ARALKYL PIPERIDINE DERIVATIVES AND THEIR USES AS ANTALGIC OR ATARACTIC AGENT

• US 20110105503A1
• Filed: 06/20/2008
• Published: 05/05/2011
• Est. Priority Date: 06/20/2008
• Status: Active Grant

• Current Assignee: Shanghai Institute of Pharmaceutical Industry (China National Pharmaceutical Group Co., Ltd.), Nhwa Pharma. Corporation
• Original Assignee: Shanghai Institute of Pharmaceutical Industry (China National Pharmaceutical Group Co., Ltd.), Nhwa Pharma. Corporation
• Inventors: Ji, Wenhua, Zhang, Guisen, Wang, Guan, Zhang, Yuan, Ma, Yanqin, Guo, Lin, Li, Jianqi
• Granted Patent: US 8,501,778 B2
• Time in Patent Office: Days
• US Class Current: 514/235.5
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4523 containing further heterocyclic ring systems
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: C07D 211/48 having an acyclic carbon atom attached in position 4
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 405/06 linked by a carbon chain containing only aliphatic carbon atoms

Abstract

The present invention relates to aralkyl piperidine derivatives, compositions containing the same, and their uses in the preparation of antalgic or ataractic medicament. The said derivatives are a free base of the compound represented by the following formula or a salt thereof. The pharmacological experiments show that they display favorable antalgic, ataractic activity and low side effects.

Claims

1. An aralkyl piperidine derivative, which is a free base of the compound represented by the following formula or a salt thereof:

2. The aralkyl piperidine derivative according to claim 1, wherein A is one of OH, F or Cl.

3. The aralkyl piperidine derivative according to claim 1, wherein R₁, R₂ are one of hydrogen, C₁-C₄ alkyl or phenyl and substituted phenyl.

4. The aralkyl piperidine derivative according to claim 1, wherein R₃, R₄, R₅ are one of hydrogen, C₁-C₄ alkyl, hydroxy, methoxy, ethoxy, amino and substituted amino, morpholino, pyrrolidinyl, piperidinyl, halo or nitro.

5. The aralkyl piperidine derivative according to claim 1, wherein R₆, R₇, R₈ are one of hydrogen, C₁-C₄ alkyl, hydroxy, methoxy, ethoxy, halo, morpholino, pyrrolidinyl or piperidinyl.

6. The aralkyl piperidine derivative according to claim 1, wherein the salt is a hydrochloride, hydrobromide, sulfate, trifluoroacetate or methylsulfonate.

7. The aralkyl piperidine derivative according to claim 6, wherein the salt is a hydrochloride or hydrobromide.

8. The aralkyl piperidine derivative according to claim 7, wherein the salt contains 0.5-3 molecules of crystal waters.

9. The aralkyl piperidine derivative according to claim 1, wherein the compound is selected from:

III-1 N-benzyl-4-benzoylmethyl-4-piperidinol

III-2 N-p-chlorobenzyl-4-benzoylmethyl-4-piperidinol

III-3 N-p-fluorobenzyl-4-benzoylmethyl-4-piperidinol

III-4 N-p-nitrobenzyl-4-benzoylmethyl-4-piperidinol

III-5 N-p-aminobenzyl-4-benzoylmethyl-4-piperidinol

III-6 N-p-acetylaminobenzyl-4-benzoylmethyl-4-piperidinol

III-7 N-diphenylmethyl-4-benzoylmethyl-4-piperidinol

III-8 N-(2-pyridyl)methyl-4-benzoylmethyl-4-piperidinol

III-9 N-(2-pyrimidinyl)-4-benzoylmethyl-4-piperidinol

III-10 N-(2-pyrimidinyl)methyl-4-benzoylmethyl-4-piperidinol

III-11 N-(2-quinolyl)-4-benzoylmethyl-4-piperidinol

III-12 N-(2-methoxyphenyl)-4-benzoylmethyl-4-piperidinol

III-13 N-(benzo[d][1,3]dioxol-5-ylmethyl)-4-benzoylmethyl-4-piperidinol

III-14 N-(3,4,5-trimethoxybenzyl)-4-benzoylmethyl-4-piperidinol

III-15 N-p-methoxybenzyl-4-benzoylmethyl-4-piperidinol

III-16 N-(1-phenylethyl)-4-benzoylmethyl-4-piperidinol

III-17 (R)—

N-(1-phenylethyl)-4-benzoylmethyl-4-piperidinol

III-18 (S)—

N-(1-phenylethyl)-4-benzoylmethyl-4-piperidinol

III-19 N-(1-(4-methoxyphenyl)ethyl)-4-benzoylmethyl-4-piperidinol

III-20 N-(1-(4-fluorophenyl)ethyl)-4-benzoylmethyl-4-piperidinol

III-21 N-(1-(4-aminophenyl)ethyl)-4-benzoylmethyl-4-piperidinol

III-22 N-(1-(benzo[d][1,3]dioxol-5-yl)ethyl)-4-benzoylmethyl-4-piperidinol

III-23 N-(2-naphthylmethyl)-4-benzoylmethyl-4-piperidinol

III-24 N-(4-(1-pyrrolidinyl)benzyl)-4-benzoylmethyl-4-piperidinol

III-25 N-(1-(4-(1-pyrrolidinyl)phenyl)ethyl)-4-benzoylmethyl-4-piperidinol

III-26 N-(4-morpholinobenzyl)-4-benzoylmethyl-4-piperidinol

III-27 N-(1-(4-morpholinophenyl)ethyl)-4-benzoylmethyl-4-piperidinol

III-28 N-(4-(1-piperidinyl)benzyl)-4-benzoylmethyl-4-piperidinol

III-29 N-(2-oxo-5-indolinyl)methyl-4-benzoylmethyl-4-piperidinol

III-30 N-(5-indolinyl)methyl-4-benzoylmethyl-4-piperidinol

III-31 N-benzyl-4-(p-fluorobenzoylmethyl)-4-piperidinol

III-32 N-benzyl-4-(p-methoxybenzoylmethyl)-4-piperidinol

III-33 N-benzyl-4-(p-chlorobenzoylmethyl)-4-piperidinol

III-34 N-benzyl-4-(2-pyridinylformylmethyl)-4-piperidinol

III-35 N-benzyl-4-(4-(pyrrolidinyl)benzoylmethyl)-4-piperidinol

III-36 N-benzyl-4-((4-morpholinobenzoyl)methyl)-4-piperidinol

III-37 N-benzyl-4-(2-(5-indolinyl)-2-oxoethyl)-4-piperidinol

III-38 N-benzyl-4-(2-(benzo[d][1,3]dioxol-5-yl)-2-oxoethyl)-4-piperidinol

III-39 N-benzyl-4-(1-benzoylethyl)-4-piperidinol

V-1 N-p-methoxybenzyl-4-(2-hydroxy-2-phenylethyl)-4-piperidinol

V-2 N-p-acetylaminobenzyl-4-(2-hydroxy-2-phenylethyl)-4-piperidinol

V-3 N-diphenylmethyl-4-(2-hydroxy-2-phenylethyl)-4-piperidinol

V-4

N-(benzo[d][1,3]dioxol-5-ylmethyl)-4-(2-hydroxy-2-phenylethyl)-4-piperidinol

V-5 N-(2-methoxyphenyl)-4-(2-hydroxy-2-phenylethyl)-4-piperidinol

V-6 N-(5-indolinyl)methyl-4-(2-hydroxy-2-phenylethyl)-4-piperidinol

V-7N-(1-(4-(pyrrolidinyl)phenyl)ethyl)-4-(2-hydroxy-2-phenylethyl)-4-piperidinol

V-8 N-(1-(4-morpholinophenyl)ethyl)-4-(2-hydroxy-2-phenylethyl)-4-piperidinol

VIII-1 N-p-acetylaminobenzyl-4-benzoylmethyl-4-methoxylpiperidine

VIII-2 N-(1-(p-methoxyphenyl)ethyl)-4-benzoylmethyl-4-methoxylpiperidine

VIII-3 N-(1-(4-morpholinophenyl)ethyl)-4-benzoylmethyl-4-methoxylpiperidine

IX-1 N-(1-(p-methoxyphenyl)ethyl)-4-benzoylmethyl-4-fluoropiperidine

IX-2 N-(benzo[d][1,3]dioxol-5-ylmethyl)-4-benzoylmethyl-4-fluoropiperidine

IX-3 N-(1-(4-morpholinophenyl)ethyl)-4-benzoylmethyl-4-fluoropiperidine

IX-4 N-(1-(4-(pyrrolidinyl)phenyl)ethyl)-4-benzoylmethyl-4-fluoropiperidine

IX-5 N-(1-(p-methoxyphenyl)ethyl)-4-benzoylmethyl-4-chloropiperidine

IX-6 N-(benzo[d][1,3]dioxol-5-ylmethyl)-4-benzoylmethyl-4-chloropiperidine

IX-7 N-(1-(4-morpholinophenyl)ethyl)-4-benzoylmethyl-4-chloropiperidine

10. A pharmaceutical composition comprising a therapeutically effective amount of the aralkyl piperidine derivative according to claim 1 and a pharmaceutically acceptable carrier.

11. Use of the aralkyl piperidine derivative according to claim 1 for the preparation of an antalgic or ataractic agent.