SCH-486757(SCH-486757) - 药物靶点：OOR_在研适应症：咳嗽_专利_临床

概要

基本信息

药物类型

小分子化药

别名

SCH486757

靶点

OOR

作用机制

OOR激动剂(孤啡肽受体激动剂)

治疗领域

呼吸系统疾病

在研适应症

咳嗽

非在研适应症

慢性咳嗽持续咳嗽

原研机构

Merck Sharp & Dohme Corp.

在研机构

The University of Manchester

非在研机构

Merck Sharp & Dohme Corp.

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C24H23Cl2N3O

InChIKeyMQWMHMZNBGQNMT-UHFFFAOYSA-N

CAS号524019-25-8

关联

4

项与 SCH-486757 相关的临床试验

NCT00506987 / Completed临床2期

Study of the Efficacy and Safety of SCH 486757 in Subjects With Chronic Idiopathic Cough

This is a randomized, double-blind, placebo-controlled, crossover, single center study of SCH 486757 in subjects with chronic cough. Subjects will be randomized to receive SCH 486757 or placebo for 14 days. After a 2-week washout period, subjects will be crossed over to the other treatment. The primary objective is to evaluate the effectiveness of SCH 486757 in reducing cough reflex sensitivity as determined by a challenge with capsaicin, an agent that induces cough.

开始日期2007-01-01

申办/合作机构

Merck Sharp & Dohme Corp.

EUCTR2006-002165-39-GB / Not yet recruiting临床2期

Study of the Efficacy and Safety of SCH486757 in Subjects With Chronic Idiopathic Cough

开始日期2006-11-30

申办/合作机构

Schering-Plough Research Institute

NCT00230230 / Completed临床2期

SCH 486757 vs Codeine and Placebo in Subjects With Persistent Postviral Cough

This randomized, multicenter, parallel-group, double-blind, double-dummy, placebo- and active-controlled study will evaluate the efficacy and safety of SCH 486757 in subjects with persistent cough resulting from a recent viral upper respiratory infection (URI). The primary objective is to assess the efficacy of SCH 486757 administered at a dose of 100 mg twice daily for 5 days in the reduction of cough severity score compared with placebo. The key secondary objective is to evaluate the reduction in the number of coughs with SCH 486757 compared with placebo. Because codeine is a widely used as a cough medication, it is included as a treatment arm in the study.

开始日期2005-10-01

申办/合作机构

Merck Sharp & Dohme Corp.

100 项与 SCH-486757 相关的临床结果

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100 项与 SCH-486757 相关的转化医学

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100 项与 SCH-486757 相关的专利（医药）

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5

项与 SCH-486757 相关的文献（医药）

2012-02-01·Birth Defects Research Part B: Developmental and Reproductive Toxicology

Effects of SCH 486757, A Nociceptin‐1 Receptor Agonist, on Fertility and Reproductive Hormone Levels in Female CRL:CD®[SD] Rats

Article

作者: Kimberley A. Treinen ; Stephan J. Kopytek ; Brian P. Enright ; Barry S. McIntyre ; Stephen A. Barat

AbstractBACKGROUNDSCH 486757 is a nociceptin‐1 receptor agonist that was in development as an antitussive. Studies were conducted to characterize its effects on female fertility and to examine its potential modes of action.METHODSFemale rats were administered up to 20 mg/kg SCH 486757 before/during mating through gestation day (GD) 7; female fertility and embryonic development were assessed on GD 14. In a subsequent study, pregnant rats were dosed up to 50 mg/kg SCH 486757 from GD 0 to 7. Reproductive hormones were assessed on GD 1, 3, 5, and 7, and embryonic development was assessed on GD 14. A subset of dosed dams were allowed to deliver, were subsequently re‐mated, and reproductive hormones and fertility were assessed on GD 7 and 14, respectively. To determine the effects of SCH 486757 on nonpregnant rats, doses of up to 50 mg/kg SCH 486757 were administered for 4 days beginning on the day of estrus; reproductive hormones were assessed after the final dose.RESULTSFemale rats administered ≥20 mg/kg SCH 486757 exhibited abnormal estrous cycles; decreased fertility, number of corpora lutea, and implantation sites; and increased pre‐ and postimplantation loss. In general, administration of SCH486757 was associated with lower luteinizing hormone (LH) progesterone (P4), and estradiol (E2) levels in pregnant rats. These effects on fertility/embryonic development and reproductive hormones exhibited reversibility post dosing. Nonpregnant rats in the 50‐mg/kg group exhibited apparent decreases in P4 and E2 levels, with no apparent effects on LH values.CONCLUSIONSThe SCH 486757‐related effects on fertility and embryonic development were likely the result of decreases in P4, E2, and/or LH, rather than being due to decreased prolactin levels.

2011-01-01·Pharmacology4区 · 医学

Where Are the New Cough Treatments: A Debriefing of Recent Clinical Proof-of-Concept Trials with the NOP Agonist SCH 486757

4区 · 医学

Review

作者: Sadeh, Jonathan ; McLeod, Robbie L. ; Tulshian, Deen B.

Cough continues to be one of the top reasons why patients seek medical attention from health care providers. The prescription antitussive market is dominated by opioids, such as codeine that produces inconsistent efficacy and is often accompanied by significant side effect liabilities. Consequently, cough represents an unmet medical need and an underserved market. Yet, against the backdrop of increasing cough research, the development of novel treatments has been exceptionally challenging with dextromethorphan being the last US drug approved for cough almost a half century ago. We support the position that an unambiguous and actionable ‘road map’ that clearly delineates the pathway forward for new cough suppressants from basic research to and beyond clinical proof-of-concept studies will be an important aspect for future success of this pharmacological class of drug. Pivotal to the establishment of such a road map will be the review of lessons learned from antitussive agents that have been recently progressed to proof-of-concept trials. In the present commentary, we briefly discuss observations and challenges pertaining to SCH 486757, a selective orally active NOP agonist that has recently advanced to human antitussive testing.

2010-11-01·Drug Metabolism and Disposition2区 · 医学

Identification of Two Novel Metabolites of SCH 486757, a Nociceptin/Orphanin FQ Peptide Receptor Agonist, in Humans

2区 · 医学

Article

作者: Ho, Ginny ; Bercovici, Ana ; Alton, Kevin B. ; Chowdhury, Swapan K. ; Penner, Natalia A.

The study of human metabolism of endo-8[bis(2-chlorophenyl)methyl]-3-(2-pyrimidinyl)-8-azabicyclo[3.2.1]octan-3-ol (SCH 486757) after a 200-mg oral dose of the drug to healthy volunteers in the first-in-human study is presented. The structural elucidation of two unique metabolites, which were detected in the process of metabolite characterization in human plasma and urine by liquid chromatography-mass spectrometry (LC-MS), is described. These metabolites (M27 and M34) were initially detected in human plasma at high levels (>35% of the LC-MS response of the parent drug). Additional LC-MS experiments (hydrogen/deuterium exchange and accurate mass measurement) were used to determine structures of metabolites. It was found that both metabolites were formed through a loss of the C-C bridge from the tropane moiety with the conversion into a substituted pyridinium compound. This metabolic process has not been reported previously. Because of the apparent high abundance of metabolites based on the LC-MS response, actual circulating amounts of these metabolites relative to the parent drug were determined semiquantitatively to evaluate their coverage in preclinical species. With the use of reference standards, it was shown that the LC-MS response of M27 and M34 in human plasma was much higher than that of the parent compound. Actual amounts of M27 and M34 metabolites were less than 5% of the level of the parent drug; therefore, additional assessment was not required.

100 项与 SCH-486757 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12782

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
慢性咳嗽	临床2期	-	Merck Sharp & Dohme Corp.	2007-01-01
持续咳嗽	临床2期	-	Merck Sharp & Dohme Corp.	2005-10-01
咳嗽	临床前	英国	The University of Manchester	2010-01-01