57464-25-2

Upstream product

• 132-60-5 cinchophen 
• 91-56-5 indole-2,3-dione 
• 70-11-1 α-bromoacetophenone 
• 36735-26-9 3-amino-2-phenylquinoline-4-carboxylic acid 
• 613-89-8 2-Aminoacetophenone 
• 5468-37-1 2-aminoacetophenone hydrochloride 

Downstream Products

• 57464-07-0 3-bromo-2-phenyl-quinoline-4-carbonyl chloride 
• 174636-18-1 (S)-N-(1-phenylpropyl)-3-bromo-2-phenylquinoline-4-carboxamide 

Relevant academic research and scientific papers

Discovery of a novel class of selective non-peptide antagonists for the human neurokinin-3 receptor. 2. Identification of (S)-N-(1-phenylpropyl)-3- hydroxy-2-phenylquinoline-4-carboxamide (SB 223412)

Optimization of the previously reported 2-phenyl-4-quinolinecarboxamide NK-3 receptor antagonist 14, with regard to potential metabolic instability of the ester moiety and affinity and selectivity for the human neurokinin-3 (hNK-3) receptor, is described. The ester functionality could be successfully replaced by the ketone (31) or by lower alkyl groups (Et, 21, or n-Pr, 24). Investigation of the substitution pattern of the quinoline ring resulted in the identification of position 3 as a key position to enhance hNK-3 binding affinity and selectivity for the hNK-3 versus the hNK-2 receptor. All of the chemical groups introduced at this position, with the exception of halogens, increased the hNK-3 binding affinity, and compounds 53 (3-OH, SB 223412, hNK- 3-CHO binding K(i) = 1.4 nM) and 55 (3-NH2, hNK-3-CHO binding K(i) = 1.2 nM) were the most potent compounds of this series. Selectivity studies versus the other neurokinin receptors (hNK-2-CHO and hNK-1-CHO) revealed that 53 is about 100-fold selective for the hNK-3 versus hNK-2 receptor, with no affinity for the hNK-1 at concentrations up to 100 μM. In vitro studies demonstrated that 53 is a potent functional antagonist of the hNK-3 receptor (reversal of senktide-induced contractions in rabbit isolated iris sphincter muscles and reversal of NKB-induced Ca2+ mobilization in CHO cells stably expressing the hNK-3 receptor), while in vive this compound showed oral and intravenous activity in NK-3 receptor-driven models (senktide-induced behavioral responses in mice and senktide-induced miosis in rabbits). Overall, the biological data indicate that (S)-N-(1-phenylpropyl)-3-hydroxy- 2-phenylquinoline-4-carboxamide (53, SB 223412) may serve as a pharmacological tool in animal models of disease to assess the functional and pathophysiological role of the NK-3 receptor and to establish therapeutic indications for non-peptide NK-3 receptor antagonists.

A novel synthesis of 3-halo-2-phenylquinoline-4-carboxylic acids

The 3-chloro and 3-bromo-2-phenylquinoline-4-carboxylic acids were obtained in good yields through a novel procedure, entailing the synthesis of the 3-amino intermediate and the subsequent replacement of the amino group with chlorine or bromine, according to the Sandmeyer reaction.