174636-32-9

Usage

Uses

Used in Pharmaceutical Industry:
SB 223412 is used as a research compound for studying the role of the NK3 receptor in various physiological processes and diseases. Its high selectivity and potency make it a valuable tool in understanding the NK3 receptor's function and its potential as a therapeutic target.
Used in Neurological Applications:
SB 223412 is used as a potential therapeutic agent for neurological disorders, such as migraines and other conditions involving the neurokinin system. By blocking the NK3 receptor, it may help alleviate symptoms and improve patient outcomes.
Used in Preclinical Research:
SB 223412 is used in preclinical research to evaluate its efficacy and safety in animal models of various diseases, including neurological and psychiatric conditions. This helps researchers understand its potential therapeutic applications and guide further drug development efforts.
Used in Drug Development:
SB 223412 serves as a lead compound in the development of new drugs targeting the NK3 receptor. Its properties, such as high selectivity and potency, make it an attractive starting point for designing more effective and safer therapeutic agents for a range of conditions.

InChI:InChI=1/C25H22N2O2/c1-2-20(17-11-5-3-6-12-17)27-25(29)22-19-15-9-10-16-21(19)26-23(24(22)28)18-13-7-4-8-14-18/h3-16,20,28H,2H2,1H3,(H,27,29)/t20-/m0/s1

Upstream product

• 485-89-2 oxycinchophen 
• 3789-59-1 (R)-1-phenylpropylamine 
• 4079-52-1 methoxymethyl phenyl ketone 
• 41957-64-6 3-methoxy-2-phenylquinoline-4-carboxylic cid 
• 91-56-5 indole-2,3-dione 

Downstream Products

• 191796-72-2 (S)-N-(α-ethylbenzyl)-3-(ethoxycarbonylmethoxy)-2-phenylquinoline-4-carboxamide 
• 191796-46-0 (S)-N-(α-ethylbenzyl)-3-[2-(3,4-dihydro-1(2H)-isoquinolinon-2-yl)ethoxy]-2-phenylquinoline-4-carboxamide 
• 191796-33-5 (S)-N-(α-ethylbenzyl)-3-(3-phthalimidopropoxy)-2-phenylquinoline-4-carboxamide 
• 192704-78-2 (S)-N-(a-ethylbenzyl)-3-(cyanomethoxy)-2-phenylquinoline-4-carboxamide 

Relevant academic research and scientific papers

Harnessing the anti-nociceptive potential of nk2 and nk3 ligands in the design of new multifunctional μ/δ-opioid agonist–neurokinin antagonist peptidomimetics

Opioid agonists are well-established analgesics, widely prescribed for acute but also chronic pain. However, their efficiency comes with the price of drastically impacting side effects that are inherently linked to their prolonged use. To answer these liabilities, designed multiple ligands (DMLs) offer a promising strategy by co-targeting opioid and non-opioid signaling pathways involved in nociception. Despite being intimately linked to the Substance P (SP)/neurokinin 1 (NK1) system, which is broadly examined for pain treatment, the neurokinin receptors NK2 and NK3 have so far been neglected in such DMLs. Herein, a series of newly designed opioid agonist-NK2 or-NK3 antagonists is reported. A selection of reported peptidic, pseudo-peptidic, and non-peptide neurokinin NK2 and NK3 ligands were covalently linked to the peptidic μ-opioid selective pharma-cophore Dmt-DALDA (H-Dmt-D-Arg-Phe-Lys-NH2 ) and the dual μ/δ opioid agonist H-Dmt-D-Arg-Aba-βAla-NH2 (KGOP01). Opioid binding assays unequivocally demonstrated that only hybrids SBL-OPNK-5, SBL-OPNK-7 and SBL-OPNK-9, bearing the KGOP01 scaffold, conserved nanomo-lar range μ-opioid receptor (MOR) affinity, and slightly reduced affinity for the δ-opioid receptor (DOR). Moreover, NK binding experiments proved that compounds SBL-OPNK-5, SBL-OPNK-7, and SBL-OPNK-9 exhibited (sub)nanomolar binding affinity for NK2 and NK3, opening promising opportunities for the design of next-generation opioid hybrids.

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.

METHOD FOR THE SYNTHESIS OF QUINOLIΝE 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.

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%).

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.