Takeda Chemical Industries, Inc.

Takeda Pharmaceutical Company Limited

Kohei Nishikawa

Takehiko Naka

Hirosada Sugihara

Takeshi Kato

Shinji Terao

Katsumi Ito

Keiji Kubo

Susumu Tsushima

Yumiko Shibouta

Yoshikazu Oka

Hiroaki Nomura

Akio Miyake

Yoshiyasu Furukawa

Akira Morimoto

Kanji Meguro

Shoji Kishimoto

Katsumi Itoh

Muneo Takatani

Masahiko Fujino

Mitsuhiro Wakimasu

Muneo Nonomura

Yoshio Kozai

Masayuki Yamada

Benzimidazole derivatives of the formula (I): wherein the ring A is a benzene ring which may optionally contain substitution in addition to the R' group; Ris hydrogen or an optionally substituted hydrocarbon residue; Ris a group capable of forming an anion or a group convertible thereinto; X is a direct bond or a spacer having an atomic length of two or less between the phenylene group and the phenyl group; R&#x2032; is carboxyl, an ester thereof, an amide thereof or a group capable of forming an anion or convertible to an anion; Y is &#x2014;O&#x2014;, &#x2014;S(O)&#x2014; or &#x2014;N(R)&#x2014; wherein m is an integer of 0, 1 or 2 and Ris hydrogen or an optionally substituted alkyl group; and n is an integer of 1 or 2; and the pharmaceutically acceptable salts thereof, have potent angiotensin II antagonistic activity and antihypertensive activity, thus being useful as therapeutic agents for treating circulatory system diseases such as hypertensive diseases, heart diseases (e.g. hypercardia, heart failure, cardiac infarction, etc.), strokes, cerebral apoplexy, nephritis, etc.

Benzimidazole derivatives, their production and use

A method for producing a compound represented by the formula: wherein the ring A is a benzene ring which may be substituted in addition to the R' group; Ris hydrogen or an optionally substituted hydrocarbon residue; X is a direct bond or a spacer having an atomic length or two or less between the phenylene group and the phenyl group; Y is &#x2014;O&#x2014;, &#x2014;S(O)m- or &#x2014;N(R)&#x2014; wherein m is an integer of 0, 1 or 2 and Ris hydrogen or an optionally substituted alkyl group; R&#x2032; is carboxyl, an ester thereof, an amide thereof or a group capable of forming an anion or a group convertible thereinto; n is an integer of 1 or 2; or a salt thereof, which comprises deprotecting a compound represented by the formula: wherein R is triphenylmethyl, 2-tetrahydropyranyl, methoxymethyl or ethoxy methyl, the other symbols as defined above; or a salt thereof.

A treatment for glomerulonephritis is disclosed comprising administering (&#xb1;)-1-(cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1 -[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-benzimidazole-7-carboxylate.

Method for the treatment of glomerulonephritis

A method for producing a compound represented by the formula:wherein the ring A is a benzene ring which may be substituted in addition to the R' group; Ris hydrogen or an optionally substituted hydrocarbon residue; X is a direct bond or a spacer having an atomic length or two or less between the phenylene group and the phenyl group; Y is &#x2014;O&#x2014;, &#x2014;S(O)m- or &#x2014;N(R)&#x2014; wherein m is an integer of 0, 1 or 2 and Ris hydrogen or an optionally substituted alkyl group; R&#x2032; is carboxyl, an ester thereof, an amide thereof or a group capable of forming an anion or a group convertible thereinto; n is an integer of 1 or 2; or a salt thereof, which comprises deprotecting a compound represented by the formula:wherein R is triphenylmethyl, 2-tetrahydropyranyl, methoxymethyl or ethoxy methyl, the other symbols as defined above; or a salt thereof.

Prophylactic or therapeutic drug for renal diseases

Benzimidazole compounds, their production and use

Prophylactic or therapeutic drugs for diabetic nephropathy or glomerulonephritis, comprising, as an active ingredient, a compound or salt thereof represented by formula (I)

Benzimidazole derivatives of the formula (I):

This invention relates to prophylactic or therapeutic drug for diabetic nephropathy or glomerulonephritis, comprising, as an active ingredient, a compound or salt thereof represented by general formula (I) ##STR1## wherein R.sup.1 stands for H or an optionally substituted hydrocarbon residue; R.sup.2 stands for an optionally esterified carboxyl group; R.sup.3 stands for a group actually or potentially capable of forming an anion; X shows that the phenylene and phenyl groups bind to each other directly or through a spacer having an atomic chain length of two or less; n stands for 1 or 2; ring A stands for a benzene ring having an optional substituent in addition to R.sup.2 ; Y stands for a bond, --O--, --S(O).sub.m -- (wherein m stands for 0, 1 or 2), or --N(R.sup.4)-- (wherein R.sup.4 stands for H or an optionally substituted alkyl group).

Benzimidazole derivatives of the formula (I): ##STR1## wherein the ring A is a benzene ring which may optionally contain substitution in addition to the R' group; R.sup.1 is hydrogen or an optionally substituted hydrocarbon residue; R.sup.2 is a group capable of forming an anion or a group convertible thereinto; X is a direct bond or a spacer having an atomic length of two or less between the phenylene group and the phenyl group; R' is carboxyl, an ester thereof, an amide thereof or a group capable of forming an anion or convertible to an anion; Y is --O--, --S(O).sub.m -- or --N(R.sup.4)-- wherein m is an integer of 0, 1 or 2 and R.sup.4 is hydrogen or an optionally substituted alkyl group; and n is an integer of 1 or 2; and the pharmaceutically acceptable salts thereof, have potent angiotensin II antagonistic activity and antihypertensive activity, thus being useful as therapeutic agents for treating circulatory system diseases such as hypertensive diseases, heart diseases (e.g. hypercardia, heart failure, cardiac infarction, etc.), strokes, cerebral apoplexy, nephritis, etc.

Benzimidazole derivatives and use thereof

This invention relates to a method for the prophylaxis or treatment of vascular hypertropy in a mammal by administering a pharmaceutically effective amount of a compound represented by the formula (I): ##STR1## wherein ring W is a nitrogen-containing heterocyclic ring residue which may be substituted; R.sup.1 is hydrogen or an optionally substituted hydrocarbon residue which optionally binds through a hetero-atom; R.sup.3 represents a group capable of forming an anion or a group capable of changing thereto; X shows that the phenylene and phenyl groups bind to each other directly or through a spacer having an atomic length of two or less; n denotes 1 or 2; a and b forming the heterocyclic ring residue are independently one or two optionally substituted carbon or hetero atoms; c is an optionally substituted carbon or hetero atom; provided that, when the ring W is a condensed ring, R.sup.1 is hydrogen or an optionally substituted hydrocarbon residue which binds through a hetero atom, or a salt thereof to a mammal in need thereof.

Growing community of inventors

Kyoto, Japan

Kohei Nishikawa