Beta-lactams derived from the reaction of phenanthridines and 11H- dibenzo[b,e]azepin-11-one with phenyivaleryl chloride. Synthesis of fused analogs of the cholesterol absorption inhibitor Sch 48461

Tetrahedron Letters

Volumn 39, Issue 41, 1998, Pages 7431-7434

  Afonso, Adriano ^a   Rosenblum, Stuart B ^a   Puar, Mohindar S ^a   McPhail, Andrew T ^b  

^a MERCK RESEARCH LABORATORIES   (United States)

^b DUKE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,4 BIS(4 METHOXYPHENYL) 3 (3 PHENYLPROPYL) 2 AZETIDINONE; 11H DIBENZO[B,E]AZEPIN 11 ONE; ANTILIPEMIC AGENT; BETA LACTAM; PHENANTHRIDINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG ACTIVITY; DRUG SYNTHESIS; LIPID ABSORPTION; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

EID: 0032497605     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)01648-7     Document Type: Article

References (13)

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2. 2. Rosenblum, S. B.; Huynh, T.; Afonso, A.; Davis, H.R. Jr.; Yumibe, N.; Clader, J. W.; Burnett, D. A. J. Med. Chem. 1998, 41, 973.
3. 3. (a) Georg, G. I.,Ed.; The Organic Chemistry of betalactams, Verlag Chemie, New york, 1992, Ch. 6;
4. (b) Ghosez, L.; Marchand-Brynaert, J.; in Comprehensive Organic Synthesis; Trost, B. M.; Ed,; Pergamon Press, New York, 1991; Vol. 5, p 90.
5. 4. Browne, M.; Burnett, D. A.; Caplen, M. A.; Chen, L.-Y.; Clader, J. W.; Domalski, M.; Dugar, S.; Pushpavanam, P.; Sher, R.; Vaccaro, W.; Viziano, M.; Zhao, H. Tetrahedron Lett.,1995, 36, 2555.
6. 2O-hexanes) followed by HPLC on Whatman Porasil columns. Recovered unreacted starting imines ranged from 60-70%. Yields of products are based on the reacted portion of the starting imine.
7. 6. Kessar, S. V.; Gopal, R.; Singh, M. Tetrahedron, 1973, 29, 167.
8. 7. Crystal structure data may be obtained from the Cambridge Crystallographic Data Centre, 12 Union Road, GB-Cambridge CB2 1EZ (UK).
9. 8. Bevan, F. M.; Euerby, M. R.; Qureshi, S. J. J. Chem Res., 1989, (S), 116.
10. 9. Errede, L. A.; Oien, H. T.; Yarian, D. R. J. Org. Chem. 1977, 42, 12.
11. 10. This acylation is best carried out by adding the lithiated 13 to a solution of 14.
12. +).
13. 12. The compounds showed less than 30% reduction in cholesteryl esters @10 mpk in the CAI assay (for assay details see ref. 2) in hamsters.