Nonpeptide α vβ 3 antagonists. Part 9: Improved pharmacokinetic profile through the use of an aliphatic, des-amide backbone

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 17, 2004, Pages 4411-4415

  Whitman, David B ^a   Askew, Ben C ^a   Duong, Le T ^a   Fernandez Metzler, Carmen ^a   Halczenko, Wasyl ^a   Hartman, George D ^a   Hutchinson, John H ^a   Leu, Chih Tai ^a   Prueksaritanont, Thomayant ^a   Rodan, Gideon A ^a   Rodan, Sevgi B ^a   Duggan, Mark E ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALIPHATIC COMPOUND; AMIDE; CARBENE; PROTEIN INHIBITOR; SULFONAMIDE; VITRONECTIN RECEPTOR;

ANIMAL EXPERIMENT; ARTICLE; DOG; DRUG BIOAVAILABILITY; DRUG CLEARANCE; EXPERIMENTAL ANIMAL; HALF LIFE TIME; LIPOPHILICITY; NONHUMAN;

ANIMALS; BENZENESULFONATES; DOGS; HUMANS; INTEGRIN ALPHAVBETA3; IODOBENZENES;

CANIS FAMILIARIS;

EID: 3843065733     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.06.068     Document Type: Article

References (12)

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8. The 2-methyl-1,8-naphthyridine regioisomer (methyl 8-(2-methyl-1,8- naphthyridin-3-yl)octanoate, in this case) typically generated in these Friedlander condensations was formed in a ratio of approximately 1:3 to desired product. It was easily separable by flash chromatography on silica gel
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10. Dogs were dosed at 1 mpk po and 0.2 mpk iv. All animal studies described in this report were approved by the Merck Research Laboratories Institutional Animal Care and Use Committee
11. 3. The procedure is described in Refs. 3,12
12. A representative synthesis of the chain-shortened compounds listed in Table 1 is described in Merck and Co., Inc. U.S. Patent 6,048,861; 2000