公开(公告)号：JPS52131529A

公开(公告)日：1977-11-04

申请号：JP4811376

申请日：1976-04-26

Applicant: TAKEDA CHEMICAL INDUSTRIES LTD

Inventor： MIYASHITA OSAMU ,  MATSUMURA KOUICHI ,  SHIMAZU HIROSHI ,  HASHIMOTO NAOTO

IPC: C07C275/16 ,  C07C67/00 ,  C07C239/00

Abstract: PURPOSE:One step reaction of urea, an orthoformic ester, and a malonic ester forms a ureidomethylene malonic ester in high yields.

公开(公告)号：JPH06190032A

公开(公告)日：1994-07-12

申请号：JP13678091

申请日：1991-06-07

Applicant: TAKEDA CHEMICAL INDUSTRIES LTD

Inventor： HATA YOSHIO ,  NAKAGAWA YASUSHI ,  HASHIMOTO NAOTO

IPC: A61L33/00

Abstract: PURPOSE:To obtain a material which can suppress coagulation of blood without using anti-coagulation agent by graft-polymerizing acrylic acid or methacrylic acid onto a polymer material and preparing an anticoagulant polymer material. CONSTITUTION:An anticoagulant polymer material is prepd. by graft- polymerizing-acryllc acid or methacrylic acid on a general-purpose polymer material. This anticoagulant polymer material can be used as a material for medical instruments and tools which are possibly brought into contact with blood, e.g. a blood tube and a catheter which are medical tubes, a blood bag, a blood spit roll, a vial bottle, a test tube and a centrifugal tube and a syringe tube which are materials for medical containers, a culture medium such as a bacterium and a cell, a Petri dish and a vial, which are materials for culture tools and a sample cup, a sample rack, a funnel, a filter and a pipette which are diagnosis tools.

公开(公告)号：JPH01216961A

公开(公告)日：1989-08-30

申请号：JP4342388

申请日：1988-02-25

Applicant: TAKEDA CHEMICAL INDUSTRIES LTD

Inventor： KATOU KANEYOSHI ,  MARUI SHOGO ,  HASHIMOTO NAOTO

IPC: C07C259/06 ,  C07C67/00 ,  C07C239/00

Abstract: PURPOSE:To provide the subject preparation useful as a preventing and treating agent for ischemic circulatory diseases, organ inflammation, vulgaris psoriasis, arterial sclerosis, etc., and having low toxicity and a little adverse effect, by containing a hydroxamic acid derivative or a salt thereof. CONSTITUTION:The subject preparation contains a compound of the formula (R is H, lower alkyl or phenyl; A is a connecting bond, alkylene or alkenylene; R is H or aromatic ring group) or a salt thereof. The preparation can be orally or parenterally administered to mammals and is preferably administered in a dose of 0.2-10mg/kg body for an adult one - two times a day when administered orally. The compound of the formula includes new substances.

公开(公告)号：JPS63174990A

公开(公告)日：1988-07-19

申请号：JP476087

申请日：1987-01-12

Applicant: TAKEDA CHEMICAL INDUSTRIES LTD

Inventor： KISHIMOTO SHOJI ,  TOMIMOTO MITSUYOSHI ,  HASHIMOTO NAOTO

IPC: C07D501/38 ,  A61K31/545 ,  A61K31/546 ,  A61P31/04

Abstract: NEW MATERIAL:A compound shown by formula I [R is acyl; R is COOQ, COQ or SQ (Q is hydrocarbon which may be substituted); A is vinylene which may be substituted; COOR is carboxyl which may be substituted] or a salt thereof. EXAMPLE:7beta-[ 2-(2-Aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido ]-3-{[N-form yl-N-(2-acetylthio-1-cyclohexenyl]amino]methyl}-3-cephem-4-carboxylic acid pivaloyloxymethyl ester. USE:An antibacterial agent Gram-positive and Gram-negative bacteria, having low toxicity. PREPARATION:A compound shown by formula II (M is alkali metal) is reacted with a compound shown by the formula R -X (X and M are bonded to give eliminable group).

公开(公告)号：JPS62240687A

公开(公告)日：1987-10-21

申请号：JP23878886

申请日：1986-10-06

Applicant: TAKEDA CHEMICAL INDUSTRIES LTD

Inventor： MINAMIDA ISAO ,  HASHIMOTO NAOTO

IPC: A61K31/365 ,  A61K31/40 ,  A61K31/44 ,  A61K31/445 ,  A61K31/495 ,  A61K31/535 ,  A61K31/54 ,  A61P31/00 ,  C07D311/00 ,  C07D313/00 ,  C07D493/08 ,  C07H15/00

Abstract: NEW MATERIAL:A compound expressed by formula I [one of R and R represents H and the other represents formula II (Z represents O or S; R represents organic residue bonded through C atom) or R and R are linked with each other and represent formula III (R represents acyl, sulfonyl, etc.; R represents lower alkyl); R and R represent OH, halogen atom, aride, etc., provided that when R represents H and R represents -COCOCH3, etc., then R represents OH or -OCOR (R represents alkyl, alkenyl, etc.) and R does not represent OH or -OCOR or both R and R do not represent formyl, when R represent H, R represents -COCOCH3 and R represents -OCOCH3, then R does not represent Cl, -OSO2CH3, etc., and when R represents H, R represents -COCOCH3 and R represents -OCH3, then R does not represent -OCH3] or salt thereof. EXAMPLE:Lankacidin C-8,14-bis(2,2,2-trichloroethyl)carbonate. USE:An antimicrobial agent. PREPARATION:A compound expressed by formula IV is subjected to alkylation reaction.

公开(公告)号：JPS61143367A

公开(公告)日：1986-07-01

申请号：JP25631485

申请日：1985-11-14

Applicant: TAKEDA CHEMICAL INDUSTRIES LTD

Inventor： MIYASHITA OSAMU ,  MATSUMURA KOICHI ,  SHIMAZU HIROSHI ,  HASHIMOTO NAOTO

IPC: C07D239/557 ,  A61K31/505 ,  A61P31/12 ,  A61P35/00 ,  C07D239/22 ,  C07D239/54

Abstract: NEW MATERIAL:A compound shown by the formula I (R is isopropyl, isobutyl, or sec-butyl). EXAMPLE:1, 2, 3, 4-Tetrahydro-2,4-dioxopyrimidin-5-carboxylic acid isopropyl ester. USE:An intermediate for a drug having strong multiplication inhibitory action on various tumor cells of mammals, life prolonging effects on leukemia and antiviral effects. PREPARATION:A carboxlic acid corresponding to a compound shown by the formula I is treated with a chlorinating agent in dimethylformamide (DMF) to give a corresponding carboxylic acid chloride-DMF.(1/2)HCl complex, which is reacted with a compound shown by the formula R-OH, to give a compound shown by the formula I. This compound is fluorinated in the presence of water, etc., to give a compound shown by the formula II (R1 is OH which may be optionally etheriifed) useful as the above-mentioned drug.

公开(公告)号：JPS57192390A

公开(公告)日：1982-11-26

申请号：JP7699481

申请日：1981-05-20

Applicant: TAKEDA CHEMICAL INDUSTRIES LTD

Inventor： HASHIMOTO NAOTO ,  SHIMAZU HIROSHI

IPC: C07D498/18 ,  A61K31/535 ,  A61P35/00

Abstract: NEW MATERIAL:A compound of formulaI(R is H, acyl originating from carboxylic acid; X is Cl, H; Y is H, lower alkylsulfonyl, arbitrarily substituted alkyl, aralkyl; R', R'' are H, alkyl, aralkyl, phenyl, or cyclic amino as -NR'R''). EXAMPLE:9-Methylamino-ansamitocin P-3. USE:Antitumor, antibacterial, antifungal or antiprotozoal agent: It has strong mitosis-inhibiting and antitumor activity and shows low toxicity. PREPARATION:For example, the reaction of 9-thiomaytansinoid of formula II with an amine of formula III gives the compound of formulaI. The amount of the amine of formula III is about 2-1,000 times the molar quantity of the compound of formula II and it acts as an solvent, too, when an excessive amount is used.

公开(公告)号：JPS57192388A

公开(公告)日：1982-11-26

申请号：JP7699281

申请日：1981-05-20

Applicant: TAKEDA CHEMICAL INDUSTRIES LTD

Inventor： HASHIMOTO NAOTO ,  SHIMAZU HIROSHI

IPC: C07D498/18 ,  A61K31/535 ,  A61P35/00

Abstract: NEW MATERIAL:A compound of formulaI(R is lower alkanoyl; X is hydroxyl, lower alkoxy; A is lower alkylene, which may be substituted with hydroxyl; Y is H, acyl, group of formula II or -AOY represents tetrahydrofurfuryl or tetrahydropyranyl). EXAMPLE:Ethylene glycol-bis-(maytansinol 3-isobutylate 9-yl) ether. USE:Antitumor, antibacterial, antifungal, antiprotozoal agent: it has strong activity of inhibiting mitosis and resisting tumor and shows low toxicity. PREPARATION:For example, the reaction of a compound of formula III with a diol or triol of formula IV gives the compound of formulaI. The reaction is effected in a solvent such as dichloromethane in the presence of an acid catalyst such as trifluoroacetic acid.

公开(公告)号：JPS5553294A

公开(公告)日：1980-04-18

申请号：JP12598978

申请日：1978-10-12

Applicant: TAKEDA CHEMICAL INDUSTRIES LTD

Inventor： HASHIMOTO NAOTO ,  KISHI TOYOKAZU

IPC: C07D498/18 ,  A61K31/535 ,  A61P35/00

Abstract: NEW MATERIAL:An ansamitocin derivative of formula I (R is 5-15C alkyl). EXAMPLE:Maytansinol 3-hexanate. USE:Agent for suppressing the mitotic cell division. An anti-tumor agent. Effective to elongate the life of a warm-blooded animal. affected by cancer, by oral or parenteral administration. Also useful as an antibacterial agent. PROCESS:The compound I is prepared by reacting maytansinol with a carboxylic acid II or its reactive derivative pref. in the presence of a carbodiimide and a catalyst (e.g. tert-amine). The maytansinol can be prepared by the reductive hydrolysis of an ansamitocin III (R is acetyl, propionyl, etc.) produced by bacteria belonging to Nocardia genus.

公开(公告)号：JPS54128597A

公开(公告)日：1979-10-05

申请号：JP3464478

申请日：1978-03-24

Applicant: TAKEDA CHEMICAL INDUSTRIES LTD

Inventor： HASHIMOTO NAOTO ,  KISHI TOYOKAZU

IPC: A01N43/90 ,  A61K31/535 ,  A61P9/12 ,  C07D498/18

Abstract: PURPOSE:To prepare an ansamytocin having an antitumor, antibacterial, and antifungal activities advantageously, by acylating maytansinol obtained by reductive hydrolysis of an antibiotic C-15003. CONSTITUTION:One type of antibiotic C-15003 of formula I: (R1 is acetyl, propionitrile, butyryl, isobutyryl, or isovaleryl group) or a mixture of two or more types is subjected to reductive hydrolysis to form maytansinol, which is acylated by a reactive derivative of a carboxylic acid at the carboxyl group of formula II: (R2 is H or 1-4C alkyl group) in a solvent) e.g. ether or nitrile, in the presence of a base, e.g. pyridine, at about -40-20 deg.C to give an ansamytocin of formula III.