公开(公告)号：JPH1143482A

公开(公告)日：1999-02-16

申请号：JP20135497

申请日：1997-07-28

Applicant: KOWA CO

Inventor： HIRATA MITSUTERU ,  IDEUSHI TAKEO ,  TAKAHASHI YOSHIO ,  OSHIMA TAKESHI ,  ODA TOSHIAKI ,  ISHIKAWA TETSUYA ,  OZAKI CHIYOKA ,  SHIRATO SHOZO

IPC: C07D239/46 ,  A61K31/505 ,  A61P9/00 ,  A61P9/06 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  A61P43/00 ,  C07D401/04 ,  C07D401/12 ,  C07D405/04

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound that has excellent endothelin antagonistic action and is useful as a medicine typified by a treatment agent for cardiovascular diseases. SOLUTION: This new compound is represented by formula I R is -OR , -NR R [R is H, a lower alkyl, benzyl; R and R are each H, a lower alkyl, phenyl which may be substituted]; R is pyridyl, formula II (R , R are H, a lower alkyl); n is 1, 2], typically 3-[6-(4-t-butyl-phenylsulfonylamino)-5-(2- methoxyphenoxy)-2-(4-methoxyphenyl)-4-pyrimidinyloxy]propionic acid. The compound of the formula I is prepared, for example, by oxidizing a compound of formula III with an oxidizing agent in a polar solvent to form the compound of formula IV.

公开(公告)号：JPH05213852A

公开(公告)日：1993-08-24

申请号：JP24029491

申请日：1991-08-28

Applicant: KOWA CO

Inventor： NAKAYAMA MASATO ,  IDEUSHI TAKEO ,  TAKAHASHI YOSHIO ,  ISHIWATARI HIROYUKI ,  OKUNO YUKIHIRO ,  ITOU HISAKATSU ,  SHIRATO SHOZO

IPC: A61K31/655 ,  A01N51/00 ,  A61P17/00 ,  A61P31/04 ,  A61P31/10 ,  C07C291/08

Abstract: PURPOSE:To provide a novel compound useful as an antimycotic agent for medical, veterinary and agri- and horticultural purposes. CONSTITUTION:A compound of formula I (R1, R2 are H, lower alkyl, lower alkenyl, lower alkinyl, lower alkoxy, aryl, aralkyl; R3 is H, lower alkyl, benzoyl; when R1 is n-butyl, R3 is halogenated lower-alkyl), for example, 2- hydroxyimino-3-[2-(4-(3-iodopropargyl)oxyphenyl)-1-propenyl-ONN-azoxy] -butane. The compound of formula I is obtained by allowing an acid to act on a compound of formula II (n is 2, 3) such as hydrochloric acid followed by reaction of the product with a compound of the formula: H2N-OR3 in the presence of a base such as sodium carbonate in a solvent such as THR at -10 deg.C to the refluxing temperature. It is useful against molds infectious to warm-blood animal such as Candida, Cryptococcus, Aspergillus or the like and infectious to cropping plants in agriculture and horticulture such as piricularia, botrytis or saccharomyces.

公开(公告)号：JPH0528716B2

公开(公告)日：1993-04-27

申请号：JP4280885

申请日：1985-03-06

Applicant: KOWA CO

Inventor： KAWAMURA KYOSHI ,  AKASHI TOSHIHIRO ,  SHIRATO SHOZO ,  ISHIHAMA HIROSHI ,  OOTA TOMIO

IPC: C07D311/58

公开(公告)号：JPH0488993A

公开(公告)日：1992-03-23

申请号：JP20416590

申请日：1990-08-01

Applicant: KOWA CO

Inventor： NAKAYAMA MASATO ,  ITOU HISAKATSU ,  WATANABE ISAMU ,  SHIRATO SHOZO

IPC: C12P13/08 ,  C12N1/20 ,  C12R1/365

Abstract: PURPOSE:To obtain the title compound useful as an antifungal agent industrially and advantageously by culturing a specific strain belonging to the genus Nocardiopsis. CONSTITUTION:A strain [preferably Nocardiopsis sp.KC-7,223 (FERM BP-2,993)] belonging to the genus Nocardiopsis, capable of producing trans-4,5-dehydro-L- lysine, is cultured by submerged culture under an aerobic condition at 25-30 deg.C for 2-6 days and the objective compound is obtained from the culture solution.

公开(公告)号：JPH0134991B2

公开(公告)日：1989-07-21

申请号：JP5167481

申请日：1981-04-08

Applicant: KOWA CO

Inventor： SHIRATO SHOZO ,  SHIMIZU NOBORU ,  SHIGYO HIROMICHI ,  KYOTANI YOSHINORI ,  KAWAMURA KYOSHI ,  SATO SEIICHI ,  AKASHI TOSHIHIRO

IPC: C07D311/58 ,  A61K31/35 ,  A61K31/352 ,  A61P9/08 ,  A61P9/10 ,  A61P9/12 ,  C07D311/04 ,  C07D407/12

公开(公告)号：JPH0692927A

公开(公告)日：1994-04-05

申请号：JP26682792

申请日：1992-09-10

Applicant: KOWA CO

Inventor： IDEUSHI TAKEO ,  TAKAHASHI YOSHIO ,  ISHIWATARI HIROYUKI ,  OKUNO YUKIHIRO ,  ODA TOSHIAKI ,  SHIRATO SHOZO

IPC: A61K31/655 ,  A61P31/04 ,  A61P31/10 ,  C07C291/08

Abstract: PURPOSE:To provide a compound having excellent antimycotic activity, useful as an antimycotic agent for medicines, veterinary medicines and agricultural/ horticultural applications. CONSTITUTION:The compound of formula I(R1 and R2 are each H, alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, aryl, etc.; R3 and R4 are each H or alkyl; R5 is H, alkyl, alkenyl, alkynyl, alkoxy, alkenyloxy, etc.), e.g. 1-(1-hexenyl-ONN- azoxy)-2-propanol. The compound of the formula I (for example, R5 is H) can be obtained by reducing a compound of formula II. The compound of the formula II, in turn, can be obtained from a compound of formula III via a compound of formula IV and a compound of formula V.

公开(公告)号：JPH0422887B2

公开(公告)日：1992-04-20

申请号：JP6217784

申请日：1984-03-31

Applicant: KOWA CO

Inventor： SHIRATO SHOZO ,  KAWAMURA KYOSHI ,  AKASHI TOSHIHIRO ,  ISHIHAMA HIROSHI ,  UCHIDA YASUYOSHI

IPC: A61K31/35 ,  A61K31/352 ,  A61P9/08 ,  A61P9/12 ,  A61P25/02 ,  C07D303/16 ,  C07D311/64 ,  C07D407/12

公开(公告)号：JPH0488992A

公开(公告)日：1992-03-23

申请号：JP20416490

申请日：1990-08-01

Applicant: KOWA CO

Inventor： NAKAYAMA MASATO ,  ITOU HISAKATSU ,  WATANABE ISAMU ,  SHIRATO SHOZO

IPC: C12P13/08 ,  C12N1/20 ,  C12R1/60

Abstract: PURPOSE:To obtain the title compound useful as an antifungal agent industrially and advantageously by culturing a specific strain belonging to the genus Streptomyces. CONSTITUTION:A strain [preferably Streptomyces sp.KC-7,161 (FERM BP-2,992)] belonging to the genus Streptomyces, capable of producing 4-oxo-L-lysine, is cultured by submerged culture under an aerobic condition at 25-30 deg.C for 2-6 days and the objective compound is obtained from the culture solution.

公开(公告)号：JPS6330423A

公开(公告)日：1988-02-09

申请号：JP17262686

申请日：1986-07-22

Applicant: KOWA CO

Inventor： AOKI NOBUO ,  KIMURA SHIGERU ,  SHIRATO SHOZO

IPC: A61K35/22 ,  A61P7/02

Abstract: NEW MATERIAL:A thrombin-bonding substance having the following properties. Molecular weight, 185,000, 92,000, 46,500 and 31,000 in reduced state and 200,000, 48,000 and 40,000 in unreduced state; affinity, having strong affinity to thrombin; activity, capable of activating protein C by bonding with active thrombin and prolonging the coagulation time of blood; stability, stable to denaturation agent (sodium dodecylsulfate or urea). USE:A fibrinolysis-promoting agent and anticoagulant. PREPARATION:Fresh human urine is added with benzamidine hydrochloride and aprotinin and subjected to ion-exchange chromatography. The adsorbed fraction is eluted with tris-HCl buffer solution, concentrated and passed through a column packed with thrombin bonded to a carrier. The adsorbed active fraction is eluted with a tris-HCl buffer solution and subjected to concentration and gel-filtration to obtain the objective thrombin-bonding substance.

公开(公告)号：JPS6148514B2

公开(公告)日：1986-10-24

申请号：JP11430278

申请日：1978-09-18

Applicant: KOWA CO

Inventor： ONOKI KAZUHIRO ,  KUNIEDA HISASHI ,  KAWAMURA KYOSHI ,  MACHIDA NAOKI ,  SHIRATO SHOZO ,  NAGAKURA MASAHIKO

IPC: C07D311/94 ,  A61K31/35 ,  A61K31/352 ,  A61K31/41 ,  A61P25/04 ,  A61P29/00 ,  A61P37/08 ,  C07D311/80 ,  C07D405/04