485-89-2

Usage

Uses

Used in Pharmaceutical Research:
Oxicinchophen is used as a research tool for studying P-selectin antagonistic activity, which is relevant in the context of inflammation and vascular biology. Its application in this area helps researchers understand the underlying mechanisms of these processes and develop potential therapeutic strategies.
Used in Enzyme Inhibition Studies:
Oxicinchophen is utilized as a DHOD (dihydroorotate dehydrogenase) inhibitor, which is an important enzyme in the pyrimidine biosynthesis pathway. Inhibition of this enzyme can have implications in the development of antiviral and anticancer drugs.
Used in Structure-Activity Relationship (SAR) Studies:
Oxicinchophen is employed in the investigation of the structure-activity relationship of quinoline salicylic acids using the Pfitzinger reaction of isatin derivatives with (acetyloxy)acetophenone derivatives. This helps in understanding the relationship between the chemical structure of these compounds and their biological activities.
Used in Anti-inflammatory Drug Research:
Oxicinchophen is used to study the effects of anti-inflammatory drugs on vascular smooth muscle. This application aids in the development of novel anti-inflammatory agents with improved efficacy and reduced side effects.
Used in Mitochondrial Function Studies:
Oxicinchophen is utilized to investigate the increase in oxygen consumption in the absence of a phosphate acceptor and to inhibit ATP synthesis in isolated rat liver mitochondria. This application provides insights into the role of oxycinchophen in cellular energy metabolism and its potential implications in various diseases related to mitochondrial dysfunction.

Safety Profile

Low toxicity by ingestion and skin contact. When heated to decomposition it emits toxic fumes of NOx.

Purification Methods

It is precipitated from alkaline solution on acidification and crystallises from EtOH or AcOH in yellow crystals. [Marshall & Blanchard J Pharmacol 95 186 1949, Beilstein 22 H 245, 22 II 183, 22 III/IV 2383.]

InChI:InChI=1/C16H11NO3/c18-15-13(16(19)20)11-8-4-5-9-12(11)17-14(15)10-6-2-1-3-7-10/h1-9,18H,(H,19,20)

Upstream product

• 2243-35-8 2-acetoxyacetophenone 
• 91-56-5 indole-2,3-dione 
• 70-11-1 α-bromoacetophenone 
• 532-27-4 1-chloroacetophenone 
• 484-38-8 isatic acid 
• 36735-26-9 3-amino-2-phenylquinoline-4-carboxylic acid 
• 41957-64-6 3-methoxy-2-phenylquinoline-4-carboxylic cid 
• 1000007-26-0 2-phenyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-quinoline-4-carboxylic acid ethyl ester 
• 1224598-16-6 ethyl 3-([bis(dimethylamino)phosphoryl]oxy)-2-phenylquinoline-4-carboxylate 
• 7631-34-7 (2-Amino-phenyl)-oxo-acetic acid anion 
• 4079-52-1 methoxymethyl phenyl ketone 

Downstream Products

• 5855-50-5 3-hydroxy-2-phenylquinoline 
• 174636-32-9 talnetant 
• 875754-97-5 2-phenyl-3-(phenylmethoxy)quinoline-4-carboxylic acid 
• 1197391-19-7 4-bromo-2-phenylquinolin-3-ol 
• 1197391-36-8 4-(4-fluorophenyl)-2-phenylquinolin-3-ol 
• 1197391-35-7 4-(4-methoxyphenyl)-2-phenylquinolin-3-ol 
• 1197391-37-9 2-phenyl-4-(phenylamino)quinolin-3-ol 
• 5855-64-1 2,4-diphenylquinolin-3-ol 
• 2387-23-7 1,3-Dicyclohexylurea 
• 174636-33-0 (S)-(-)-N-(α-ethylbenzyl)-3-hydroxy-2-phenyl-4-quinoline carboxamide 
• 191796-72-2 (S)-N-(α-ethylbenzyl)-3-(ethoxycarbonylmethoxy)-2-phenylquinoline-4-carboxamide 

Relevant academic research and scientific papers

Phosphorodiamidate-directed metalation of N -heterocycles using Mg- and Zn-TMP bases

Figure presented The strong directing ability of the N,N,N′,N′- tetramethyldiaminophosphorodiamidate group has been used to achieve selective metalations on various heterocycles such as pyridines, quinolines and quinoxalines with TMP-derived bases like TMPMgCl·LiCl, TMP 2Mg·2LiCl, and TMP2Zn·2MgCl 2·2LiCl. This protocol was applied in the synthesis of etoricoxib, talnetant and a P-selectin inhibitor.

Bromodecarboxylation of quinoline salicylic acids: Increasing the diversity of accessible substituted quinolines

(Chemical Equation Presented) Quinoline salicylic acids underwent bromodecarboxylation at room temperature upon treatment with N-bromosuccinimide. A wide variety of functional groups was tolerated. Several one-pot transformations were also carried out, allowing the preparation of diverse 4-substituted quinolines.

Multiple regioselective functionalizations of quinolines via magnesiations

A wide range of polyfunctionalized quinolines was prepared via chemo- and regioselective magnesiation reactions using appropriate Mg reagents, such as i-PrMgCl-LiCl, MesMgBr·LiCl, Mes2Mg·2LiBr, TMPMgCl·LiCl, and TMP2Mg·2LiCl. An application to the total synthesis of the biologically active compound talnetant was performed (six steps, 28%).

2-(4-Chlorobenzyl)-3-hydroxy-7,8,9,10-tetrahydrobenzo[H] quinoline-4-carboxylic acid (PSI-697): Identification of a clinical candidate from the quinoline salicylic acid series of P-selectin antagonists

P-selectin-PSGL-1 interaction causes rolling of leukocytes on the endothelial cell surface, which subsequently leads to firm adherence and leukocyte transmigration through the vessel wall into the surrounding tissues. P-selectin is upregulated on the surface of both platelets and endothelium in a variety of atherosclerosis-associated conditions. Consequently, inhibition of this interaction by means of a small molecule P-selectin antagonist is an attractive strategy for the treatment of atherosclerosis. High-throughput screening and subsequent analoging had led to the identification of compound 1 as the lead candidate. Herein, we report the continuation of this work and the discovery of a second-generation series, the tetrahydrobenzoquinoline salicylic acids. These compounds have improved pharmacokinetic properties, and a number of them have shown oral efficacy in mouse and rat models of atherogenesis and vascular injury. The lead 31 (PSI-697), is currently in clinical development for the treatment of atherothrombotic vascular events.

Method for the synthesis of quinoline derivatives

This invention relates to novel intermediates and processes for preparing pharmaceutically active quinoline compounds, including (?)-(S)-N-(α-ethylbenzyl)-3-hydroxy-2-phenylquinoline-4-carboxamide.

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.

Formation of 4-Nitro-2-phenylquinoline on Attempted Diazotization of 3-Amino-2-phenylquinoline-4-carboxylic Acid

Treatment of 3-amino-2-phenylquinoline-4-carboxylic acid with isoamyl nitrite in acidic dimethylformamide gave 4-nitro-2-phenylquinoline.