公开(公告)号：JPH08231584A

公开(公告)日：1996-09-10

申请号：JP2499596

申请日：1996-02-13

Applicant: AGENCY IND SCIENCE TECHN

Inventor： YAMAZAKI YUKINAE ,  OGAWA MASAKATSU ,  OKUNO HIROAKI

IPC: C07H1/00 ,  A61K31/70 ,  A61K31/7042 ,  A61K31/7052 ,  A61K31/7064 ,  A61K31/7072 ,  A61P35/00 ,  C07H19/067 ,  C07H19/073

Abstract: PURPOSE: To obtain the subject new compound hardly decomposable in blood, rapidly decomposing in a cancer cell to show carcinostatic action, by reacting a protected substance of a 5-fluorouridine compound with a carboxylic acid chloride in the presence of a condensation agent and deprotecting the reaction product. CONSTITUTION: This new ester compound has the structure of formula I (R1 is methyl, methoxy or trifluoroacetamido; R2 is phenyl or phenylmethyl; the absolute configuration at the asymmetric center with an asterisk is R), is hardly decomposable in blood, is rapidly hydrolyzed in a cancer cell by hydrolyzing action of esterase in the cancer cell, is changed into an active type and acts as a carcinostatic agent. The compound is obtained by reacting a 5-fluorouridine compound or a 2',3'-isopropylidene protected substance of 5-fluorodeoxyuridine compound corresponding thereto with an acid chloride of an optically active carboxylic acid of formula III or a substance obtained by activating the carboxylic acid to acylate the hydroxyl group at the 5'-position and deprotecting the resultant substance.

公开(公告)号：JPH08208676A

公开(公告)日：1996-08-13

申请号：JP28689395

申请日：1995-11-06

Applicant: AGENCY IND SCIENCE TECHN

Inventor： YAMAZAKI YUKINAE ,  OGAWA MASAKATSU ,  SHIMURA TAKEHIKO ,  OKA SHUICHI ,  OKUNO HIROAKI ,  GOTO MIDORI

IPC: A61K31/28 ,  A61P35/00 ,  C07F17/00

Abstract: PURPOSE: To inexpensively and safely obtain purified chloroosomocenium salt useful as an antitumor agent stable in an aqueous solution, having strongly inhibitory action on proliferation of cancerous cells, by preparing a saturated aqueous solution of a crude chloroosomocenium salt and recrystallizing chloroosomocenium salt from the aqueous solution. CONSTITUTION: This purified chloroosomocenium salt of the formula (Y is an anion) is obtained by preparing a saturated aqueous solution of a crude chloroosomocenium salt and recrystallizing the aqueous solution. Hexafluorophosphate ions or tetrafluoroborate ions are used as the anion. The chloroosomocenium salt, for example, is obtained by oxidizing osomocene on the market with ferric chloride in the presence of hydrochloric acid and precipitating the purified chloroosomocenium by adding a salt of a proper anion.

公开(公告)号：JPH07316108A

公开(公告)日：1995-12-05

申请号：JP13130394

申请日：1994-05-20

Applicant: AGENCY IND SCIENCE TECHN

Inventor： YAMAZAKI YUKINAE ,  OGAWA MASAKATSU ,  OKUNO HIROAKI

IPC: C07D405/04 ,  A61K31/235 ,  A61K31/505 ,  A61P35/00 ,  C07C213/06 ,  C07C219/34 ,  C07C233/47 ,  C07H19/06

Abstract: PURPOSE:To obtain a new carcinostatic ester compound useful as an ester-type carcinostatic capable of being quickly hydrolyzed and activated in a cancer cell whereas it is resistive to decomposition in the blood. CONSTITUTION:Ester compounds of formula I and formula II (R1 is methyl, methoxy or trifluoroacetamide; R2 is phenyl or phenylhmethyl ; absolute configuration of the asymmetric center marked with an asterisk is R), e.g. (+ or -)-4-bis(2- chloroethyl)aminophenyl-2-phenylpropionate and 5'-(RS)-(2-phenylpropionyl)-5- fluorouridine. The compound of formula I or formula II is synthesized by acylating p-position hydroxyl group of a compound of formula III or formula IV with acyl group of formula V. Since a carcinostatic is esterified so that it may be more readily activated by hydrolysis in a cancer cell than in the blood or a normal cell, this method enables improvement of stability in the blood, reduction of side-effects on normal cells and enhancement of selective aggressivity to a cancer cell.

公开(公告)号：JPH07101972A

公开(公告)日：1995-04-18

申请号：JP27133193

申请日：1993-10-04

Applicant: AGENCY IND SCIENCE TECHN

Inventor： YAMAZAKI YUKINAE ,  OGAWA MASAKATSU ,  SHIMURA TAKEHIKO ,  OKA SHUICHI ,  OKUNO HIROAKI ,  GOTO MIDORI

IPC: A61K31/28 ,  A61P35/00 ,  C07F17/02

Abstract: PURPOSE:To inexpensively and safely obtain an anti-tumor agent which has the action to increase the carcinostatic action of cisplatin in addition to its own powerful action to inhibit the growth of cancer cells by preparing a saturated solution of a crude chloro-osmocenium salt and effecting the recrystallization of the salt. CONSTITUTION:The objective antitumor agent containing a chloro-osmocenium salt of the formula [Y is anion, preferably hexafluorophosphate ion (PF6 ), tetrafluoroborate ion or picrate ion] is obtained by preparing a saturated aqueous solution of a crude chloro-osmocenium salt and effecting the recrystallization.