公开(公告)号：JP2000001486A

公开(公告)日：2000-01-07

申请号：JP12937699

申请日：1999-05-11

Applicant: FUJISAWA PHARMACEUTICAL CO

Inventor： TAKENAKA KOHEI ,  INOUE ZENICHI ,  AKAHA ATSUSHI ,  MACHITANI KOJI ,  NAKAMURA TAKASHI

IPC: C07D333/28 ,  A61K31/00 ,  A61K31/165 ,  A61K31/166 ,  A61K31/38 ,  A61K31/381 ,  A61P3/00 ,  A61P3/06 ,  A61P9/00 ,  A61P9/10 ,  A61P13/00 ,  A61P13/12 ,  A61P43/00

Abstract: PROBLEM TO BE SOLVED: To obtain a new compound having strong inhibiting action on Na+/H+ exchange in a human or animal cell and having further high effect as a medicine such as preventing and therapeutic agent for cardiovascular diseases. SOLUTION: This compound is represented by formula I [R1 is a group of formula II or III (R5 and R6 are each H, a lower alkyl or the like; X is carbonyl or sulfonyl); R2 is an arylyl or heterocycle; (n) is 1-6] and its salt, e.g. [3-(2,5-dichlorothiophen-3-yl)-5-[2-(methylaminoethyl)- aminocarbonyl]benzoyl]guanidine dihydrochloride. The compound of formula I is obtained by reacting a compound of formula IV, its derivative or a salt thereof with a compound of formula V, its derivative or a salt thereof. The reaction is usually carried out in water and an organic solvent under cooling or under heating. Furthermore, when the compound of formula V is used in a form of a free acid or its salt, the reaction is preferably carried out in the presence of a condensing agent.

公开(公告)号：JP2003171395A

公开(公告)日：2003-06-20

申请号：JP25974299

申请日：1999-09-14

Applicant: FUJISAWA PHARMACEUTICAL CO

Inventor： ICHIHARA MASAHARU ,  MACHITANI KOJI ,  MORINAGA YASUHIRO ,  KAWAI NOBUTAKA ,  IKE KAZUO

IPC: C07D401/06 ,  C07K1/02 ,  C07K5/06

Abstract: PROBLEM TO BE SOLVED: To provide a new production method for a peptide compound (I) in an industrial scale. SOLUTION: This method produces the peptide compound expressed by formula (III) [R 1 , R 2 and R 3 have each the same meaning to the followings] or its salts by reacting a compound expressed by formula (I) or its reactive derivative of an amino group or its salt [R 2 is a lower alkyl group, R 3 is an ar(lower)alkyl group], with a compound expressed by formula (II) or its reactive derivative of the carboxyl group or its salt [R 1 is a lower alkyl group]. COPYRIGHT: (C)2003,JPO

公开(公告)号：JPH0616645A

公开(公告)日：1994-01-25

申请号：JP17580692

申请日：1992-07-02

Applicant: FUJISAWA PHARMACEUTICAL CO

Inventor： KAGARA KOUJI ,  KAWAI NOBUTAKA ,  MACHITANI KOJI ,  KODERA TETSUO ,  NAKAMURA TAKASHI

IPC: C07D233/64

Abstract: PURPOSE:To obtain a new synthetic intermediate useful for producing an amino acid derivative having renin inhibiting activity in good yield at a reduced cost. CONSTITUTION:The compound of formula I [R is lower alkyl which may be substituted with a substituent group selected from acyl, OH, lower alkoxy, aryl, lower alkylthio and formula II (R is H or acyl; R is H or lower alkyl), aryl or amino which may be substituted with lower alkyl or acyl; R is H or lower alkyl or R and R , together with the adjacent N atom, form a heterocyclic group which may be substituted (with alkyl, hydroxyalkyl, acyl, etc.); R is H or lower alkyl; R is H or N-protecting group; R is H or carboxy- protecting group]. This compound is obtained by reacting a compound of formula III with a compound of formula IV. The objective amino acid derivative of formula VI is prepared by reacting the compound of formula I or a reactive derivative at the carboxyl group thereof with a compound of formula V (R is lower alkyl) and, as necessary, releasing the N-protecting group.

公开(公告)号：JPH0525111A

公开(公告)日：1993-02-02

申请号：JP29820791

申请日：1991-10-17

Applicant: FUJISAWA PHARMACEUTICAL CO

Inventor： KAGARA KOUJI ,  KAWAI NOBUTAKA ,  MACHITANI KOJI ,  TAKASUKA KIYOAKI

IPC: C07C249/06 ,  C07C251/40

Abstract: PURPOSE:To obtain the subject compound in a short process and good yield by reacting an aliphatic aldehyde or salt thereof with a wittig reagent having a carbamoyl group and then reacting the reactional product with dinitrogen trioxide or with a nitrous acid salt in the presence of an acid. CONSTITUTION:An aliphatic aldehyde expressed by formula I (R to R are H or lower alkyl) or salt thereof (especially preferably 2-ethylcrotonaldehyde, etc.) is reacted with a Wittig reagent (especially preferably diethylphosphonoacetoamide) and then with dinitrogen trioxide without isolating the intermediate product. Otherwise, the reactional product with the Wittig reagent is reacted with nitrous acid salt in the presence of an acid to provide an aliphatic amide expressed by formula II or salt thereof [especially preferably (+ or -)-(E)-4-ethyl-2 [(E)-hydroxyimino]-5-nitro-3-hexeneamide]. The compound expressed by formula II is useful as a treating agent for vasodilation, antithrombotic agent, treating agent for angina pectoris, etc.

公开(公告)号：JP2003206299A

公开(公告)日：2003-07-22

申请号：JP28505999

申请日：1999-10-06

Applicant: FUJISAWA PHARMACEUTICAL CO

Inventor： ICHIHARA MASAHARU ,  MACHITANI KOJI ,  MORINAGA YASUHIRO ,  KAWAI NOBUTAKA ,  IKE KAZUO

IPC: A61K38/00 ,  A61P17/00 ,  A61P27/00 ,  A61P29/00 ,  C07K5/078

Abstract: PROBLEM TO BE SOLVED: To provide a new method for industrially producing a peptide compound (I). SOLUTION: This method for producing the peptide compound of formula (I) [R 1 is a lower alkyl; R 2 is a lower alkyl; R 3 is an air (lower) alkyl] or its salt comprises reacting a compound of formula (II) or its reactive derivative at the carboxyl group or its salt with a compound of formula (III) or its reactive derivative at the amino group or its salt. COPYRIGHT: (C)2003,JPO

公开(公告)号：JPH06172318A

公开(公告)日：1994-06-21

申请号：JP32348392

申请日：1992-12-02

Applicant: FUJISAWA PHARMACEUTICAL CO

Inventor： KAGARA KOUJI ,  KAWAI NOBUTAKA ,  MACHITANI KOJI ,  KODERA TETSUO ,  NAKAMURA TAKASHI ,  OMORI HIROKI

IPC: A61K31/415 ,  A61P9/04 ,  A61P35/00 ,  A61P43/00 ,  C07D233/64

Abstract: PURPOSE:To industrially advantageously produce a amino acid derivative having a renin-inhibiting activity in high yield from inexpensive starting raw materials through a new synthetic intermediate. CONSTITUTION:The compound of formula I [R is alkyl or aryl which may be substituted with one or more substituents selected from acyl, OH, alkoxy, aryl, alkylthio, and group of formula II (R is H, acyl; R is H, alkyl), amino which may be substituted with alkyl or acyl; R and R form a substitutable heterocyclic group together with the adjacent nitrogen atom; R , R are H, alkyl; R is H, N-protected group; R'' is H, carboxy-protecting group], e.g. Nalpha-[2(S)-[N-methyl-N-[2-{N-(morpholinocarbonyl)-N- methylamino}ethyl]aminocarbonyloxy]-3-phenylpropionyl]-N -trityl-L- histidine. The compound is produced by reacting a compound of formula III with a compound of formula IV, and can be converted into an amino acid derivative of formula VI by reacting the compound of formula I with a compound of formula V (R is alkyl) and, if necessary, releasing the N-protecting group.

公开(公告)号：JPH0489452A

公开(公告)日：1992-03-23

申请号：JP20422390

申请日：1990-07-31

Applicant: FUJISAWA PHARMACEUTICAL CO

Inventor： KAGARA KOUJI ,  MACHITANI KOJI ,  TAKASUKA KIYOAKI

IPC: C07D215/14 ,  A61K31/47 ,  A61P29/00 ,  A61P37/08 ,  C07C67/14 ,  C07C69/708 ,  C07D309/12

Abstract: NEW MATERIAL:Cyclic compounds of formula {A is =C=O or =CHOR [R is cyclic terpenoxy(lower)alkanoyl]; R is oxygen-containing heterocycle or cyclic terpenoxy(lower)alkanoyl; Both R are H or lower alkyl}. EXAMPLE:5-[2H-3,4,5,6-tetrahydropyran-2-yloxy]-alpha-tetrarone. USE:An intermediate for production of a 1,2,3,4-tetrahydro-1-naphthol derivative, etc. PREPARATION:For example, a compound of formula III is added to a compound of formula II to obtain a compound of formula Ia (Z is alkylene containing 0 at terminal or on its middle part) belonging to a group of compounds of formula I.

公开(公告)号：JPH01301660A

公开(公告)日：1989-12-05

申请号：JP13219888

申请日：1988-05-30

Applicant: FUJISAWA PHARMACEUTICAL CO

Inventor： KAGARA KOUJI ,  MOMONAGA SHINJI ,  MACHITANI KOJI ,  TAKASUKA KIYOAKI

IPC: C07D213/55 ,  A61K31/44 ,  A61K31/4402 ,  A61K31/4418 ,  A61P7/02 ,  C07D521/00 ,  C12P41/00

Abstract: PURPOSE:To obtain the subject compound useful for intermediate of drug in optically high purity and high yield without reagent of high cost, by reacting a mixture of D-modification and L-modification of a monocyclic heterocyclic alanine esters containing 3-nitrogen with an enzyme having esterase activity. CONSTITUTION:A mixture of D- and L-modifications of monocyclic heterocyclic alanine ester containing 3-nitrogen and salts of said ester (e.g., salt of HCl, H2SO4, nitric acid or phosphoric acid) is reacted with an enzyme having esterase activity (e.g., alpha-chymotrypsin, subtilisin) preferably at about neutral and a temperature of near 37 deg.C, in a solvent having no adverse effect to the reaction. By said method, only L-modification of said mixture is selectively deesterified and D-modificationis obtained.