PDBsum entry 2d1j

Hydrolase

PDB id: 2d1j

Contents

Protein chains

233 a.a.

54 a.a.

Ligands

D01

Metals

_CA ×2

Waters ×111

References listed in PDB file

Key reference

• Title: Design, Synthesis, And biological activity of non-Basic compounds as factor xa inhibitors: sar study of s1 and aryl binding sites.
• Authors: S.Komoriya, N.Haginoya, S.Kobayashi, T.Nagata, A.Mochizuki, M.Suzuki, T.Yoshino, H.Horino, T.Nagahara, M.Suzuki, Y.Isobe, T.Furugoori.
• Ref.: Bioorg Med Chem Lett, 2005, 13, 3927-3954.
• PubMed id: 15911309

Note: In the PDB file this reference is annotated as "TO BE PUBLISHED". The citation details given above have been manually determined.

Abstract

Compound 7 was identified as the active metabolite of 6 by HPLC and mass spectral analysis. Modification of lead compound 7 by transformation of its N-oxide 6-6 biaryl ring system and fused aromatics produced a series of non-basic fXa inhibitors with excellent potency in anti-fXa and anticoagulant assays. The optimized compounds 73b and 75b showed sub to one digit micromolar anticoagulant activity (PTCT2). Particularly, anti-fXa activity was detected in plasma of rats orally administered with 1mg/kg of compound 75b.

Secondary reference #1

• Title: Design, Synthesis, And biological activity of non-Basic compounds as factor xa inhibitors: sar study of s1 and aryl binding sites.
• Authors: S.Komoriya, N.Haginoya, S.Kobayashi, T.Nagata, A.Mochizuki, M.Suzuki, T.Yoshino, H.Horino, T.Nagahara, M.Suzuki, Y.Isobe, T.Furugoori.
• Ref.: Bioorg Med Chem Lett, 2005, 13, 3927-3954.
• PubMed id: 15911309

Secondary reference #2

• Title: Synthesis and conformational analysis of a non-Amidine factor xa inhibitor that incorporates 5-Methyl-4,5,6,7-Tetrahydrothiazolo[5,4-C]pyridine as s4 binding element.
• Authors: N.Haginoya, S.Kobayashi, S.Komoriya, T.Yoshino, M.Suzuki, T.Shimada, K.Watanabe, Y.Hirokawa, T.Furugori, T.Nagahara.
• Ref.: J Med Chem, 2004, 47, 5167-5182. [DOI no: 10.1021/jm049884d]
• PubMed id: 15456260