284035-33-2

Basic information

• Product Name: NPS 2143
• Synonyms: Benzonitrile, 2-chloro-6-[(2R)-3-[[1,1-dimethyl-2-(2-naphthalenyl)ethyl]amino]-2-hydroxypropoxy]-;NPS 2143;2-Chloro-6-[3-[1, 1-dimethyl-2-(2-naphthyl)ethylamino]-2(R)-hydroxypropoxy]benzonitrile(NPS 2143);2-Chloro-6-[(2R)-3-[[1,1-dimethyl-2-(2-naphthalenyl)ethyl]amino]-2-hydroxypropoxy]benzonitrile;NPS 2143 hydrochloride;SB-262470(NPS-2143);1-diMethyl-2-(2-naphthalenyl)ethyl]aMino]-2-hydroxypropoxy]-;2-chloro-6-[(2R)-3-[[1
• CAS NO: 284035-33-2
• Molecular Formula: C24H25ClN2O2
• Molecular Weight: 408.92
• Product Categories: API intermediates
• Mol File: 284035-33-2.mol
• Article Data: 4

Chemical Properties

• Boiling Point: 608.4 °C at 760 mmHg
• Flash Point: 321.8 °C
• Appearance: /
• Density: 1.23 g/cm³
• Vapor Pressure: 1.17E-15mmHg at 25°C
• Refractive Index: 1.631
• Storage Temp.: Desiccate at RT
• Solubility: ≥40.9 mg/mL in DMSO; insoluble in H2O; ≥28.35 mg/mL in EtOH
• PKA: 13.67±0.20(Predicted)
• CAS DataBase Reference: NPS 2143(CAS DataBase Reference)
• NIST Chemistry Reference: NPS 2143(284035-33-2)
• EPA Substance Registry System: NPS 2143(284035-33-2)

Safety Data

• Hazardous Substances Data: 284035-33-2(Hazardous Substances Data)

Usage

Description

NPS 2143 is a compound that acts as a potent and selective antagonist for the Calcium-sensing receptor (CaSR), a protein that plays a crucial role in maintaining calcium blood concentration homeostasis.

Uses

Used in Pharmaceutical Industry:
NPS 2143 is used as a therapeutic agent for conditions related to calcium homeostasis. By acting as an antagonist for CaSR, it can potentially help regulate calcium levels in the blood, which may be beneficial for patients with disorders affecting calcium metabolism.
Used in Research Applications:
NPS 2143 is used as a research tool to study the role of CaSR in various physiological processes and diseases. Its potent and selective antagonism allows researchers to investigate the function of CaSR and its potential as a target for therapeutic intervention in conditions related to calcium homeostasis.

Biological Activity

nps-2143 is a novel and selective antagonist of casr (ca2+-sensing receptor) with the ec50 value of 4.27mm for [ca2+]o [1].calcilytics nps-2143 has been reported to diminish the sensitivity of the casr for [ca2+]o, resulting in an attenuated signal transduction in vitro and increased secretion of pth in vivo. in addition, the ec50 values of nps-2143 are 4.27, 1.56, 1.61, 2.46, 2.07 and 3.15mm for the wild-type casr, mutant casr (t151r, p221l, e767q, g830s, and a844t), respectively. apart from these, in hek 293t cells expressing casr, nps-2143 has been revealed to inhibit the [ca2+]o-induced cytosolic calcium signal in a concentration-dependent manner [1]..

references

[1] letz s1, rus r, haag c, d?rr hg, schnabel d, m?hlig m, schulze e, frank-raue k, raue f, mayr b, sch?fl c. novel activating mutations of the calcium-sensing receptor: the calcilytic nps-2143 mitigates excessive signal transduction of mutant receptors. j clin endocrinol metab. 2010 oct;95(10):e229-33.

InChI:InChI=1/C24H25ClN2O2/c1-24(2,13-17-10-11-18-6-3-4-7-19(18)12-17)27-15-20(28)16-29-23-9-5-8-22(25)21(23)14-26/h3-12,20,27-28H,13,15-16H2,1-2H3/t20-/m1/s1

Upstream product

• 198226-63-0 [2-methyl-1-(naphthalen-2-yl)propan-2-yl]amine 
• 198226-53-8 2-chloro-6-([(2R)-2-oxiranylmethyl]oxy)benzonitrile 
• 400613-92-5 2-(2-methyl-2-nitropropyl)naphthalene 
• 867040-04-8 (+/-)-2-chloro-6-(3-chloro-2-hydroxypropoxy)benzonitrile 
• 867040-05-9 Acetic acid (S)-2-(3-chloro-2-cyano-phenoxy)-1-chloromethyl-ethyl ester 
• 668-45-1 2-chloro-6-fluorobenzonitrile 
• 2018-90-8 naphthalen-2-ylmethylamine 
• 89999-90-6 3-chloro-2-cyanophenol 
• 198226-62-9 (+/-)-2-chloro-6-(oxiran-2-ylmethoxy)benzonitrile 
• 613-46-7 2-naphthalenecarbonitrile 
• 1056958-45-2 C₉H₆ClNO₂ 
• 351490-95-4 2-methyl-1-(naphthalen-2-yl)propan-2-amine hydrochloride 

Relevant articles and documents

Stereo-specific modulation of the extracellular calcium-sensing receptor in colon cancer cells

Pharmacological allosteric agonists (calcimimetics) of the extracellular calcium-sensing receptor (CaSR) have substantial gastro-intestinal side effects and induce the expression of inflammatory markers in colon cancer cells. Here, we compared the effects of both CaSR-specific (R enantiomers) and-unspecific (S enantiomers) enantiomers of a calcimimetic (NPS 568) and a calcilytic (allosteric CaSR antagonists; NPS 2143) to prove that these effects are indeed mediated via the CaSR, rather than via off-target effects, e.g., on β-adrenoceptors or calcium channels, of these drugs. The unspecific S enantiomer of NPS 2143 and NPS S-2143 was prepared using synthetic chemistry and characterized using crystallography. NPS S-2143 was then tested in HEK-293 cells stably transfected with the human CaSR (HEK-CaSR), where it did not inhibit CaSR-mediated intracellular Ca2+ signals, as expected. HT29 colon cancer cells transfected with the CaSR were treated with both enantiomers of NPS 568 and NPS 2143 alone or in combination, and the expression of CaSR and the pro-inflammatory cytokine interleukin 8 (IL-8) was measured by RT-qPCR and ELISA. Only the CaSR-selective enantiomers of the calcimimetic NPS 568 and NPS 2143 were able to modulate CaSR and IL-8 expression. We proved that pro-inflammatory effects in colon cancer cells are indeed mediated through CaSR activation. The non-CaSR selective enantiomer NPS S-2143 will be a valuable tool for investigations in CaSR-mediated processes.

Synthesis of the calcilytic ligand NPS 2143

(R)-3 (NPS 2143) is a negative allosteric modulator of the human calcium-sensing receptor (CaSR) and as such represents an important pharmacological tool compound for studying the CaSR. Herein, we disclose for the first time a complete experimental description, detailed characterisation and assessment of enantiomeric purity for (R)-3. An efficient, reproducible and scalable synthesis of (R)-3 that requires a minimum of chromatographic purification steps is presented. (R)-3 was obtained in excellent optical purity (er > 99:1) as demonstrated by chiral HPLC and the pharmacological profile for (R)-3 is in full accordance with that reported in the literature.