Synthesis and bioactivities of 2-Azetidinone derivatives as cholesterol absorption inhibitors

Medicinal Chemistry

Volumn 7, Issue 6, 2011, Pages 534-542

  Wang, Yubin ^a   Qian, Hai ^b   Zhou, Jinpei ^b   Zhang, Huibin ^b   Ji, Jianfeng ^b   Huang, Wenlong ^b  

^a NANJING TECH UNIVERSITY   (China)

^b CHINA PHARMACEUTICAL UNIVERSITY   (China)

Author keywords

2 Azetidinones; Bioactivities; Cholesterol absorption inhibitor; Synthesis

Indexed keywords

1 (2 METHYLPHENYL) 3 (3 HYDROXY 3,3 DIPHENYLPROPYL) 4 (BENZO[D][1,3]DIOXOL 5 YL) 2 AZETIDINONE; 1 (4 CHLOROPHENYL) 3 (3 HYDROXY 3,3 DIPHENYLPROPYL) 4 (4 METHOXYPHENYL) 2 AZETIDINONE; 1 (4 FLUOROPHENYL) 3 [3 HYDROXY 3,3 BIS(4 FLUOROPHENYL)PROPYL] 4 (4 METHOXYPHENYL) 2 AZETIDINONE; 1 (4 METHYLPHENYL) 3 [3 HYDROXY 3,3 BIS(4 FLUOROPHENYL)PROPYL] 4 (BENZO[D][1,3]DIOXOL 5 YL) 2 AZETIDINONE; 3 [3 [2 OXO 4 (BENZO[D][1,3]DIOXOL 5 YL) 1 (2 METHYLPHENYL)AZETIDINYL]]PROPYL NICOTINATE; AZETIDINONE DERIVATIVE; CHOLESTEROL; EZETIMIBE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; HYPOCHOLESTEROLEMIC AGENT; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ARTICLE; CHOLESTEROL BLOOD LEVEL; DRUG DESIGN; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; HAMSTER; MALE; NONHUMAN; PRIORITY JOURNAL; REACTION ANALYSIS; STRUCTURE ACTIVITY RELATION;

EID: 80755152293     PISSN: 15734064     EISSN: 18756638     Source Type: Journal    
DOI: 10.2174/157340611797928271     Document Type: Article

References (16)

1. Iyer, S.P.; Yao, X.; Crona, J.H.; Hoos, L.M.; Tetzloff, G.; Davis, H.R.Jr.; Graziano, M.P.; Altmann, S.W. Characterization of the putative native and recombinant rat sterol transporter Niemann-Pick C1 Like 1 (NPC1L1) protein. Biochim. Biophys. Acta., 2005, 1722(3), 282-292. (Pubitemid 40354166)
2. Shepherd, J. The role of the exogenous pathway in hypercholesterolaemia. Eur. Heart. J., 2001, 3 (Suppl E), A2-A5.
3. Stone, N. Combination therapy: Its rationale and the role of ezetimibe. Eur. Heart. J., 2002, 4 (Suppl J), J19-J22. (Pubitemid 35423722)
4. Siegel-Axel, D. I. Cerivastatin: A cellular and molecular drug for the future? Cell. Mol. Life. Sci., 2003, 60, 144-164. (Pubitemid 36223123)
5. Ros, E. Intestinal absorption of triglyceride and cholesterol. Dietary and pharmacological inhibition to reduce cardiovascular risk. Atherosclerosis, 2000, 151(2), 357-379. (Pubitemid 30618753)
6. Heek, M.V.; Davis, H. Pharmacology of ezetimibe. Eur. Heart. J., 2002, 4 (Suppl J), J5-J8. (Pubitemid 35423720)
7. Vaccaro, W.D.; Sher, R.; Davis, H.R.Jr. 2-Azetidinone cholesterol absorption inhibitors: Increased potency by substitution of the C-4 phenyl ring. Bioorg. Med. Chem., 1998, 6(9), 1429-1437. (Pubitemid 28446221)
8. Burnett, D.A. β-Lactam Cholesterol Absorption Inhibitor. Curr. Med. Chem., 2004, 11(14), 1873-1887.
9. Rosenblum, S.B.; Huynh, T.; Afonso, A.; Davis, H.R.Jr. Synthesis of 3-Arylpropenyl, 3-Arylpropynyl and 3-Arylpropyl 2-Azetidinones as Cholesterol Absorption Inhibitors: Application of the Palladium-Catalyzed Arylation of Alkenes and Alkynes. Tetrahedron, 2000, 56(31), 5735-5742. (Pubitemid 30619323)
10. Pfefferkorn, J. A.; Larsen, S. D.; Huis, C.V.; Sorenson, R.; Barton, T.; Winters, T.; Auerbach, B.; Wu, C.; Wolfram , T. J.; Cai, H.; Welch, K.; Esmaiel, N.; Davis, J.; Bousley, R.; Olsen, K.; Mueller, S. B.; Mertz, T. Bioorg. Med. Chem. Lett. 2008, 18, 546.
11. Xu, X.X.; Fu, R.Z.; Chen, J.; Chen, S.W.; Bai, X. Ezetimibe analogs with a reorganized azetidinone ring: Design, synthesis, and evaluation of cholesterol absorption inhibitions. Bioorg. Med. Chem. Lett. 2007, 17, 101-104. (Pubitemid 44959974)
12. Buttero, P.D.; Molteni, G.; Roncoroni, M. Reductive ring opening of 2-azetidinones promoted by sodium borohydride. Tetrahedron. Lett., 2006, 47(13), 2209-2211. (Pubitemid 43287884)
13. Baldwin, J.E.; Adlington, R.M.; Elend, A.S.; Smith, M.L. Enantiospecific synthesis of (3R, 4R)-3-amino-1-hydroxy-4-methyl pyrrolidin-2-one(I-687,4140), an nmda receptor antagonist. Tetrahedron, 1995, 51(42), 11581-11594.
14. Kanth, J.V.Bhaskar.; Periasamy, M. Selective reduction of carboxylic acids into alcohols using sodium borohydride and iodine. J. Org. Chem., 1991, 56, 5964-5965.
15. Palomo, C.; Aizpurua, J.M.; Carcia, J.M.; Iturburu, M.; Odriozola, J. M. Concise General Synthesis of .alpha.,.gamma.-Disubstituted beta.-Amino Ketones from .beta.-Lactams. J. Org. Chem. 1994, 59, 5184-5188.
16. Salisbury, B.G.; Davis, H.R.; Burrier, R.E.; Burnett, D.A.; Bowkow, G.; Caplen, M.A.; Clemmons, A.L.; Compton, D.S.; Hoos, L.M.; McGregor, D.G. Hypocholesterolemic activity of a novel inhibitor of cholesterol absorption, SCH 48461. Atherosclerosis, 1995, 115(1), 45-63.