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2004
Benzimidazole derivatives
R 0200
Halothiophene Benzimidazoles as P1 Surrogates of Inhibitors of Blood CoagulaFactor Xa. — Initiated by the X-ray crystallographic data of a weakly active
46- 121 tion
halothiophene benzimidazole inhibitor of serine protease factor Xa, potent achiral and
nonbasic factor Xa inhibitors containing a halothiophene benzimidazole as P1 residue
and tethered cyclic anilino amides as P4 ligands are synthesized. The length and nature
of the linker between benzimidazole and P4 residue have influence on the potency.
Variation of these parameter affords the low nanomolar inhibitors (V) and (VII). Novel
anti-coagulation drugs may be obtained by improvements with respect to their
physico-chemical and pharmacokinetic properties. — (MEDERSKI*, W. W. K. R.;
DORSCH, D.; ANZALI, S.; GLEITZ, J.; CEZANNE, B.; TSAKLAKIDIS, C.;
Bioorg. Med. Chem. Lett. 14 (2004) 14, 3763-3769; Preclin. Pharm. Res., Merck
KGaA, D-64271 Darmstadt, Germany; Eng.) — H. Hoennerscheid
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