Deuterium substituted 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]piperazine compound or derivatives thereof, and pharmaceutical composition and use thereof

• US 9,896,423 B2
• Filed: 09/28/2014
• Issued: 02/20/2018
• Est. Priority Date: 05/30/2014
• Status: Active Grant

• Current Assignee: Jiangsu Jibeier Pharmaceutical Co.,Ltd., Zhenjiang San An Pharmaceutical Co., Ltd.
• Original Assignee: Jiangsu Jibeier Pharmaceutical Co.,Ltd., Zhenjiang San An Pharmaceutical Co., Ltd.
• Inventors: Geng, Zhongyi, Chen, Xinghai, Aulma, Parker, Peng, Wei
• Primary Examiner(s): Rao, Deepak R
• Assistant Examiner(s): Daniel, Laura M
• Application Number:
  US15/315,182
• Publication Number:
  US 20170197927A1
• Time in Patent Office: 1,241 Days
• Field of Search: None
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/22 Anxiolytics
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 25/32 Alcohol-abuse
• 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 7/12 Antidiuretics, e.g. drugs for diabetes insipidus ADH A61P5/10
• CPC Class Codes: C07B 2200/05 Isotopically modified compounds, e.g. labelled
• CPC Class Codes: C07B 59/002 Heterocyclic compounds
• CPC Class Codes: C07D 295/096 with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings

Abstract

The present disclosure provides a deuterium substituted 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]piperazine compound with a structure represented by formula (I) or a derivative thereof, a pharmaceutical composition containing the compound or the derivative thereof, and an application of the compound or the derivative thereof in preparing drugs. The compound can reduce oxidative metabolism thereof, increase the drug concentration in blood and the effective bioavailability, so as to lower the dosage and reduce the toxicity and other side effects. The deuterium 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]piperazine compound and its derivative thereof provided by the present disclosure can be used to treat related diseases such as affective disorders, depression and anxiety.

Claims

1. A deuterium substituted 1-[2-(2,4-dimethyl-phenylsulfanyl)-phenyl]piperazine compound of formula (I) or a pharmaceutically acceptable salt, an N-oxide;

or their stereoisomer(s), geometrical isomer(s), tautomer(s) or a mixture thereof,

2. The compound according to claim 1, wherein the pharmaceutically acceptable salt is an addition salt of the compound of formula (I) with hydrobromic acid.

3. A pharmaceutical composition, comprising:

the compound according to claim 1; and

one of a pharmaceutically acceptable carrier, excipient, diluent, adjuvant and medium, or a combination thereof.

4. A method of treating a disease, comprising administering the compound of claim 1 to a person in need thereof, wherein the disease is selected from depression, flush, affective disturbance, sleep apnea, anxiety, attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), irritable bowel syndrome (IBS), alcoholism, drug addiction and drug abuse.

5. A pharmaceutical composition, comprising:

the compound according to claim 2; and

one of a pharmaceutically acceptable carrier, excipient, diluent, adjuvant and medium, or a combination thereof.

6. A method of treating a disease, comprising administering the compound of claim 2 to a person in need thereof, wherein the disease is selected from depression, flush, affective disturbance, sleep apnea, anxiety, attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), irritable bowel syndrome (IBS), alcoholism, drug addiction and drug abuse.