Takeda Chemical Industries, Inc.

Takeda Pharmaceutical Company Limited

Mita Industrial Co., Ltd.

Senju Pharmaceutical Co., Ltd.

Keiji Kubo

Kohei Nishikawa

Yoshiyuki Inada

Yumiko Shibouta

Masaki Kawamura

Yasuhiro Imaeda

Takehiko Naka

Motoyuki Fukuda

Kenji Yamamura

Hiroki Sakamoto

Takahiko Taniguchi

Takahiro Ogawa

Takanobu Kuroita

Yoshiyuki Fukase

Eiji Honda

Fumio Itoh

Satoshi Tanaka

Takaaki Deguchi

Hiroshi Hosono

Mamoru Tobisu

Katsumi Fujimoto

Masaharu Nakayama

The present invention provides a cyclic amide derivative useful as a drug for treating thrombosis, which is represented by the formula (I): wherein Rrepresents an optionally substituted cyclic hydrocarbon group or an optionally substituted heterocyclic group, W represents a bond or an optionally substituted divalent chain hydrocarbon group, a represents 0, 1, or 2, Xrepresents an optionally substituted lower alkylene or an optionally substituted lower alkenylene, Yrepresents &#x2014;C(O)&#x2014;, &#x2014;S(O)&#x2014; or &#x2014;S(O)&#x2014;, A represents a piperazine ring which may be further substituted or a piperidine ring which may be further substituted, Xrepresents a bond or an optionally substituted lower alkylene, Yrepresents &#x2014;C(O)&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;S(O)&#x2014; or &#x2014;C(&#x2550;NR)&#x2014;, Xrepresents an optionally substituted Calkylene or an optionally substituted Calkenylene, Zrepresents &#x2014;N(R)&#x2014;, &#x2014;O&#x2014; or a bond, Zrepresents &#x2014;C(R) (R)&#x2014;, &#x2014;N(R)&#x2014;, etc., and Zrepresents &#x2014;C(R)(R)&#x2014;, &#x2014;N(R)&#x2014;, etc., or a salt thereof.

Cyclic amide derivative, and its production and use

The present invention provides a urea derivative or a salt thereof, which is useful as a therapeutic agent for thrombosis. The derivative is represented by Formula (I): wherein Cy is an aromatic hydrocarbon group which may be substituted or an aromatic heterocyclic group which may be substituted; Ris a hydrogen atom or a hydrocarbon group which may be substituted; V is &#x2014;C(O)&#x2014;, &#x2014;S(O)&#x2014;, or &#x2014;S(O)&#x2014;; W is &#x2014;N(R)&#x2014;, &#x2014;O&#x2014;, or a bond (wherein Ris a hydrogen atom or a hydrocarbon group which may be substituted); X is alkylene which may be substituted; Y is &#x2014;C(O)&#x2014;, &#x2014;S(O)&#x2014;, or &#x2014;S(O)&#x2014;; Z is a bond, a chain hydrocarbon group which may be substituted, or &#x2014;N&#x2550;; ring A is a non-aromatic nitrogen-containing heterocyclic ring which may be substituted; ring B is a nitrogen-containing heterocyclic ring which may be substituted; and[Chemical formula 2],are each independently a single bond or a double bond; provided that Rmay be bonded to Rto form a non-aromatic nitrogen-containing heterocyclic ring and that Rmay be bonded to a substituent of X to form a non-aromatic nitrogen-containing heterocyclic ring which may be substituted.

Urea derivative, process for producing the same, and use

The present invention relates to a thrombin receptor antagonist containing a compound represented by the formula (I) wherein R, Rand Rare each a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, or an optionally substituted alkoxy, Ris a group represented by the formula &#x2014;NHCOR, &#x2014;NHSOR, &#x2014;NHCON(R)(R), &#x2014;NHCOORor &#x2014;CONHRwherein R, R, R, R, Rand Rare each a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group and the like), ring A is monocyclic aromatic ring optionally further having substituent(s), Rand Rare optionally bonded to each other to form an optionally substituted nitrogen-containing non-aromatic heterocycle, or a salt thereof or a prodrug thereof. The thrombin receptor antagonist of the present invention has a thrombin receptor (particularly PAR-1) antagonistic action and is useful for the prophylaxis or treatment of PAR-1 mediated pathological condition or disease.

Triazole derivative and use thereof

The present invention provides a cyclic amide derivative useful as a drug for treating thrombosis, which is represented by the formula (I): wherein Rrepresents an optionally substituted cyclic hydrocarbon group or an optionally substituted heterocyclic group, W represents a bond or an optionally substituted divalent chain hydrocarbon group, a represents 0, 1, or 2, Xrepresents an optionally substituted lower alkylene or an optionally substituted lower alkenylene, Yrepresents &#x2014;C(O)&#x2014;, &#x2014;S(O)&#x2014; or &#x2014;S(O)&#x2014;, A represents a piperazine ring which may be further substituted or a piperidine ring which may be further substituted, Xrepresents a bond or an optionally substituted lower alkylene, Yrepresents &#x2014;C(O)&#x2014;, &#x2014;S(O)&#x2014;, &#x2014;S(O)&#x2014; or &#x2014;C(&#x2550;NR)&#x2014;, Xrepresents an optionally substituted Calkylene or an optionally substituted Calkenylene, Zrepresents &#x2014;N(R)&#x2014;, &#x2014;O&#x2014; or a bond, Zrepresents &#x2014;C(R)(R)&#x2014;, &#x2014;N(R)&#x2014;, etc., and Zrepresents &#x2014;C(R)(R)&#x2014;, &#x2014;N(R)&#x2014;, etc., or a salt thereof.

A thiazoline derivative represented by Formula (I): wherein R is a cyclic hydrocarbon group which may be substituted, or a heterocyclic group which may be substituted; X is a bond or a divalent chain hydrocarbon group which may be substituted; X' is a bond or &#x2014;N(R)&#x2014;; Y is a divalent hydrocarbon group which may be substituted; Y&#x2032; is a bond or &#x2014;C(&#x2550;O)&#x2014;; ring A is a nitrogen-containing heterocycle which may be substituted; Zand Zare each independently a bond or a divalent chain hydrocarbon group which may be substituted; Zis a bond or &#x2014;N(R)&#x2014;; and B is a group represented by the formula: which is useful as a therapeutic drug for thrombosis, is provided.

Thiazoline derivative and use of the same

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

Acylhydrazine derivatives, their production and use

Prophylactic or therapeutic drug for renal diseases

Pharmaceutical composition for angiotensin II-mediated diseases

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

This invention relates to a pharmaceutical composition for angiotensin II-mediated diseases, which comprises a compound having angiotensin II antagonistic activity of the formula

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).

This invention relates to a pharmaceutical composition for angiotensin II-mediated diseases, which comprises a compound having angiotensin II antagonistic activity of the formula ##STR1## wherein R.sup.1 is H or an optionally substituted hydrocarbon residue; R.sup.2 is an optionally esterified carboxyl group; R.sup.3 is a group capable of forming an anion or a group convertible thereinto; X is a covalent bond between the 2 phenyl rings or a spacer having a chain length of 1 to 2 atoms as the linear moiety between the adjoining phenylene group and phenyl group; n is 1 or 2; the ring A is a benzene ring having 1 or 2 optional substituents in addition to R.sup.2 ; and Y is a bond, --O--, --S(O)m- (wherein m is 0, 1 or 2) or --N(R.sup.4)-- (wherein R.sup.4 is H or an optionally substituted alkyl group), or a pharmaceutically acceptable salt thereof in combination with a compound having diuretic activity or a compound having calcium antagonistic activity.

Growing community of inventors

Osaka, Japan

Keiji Kubo