公开(公告)号：JPH06293666A

公开(公告)日：1994-10-21

申请号：JP29384693

申请日：1993-11-01

Applicant: HISAMITSU PHARMACEUTICAL CO

Inventor： TSUJI MASAYOSHI ,  INOUE TOSHITAKA ,  YATANI TERUMI ,  NAKAJIMA MIKIO ,  SAIDA MASARU ,  SHIMOZONO YUJI ,  KATSUKI MASUMI ,  SAKAI MICHIYORI

IPC: A61K9/06 ,  A61K47/22 ,  C07D207/27 ,  C07D211/76

Abstract: PURPOSE:To obtain the subject composition containing an azacycloalkane derivative having a specific structural formula, exhibiting high penetration, permeation and absorption to the skin and other biomembranes, giving little local toxicity by itself and having high safety. CONSTITUTION:The objective compound of formula II can be produced e.g. by using a compound of formula I (M is alkali metal ion; X is halogen; R is alkyl; (m) is 2-4; (n) is 1-15) as a starting substance, producing an intermediate compound of formula III and, for example, reacting the intermediate compound with a halogenoalkyl in the presence of a phase transfer catalyst (e.g. cetyltributyl phosphonium bromide) in an alkaline aqueous solution of sodium sulfide at 0-100 deg.C) for 2-10hr in nitrogen atmosphere.

公开(公告)号：JPS62129274A

公开(公告)日：1987-06-11

申请号：JP24688385

申请日：1985-11-03

Applicant: HISAMITSU PHARMACEUTICAL CO

Inventor： TSUJI MASAYOSHI ,  INOUE TOSHITAKA ,  YATANI TERUMI ,  NAKAJIMA MIKIO ,  SAIDA MASARU ,  SHIMOZONO YUJI ,  KATSUKI MASUMI ,  SAKAI MICHIYORI

IPC: A61K8/49 ,  A01N25/00 ,  A01N43/46 ,  A61K8/00 ,  A61K31/395 ,  A61K31/55 ,  A61K47/00 ,  A61K47/22 ,  A61P17/00 ,  A61P31/04 ,  A61P43/00 ,  A61Q19/00 ,  C07D223/10 ,  C07D225/02 ,  C07D227/087

Abstract: NEW MATERIAL:An azacycloalkane derivative shown by formula I (R is alkyl; m is 5-7; n is 3-15). EXAMPLE:1-(3-Octyloxypropyl)azacycloheptan-2-one. USE:Useful as an absorption promotor having improved action on permeability and permeation of drug by blending drug with a specific amount of the promotor. The promotor itself has antimicrobial action. Use of the promotor can maintain durability of drug, further adjusts absorption rate of drug and prevents side effects caused by excess administration. The promotor has merits wherein a drug causing liver disorder can be relatively safely administered. PREPARATION:As shown a reaction formula (M is alkali metallic ion and X is halogen, etc.,), a compound shown by formula III obtained from an azacycloalkane-2-one and an alkali catalyst is reacted with an alcohol in the presence of an alkali catalyst to give a compound shown by formula I.

公开(公告)号：JPH0625164B2

公开(公告)日：1994-04-06

申请号：JP5867085

申请日：1985-03-22

Applicant: HISAMITSU PHARMACEUTICAL CO

Inventor： TSUJI MASAYOSHI ,  NAKAGAWA AKIRA ,  INOE TOSHITAKA ,  NAKAJIMA MIKIO

IPC: A61K31/505 ,  A61K31/517 ,  A61P11/14 ,  A61P25/00 ,  A61P25/04 ,  A61P29/00 ,  A61P37/08 ,  C07D239/90

公开(公告)号：JPS6330465A

公开(公告)日：1988-02-09

申请号：JP17534686

申请日：1986-07-24

Applicant: HISAMITSU PHARMACEUTICAL CO

Inventor： TSUJI MASAYOSHI ,  INOUE TOSHITAKA ,  YATANI TERUMI ,  NAKAJIMA MIKIO ,  SAIDA MASARU ,  SHIMOZONO YUJI ,  SAKAI MICHIYORI

IPC: C07D207/27 ,  A61K47/00 ,  A61K47/22 ,  C07D211/06 ,  C07D223/10 ,  C07D225/02 ,  C07D227/087

Abstract: NEW MATERIAL:A cyclic compound expressed by formula I (R is substituted amino; m is 2-7; n is 1-15). EXAMPLE:1-(4-Heptylaminobutyl)azacycloheptan-2-one. USE:Useful as an absorption promoter, having remarkable enhancing action on penetrability and permeability of chemicals through biomembranes as well as extremely weak local irritation to biomembranes, systemic toxicity, etc., exhibiting high safety, individually showing antimicrobial action and further utilizable as a drug for promoting drug transmission in not only medicines but also cosmetics which are quasi-drugs, agricultural chemicals, insecticides, etc. PREPARATION:For example, as shown in the reaction formulas, an azacycloalkan-2-one is reacted in the presence of a catalyst and the resultant compound is reacted with a dihalogenoalkyl. The reaction product is then reacted with an amine in the presence of a dehalogenating agent to afford the aimed compound expressed by formula I.

公开(公告)号：JPS62238261A

公开(公告)日：1987-10-19

申请号：JP7917486

申请日：1986-04-08

Applicant: HISAMITSU PHARMACEUTICAL CO

Inventor： TSUJI MASAYOSHI ,  INOUE TOSHITAKA ,  YATANI TERUMI ,  NAKAJIMA MIKIO ,  SAIDA MASARU ,  SHIMOZONO YUJI ,  KATSUKI MASUMI ,  SAKAI MICHIYORI

IPC: C07D207/12 ,  A61K31/395 ,  A61K31/4015 ,  A61K31/435 ,  A61K31/55 ,  A61K47/00 ,  A61K47/22 ,  A61P43/00 ,  C07D207/26 ,  C07D207/267 ,  C07D207/27 ,  C07D211/76 ,  C07D223/10 ,  C07D227/087 ,  C07D263/18 ,  C07D265/30 ,  C07D265/32 ,  C07D267/10 ,  C07D277/14 ,  C07D279/12 ,  C07D281/06

Abstract: NEW MATERIAL:An azacycloalkane derivative of formula I (R is alkyl; m is 2, 3 or 4; n is integer of 1-15; R is 5-11C alkyl when n is 1-3). EXAMPLE:1-(2-Nonylthioethyl)azacyclopentan-2-one. USE:An absorbefacient having remarkable effect to promote the impregnation and permeation of drug in a bio-membrane, extremely low topical toxicity and systemic toxicity to bio-membrane and high safety. PREPARATION:The compound of formula I can be produced by reacting a compound of formula IV (n is integer of 2-15) with a compound of formula RSH in a solvent inert to the reaction (e.g. benzene, toluene, etc.) in the presence of a radical polymerization initiator (e.g. benzoyl peroxide, azobisisobutyronitrile, etc.) at 0-150 deg.C for 2-18hr in nitrogen atmosphere or in the absence of the atmosphere.

公开(公告)号：JPS62164662A

公开(公告)日：1987-07-21

申请号：JP763886

申请日：1986-01-16

Applicant: HISAMITSU PHARMACEUTICAL CO

Inventor： TSUJI MASAYOSHI ,  INOUE TOSHITAKA ,  YATANI TERUMI ,  NAKAJIMA MIKIO ,  SAIDA MASARU ,  SHIMOZONO YUJI ,  KATSUKI MASUMI ,  SAKAI MICHIYORI

IPC: C07D207/27 ,  A61K47/00 ,  A61K47/22 ,  C07D211/76

Abstract: NEW MATERIAL:An azacycloalkane derivative expressed by formula I (R is alkyl; m is 2-4; n is 2-15). EXAMPLE:1-(6-Pentyloxycyclohexyl)azacyclopentan-2-one. USE:Capable of being blended with an absorption accelerator useful for the pharmaceutical industry or cosmetics, e.g. quasi-drugs, etc., and agricultural chemicals, insecticides, etc., having improved enhancing action on penetrability and permeability of drugs into biomembranes, e.g. skin, mucosa, etc., and further individual antimicrobial action and high safety with very weak local irritancy to the biomembranes and systemic toxicity, etc. PREPARATION:For example, a compound expressed by formula IV is reacted in the presence of an alkali catalyst, etc., to form a compound expressed by formula II (M is alkali metal ion), which is then reacted with a compound expressed by formula V (X is halogen, mesyl, etc.) to afford a compound expressed by formula III. The resultant compound expressed by formula III is further reacted with an alcohol expressed by the formula R-OH in the presence of an alkali catalyst to give the aimed compound expressed by formula I.

公开(公告)号：JPH0643390B2

公开(公告)日：1994-06-08

申请号：JP7917486

申请日：1986-04-08

Applicant: HISAMITSU PHARMACEUTICAL CO

Inventor： TSUJI MASAYOSHI ,  INOUE TOSHITAKA ,  YATANI TERUMI ,  NAKAJIMA MIKIO ,  SAIDA MASARU ,  SHIMOZONO YUJI ,  KATSUKI MASUMI ,  SAKAI MICHIYORI

IPC: C07D207/12 ,  A61K31/395 ,  A61K31/4015 ,  A61K31/435 ,  A61K31/55 ,  A61K47/00 ,  A61K47/22 ,  A61P43/00 ,  C07D207/26 ,  C07D207/267 ,  C07D207/27 ,  C07D211/76 ,  C07D223/10 ,  C07D227/087 ,  C07D263/18 ,  C07D265/30 ,  C07D265/32 ,  C07D267/10 ,  C07D277/14 ,  C07D279/12 ,  C07D281/06

公开(公告)号：JPH03173876A

公开(公告)日：1991-07-29

申请号：JP24299490

申请日：1990-09-12

Applicant: HISAMITSU PHARMACEUTICAL CO

Inventor： SAIDA MASARU ,  INOUE TOSHITAKA ,  IKESUE KOICHI ,  FUJIMOTO NORIYUKI ,  SHINOHARA IKUO ,  NAKAJIMA MIKIO ,  YOSHIDA TOSHIO ,  TANIGUCHI YASUAKI ,  DEGUCHI YOSHIKI ,  MINAMI HIDENAO ,  NODA KANJI

IPC: C07D277/20 ,  A61K31/425 ,  A61K31/426 ,  A61P7/02 ,  A61P19/06 ,  A61P25/04 ,  A61P29/00 ,  A61P37/08 ,  C07D277/46

Abstract: NEW MATERIAL:A compound expressed by formula I (m and n are 1 or 2; R and R are H, lower alkyl, lower alkoxy, lower alkylsulfenyl, NO2, NH2, methanesulfonyloxy or halogen; A is lower alkanesulfonyl, halo-lower alkanesulfonyl, substituted benzenesulfonyl or halo-lower alkoxyl; A is H, lower alkanesulfonyl, halo-lower alkanesulfonyl or lower alkyl). EXAMPLE:2-Trifluoromethanesulfonylamino-4,5-diphenylthiazole. USE:A nonsteroidal anti-inflammatory agent. PREPARATION:A compound expressed by formula V is mixed with a compound expressed by formula IV in a suitable solvent (e.g. methanol, ethanol or THF) at ambient temperature or while being heated to afford the compound expressed by formula I.

公开(公告)号：JPS6440458A

公开(公告)日：1989-02-10

申请号：JP19611587

申请日：1987-08-04

Applicant: HISAMITSU PHARMACEUTICAL CO

Inventor： TSUJI MASAYOSHI ,  INOUE TOSHITAKA ,  YATANI TERUMI ,  NAKAJIMA MIKIO ,  NODA KANJI

IPC: C07D207/27 ,  A61K31/40 ,  A61K31/4015 ,  A61K31/4427 ,  A61K31/445 ,  A61P25/04 ,  A61P29/00 ,  C07D211/76 ,  C07D401/12

Abstract: NEW MATERIAL:A compound expressed by formula I (X is S, SO, SO2, O or NH; R is antiphlogistic and analgesic compound having carboxyl group at the end; l is 1-15; m is 2-15; n is 2-7). EXAMPLE:2-[{2-(2-Oxo-1-pyrrolidinyl)ethyl}thio] ethyl-d-2-(6-methoxy-2-naphthyl) propionate. USE:An antiphlogistics and analgesic remarkably reduced in side effect such as gastic disease. PREPARATION:An antiphlogistic and analgesic compound having carboxyl group at the end is reacted with thionyl chloride in an inert solvent (e.g. benzene or toluene) which does not participate in reaction under reflux for 1-5hr to give aid chloride compound, which is then reacted with azacycloalkane-2-one derivative expressed by formula II in the presence of a dehalogenating agent to provide the compound expressed by formula I.

公开(公告)号：JPS61246170A

公开(公告)日：1986-11-01

申请号：JP5867085

申请日：1985-03-22

Applicant: HISAMITSU PHARMACEUTICAL CO

Inventor： TSUJI MASAYOSHI ,  NAKAGAWA AKIRA ,  INOUE TOSHITAKA ,  NAKAJIMA MIKIO

IPC: A61K31/505 ,  A61K31/517 ,  A61P11/14 ,  A61P25/00 ,  A61P25/04 ,  A61P29/00 ,  A61P37/08 ,  C07D239/90

Abstract: NEW MATERIAL:A compound expressed by formula I (R is lower alkyl; R is amino). EXAMPLE:1-Methyl-2-(3-pyrrolidino-2-oxopropyl)-4-oxo-1,4-dihydro-quina zoline. USE:An anti-inflammatory agent, antiallergic agent, analgesic agent, antitussive agent, central nervous system depressant and antipyretic agent. PREPARATION:A 1-lower alkyl-2-halochloroacetonitrile-4-oxo-1,4- dihydroquinalzoline derivative expressed by formula II (X is halogen) is reacted with an amine expressed by the formula R4u2H, e.g., methylamine, benzylamine, dimethylamine or piperidine, at 1:1-3 molar ratio and 0-120 deg.C for 0.5-30hr to afford the aimed compound expressed by formula I.