selected from the group consisting of bromo, fluoro, chloro, alkyl, alkoxy, CF₃ and OCF₃.

3. A compound of claim 1 wherein R₂ is —

C(Y)NHX₁,

X₁ is —

(CH₂)_p-Z₂₂,

Z₂₂ is selected from the group consisting of bis-phenyl, or phenyl and naphthyl, all optionally substituted by at least one member selected from the group consisting of fluoro, chloro, bromo, iodo, alkyl, alkoxy, alkylthio, CF₃, OCF₃, nitro, cyano, azido, piperidinosulfonyl, —

C(O)—

O-alkyl, —

C(O)-alkyl and phenyl.

4. A compound of claim 1 wherein R₃ is methyl.

5. A process for the preparation, in liquid phase, of a compound of claim 1 comprising reducing amination of a N-substituted piperidone of the formula

6. The process, in solid phase, for a compound of claim 1 comprising reducing amination of a ketonic resin of the formula

7. A pharmaceutical composition containing, as active ingredient, a compound of claim 1, in combination with a pharmaceutically acceptable support.

8. A composition for treating acromegalia, hypophyseal adenomas and endocrine gastroenteropancreatic tumors comprising an effective amount of a compound of claim 1 and a pharmaceutical carrier.

9. A method of treating acromegalia, hypophyseal adenomas and endocrine gastroenteropancreatic tumors in warm-blooded animals comprising administering to warm-blooded animals in need thereof an effective amount of a compound of claim 1.