168273-06-1 Usage
Description
Rimonabant, also known as Acomplia, is a first-in-class drug that functions as an inverse antagonist for the cannabinoid receptor (CB1). It selectively blocks CB1 receptors found in the brain and peripheral organs involved in glucose and lipid metabolism, such as adipose tissue, the liver, gastrointestinal tract, and muscle. This selective antagonism makes rimonabant a therapeutic approach to obesity and cardiovascular risk factors.
Uses
Used in Obesity Treatment:
Rimonabant is used as an anorectic antiobesity drug for obese or overweight patients with associated risk factors. It was initially used as an adjunct to diet and exercise in Europe in 2006. It works by reducing food intake and improving lipid and glucose metabolism through the selective blocking of central and peripheral CB1 receptors.
Used in Cardiovascular Risk Reduction:
Rimonabant is also used to address cardiovascular risk factors associated with obesity. By improving lipid and glucose metabolism, it helps in managing conditions like type 2 diabetes and dyslipidemia.
Used in Anti-smoking Treatment:
Rimonabant is under development as a potential treatment for nicotine dependence. As a cannabinoid receptor blocker, it is being tested for its effectiveness in reducing the pleasurable effects of nicotine, which could aid in smoking cessation.
Used in Pharmaceutical Industry:
Rimonabant is used in the pharmaceutical industry for the development of drugs targeting the endocannabinoid system. Its mechanism of action involves the selective antagonism of cannabinoid type 1 (CB1) receptor, which has potential applications in various therapeutic areas beyond obesity and smoking cessation.
Please note that due to adverse effects including suicidality, depression, and anxiety, rimonabant was withdrawn worldwide in 2008. However, the information provided here is based on the materials given and serves as a historical reference for the drug's description and uses.
References
[1] https://www.drugs.com/acomplia.html
[2] Leite CE, Mocelin CA, Petersen GO, Leal MB, Thiesen FV (2009) Rimonabant: an antagonist drug of the endocannabinoid system for the treatment of obesity, Pharmacol Rep., 61, 217-224
References
1) Rinaldi-Carmona et al. (1994) SR141716A, a potent and selective antagonist of the brain cannabinoid receptor; FEBS Lett. 350 240
2) Rinaldi-Carmona et al. (1995) Biochemical and pharmacological characterization of SR141716A, the first potent and selective cannabinoid receptor antagonist; Life Sci. 56 1941
Synthesis
The reported preparation of rimonabant,
both in small and large scale, is shown in the scheme. Lithium enolate formation of p-chlorophenyl ethyl ketone 54 with LiHMDS in THF at -78oC for 45 min followed
by reaction with diethyl oxalate at -78oC and warming
to room temperature over 16 h provided the lithium enolate
salt of the diketoester 55. Reaction of diketoester salt 55 with
2,4-dichlorophenyl hydrazine (56) in ethanol at room temperature
gave intermediate hydrazone 57 which is then cyclized
in refluxing acetic acid for 24 h to obtain pyrazole
ester 58. Hydrolysis of ester 58 with KOH in refluxing
methanol:water mixture gave acid 59 which was then converted
to the acid chloride 60 with thionyl chloride in refluxing
toluene in very good yield. On scale, the synthesis of the
acid chloride was performed in cyclohexane at 83oC. Reaction
of acid chloride 60 with 1-aminopiperidine (61) in the
presence of triethylamine at 0oC to room temperature over 3h
gave rimonabant (VIII) which was isolated as the HCl salt
by treating it with HCl in ether.
Check Digit Verification of cas no
The CAS Registry Mumber 168273-06-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,6,8,2,7 and 3 respectively; the second part has 2 digits, 0 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 168273-06:
(8*1)+(7*6)+(6*8)+(5*2)+(4*7)+(3*3)+(2*0)+(1*6)=151
151 % 10 = 1
So 168273-06-1 is a valid CAS Registry Number.
InChI:InChI=1/C22H21Cl3N4O/c1-14-20(22(30)27-28-11-3-2-4-12-28)26-29(19-10-9-17(24)13-18(19)25)21(14)15-5-7-16(23)8-6-15/h5-10,13H,2-4,11-12H2,1H3,(H,27,30)
168273-06-1Relevant articles and documents
Process for Making Biologically Active Compounds and Intermediates Thereof
-
, (2022/02/05)
A process of manufacturing biologically active compounds, their analogs, pharmaceutically acceptable salts, solvates, polymorphs, isotopic variants, and intermediates thereof. Notably, the compounds of the formula IA, 1B, 1C. 1D. 1E, 1F and IG for which novel processes have been disclosed, selectively act on the cannabinoid receptors, and with high affinity. The processes for the preparation of the compounds enable the syntheses of cannabinoid modulators on a large-scale that are eco-friendly and economically viable. Additionally, the processes disclosed enable the synthesis of cannabinoid modulators with high purity and in high yield for their use in making drug substance and drug products.
PYRAZOLE CARBOXYLIC ACID ANALOGUES AS ANTI-MYCOBACTERIAL DRUG CANDIDATES
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Page/Page column 14; 15, (2014/11/13)
The present invention relates to the pyrazole carboxylic acid analogues of Formula (1) or stereoisomers, or esters or pharmaceutically acceptable salts thereof, as potent anti- mycobacterial agents. Formula Further it discloses the pharmaceutical composition comprising compounds of Formula-I for the treatment of mycobacterial infections.
PROCESS FOR THE PREPARATION OF RIMONABANT
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Page/Page column 8-9, (2009/10/22)
The present invention relates to a new process for the preparation of Rimonabant through the formation of an intermediate compound of formula (VII). The invention further relates to a process for the preparation of the compound of formula (VII).
