Structure-activity relationships of potent and selective factor Xa inhibitors: Benzimidazole derivatives with the side chain oriented to the prime site of factor Xa

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 16, 2004, Pages 4217-4220

  Ueno, Hiroshi ^a   Katoh, Susumu ^a   Yokota, Katsuyuki ^a   Hoshi, Jun Ichi ^a   Hayashi, Mikio ^a   Uchida, Itsuo ^a   Aisaka, Kazuo ^a   Hase, Yasunori ^a   Cho, Hidetsura ^a  

^a JAPAN TOBACCO INC   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

BENZIMIDAZOLE DERIVATIVE; BLOOD CLOTTING FACTOR 10A; BLOOD CLOTTING FACTOR 10A INHIBITOR; NITROGEN; SERINE PROTEINASE INHIBITOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTICOAGULATION; ARTICLE; DISSEMINATED INTRAVASCULAR CLOTTING; DRUG DESIGN; DRUG POTENCY; DRUG SYNTHESIS; EXPERIMENTAL MODEL; LOW DRUG DOSE; MOUSE; NONHUMAN; STRUCTURE ACTIVITY RELATION; CHEMISTRY; DRUG ANTAGONISM;

BENZIMIDAZOLES; FACTOR XA; SERINE PROTEINASE INHIBITORS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 3142674924     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.06.009     Document Type: Article

References (12)

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10. After pre-incubation for 2 h, enzyme inhibitory activity was unchanged. This indicated that the amide moiety was not hydrolyzed even though the carbonyl group was designed to interact with Gly 193, which formed an oxi-anion hole
11. Pharmacokinetic evaluation was carried out by an ex vivo inhibitory assay in mice (po 10 mg/kg). Compound 1 showed 25% inhibition at 0.5 h and 15% inhibition at 1.0 h, while compounds 19 and 20 showed no inhibition.
12. 50 values express the drug concentration required to produce 50% inhibition of tissue factor-induced platelet aggregation in comparison with the vehicle