Kissei Pharmaceutical Co., Ltd.

In-silico Sciences, Inc.

Hideaki Umeyama

Kinji Iizuka

Tetsuhide Kamijo

Kenji Akahane

Yoshiaki Kiso

Tetsuhiro Kubota

Ryoichi Arai

Yoshiaki Watanabe

The present invention is directed to serve ligand screening apparatuses, ligand screening methods, programs and a recording medium for studying the binding analysis between a receptor including an induced-fit type receptor and a ligand. First, analysis and calculation of normal mode are conducted, and then fluctuation of a dihedral angle of a main chain in a steady state is calculated. Then by carrying out a molecular dynamic calculation while imposing constraint on each atom based on the fluctuation, a dynamic structure of the receptor is predicted more accurately. By using the dynamic structure obtained in the molecular dynamic calculation and an interaction function, receptor/ligand binding which is also applicable to an induced-fit type receptor is predicted with high accuracy.

Ligand searching device, ligand searching method, program, and recording medium

Novel amino acid derivatives useful as a therapeutic agent are disclosed. These amino acid derivatives and the pharmaceutically acceptable salts thereof have a human renin inhibitory effect when administered orally and are useful for treatment of hypertension, especially renin-associated hypertension.

Novel amino acid derivatives

Dipeptides are described which are represented by the formula ##STR1## wherein the various substituents are defined hereinbelow. These compounds have a strong inhibitory efect on human renin, and are useful as a therapeutically active agent for the treatment of hypertension, especially renin-associated hypertension.

Dipeptides as renin inhibitors

New renin inhibitory amino acid derivatives represented by formula (I): ##STR1## wherein A represents an alkoxycarbonyl group having 2 to 7 carbon atoms, ##STR2## wherein R.sup.1 and R.sup.2 are defined as in the specification below or ##STR3## wherein X and Y are defined as in the specification herein below, n represents zero or one, Z represents --O-- or --NH--, and R represents a straight- or branched chain alkyl group having 1 to 7 carbon atoms, and pharmaceutically acceptable salts thereof, useful as a therapeutic agent are disclosed. The amino acid derivatives have a renin inhibitory effect when administered orally and are useful for treatment of hypertension, especially renin-associated hypertension.

Novel renin inhibitory amino acid derivatives

Amino acid derivatives

Amino acid derivatives represented by formula ##STR1## wherein His represents an L-histidyl group, X represents a straight or branched alkoxy group having 1 to 7 carbon atoms, a straight or branched alkylamino group having 1 to 7 carbon atoms, a cycloalkyloxy group having 3 to 7 carbon atoms, a morpholino group, said alkoxy group having one or more halogen atoms as substituents; or a pharmaceutically acceptable salt, are useful in the treatment of hypertension.

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Chiba, Japan

Hideaki Umeyama