Takeda Chemical Industries, Inc.

Takeda Pharmaceutical Company Limited

Takeda Chemical Industires, Ltd.

Tetsuo Miwa

Hiroshi Akimoto

Takenori Hitaka

Hiroaki Nomura

Naoki Tarui

Michiyuki Sendai

Shinichi Imamura

Hiroyuki Watanabe

Mitsuo Yamamoto

Takayuki Doi

Kazuyoshi Aso

Shiro Takekawa

Yukio Ishibashi

Takashi Santo

Katsunori Nagai

Akimoto Hiroshi

A novel biphenyl compound having GPR 14 antagonistic activity. It is a compound represented by the formula (I): wherein Rrepresents hydrogen, etc.; X represents 1 to 12 spacers; A represents amino, etc., Rand Reach represents a hydrocarbon group, etc.; and rings B and C each represents an optionally further substituted benzene ring, or a salt thereof.

Biphenyl compound

Compounds of the formula wherein R, R, R, R, X and Y are as defined, which have a superior cGMP specific phosphodiesterase (PDE) inhibitory activity, and can be used as an agent for the treatment of cardiovascular diseases such as angina pectoris, heart failure, cardiac infarction, hypertension, arteriosclerosis, and the like; allergic diseases such as asthma, or disorders of male or female genital function and the like.

Pyrimidine 5-carboxamide compounds, process for producing the same and use thereof

Linker binding carriers for organic synthesis, their production and use

Carbapenem compound, their production and use

A process of making a compound of the formula ##STR1## wherein the ring A is a pyrrole or pyrroline ring, X is an amino group or a hydroxyl group, Y is a hydrogen atom, an amino group or a hydroxyl group, R is a hydrogen atom, a fluorine atom, an alkyl group, an alkenyl group or an alkynyl group, --COOR.sup.1 and --COOR.sup.2 are independently carboxyl groups which may be esterified and n is an integer of 2 to 4, and R may be different in each of the n repeating units, and salts thereof have excellent antitumor effects, and can be used as antitumor agents in mammals.

Pyrrolopyrimidine derivatives, their production

There is provided an improved process for producing novel compounds represented by the general formula: ##STR1## wherein the ring A/ represents a pyrrole ring which may be hydrogenated; X represents an amino, hydroxyl or mercapto group; R.sup.1, R.sup.2 and R.sup.3 each, being the same as or different from the other, represents hydrogen or an alkyl, alkenyl or alkynyl group which may be substituted; R.sup.4 represents OR.sup.5 wherein R.sup.5 represents hydrogen or a hydrocarbon group which may be substituted or NHCH(COOR.sup.6)CH.sub.2 CH.sub.2 COOR.sup.7 wherein R.sup.6 and R.sup.7 each represents hydrogen or a hydrocarbon group which may be substituted; and n represents an integer of 1 to 4, or a salt thereof from compounds represented by the general formula: ##STR2## wherein X, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and n are the same as defined above; Y.sup.1 and Y.sup.2 each represents oxygen or sulfur atom; R.sup.8 and R.sup.9 each, being the same as or different from the other, represents a hydrocarbon group which may be substituted, or salts thereof by an intramolecular ring closure reaction to form a pyrrolopyrimidine ring and, if necessary, reducing pyrrole ring thus formed to pyrroline ring. The compounds are useful as antitumor agents.

Production of pyrrolopyrimidines and intermediates therefor

A polycyclic carbapenem compound of the formula (Ia'), (Ib') or (Ic') ##STR1## [wherein COOR.sup.2 is a carboxy group which may be esterified; R.sup.a' is --(CH.sub.2).sub.m --K.sup.a --(CH.sub.2).sub.n --U.sup.a' ; J is O or S; R.sup.b' is --(CH.sub.2).sub.m --K.sup.b --(CH.sub.2).sub.n U.sup.b' ; J' is O, S or CH.sub.2 ; R.sup.c' is --(CH.sub.2).sub.m --K.sup.c --(CH.sub.2).sub.n --U.sup.c', --(CH.sub.2).sub.m --K.sup.d --(CH.sub.2).sub.n --U.sup.d or a pair of groups, one of which is a hydroxy group, with the other being a hydroxzy group or an alkylsulfonylamino group, which may be substituted, in the position ortho to the first-mentioned hydroxy group] or a salt thereof are useful as an antibacterial agent.

Tricyclic or tetracyclic carbapenem compounds, their production and use

A compound of the formula ##STR1## wherein R.sup.1 is a hydrogen atom or a hydrocarbon group which may be substituted; COOR.sup.2 represents a carboxy group which may be esterified; and ring B is a cyclic group which may be substituted or a pharmaceutically acceptable salt thereof are useful as an antibacterial agent.

Tricyclic carbapenem compounds

There is provided an improved process for producing novel compounds represented by the general formula: ##STR1## wherein the ring A represents a pyrrole ring which may be hydrogenated; X represents an amino, hydroxyl or mercapto group; R.sup.1, R.sup.2 and R.sup.3 each being the same as or different from the other, represents hydrogen or an alkyl, alkenyl or alkynyl group which may be substituted; R.sup.4 represents OR.sup.5 wherein R.sup.5 represents hydrogen or a hydrocarbon group which may be substituted or NHCH(COOR.sup.6)CH.sub.2 CH.sub.2 COOR.sup.7 wherein R.sup.6 and R.sup.7 each represents hydrogen or a hydrocarbon group which may be substituted; and n represents an integer of 1 to 4, or a salt thereof from compounds represented by the general formula: ##STR2## wherein X, R.sup.1, R.sup.2, R.sup.3, R.sup.4 and n are the same as defined above; Y.sup.1 and Y.sup.2 each represents oxygen or sulfur atom; R.sup.8 and R.sup.9 each, being the same as or different from the other, represents a hydrocarbon group which may be substituted, or salts thereof by an intramolecular ring closure reaction to form a pyrrolopyrimidine ring and, if necessary, reducing the pyrrole ring thus formed to a pyrroline ring. The compounds are useful as antitumor agents.

Production of pyrrolopyrimidines

A compound of the formula ##STR1## wherein the ring A pyrrole or pyrroline ring, X is an amino group or a hydroxyl group, Y is a hydrogen atom, an amino group or a hydroxyl group, R is a hydrogen atom, a fluorine atom, an alkyl group, an alkenyl group or an alkynyl group, --COOR.sup.1 and --COOR.sup.2 are independently carboxyl groups which may be esterified and n is an integer of 2 to 4, and R may be different in each of the n repeating units, and salts thereof have excellent antitumor effects, and can be used as antitumor agents in mammals.

Pyrrolopyrimidine derivatives, their production and use

New fused pyrimidines of the general formula (I): ##STR1## wherein the ring A is a pyridine ring which may be hydrogenated or a benzene ring which may be hydrogenated, X is an amino group or a hydroxyl group, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are independently hydrogen, fluorine or a lower alkyl group, and --COOR.sup.5 and --COOR.sup.6 are independently a carboxyl group which may be esterified, and salts thereof have excellent anti-tumor effects, and they can be produced by the following reaction scheme: ##STR2## in which A is, X, R.sup.1 to R.sup.4, --COOR.sup.5 have the above meanings.

Pyrido[2,3-d]pyrimidine compounds useful as intermediates

A compound of the formula ##STR1## wherein the ring A is a pyrrole or pyrroline ring, X is an amino group or a hydroxyl group, Y is a hydrogen atom, an amino group or a hydroxyl group, R is a hydrogen atom, a fluorine atom, an alkyl group, an alkenyl group or an alkynyl group, --COOR.sup.1 and --COOR.sup.2 are independently carboxyl groups which may be esterified and n is an integer of 2 to 4, and R may be different in each of the n repeating units, and salts thereof have excellent antitumor effects, and can be used as antitumor agents in mammals.

Pyrrolopyrimidine derivatives

A compound of the formula ##STR1## wherein the ring .circle.A is a pyrrole or pyrroline ring, X is an amino group or a hydroxyl group, Y is a hydrogen atom, an amino group or a hydroxyl group, R is a hydrogen atom, a fluorine atom, an alkyl group, an alkenyl group or an alkynyl group, --COOR.sup.1 and --COOR.sup.2 are independently carboxyl groups which may be esterified and n is an integer of 2 to 4, and R may be different in each of the n repeating units, and salts thereof have excellent antitumor effects, and can be used as antitumor agents in mammals.

New fused pyrimidines of the general formula (I): ##STR1## wherein the ring .circle. A is a pyridine ring which may be hydrogenated or a benzene ring which may be hydrogenated, X is an amino group or a hydroxyl group, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are independently hydrogen, fluorine or a lower alkyl group, and --COOR.sup.5 and --COOR.sup.6 are independently a carboxyl group which may be esterified, and salts thereof have excellent anti-tumor effects, and they can be produced by the following reaction scheme: ##STR2## in which .circle. A is, X, R.sup.1 to R.sup.4, --COOR.sup.5 have the above meanings.

Growing community of inventors

Kobe, Japan

Tetsuo Miwa