Rimonabant

Base Information

• Chemical Name: Rimonabant
• CAS No.: 168273-06-1
• Molecular Formula: C22H21Cl3N4O
• Molecular Weight: 463.794
• Hs Code.: 2942000000
• European Community (EC) Number: 685-399-5
• UNII: RML78EN3XE
• DSSTox Substance ID: DTXSID3046453
• Nikkaji Number: J649.754C
• Wikipedia: Rimonabant
• Wikidata: Q412529
• NCI Thesaurus Code: C73244
• Pharos Ligand ID: 6DPN7BGNLNKX
• Metabolomics Workbench ID: 43661
• ChEMBL ID: CHEMBL111
• Mol file: 168273-06-1.mol

Synonyms:acomplia;N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide hydrochloride;rimonabant;Rimonabant Hydrochloride;SR 141716;SR 141716A;SR-141716A;SR141716;SR141716A;Zimulti

Chemical Property of Rimonabant

Chemical Property:

• Appearance/Colour: White or almost white crystalline powder
• Melting Point: 230-240oC
• Refractive Index: 1.668
• Boiling Point: 627.6oC at 760 mmHg
• PKA: 11.31±0.20(Predicted)
• Flash Point: 333.3oC
• PSA: 50.16000
• Density: 1.41 g/cm³
• LogP: 6.26740
• Storage Temp.: RT
• Solubility.: Soluble in DMSO (up to 20 mg/ml) or in Ethanol (up to 20 mg/ml).
• XLogP3: 6.5
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 4
• Exact Mass: 462.078094
• Heavy Atom Count: 30
• Complexity: 583

Purity/Quality:

99% BY HPLC ^*data from raw suppliers

5-(4-Chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide 95+% ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: CC1=C(N(N=C1C(=O)NN2CCCCC2)C3=C(C=C(C=C3)Cl)Cl)C4=CC=C(C=C4)Cl
• Recent ClinicalTrials: Effect of Rimonabant on Weight Gain and Body Composition in Adults With Prader Willi Syndrome
• Recent EU Clinical Trials: Effects of a CB1 receptor reverse antagonist/agonist (Rimonabant) on wandering ability in patients with incomplete spinal cord injuries
• Description: Rimonabant is an inverse antagonist for the cannabinoid receptor (CB1). It acts by selectively blocking CB1 receptors found in the brain and in peripheral organs important in glucose and lipid metabolism, including adipose tissue, the liver, gastrointestinal tract, and muscle. Thus, rimonabant constitutes a therapeutic approach to obesity and cardiovascular risk factors. As an anorectic antiobesity drug, it was used as an adjunct to diet and exercise for obese or overweight patients with associated risk factors in Europe in 2006. Nevertheless, adverse effects including suicidality, depression, and anxiety were reported, based on which rimonadant was withdrawn worldwide in 2008. Andogenous cannabinoids are related to the pleasurable effect of nicotine, rimonabant, as a cannabinoid receptor blocker, is also being tested as a potential anti-smoking treatment. Rimonabant is a first-in-class drug launched as an oral treatment for obesity, and its mechanism of action involves the selective antagonism of cannabinoid type 1 (CB1) receptor. It is specifically indicated as an adjunct to diet and exercise for the treatment of obese patients (body mass index [BMI]≥30 kg/m2), or overweight patients (BMI＞27 kg/m2) with associated risk factors such as type 2 diabetes or dyslipidemia. Additionally, rimonabant is currently under development as a treatment for nicotine dependence. The CB1 and CB2 receptors, along with their endogenous ligands, constitute the endocannabinoid system. The CB1 receptor is expressed in the brain, adipose tissue, and several peripheral organs; the CB2 receptor is predominantly expressed in immune cells. Activation of the CB1 receptor in the CNS is associated with appetite stimulation and the modulation of brain reward mechanism, whereas activation in the periphery favors metabolic processes that lead to hepatic lipogenesis and impaired glucose homeostasis. Rimonabant acts by selectively blocking the action of central and peripheral CB1 receptors, thereby reducing food intake and improving lipid and glucose metabolism.
• Uses: Rimonabant is a selective antagonist of CB1 with IC50 of 13.6 nM and EC50 of 17.3 nM in hCB1 transfected HEK 293 membrane

Technology Process of Rimonabant

There total 55 articles about Rimonabant which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 93.0%

rimonabant hydrochloride (158681-13-1) → rimonabant (168273-06-1)

Guidance literature:

With methanol; potassium hydroxide; water; at 0 - 5 ℃; for 1h;

Reference yield: 88.0%

1-Aminopiperidine (2213-43-6) + ethyl 1-(2,4-dichlorophenyl)-4-methyl-5-(4-chlorophenyl)-1H-pyrazole-3-carboxylate (158941-22-1) → rimonabant (168273-06-1)

Guidance literature:

With trimethylaluminum; In tetrahydrofuran; toluene; at 125 ℃; for 0.0333333h;

DOI:10.1039/b719603b

Reference yield: 82.0%

5-(4-Chloro-phenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazole-3-carboxylic acid methyl ester (168272-78-4) + 1-Aminopiperidine (2213-43-6) → rimonabant (168273-06-1)

Guidance literature:

magnesium chloride; In tetrahydrofuran; for 2h; Product distribution / selectivity; Heating / reflux;

upstream raw materials:

1-Aminopiperidine

5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbonyl chloride

4-(4-chlorophenyl)-3-methyl-2,4-dioxo-N-piperidin-1-yl-butyramide

2,4-dichlorophenyl hydrazine hydrochloride

Downstream raw materials:

5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-piperidin-1-yl-1H-pyrazole-3-carboxamide isopropyl alcohol solvate

5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)pyrazole-3-carboxamide hydrate

Refernces

• 1、 Gajbhiye,More,Patil, Manoj D.,Ummanni,Kotapalli,Yogeeswari,Sriram,Masand. "Discovery of rimonabant and its potential analogues as anti-TB drug candidates". . p. 2960 - 2971. Retrieved 2015/03/14.
• 2、 Hernández-Vázquez, Eduardo,Aguayo-Ortiz, Rodrigo,Ramírez-Espinosa, Juan José,Estrada-Soto, Samuel,Hernández-Luis, Francisco. "Synthesis, hypoglycemic activity and molecular modeling studies of pyrazole-3-carbohydrazides designed by a CoMFA model". . p. 10 - 21. Retrieved 2013/10/01.