Inhibitors of acyl-CoA:Cholesterol O-acyltransferase. 17. Structure-activity relationships of several series of compounds derived from N-chlorosulfonyl isocyanate

Journal of Medicinal Chemistry

Volumn 39, Issue 6, 1996, Pages 1243-1252

  Picard, Joseph A ^a   O'Brien, Patrick M ^a   Sliskovic, Drago R ^a   Anderson, Maureen K ^a   Bousley, Richard F ^a   Hamelehle, Katherine L ^a   Krause, Brian R ^a   Stanfield, Richard L ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

(AMINOSULFONYL)UREA DERIVATIVE; ANTILIPEMIC AGENT; CARBAMIC ACID DERIVATIVE; CHLOROSULFONYLISOCYANATE; CHOLESTEROL; CHOLESTEROL ACYLTRANSFERASE INHIBITOR; CI 999; HIGH DENSITY LIPOPROTEIN; ISOCYANIC ACID DERIVATIVE; OXYSULFONYL CARBAMIC ACID DERIVATIVE; SULFONYLUREA DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; CHOLESTEROL DIET; CONTROLLED STUDY; DRUG POTENCY; DRUG SYNTHESIS; HYPERCHOLESTEROLEMIA; NONHUMAN; ORAL DRUG ADMINISTRATION; PERILYMPH FISTULA; RAT; REVIEW; STRUCTURE ACTIVITY RELATION;

ANIMALS; ENZYME INHIBITORS; ISOCYANATES; RATS; STEROL O-ACYLTRANSFERASE; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0029892115     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm9509455     Document Type: Article

References (26)

1. Presented in part at the Xth International Symposium on Atherosclerosis, Montreal, Canada, Oct. 9-14, 1994; Treatment I - Abstract No. 277. Atherosclerosis 1994, 109, 162.
2. (a) Roark, W. H.; Roth, B. D. ACAT inhibitors: preclinical profiles of clinical candidates. Exp. Opin. Invest. Drugs 1994, 3, 1143-1152.
3. (b) Sliskovic, D. R.; Trivedi, B. K. ACAT Inhibitors: Potential Anti-atheroscierotic Agents. Curr. Med. Chem. 1994, 1, 204-225.
4. (c) Matsuda, K ACAT Inhibitors as Antiatheroselerotic Agents: Compounds and Mechanisms. Med. Res. Rev. 1994, 14, 271-305.
5. (d) Picard, J. A. Patent Update: ACAT Inhibitors. Curr. Opin. Ther. Patents 1993, 3, 151-160.
6. (e) O'Brien, P. M.; Sliskovic, D. R. ACAT Inhibitors: A Potential New Approach to the Treatment of Hypercholesterolemia and Atherosclerosis. Curr. Opin. Ther. Patents 1992, 2, 507-526.
7. (a) Hainer, J. W.; Terry, J. G.; Connell, J. M.; Zyruk, H.; Jenkins, R. M.; Shand, D. L.; Gillies, P. J.; Livak, K. J.; Hunt, T. L.; Crouse, J. R., III. Effect of the Acyl-CoA:Cholesterol Acyl Transferase Inhibitor DuP 128 on Cholesterol absorption and Serum Cholesterol in Humans. Clin. Pharmacol. Ther. 1994, 56, 65-74.
8. (b) Harris, W. S.; Dujovne, C. A.; von Bergman, K.; Neil, J.; Akester, J.; Windsor, S. L.; Greene, D.; Look, Z. Effects of the ACAT Inhibitor CL-277082 on Cholesterol Metabolism in Humans. Clin., Pharmacol. Ther. 1990, 48, 189-194.
9. (c) Peck, R. W.; Wiggs, R.; Posner, J. The tolerability, pharmacokinetics and effect on plasma cholesterol of 447C88, an ACAT inhibitor with low bioavailability, in healthy volunteers. Atherosclerosis 1994, 109, 155-156.
10. (a) Krause, B. R.; Bocan,T. M. A. ACAT Inhibitors: Physiological mechanisms for hypolipidemic and anti-atherosclerotic activities in experimental animals. Inflammation: Mediators and Pathways; CRC Press: Boco Raton, FL, 1995; pp 173-198.
11. (b) Burner, R. H.; Deren, S.; McGregor, D. G.; Hoos, L. M.; Smith, A. A.; Davis, H. R., Jr. Demonstration of a Direct Effect on Hepatic Acyl CoA:cholesterol Acyl Transferase (ACAT) Activity by an Orally Administered Enzyme Inhibitor in the Hamster. Biochem. Pharmacol. 1994, 47, 1545-1551.
12. (c) Krause, B. R.; Anderson, M.; Bisgaier, C. L.; Bocan, T.; Bousley, R.; DeHart, P.; Essenburg, A ; Hamelehle, K.; Homan, R.; Kieft, K; McNally, W.; Stanfield, R.; Newton, R. S. In Vivo Evidence that the Lipidregulating Activity of the ACAT Inhibitor CI-976 in Rats is Due to Inhibition of Both Intestinal and Liver ACAT. J. Lipid Res. 1993, 34, 279-94.
13. (d) Carr, T. P.; Hamilton, R. L., Jr.; Rudel, L. L. ACAT inhibitors decrease secretion of cholesteryl esters and apolipoportein B by perfused livers of African Green Monkeys J. Lipid Res. 1995, 36, 25-36.
14. Austel, V.; Kutter, E. Absorption, Distribution, and Metabolism of Drugs. In Quantitative Structure-Activity Relationships of Drugs; Topliss, J. G., Ed.; Academic Press: New York, 1983; pp 437-496.
15. Picard, J. A.; Bousley, R. F.; Lee, H. T.; Hamelehle, K. L.; Krause, B. R.; Minton, L. L.; Sliskovic, D. R.; Stanfield, R. L. Inhibitors of Acyl-CoA:cholesterol O-Acyltransferase. 11. Structure-Activity Relationships of Several Series of Compounds Derived from N-(Chlorocarbonyl) Isocyanate. J. Med. Chem. 1994, 37, 2394-2400.
16. Sliskovic, D. R.; Krause, B. R.; Picard, J. A.; Andersen, M.; Bousley, R. F.; Hamelehle, K. L.; Homan, R.; Julian, T. N.; Rashidbaigi, Z. A.; Stanfield, R. L. Inhibitors of Acyl-CoA: Cholesterol O-Acyl Transferase (ACAT) as Hypocholesterolemic Agents. 6. The First Water-Soluble ACAT Inhibitor with LipidRegulating Activity. J. Med. Chem. 1994, 37, 560-562.
17. Roth, B. D.; Roark, W. H.; Picard, J. A.; Stanfield, R. L.; Bousley, R. F.; Andersen, M. K.; Hamelehle, K. L.; Homan, R.; Krause, B. R. Inhibitors of Acyl-CoA:Cholesterol O-Acyl Transferase (ACAT). 15. Sulfonylurea Inhibitors with Excellent Hypocholesterolemic Activity In Vivo. BioMed. Chem. Lett. 1995, 5. 2367-2370.
18. (a) Dhar, D. N.; Murthy, K. S. K. Recent Advances in the Chemistry of Chlorosulfonyl Isocyanate. Synthesis 1986, 437-449.
19. (b) Szabo, W. A. Chlorosulfonyl Isocyanate. Silver Anniversary of a Lively Heterocumulene. Aldrichim. Acta 1977, 10, 23-29.
20. (c) Rasmussen, J. K.; Hassner, A. Recent Developments in the Synthetic Uses of Chlorosulfonyl Isoeyanate. Chem. Rev. 1976, 76, 389-408.
21. (d) Graf, R. Reactions with N-Carbonylsulfamoyl Chloride. Angew. Chem., Int. Ed. Engl. 1968, 7, 172-182.
22. Lohaus, G. Darstellung und Umsetzungen von Aryloxysulfonylisocyanaten. (Preparation and reactions of aryloxysulfonylisocyanates.) Chem. Ber. 1972, 705, 2791-2799; Chem. Abstr. 1972, 77, 139511.
23. Lohaus, G. Darstellung und Umsetzungen von Aryloxysulfonylisocyanaten. (Preparation and reactions of aryloxysulfonylisocyanates.) Chem. Ber. 1972, 705, 2791-2799; Chem. Abstr. 1972, 77, 139511.
24. Krause, B. R.; Black, A.; Bousley, R.; Essenburg, A.; Cornicelli, J.; Holmes, A.; Homan, R.; Kieft, K.; Sekerke, C.; Shaw-Hes. M. K.; Stanfield, R.; Trivedi, B.; Woolf, T. Divergent Pharmacologic Activities of PD 132301-2 and CL 277,082, Urea Inhibitors of Acyl-CoA:Cholesterol Acyltransferase (ACAT). J. Pharmacol. Exp. Ther. 1993, 267, 734-743.
25. B. Krause, unpublished results.
26. Goldman, J. M. Oral Hypoglycemic Agents: An Update of Sulfonylureas. Drugs Today 1989, 25, 689-695.