CRINECERFONT

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H28ClFN2OS
Molecular Weight	483.04
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC(Cl)=C(C=C1C)C2=C(C)SC(=N2)N(CC#C)[C@@H](CC3CC3)C4=CC(F)=C(C)C=C4

InChI

InChIKey=IEAKXXNRGSLYTQ-DEOSSOPVSA-N

InChI=1S/C27H28ClFN2OS/c1-6-11-31(24(13-19-8-9-19)20-10-7-16(2)23(29)14-20)27-30-26(18(4)33-27)21-12-17(3)25(32-5)15-22(21)28/h1,7,10,12,14-15,19,24H,8-9,11,13H2,2-5H3/t24-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23407783 | https://www.ncbi.nlm.nih.gov/pubmed/21356230
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18672365 | http://www.pharmacodia.com/yaodu/html/v1/chemicals/5f9ce39aec46f3e8e8aebbc722d8ceeb.html

SSR-125543 is a potent, selective, and orally active corticotropin-releasing factor 1 receptor (CRF1) antagonist (Ki value of 2nM). SSR-125543 attenuates long-term cognitive deficit induced by acute inescapable stress in mice, independently from the hypothalamic pituitary adrenal axis. SSR-125543 prevents stress-induced cognitive deficit associated with hippocampal dysfunction. SSR-125543 had been in phase II clinical trials by Sanofi for the treatment of Post-traumatic stress disorder. It is also in phase I trials for the treatment of anxiety. The compound had also been in phase II clinical trials for the treatment of major depression. However, in 2011, the research was discontinued.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Corticotropin releasing factor receptor 1 8 Target ID: CHEMBL1800 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21618986 \| https://www.ncbi.nlm.nih.gov/pubmed/18672365	Antagonist 2778		2.0 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Major depressive disorder 173 Sources: https://clinicaltrials.gov/ct2/show/NCT01034995 http://adisinsight.springer.com/drugs/800016669	Primary		Phase II 1132	Unknown Approved Use Unknown

Sourcing

Vendor/Aggregator	ID	URL
Axon MedChem	1799	https://www.axonmedchem.com/product/1799
Compound Cloud	5282340
MolPort	MolPort-042-665-762	https://www.molport.com/shop/molecule-link/MolPort-042-665-762
Molnova	M15862	https://www.molnova.com/en/serch-list.html?keywords=M15862
MuseChem	I009587	https://www.musechem.com/product/I009587.html
Ryan Scientific	101-93954	https://ryansci.com/products?q=101-93954&list_q=&search_type=exact
eMolecules	275122981	https://orderbb.emolecules.com/search/#?query=275122981
eMolecules	50500436	https://orderbb.emolecules.com/search/#?query=50500436

PubMed

Title	Date	PubMed
4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1, 3-thiazol-2-amine hydrochloride (SSR125543A), a potent and selective corticotrophin-releasing factor(1) receptor antagonist. II. Characterization in rodent models of stress-related disorders.	2002 Apr	11907191
4-(2-Chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]5-methyl-N-(2-propynyl)-1,3-thiazol-2-amine hydrochloride (SSR125543A): a potent and selective corticotrophin-releasing factor(1) receptor antagonist. I. Biochemical and pharmacological characterization.	2002 Apr	11907190
Discovery of N-(1-ethylpropyl)-[3-methoxy-5-(2-methoxy-4-trifluoromethoxyphenyl)-6-methyl-pyrazin-2-yl]amine 59 (NGD 98-2): an orally active corticotropin releasing factor-1 (CRF-1) receptor antagonist.	2011 Jun 23	21618986
Behavioral, biological, and chemical perspectives on targeting CRF(1) receptor antagonists to treat alcoholism.	2013 Mar 1	23294766

Patents

Sample Use Guides

In Vivo Use Guide

20 mg, 50 mg and 100 mg daily in outpatients with major depressive disorder

Route of Administration: Oral

In Vitro Use Guide

HEK 293 cells cotransfected with V1b-RL and CRHR1-YFP were preincubated for 18 h at 37 C with or without 1 uM SSR-125543 and the pharmacological properties of the V1b receptor expressed at the plasma membranes determined. SSR-125543 pretreatment significantly increased the maximal binding capacity (Bmax) for [3 H]AVP by approximately 40% without affecting the dissociation constant (Kd).

Name

Type

Language

CRINECERFONT

Official Name

English

NBI-74788

Code

English

06-RORI

Code

English

2-Thiazolamine, 4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-2-propyn-1-yl

Systematic Name

English

SSR-125543

Code

English

4-(2-chloro-4-methoxy-5-methylphenyl)-N-[(1S)-2-cyclopropyl-1-(3-fluoro-4-methylphenyl)ethyl]-5-methyl-N-prop-2-ynyl-1,3-thiazol-2-amine

Systematic Name

English

CRINECERFONT [USAN]

Common Name

English

crinecerfont [INN]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

639018