92309-78-9

Upstream product

• 7672-01-7 2-phenylquinazoline-4-carboxylic acid 
• 92566-52-4 ethyl 2-phenylquinazoline-4-carboxylate 
• 6484-25-9 4-chloro-2-phenylquinazoline 
• 67824-28-6 2-phenyl-4-quinazolinecarbonitrile 
• 38430-03-4 N-phenylbenzimidoyl chloride 
• 93-98-1 N-phenyl benzoyl amide 

Downstream Products

• 1361583-37-0 (2-phenylquinazolin-4-yl)(4-(pyridin-4-yl)piperazin-1-yl)methanone 

Relevant academic research and scientific papers

Compound AD110 Acts as Therapeutic Management for Alzheimer's Disease and Stroke in Mouse and Rat Models

Anti-inflammatory therapy may be an effective therapeutic intervention for neurological diseases, such as Alzheimer's disease (AD) and stroke. As an important anti-inflammatory cytokine, interleukin-10 (IL-10) inhibits proinflammatory responses of both innate and adaptive immune cells. We tested the hypothesis that drug-induced promotion of IL-10 expression is effective in improving cognitive abilities and neurologic outcomes of AD and stroke. An orally small molecule AD110 was synthesized and subjected to in vitro and in vivo analyses. We found that AD110 enhanced IL-10 release in lipopolysaccharide (LPS)-activated BV2 microglial cells. Y-Maze and Morris water maze tests showed improved cognitive abilities in AD mice treated with AD110. Moreover, AD110 attenuated cerebral ischemic injury in a transient middle cerebral artery occlusion (tMCAO) rat model. This study not only provides a promising lead compound with IL-10-promoting activity, but also supports the hypothesis that promoting IL-10 expression is a potential therapeutic strategy for AD and stroke.

Discovery of a novel class of selective non-peptide antagonists for the human neurokinin-3 receptor. 1. Identification of the 4-quinolinecarboxamide framework

A novel class of potent and selective non-peptide neurokinin-3 (NK-3) receptor antagonists, featuring the 4-quinolinecarboxamide framework, has been designed based upon chemically diverse NK-1 receptor antagonists. The novel compounds 33-76, prompted by chemical modifications of the prototype 4, have been characterized by binding analysis using a membrane preparation of chinese hamster ovary (CHO) cells expressing the human neurokinin-3 receptors (hNK-3-CHO), and clear structure-activity relationships (SARs) have been established. From SARs, (R)-N-[α-(methoxycarbonyl)benzyl]-2- phenylquinoline-4-carboxamide (65, SB 218795, hNK-3-CHO binding K(i) = 13 nM) emerged as one of the most potent compounds of this novel class. Selectivity studies versus the other neurokinin receptors (hNK-2-CHO and hNK-1-CHO) revealed that 65 is about 90-fold selective for hNK-3 versus hNK-2 receptors (hNK-2-CHO binding K(i) = 1221 nM) and over 7000-fold selective versus hNK-1 receptors (hNK-1-CHO binding K(i) = >100 μM). In vitro functional studies in rabbit isolated iris sphincter muscle preparation demonstrated that 65 is a competitive antagonist of the contractile response induced by the potent and selective NK-3 receptor agonist senktide with a K(b) = 43 nM. Overall, the data indicate that 65 is a potent and selective hNK-3 receptor antagonist and a useful lead for further chemical optimization.