Non-peptide αvβ3 antagonists: Identification of potent, chain-shortened RGD mimetics that incorporate a central pyrrolidinone constraint

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 24, 2003, Pages 4285-4288

  Perkins, James J ^a   Duong, L T ^a   Fernandez Metzler, Carmen ^a   Hartman, George D ^a   Kimmel, Donald B ^a   Leu, Chih Tai ^a   Lynch, Joseph J ^a   Prueksaritanont, Thomayant ^a   Rodan, Gideon A ^a   Rodan, Sevgi B ^a   Duggan, Mark E ^a   Meissner, Robert S ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BLOCKING AGENT; UNCLASSIFIED DRUG; VITRONECTIN RECEPTOR; VITRONECTIN RECEPTOR ANTAGONIST;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DOG; DRUG IDENTIFICATION; DRUG MECHANISM; MALE; NONHUMAN; OSTEOLYSIS; OSTEOPOROSIS; RAT;

CANIS FAMILIARIS;

EID: 0344064881     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2003.09.055     Document Type: Article

References (23)

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14. Duggan M.E., Duong L.T., Fisher J.E., Hamill T.G., Hoffman W.F., Huff J.R., Ihle N.C., Leu C.-T., Nagy R.M., Perkins J.J., Rodan S.B., Wesolowski G., Whitman D.B., Zartman A.E., Rodan G.R., Hartman G.D. J. Med. Chem. 43:2000;3736.
15. For reviews, see: (a) Hartman G.D., Duggan M.E. Exp. Opin. Invest. Drugs. 9:2000;1281 (b) Duggan M.E., Hutchinson J.H. Exp. Opin. Ther. Pat. 10:2000;1367.
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18. Preparation of 3(S)-β-alanine esters: (a) 3(S)-quinoline: Duggan, M. E.; Meissner, R. S.; Perkins, J. J. WO 99/30709. (b) . 3(S)- Dihydrobenzofuranyl (DHBF): Coleman P.J., Hutchinson J.H., Hunt C.A., Lu P., Delaporte E., Rushmore T. Tetrahedron Lett. 41:2000;5803.
19. Preparation of 3(S)-β-alanine esters: (a) 3(S)-quinoline: Duggan, M. E.; Meissner, R. S.; Perkins, J. J. WO 99/30709. (b) . 3(S)- Dihydrobenzofuranyl (DHBF): Coleman P.J., Hutchinson J.H., Hunt C.A., Lu P., Delaporte E., Rushmore T. Tetrahedron Lett. 41:2000;5803.
20. 3 receptor. For a detailed assay protocol, see ref 14.
21. Prueksaritanont T., Meng Y., Ma B., Leppert P., Hochman J., Tang C., Perkins J., Zrada M., Meissner R., Duggan M.E., Lin J.H. Xenobiotica. 32:2002;207.
22. Assay endpoint is the bone mineral density of the distal femoral metaphysis. Details of this rat bone resorption assay will be provided in forthcoming publications. All animal studies were approved by the Merck Research Laboratories IACUC.
23. Compound 7 produced a 5.6% increase in bone mineral density after 10 days as compared to vehicle dosing.