Download PDF
Arzneimittelforschung 2011; 61(8): 452-457
DOI: 10.1055/s-0031-1296227
Lipid Reducers
Editio Cantor Verlag Aulendorf (Germany)

Synthesis and antihyperlipidemic activity of some novel 4-(substitutedamino)-5-substituted-3-mercapto-(4H)-1,2,4-triazoles

Chhabria Mahesh T
1   Department of Pharmaceutical Chemistry, L. M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat, India
,
Suhagia Bhanubhai N
1   Department of Pharmaceutical Chemistry, L. M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat, India
,
Brahmkshatriya Pathik S
1   Department of Pharmaceutical Chemistry, L. M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat, India
,
Raval Priyesha M
1   Department of Pharmaceutical Chemistry, L. M. College of Pharmacy, Navrangpura, Ahmedabad, Gujarat, India
› Author Affiliations
Further Information

Publication History

Publication Date:
27 November 2011 (online)

    Permissions and Reprints

Abstract

Hyperlipidemia is considered one of the key factors for cardiovascular diseases. Based on earlier work on a series of 5-al-kyl-4-aryl-3-mercapto-(4H)-1,2,4-triazoles, for further lead modification, a series of 4-(substituted)amino-5-substituted-3-mercapto-(4H)-1,2,4-triazoles was designed. Target compounds were synthesized by the well known Hoggarth synthesis of substituted 1,2,4-triazoles. Synthesized compounds were screened for lipid lowering activity using the “Poloxamer 407 induced hyperlipidemia in rats” model at a dose of 100 mg/kg p. o. Compounds were found to alter serum lipid levels significantly. Most of the compounds significantly reduced serum cholesterol and triglyceride levels. Some of the compounds were found to reduce triglycerides and elevate high density lipoprotein (HDL) levels more than the standard drug atorvastatin (CAS 134523-03-8). Compounds with chloro substitution on aryl rings were found more active in reducing serum lipid levels than other substitutions.

Key words

Antihyperlipidemic activity - Cholesterol - High-density lipoprotein - Poloxamer 407 - Triazoles - Triglycerides
 

  • References

  • 1 Brahmkshatriya PS, Chhabria MT, lani MH. Recent developments in the treatment of atherosclerosis. J Enz Inhib Med Chem. 2006; 21: 1-15
    CrossrefPubMedSearch in Google Scholar
  • 2 Foley SM. Update on risk factors for atherosclerosis: the role of inflammation and apolipoprotein E. Medsurg Nurs. 2005; 14 (1) 43-50
    PubMedSearch in Google Scholar
  • 3 Kannel WB, Castelli WP, Gordon T. Cholesterol in the prediction of atherosclerotic disease: new perspective based on the Framingham Heart Study. Ann Intern Med. 1979; 90: 85-91
    PubMedSearch in Google Scholar
  • 4 Omar MA, Wilson JP. FDA adverse event reports on statin-associated rhabdomyolysis. Ann Pharmacother. 2002; 36: 288-95
    CrossrefPubMedSearch in Google Scholar
  • 5 Genest J, McNamara J, Salem DN, Schaefer EJ. Prevalence of risk factors in men with premature coronary artery disease. Am J Cardiol. 1991; 67: 1185-9
    CrossrefPubMedSearch in Google Scholar
  • 6 Tall AR. An overview of reverse cholesterol transport. Eur Heart J. 1998; 19A: A31-5
    PubMedSearch in Google Scholar
  • 7 Brahmkshatriya PS, Chhabria MT, Mandhare AB, Suhagia BN. QSAR study of a series of cholesteryl ester transfer protein inhibitors. Abstract of papers, 2008 AAPS Annual Meeting and Exposition, Atlanta, GA 2008 Abstract 1584
    PubMedSearch in Google Scholar
  • 8 Hoggarth E. Compounds related to thiosemicarbazide VIII. Oxidation of thiosemicarbazones. J Chem Soc. 1952; 4811
    CrossrefPubMedSearch in Google Scholar
  • 9 Bala S, Gupta RP, Sachdeva ML, Singh A, Pujari HK. Heterocyclic systems containing bridgehead nitrogen atom: Part XXXIII – syntheses of s-triazolo[3,4-b]quinoxaline and s-triazino[3,4-b][1,3,4]-thiadiazines. Indian J Chem. 1978; 16: 481-3
    PubMedSearch in Google Scholar
  • 10 Reid JR, Heindel ND. Improved synthesis of 5-substituted-4-amino-3-mercapto-(4H)-1,2,4-triazoles. J Heterocycl Chem. 1976; 13: 925-6
    CrossrefPubMedSearch in Google Scholar
  • 11 Saikachi H, Kanaoka M. Synthesis of related compounds of thiosemicarbazide. VII. Reaction of hydrazine hydrate with 1,3,4-thiadiazoles. Yakugaku Zasshi. 1962; 82: 683
    PubMedSearch in Google Scholar
  • 12 Wout ZGM, Pec EA, Maggiore JA, Williams RH, Palicharla P, Johnston TP. Poloxamer-407 mediated changes in plasma cholesterol and triglycerides following intraperitoneal injection in rats. J Par Sci Tech. 1992; 46: 192-200
    PubMedSearch in Google Scholar
  • 13 Deshmukh AA, Mody MK, Ramlingam T, Sattur PB. Synthesis and pharmacology of 2-aryl/aralkyl-5-aryl/aralkyl/dia-ralkyl-s-triazole[3,4-b]-1,3,4-thiadiazoles. Indian J Chem. 1984; 23: 793-5
    PubMedSearch in Google Scholar
  • 14 Mohan J, Anjaneyulu GSR. Heterocyclic systems containing bridgehead nitrogen atom: syntheses of s-triazolo[3,4-b][1,3,4]thiadiazole-6-(5H)-thiones, s-triazolo[3,4-b][1,3,4]-thiadiazines and related heterocycles. Indian J Chem. 1988; 27: 128-131
    PubMedSearch in Google Scholar
  • 15 Azaryan AS, Iradyan NS, Aroyan AA. Synthese von 1,2,4-triazol-derivaten. Arm Xim Zh. 1975; 28: 709-14 German.
    PubMedSearch in Google Scholar
  • 16 Sung K, Lee AR. Synthesis of [(4,5-disubstituted-4H-1,2,4–triazol-3-yl)thio]alkanoic acids and their analogues as possible antiinflammatory agents. J Hetereocycl Chem. 1992; 29: 1101-9
    PubMedSearch in Google Scholar
  • 17 Chande MS, Bhandari JD, Joshi VR. Investigation on the reaction of 4-anilino-5-mercapto-s-triazoles with pyrazolines and barbituric acids. Indian J Chem. 1993; 32: 1218-28
    PubMedSearch in Google Scholar