Inhibitors of acyl-CoA:cholesterol O-acyltransferase. 3. Discovery of a novel series of N-alkyl-N-[(fluorophenoxy)benzyl]-N'-arylureas with weak toxicological effects on adrenal glands

Journal of Medicinal Chemistry

Volumn 41, Issue 22, 1998, Pages 4408-4420

  Tanaka, Akira ^a   Terasawa, Takeshi ^a   Hagihara, Hiroyuki ^a   Ishibe, Noriko ^a   Sawada, Masae ^a   Sakuma, Yuri ^b   Hashimoto, Masaharu ^a   Takasugi, Hisashi ^a   Tanaka, Hirokazu ^a  

^a ASTELLAS PHARMA INC   (Japan)

^b Fujtsawa Pharmaceutical Company Ltd   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

1 CYCLOHEPTYL 1 [4 (4 FLUOROPHENOXY)BENZYL] 3 (2,4,6 TRIMETHYL 3 PYRIDINYL)UREA; 3 [2,4 BIS(METHYLSULFONYL) 6 METHYL 3 PYRIDINYL] 1 CYCLOHEPTYL 1 [4 (4 FLUOROPHENOXY)BENZYL]UREA; CHOLESTEROL ACYLTRANSFERASE; CHOLESTEROL ACYLTRANSFERASE INHIBITOR; CHOLESTEROL ESTER; UNCLASSIFIED DRUG; UREA DERIVATIVE;

ADRENAL GLAND; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ATHEROSCLEROSIS; DRUG EFFICACY; DRUG SYNTHESIS; HYPERCHOLESTEROLEMIA; MACROPHAGE; NONHUMAN; ORAL DRUG ADMINISTRATION; RAT;

ACETYLATION; ADRENAL GLANDS; ANIMALS; ANTICHOLESTEREMIC AGENTS; CHOLESTEROL, DIETARY; DRUG EVALUATION, PRECLINICAL; ENZYME INHIBITORS; INTESTINES; LIPOPROTEINS, LDL; MACROPHAGES, PERITONEAL; MICE; PYRIDINES; RABBITS; RATS; STEROL O-ACYLTRANSFERASE; STRUCTURE-ACTIVITY RELATIONSHIP; UREA;

EID: 0032561372     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm980399q     Document Type: Article

References (60)

1. (a) Kannel, W. B.; Castelli, W. P.; Gordon, T.; McNamara, P. M. Serum Cholesterol, Lipoproteins, and the Risk of Coronary Heart Disease. The Framingham Study. Ann. Intern. Med. 1971, 74, 1-12.
2. (b) Martin, M. J.; Hulley, S. B.; Browner, W. S.; Kuller, L. H.; Wentworth, D. Serum Cholesterol, Blood Pressure, and Mortality: Implications from a Cohort of 361 662 Men. Lancet 1986, 2, 933-936.
3. (c) Badimon, J. J.; Fuster, V.; Chesebro, J. H.; Badimon, L. Coronary Atherosclerosis; A Multifactorial Disease. Circulation 1993, 87 (Suppl. II), 3-16.
4. (a) The Lipid Research Clinics Program. The Lipid Research Clinics Coronary Primary Prevention Trial Results. J. Am. Med. Assoc. 1984, 251, 351-364 and 365-374. (b) Brown, G.; Albers, J. J.; Fisher, L. D.; Schaefer, S. M.; Lin, J.-T.; Kaplan, C.; Zhao, X.-Q.; Bisson, B. D.; Fitzpatrick, V. F.; Dodge, H. T. Regression of Coronary Artery Disease as a Result of Intensive Lipid-Lowering Therapy in Men with High Levels of Apolipoprotein B. N. Engl. J. Med. 1990, 323, 1289-1298. Brown, W. V. Review of Clinical Trials: Proving the Lipid Hypothesis. Eur. Heart J. 1990, 11 (Suppl. H), 15-20.
5. (a) The Lipid Research Clinics Program. The Lipid Research Clinics Coronary Primary Prevention Trial Results. J. Am. Med. Assoc. 1984, 251, 351-364 and 365-374. (b) Brown, G.; Albers, J. J.; Fisher, L. D.; Schaefer, S. M.; Lin, J.-T.; Kaplan, C.; Zhao, X.-Q.; Bisson, B. D.; Fitzpatrick, V. F.; Dodge, H. T. Regression of Coronary Artery Disease as a Result of Intensive Lipid-Lowering Therapy in Men with High Levels of Apolipoprotein B. N. Engl. J. Med. 1990, 323, 1289-1298. Brown, W. V. Review of Clinical Trials: Proving the Lipid Hypothesis. Eur. Heart J. 1990, 11 (Suppl. H), 15-20.
6. (a) The Lipid Research Clinics Program. The Lipid Research Clinics Coronary Primary Prevention Trial Results. J. Am. Med. Assoc. 1984, 251, 351-364 and 365-374. (b) Brown, G.; Albers, J. J.; Fisher, L. D.; Schaefer, S. M.; Lin, J.-T.; Kaplan, C.; Zhao, X.-Q.; Bisson, B. D.; Fitzpatrick, V. F.; Dodge, H. T. Regression of Coronary Artery Disease as a Result of Intensive Lipid-Lowering Therapy in Men with High Levels of Apolipoprotein B. N. Engl. J. Med. 1990, 323, 1289-1298. Brown, W. V. Review of Clinical Trials: Proving the Lipid Hypothesis. Eur. Heart J. 1990, 11 (Suppl. H), 15-20.
7. McCarthy, P. A. New Approaches to Atherosclerosis: An Overview. Med. Res. Rev. 1993, 13, 139-159.
8. For the role of ACAT, see: (a) Spector, A. A.; Mathur, S. N.; Kaduce, T. L. Role of Acylcoenzyme A:Cholesterol O-Acyltransferase in Cholesterol Metabolism. Prog. Lipid Res. 1979, 18, 31-53. (b) Suckling, K. E.; Stange, E. F. Role of Acyl-CoA:Cholesterol Acyltransferase in Cellular Cholesterol Metabolism. J. Lipid Res. 1985, 26, 647-671.
9. For the role of ACAT, see: (a) Spector, A. A.; Mathur, S. N.; Kaduce, T. L. Role of Acylcoenzyme A:Cholesterol O-Acyltransferase in Cholesterol Metabolism. Prog. Lipid Res. 1979, 18, 31-53. (b) Suckling, K. E.; Stange, E. F. Role of Acyl-CoA:Cholesterol Acyltransferase in Cellular Cholesterol Metabolism. J. Lipid Res. 1985, 26, 647-671.
10. (a) 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 Lipid-regulating Activity of the ACAT Inhibitor CI-976 in Rats is Due to Inhibition of Both Intestinal and Liver ACAT. J. Lipid Res. 1993, 34, 279-294.
11. (b) Largis, E. E.; Wang, C. H.; DeVries, V. G.; Schaffer, S. A. CL 277,082: A Novel Inhibitor of ACAT-Catalyzed Cholesterol Esterification and Cholesterol Absorption. J. Lipid Res. 1989, 30, 681-690.
12. (c) Carr, T. P.; Rudel, L. L. Partial Inhibition of ACAT Decreases ApoB Secretion by the Liver of African Green Monkeys. Arteriosclerosis 1990, 10, 823a.
13. (d) Carr, T. P.; Parks, J. S.; Rudel, L. L. Hepatic ACAT Activity in African Green Monkeys is Highly Correlated to Plasma LDL Cholesteryl Ester Enrichment and Coronary Atherosclerosis. Arterioscler. Thromb. 1992, 12, 1274-1283.
14. (e) Burrier, R. E.; 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.
15. (a) Brown, M. S.; Goldstein, J. L. Lipoprotein Metabolism in the Macrophage: Implications for Cholesterol Deposition in Atherosclerosis. Annu. Rev. Biochem. 1983, 52, 223-261.
16. (b) Gillies, P. J.; Robinson, C. S.; Rathgeb, K. A. Regulation of ACAT Activity by a Cholesterol Substrate Pool During the Progression and Regression Phases of Atherosclerosis: Implications for Drug Discovery. Atherosclerosis 1990, 83, 177-185.
17. (c) Bocan, T. M. A.; Mueller, S. B.; Uhlendorf, P. D.; Brown, E. Q.; Mazur, M. J.; Black, A. E. Inhibition of Acyl-CoA Cholesterol O-Acyltransferase Reduces the Cholesteryl Ester Enrichment of Atherosclerotic Lesions in the Yucatan Micropig. Atherosclerosis 1993, 99, 175-186.
18. (d) Matsuo, M.; Ito, F.; Konto, A.; Aketa, M.; Tomoi, M.; Shimomura, K. Effect of FR145237, A Novel ACAT Inhibitor, on Atherogenesis in Cholesterol-fed and WHHL Rabbits. Evidence for a Direct Effect on the Arterial Wall. Biochim. Biophys. Acta 1995, 1259, 254-260.
19. Sliskovic, D. R.; White, A. D. Therapeutic Potential of ACAT Inhibitors as Lipid Lowering and Anti-Atherosclerotic Agents. Trends Pharmacol. Sci. 1991, 12, 194-199.
20. For recent reviews of ACAT inhibitors, see: (a) Picard, J. A. Patent Update: ACAT Inhibitors. Curr. Opin. Ther. Pat. 1993, 3, 151-160. (b) Matsuda, K. ACAT Inhibitors as Antiatherosclerotic Agents: Compounds and Mechanisms. Med. Res. Rev. 1994, 14, 271-305. (c) Sliskovic, D. R.; Trivedi, B. K. ACAT Inhibitors: Potential Anti-atherosclerotic Agents. Curr. Med. Chem. 1994, 1, 204-225.
21. For recent reviews of ACAT inhibitors, see: (a) Picard, J. A. Patent Update: ACAT Inhibitors. Curr. Opin. Ther. Pat. 1993, 3, 151-160. (b) Matsuda, K. ACAT Inhibitors as Antiatherosclerotic Agents: Compounds and Mechanisms. Med. Res. Rev. 1994, 14, 271-305. (c) Sliskovic, D. R.; Trivedi, B. K. ACAT Inhibitors: Potential Anti-atherosclerotic Agents. Curr. Med. Chem. 1994, 1, 204-225.
22. For recent reviews of ACAT inhibitors, see: (a) Picard, J. A. Patent Update: ACAT Inhibitors. Curr. Opin. Ther. Pat. 1993, 3, 151-160. (b) Matsuda, K. ACAT Inhibitors as Antiatherosclerotic Agents: Compounds and Mechanisms. Med. Res. Rev. 1994, 14, 271-305. (c) Sliskovic, D. R.; Trivedi, B. K. ACAT Inhibitors: Potential Anti-atherosclerotic Agents. Curr. Med. Chem. 1994, 1, 204-225.
23. For recent results of clinical trials, see: (a) Roark, W. H.; Roth, B. D. ACAT Inhibitors: Preclinical Profiles of Clinical Candidates. Exp. Opm. Invest. Drugs 1994, 3, 1143-1152. (b) Lee, H. T.; Picard, J. A. Recent Developments in Hypocholesterolemic Agents. Exp. Opin. Ther. Pat. 1995, 5, 397-416 and references therein.
24. For recent results of clinical trials, see: (a) Roark, W. H.; Roth, B. D. ACAT Inhibitors: Preclinical Profiles of Clinical Candidates. Exp. Opm. Invest. Drugs 1994, 3, 1143-1152. (b) Lee, H. T.; Picard, J. A. Recent Developments in Hypocholesterolemic Agents. Exp. Opin. Ther. Pat. 1995, 5, 397-416 and references therein.
25. Trivedi, B. K.; Purchase, T. S.; Holmes, A.; Augelli-Szafran, C. E.; Essenburg, A. D.; Hamelehle, K. L.; Stanfield, R. L.; Bousley, R. F.; Krause, B. R. Inhibitors of Acyl-CoA:Cholesterol Acyl-transferase (ACAT). 7. Development of a Series of Substituted N-Phenyl-N'-[(1-phenylcyclopentyl)methyl]ureas with Enhanced Hypocholesterolemic Activity. J. Med. Chem. 1994, 37, 1652-1059.
26. (a) Dominick, M. A.; Bobrowski, W. A.; MacDonald, J. R.; Gough, A. W. Morphogenesis of a Zone-Specific Adrenocortical Cytotoxicity in Guinea Pigs Administered PD 132301-2, an Inhibitor of Acyl-CoA:Cholesterol Acyltransferase. Toxicol. Pathol. 1993, 21, 54-62.
27. (b) Vernetti, L. A.; MacDonald, J. R.; Wolfgang, G. H. I.; Dominick, M. A.; Pegg, D. G. ATP Depletion is Associated with Cytotoxicity of a Novel Lipid Regulator in Guinea Pig Adrenocortical Cells. Toxicol. Appl. Pharmacol. 1993, 118, 30-38.
28. (c) Dominick, M. A.; McGuire, E. J.; Reindel, J. F.; Bobrowski, W. F.; Bocan, T. M. A.; Gough, A. W. Subacute Toxicity of a Novel Inhibitor of Acyl-CoA:Cholesterol Acyltransferase in Beagle Dogs. Fundam. Appl. Toxicol. 1993, 20, 217-224.
29. (d) Reindel, J. F.; Dominick, M. A.; Bocan, T. M. A.; Gough, A. W.; McGuire, E. J. Toxicologie Effects of a Novel Acyl-CoA:Cholesterol Acyltransferase Inhibitor in Cynomolgus Monkeys. Toxicol. Pathol. 1994, 22, 510-518.
30. (e) Wolfgang, G. H. I.; MacDonald, J. R.; Vernetti, L. A.; Pegg, D. G.; Robertson, D. G. Biochemical Alterations in Guinea Pig Adrenal Cortex Following Administration of PD 132301-2, an Inhibitor of Acyl-CoA:Cholesterol Acyltransferasc. Life Sci. 1995, 13, 1089-1093.
31. Wolfgang, G. H. L; Robertson, D. G.; Welty, D. F.; Metz, A. L. Hepatic and Adrenal Toxicity of a Novel Lipid Regulator in Beagle Dogs. Fundam. Appl. Toxicol. 1995, 26, 272-281.
32. (a) Smith, C.; Ashton, M. J.; Bush, R. C.; Facchini, V.; Harris, N. V.; Hart, T. W.; Jordan, R.; McKenzie, R.; Riddell, D. RP 73163: A Bioavailable Alkylsulphinyl-Diphenylimidazole ACAT Inhibitor. Bioorg. Med. Chem. Lett. 1996, 6, 47-50.
33. (b) Albaladejo, V.; Catinot, R.; Moronvalle-Halley, V.; Kriszt, W.; Schorsch, F.; Picaut, Ph.; Baron, H.; Ballet, F. RP 73163, A Novel Systemic ACAT-Inhibitor Induces Coarse Vacuolation and Impairs Steroid Hormone Metabolism in Guinea Pig Adrenocortical Cells. Toxicol. Lett. 1994, 74 (Suppl. 1), 3.
34. (a) Sliskovic, D. R.; Picard, J. A.; Roark, W. H.; Essenburg, A. D.; Krause, B. R.; Minton, L. L.; Reindel, J. F.; Stanfield, R. L. Inhibitors of Acyl-CoA:Cholesterol O-Acyl Transferase (ACAT) as Hypocholesterolemic Agents. The Synthesis and Biological Activity of a Series of Malonester Amides. Bioorg. Med. Chem. Lett. 1996, 6, 713-718.
35. (b) O'Brien, P. M.; Sliskovic, D. R.; Picard, J. A.; Lee, H. T.; Purchase, C. F., II; Roth, B. D.; White, A. D.; Anderson, M.; Mueller, S. B.; Bocan, T.; Bousley, R.; Hamelehle, K. L.; Homan, R.; Lee, P.; Krause, B. R.; Reindel, J. F.; Stanfield, R. L.; Turluck, D. Inhibitors of Acyl-CoA:Cholesterol O-Acyltransferase. Synthesis and Pharmacological Activity of(±)-2-Dodecyl-α-phenyl-N-(2,4,6-trimethoxyphenyl)-2H-tetrazole-5- acetamide and Structurally Related Tetrazole Amide Derivatives. J. Med. Chem. 1996, 39, 2354-2366.
36. (c) Purchase, C. F., II; White, A. D.; Anderson, M. K.; Bocan, T. M. A.; Bousley, R. F.; Hamelehle, K. L.; Homan, R.; Krause, B. R.; Lee, P.; Mueller, S. B.; Speyer, C.; Stanfield, R. L.; Reindel, J. F. Tetrazole-substituted Ureas as Inhibitors of Acyl-CoA:Cholesterol O-Acyltransferase (ACAT). A Novel Preparation of Ureas from Weakly Nucleophilic Amines. Bioorg. Med. Chem. Lett. 1996, 6, 1753-1758.
37. (d) Wilde, R. G.; Billheimer, J. T.; Germain, S. J.; Hausner, E. A.; Meunier, P. C.; Munzer, D. A.; Stoltenborg, J. K.; Gillies, P. J.; Burcham, D. L.; Huang, S.-M.; Klaczkiewicz, J. D.; Ko, S. S.; Wexler, R. R. ACAT Inhibitors Derived from Hetero-Diels-Alder Cycloadducts of Thioaldehydes. Bioorg. Med. Chem. 1996, 4, 1493-1513.
38. (e) White, A. D.; Creswell, M. W.; Chucholowski, A. W. Blankley, C. J.; Wilson, M. W.; Bousley, R. F.; Essenburg, A. D.; Hamelehle, K. L.; Krause, B. R.; Stanfield, R. L.; Dominick, M. A.; Neub, M. Heterocyclic Ureas: Inhibitors of Acyl-CoA:Cholesterol O-Acyltransferase as Hypocholesterolemic Agents. J. Med. Chem. 1996, 39, 4382-4395.
39. (f) Sliskovic, D. R.; Picard, J. A.; O'Brien, P. M.; Liao, P.; Roark, W. H.; Roth, B. D.; Anderson, M. A.; Mueller, S. B.; Bocan, T. M. A. Bousley, R. F.; Hamelehle, K. L.; Homan, R.; Reindel, J. F.; Stanfield, R. L.; Turluck, D.; Krause, B. R. α-Substituted Malonester Amides:Tools to Define the Relationship between ACAT Inhibition and Adrenal Toxicity. J. Med. Chem. 1998, 41, 682-690.
40. Warner, G. J.; Stoudt, G.; Bamberger, M.; Johnson, W. J.; Rothblat, G. H. Cell Toxicity Induced by Inhibition of Acyl Coenzyme A:Cholesterol Acyltransferase and Accumulation of Unesterified Cholesterol. J. Biol. Chem. 1995, 270, 5772-5778.
41. Matsuo, M.; Hashimoto, M.; Suzuki, J.; Iwanami, K.; Tomoi, M.; Shimomura, K. Difference between Normal and WHHL Rabbits in Susceptibility to the Adrenal Toxicity of an Acyl-CoA: Cholesterol Acyltransferase Inhibitor, FR145237. Toxicol. Appl. Pharmacol. 1996, 140, 387-392.
42. (a) Tanaka, A.; Terasawa, T.; Hagihara, H.; Sakuma, Y.; Ishibe, N.; Sawada, M.; Takasugi, H.; Tanaka, H. Inhibitors of Acyl-CoA:Choleaterol O-Acyltransferase (ACAT). Part 1: Identification and Structure-Activity Relationships of a Novel Series of Substituted N-Alkyl-W-biphenylylmethyl-N'-arylureas. Bioorg. Med. Chem. 1998, 6, 15-30.
43. (b) Tanaka, A.; Terasawa, T.; Hagihara, H.; Kinoshita, T.; Sakuma, Y.; Ishibe, N.; Sawada, M.; Takasugi, H.; Tanaka, H. Synthesis, X-ray Crystal Structure, and Biological Activity of FR186054, a Novel, Potent, Orally Active Inhibitor of Acyl-CoA:Cholesterol O-Acyltransferase (ACAT) Bearing a Pyrazole Ring. Bioorg. Med. Chem. Lett. 1998, 8, 81-86.
44. (c) Tanaka, A.; Terasawa, T.; Hagihara, H.; Sakuma, Y.; Ishibe, N.; Sawada, M.; Takasugi, H.; Tanaka, H. Inhibitors of Acyl-CoA:Cholesterol O-Acyltransferase. 2. Identification and Structure-Activity Relationships of a Novel Series of N-Alkyl-N-(heteroaryl-substituted benzyl)-N'-arylureas. J. Med. Chem. 1998, 41, 2390-2410.
45. McCarthy, P. A.; Hamanaka, E. S.; Marzetta, C. A.; Bamberger, M. J.; Gaynor, B. J.; Chang, G.; Kelly, S. E.; Inskeep, P. B.; Mayne, J. T.; Beyer, T. A.; Walker, F. J.; Goldberg, D. I.; Savoy, Y. E.; Davis, K. M.; Diaz, C. L.; Freeman, A. M.; Johnson, D. A.; LaCour, T. G.; Long, C. A.; Maloney, M. E.; Martingano, R. J.; Pettini, J. L.; Sand, T. M.; Wint, L. T. Potent, Selective, and Systemically-Available Inhibitors of Acyl-Coenzyme A:Cholesterol Acyl Transferase (ACAT). J. Med. Chem. 1994, 37, 1252-1255.
46. Plazek, E. Über die Nitrierung von einigen Methylhomologen des Pyridins. Chem. Ber. 1939, 72, 577-581.
47. Oi, R.; Shimakawa, C.; Takenaka, S. Ullmann Ether Synthesis in DMI. Preparation of m-Phenoxybenzyl Alcohol. Chem. Lett. 1988, 899-900.
48. Albert, A.; Brown, D. J.; Wood, H. C. S. Pteridine Studies. Part V. The Monosubstituted Pteridines. J. Chem. Soc. 1954, 3832-3839.
49. (a) Inskeep, P. B.; Davis, K. M.; Reed, A. E. Pharmacokinetics of the Acyl Coenzyme A:Cholesterol Acyl Transferase Inhibitor CP-105,191 in Dogs-The Effect of Food and Sesame Oil on Systemic Exposure following Oral Dosing. J. Pharm. Sci. 1995, 84, 131-133.
50. (b) Kataoka, K.-i.; Shiota, T.; Takeyasu, T.; Minoshima, T.; Watanabe, K.; Tanaka, H.; Mochizuki, T.; Taneda, K.; Ota, M.; Tanabe, H.; Yamaguchi, H. Potent Inhibitors of Acyl-CoA:Cholesterol Acyltransferase. 2. Structure-Activity Relationships of Novel N-(2,2-Dimethyl-2,3-dihydrobenzofuran-7-yl)amides. J. Med. Chem. 1998, 39, 1262-1270.
51. Reindel, J. F.; Dominick, M. A.; Krause, B. R. Comparative Adrenotoxicity of a Novel ACYL-COA:Cholesterol Acyltransferase (ACT) Inhibitor (PD 132301-2) in Laboratory Animals. Toxicol. Pathol. 1992, 20, 642.
52. (a) Chang, T. Y.; Chang, C. C. Y.; Cheng, D. Acyl-Coenzyme A:Cholesterol Acyltransferase. Annu. Rev. Biochem. 1997, 66, 613-638.
53. (b) Sturley, S. L. Molecular Aspects of Intracellular Sterol Esterification: the Acyl Coenzyme A:Cholesterol Acyl-transferase Reaction. Curr. Opin. Lipidol. 1997, 8, 167-173 and references therein.
54. (a) Matsuda, H.; Hakamata, H.; Kawasaki, T.; Sakashita, N.; Miyazaki, A.; Takahashi, K.; Shichiri, M.; Horiuchi, S. Molecular Cloning, Functional Expression and Tissue Distribution of Rat Acyl-Coenzyme A:Cholesterol Acyltransferase. Biochim. Biophys. Acta 1998, 1391, 193-203.
55. (b) Kawasaki, T.; Hakamata, H.; Matsuda, H.; Chang, C. C. Y.; Chang, T. Y.; Horiuchi, S. Liver Acyl-Coenzyme A:cholesterol Acyltransferase (ACAT) is Different from Adrenal ACAT in Rats. Circulation 1997, 96 (Suppl. I), 230.
56. (c) Kawasaki, T.; Miyazaki, A.; Hakamata, H.; Matsuda, H.; Horiuchi, S. Biochemical Evidence for Oligomerization of Rat Adrenal Acyl-Coenzyme A:Cholesterol Acyltransferase. Biochem. Biophys. Res. Commun. 1998, 244, 347-352.
57. Meiner, V. L.; Cases, S.; Myers, H. M.; Sande, E. R.; Bellosta, S.; Schambelan, M.; Pitas, R. E.; McGuire, J.; Herz, J.; Farese, R. V., Jr. Disruption of the Acyl-CoA:Cholesterol Acyltransferase Gene in Mice: Evidence Suggesting Multiple Cholesterol Esterification Enzymes in Mammals. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 14041-14046.
58. Meiner, V.; Tam, C.; Gunn, M. D.; Dong, L.-M.; Weisgraber, K. H.; Novak, S.; Myers, H. M.; Erickson, S. K.; Farese, R. V., Jr. Tissue Expression Studies on the Mouse Acyl-CoA: Cholesterol Acyltransferase Gene (Acact). Findings Supporting the Existence of Multiple Cholesterol Esterification Enzymes in Mice. J. Lipid Res. 1997, 35, 1928-1933.
59. (a) Sturley, S. L.; Oelker, P. M.; Behari, A. Isolation and Characterization of Two Human Genes Encoding Enzymes Related to Acyl Coenzyme A-Cholesterol Acyltransferase. Circulation 1997, 96 (Suppl. I), 411.
60. (b) Cases, S.; Zheng, Y.-W.; Novak, S.; Meiner, V.; Myers, H.; Erickson, S. K.; Farese, R. V., Jr. Identification and Cloning of Two New Mammalian ACAT Gene Family Members. Circulation 1997, 96 (Suppl. I), 230.