202823-24-3

Usage

Uses

Used in Pharmaceutical Industry:
Hydrazine, (5-chloro-2-methoxyphenyl)(9CI) is used as a reactant/reagent in the synthesis and structure-activity relationships of 1,3-diaryl 1,2,4-(4H)-triazol-5-ones. These compounds represent a new class of calcium-dependent, large conductance, potassium (maxi-k) channel openers, which are being targeted for the treatment of urge urinary incontinence. The development of these channel openers aims to provide a more effective and safer treatment option for patients suffering from this condition.

InChI:InChI=1/C7H9ClN2O.ClH/c1-11-7-3-2-5(8)4-6(7)10-9;/h2-4,10H,9H2,1H3;1H

Upstream product

• 95-03-4 5-chloro-2-methoxyaniline 

Downstream Products

• 1226010-80-5 1-(5-chloro-2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-amine 
• 1402585-42-5 1-(5-chloro-2-methoxyphenyl)-5-iodo-3-(trifluoromethyl)-1H-pyrazole 
• 1402585-43-6 1-(5-chloro-2-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole-5-carbonitrile 
• 1554015-52-9 1-(4-chloro-7-methoxy-1-(2-nitrophenyl)spiro[indoline-3,4'-piperidine]-1'-yl)-2,2-dimethylpropan-1-one 
• 1554015-56-3 1-(1-(2-aminophenyl)-4-chloro-7-methoxyspiro[indoline-3,4'-piperidine]-1'-yl)-2,2-dimethylpropan-1-one 

Relevant academic research and scientific papers

Identification of 1-{2-[4-chloro-1′-(2,2-dimethylpropyl)-7-hydroxy-1, 2-dihydrospiro[indole-3,4′-piperidine]-1-yl]phenyl}-3-{5-chloro-[1,3] thiazolo[5,4-b]pyridin-2-yl}urea, a potent, efficacious and orally bioavailable P2Y1 antagonist as an antiplatelet agent

Spiropiperidine indoline-substituted diaryl ureas had been identified as antagonists of the P2Y1 receptor. Enhancements in potency were realized through the introduction of a 7-hydroxyl substitution on the spiropiperidinylindoline chemotype. SAR studies were conducted to improve PK and potency, resulting in the identification of compound 3e, a potent, orally bioavailable P2Y1 antagonist with a suitable PK profile in preclinical species. Compound 3e demonstrated a robust antithrombotic effect in vivo and improved bleeding risk profile compared to the P2Y12 antagonist clopidogrel in rat efficacy/bleeding models.

Discovery of 4-Aryl-7-hydroxyindoline-based P2Y1 antagonists as novel antiplatelet agents

Adenosine diphosphate (ADP)-mediated platelet aggregation is signaled through two distinct G protein-coupled receptors (GPCR) on the platelet surface: P2Y12 and P2Y1. Blocking P2Y12 receptor is a clinically well-validated strategy for antithrombotic therapy. P2Y1 antagonists have been shown to have the potential to provide equivalent antithrombotic efficacy as P2Y12 inhibitors with reduced bleeding in preclinical animal models. We have previously reported the discovery of a potent and orally bioavailable P2Y1 antagonist, 1. This paper describes further optimization of 1 by introducing 4-aryl groups at the hydroxylindoline in two series. In the neutral series, 10q was identified with excellent potency and desirable pharmacokinetic (PK) profile. It also demonstrated similar antithrombotic efficacy with less bleeding compared with the known P2Y 12 antagonist prasugrel in rabbit efficacy/bleeding models. In the basic series, 20c (BMS-884775) was discovered with an improved PK and liability profile over 1. These results support P2Y1 antagonism as a promising new antiplatelet target.

SUBSTITUTED PYRAZOLYL-BASED CARBOXAMIDE AND UREA DERIVATIVES BEARING A PHENYL MOIETY SUBSTITUTED WITH AN O-CONTAINING GROUP AS VANILLOID RECEPTOR LIGANDS

The invention relates to substituted pyrazolyl-based carboxamide and urea derivatives of formula (Q) as vanilloid receptor ligands, to pharmaceutical compositions containing these compounds and also to these compounds for use in the treatment and/or prophylaxis of pain and further diseases and/or disorders.