公开(公告)号：US08329694B2

公开(公告)日：2012-12-11

申请号：US11993652

申请日：2006-06-22

Applicant: Taro Kiyoto ,  Tadashi Tanaka ,  Yasuhiro Tsutsui ,  Junichi Ando ,  Mai Motono ,  Yasuko Kawaguchi ,  Toshiya Noguchi ,  Yasunobu Ushiki ,  Fumihito Ushiyama ,  Hiroki Urabe

Inventor： Taro Kiyoto ,  Tadashi Tanaka ,  Yasuhiro Tsutsui ,  Junichi Ando ,  Mai Motono ,  Yasuko Kawaguchi ,  Toshiya Noguchi ,  Yasunobu Ushiki ,  Fumihito Ushiyama ,  Hiroki Urabe

IPC: A61K31/495

CPC classification number: C07D405/14 ,  C07D215/227 ,  C07D401/06 ,  C07D401/14 ,  C07D405/12 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04 ,  C07D491/04 ,  C07D495/04 ,  C07D513/04 ,  C07D519/00

Abstract: A nitrogen-containing heterocyclic compound or pharmaceutically acceptable salt thereof represented by the general formula: which have a potent antibacterial activity and a high safety. Thus, the compounds are useful as antibacterial agents against gram-positive bacteria, gram-negative bacteria and drug resistant bacteria.

Abstract translation: 由通式表示的含氮杂环化合物或其药学上可接受的盐，其具有强的抗菌活性和高安全性。 因此，这些化合物可用作抗革兰氏阳性细菌，革兰氏阴性细菌和耐药细菌的抗菌剂。

公开(公告)号：US20120214990A1

公开(公告)日：2012-08-23

申请号：US13463434

申请日：2012-05-03

Applicant: Taro KIYOTO ,  Tadashi Tanaka ,  Yasuhiro Tsutsui ,  Junichi Ando ,  Mai Motono ,  Yasuko Kawaguchi ,  Toshiya Noguchi ,  Yasunobu Ushiki ,  Fumihito Ushiyama ,  Hiroki Urabe

Inventor： Taro KIYOTO ,  Tadashi Tanaka ,  Yasuhiro Tsutsui ,  Junichi Ando ,  Mai Motono ,  Yasuko Kawaguchi ,  Toshiya Noguchi ,  Yasunobu Ushiki ,  Fumihito Ushiyama ,  Hiroki Urabe

IPC: C07D405/14 ,  C07D491/056 ,  C07D413/14 ,  C07D417/14 ,  C07D513/04 ,  C07D498/04 ,  C07D471/04 ,  C07D401/06 ,  C07D495/04 ,  C07D401/14 ,  C07D405/12 ,  C07D215/22 ,  C07D409/14 ,  C07D455/04

CPC classification number: C07D405/14 ,  C07D215/227 ,  C07D401/06 ,  C07D401/14 ,  C07D405/12 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04 ,  C07D491/04 ,  C07D495/04 ,  C07D513/04 ,  C07D519/00

Abstract: A nitrogen-containing heterocyclic compound or pharmaceutically acceptable salt thereof represented by the general formula: which have a potent antibacterial activity and a high safety. Thus, the compounds are useful as antibacterial agents against gram-positive bacteria, gram-negative bacteria and drug resistant bacteria.

Abstract translation: 由通式表示的含氮杂环化合物或其药学上可接受的盐，其具有强的抗菌活性和高安全性。 因此，这些化合物可用作抗革兰氏阳性细菌，革兰氏阴性细菌和耐药细菌的抗菌剂。

公开(公告)号：US20100249417A1

公开(公告)日：2010-09-30

申请号：US12744633

申请日：2008-11-25

Applicant: Taro Kiyoto ,  Masahiro Takebayashi ,  Yasutaka Baba ,  Muneo Syoji ,  Toshiya Noguchi ,  Fumihito Ushiyama ,  Hiroki Urabe ,  Hiromasa Horikiri

Inventor： Taro Kiyoto ,  Masahiro Takebayashi ,  Yasutaka Baba ,  Muneo Syoji ,  Toshiya Noguchi ,  Fumihito Ushiyama ,  Hiroki Urabe ,  Hiromasa Horikiri

IPC: C07D491/056 ,  C07D315/00

CPC classification number: C07D519/00 ,  C07D309/40 ,  C07D491/04

Abstract: Disclosed is 1-(2-(4-((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)piperidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one monohydrate, which has strong antibacterial activity. The compound is highly safe and useful as an original drug for pharmaceutical preparations. Also disclosed is a method which is useful for producing 1-(2-(4-((2,3-dihydro(1,4)dioxino(2,3-c)pyridin-7-ylmethyl)amino)piperidin-1-yl)ethyl)-7-fluoro-1,5-naphthyridin-2(1H)-one monohydrate.

Abstract translation: 公开了1-（2-（4 - （（2,3-二氢（1,4）二氧杂环己烯（2,3-c）吡啶-7-基甲基）氨基）哌啶-1-基）乙基） -1,5-二氮杂萘-2（1H） - 酮一水合物，具有很强的抗菌活性。 该化合物作为药物制剂的原始药物是高度安全和有用的。 还公开了可用于制备1-（2-（4 - （（2,3-二氢（1,4）二恶英（2,3-c）吡啶-7-基甲基）氨基） 吡啶-2-基）乙基）-7-氟-1,5-二氮杂萘-2（1H） - 酮一水合物。

公开(公告)号：US06835848B1

公开(公告)日：2004-12-28

申请号：US10221113

申请日：2003-01-06

Applicant: Prosenjit Bose ,  Naresh Kumar ,  Taro Kiyoto

Inventor： Prosenjit Bose ,  Naresh Kumar ,  Taro Kiyoto

IPC: C07C22900

CPC classification number: C07C227/16 ,  C07C229/34 ,  C07C2601/02

Abstract: The present invention relates to a new and industrially advantageous one-pot process for the preparation of alkyl 3-cyclopropyl amino-2-[2,4-dibromo-3-(difluoromethoxy) benzoyl]-2-propenoates of in which R represents methyl or ethyl, which are valuable intermediates for the production of highly active antibacterial quinolone medicaments.

Abstract translation: 本发明涉及用于制备3-环丙基氨基-2- [2,4-二溴-3-（二氟甲氧基）苯甲酰基] -2-丙烯酸烷基酯的新的和工业上有利的一锅法，其中R代表甲基或 乙基，它们是生产高活性抗菌喹诺酮药物的有价值的中间体。

公开(公告)号：US08211908B2

公开(公告)日：2012-07-03

申请号：US12302451

申请日：2007-05-24

Applicant: Taro Kiyoto ,  Junichi Ando ,  Tadashi Tanaka ,  Yasuhiro Tsutsui ,  Mai Yokotani ,  Toshiya Noguchi ,  Fumihito Ushiyama ,  Hiroki Urabe ,  Hiromasa Horikiri

Inventor： Taro Kiyoto ,  Junichi Ando ,  Tadashi Tanaka ,  Yasuhiro Tsutsui ,  Mai Yokotani ,  Toshiya Noguchi ,  Fumihito Ushiyama ,  Hiroki Urabe ,  Hiromasa Horikiri

IPC: A61K31/4353 ,  C07D471/22

CPC classification number: C07D471/04 ,  C07D491/056 ,  C07D519/00 ,  Y02P20/55

Abstract: Disclosed is a compound represented by the general formula: [wherein R1 represents an aryl or heterocyclic group which may be substituted or the like; X1 represents a C2-C4 alkylene group or the like; X2, X3 and X5 independently represent NH, a bond or the like; X4 represents a lower alkylene group, a bond or the like; Y1 represents a bivalent alicyclic hydrocarbon residue which may be substituted or a bivalent alicyclic amine residue which may be substituted; and Z1, Z2, Z3, Z4, Z5 and Z6 independently represent a nitrogen atom, a group represented by the formula: CH, or the like, provided that at least one of Z3, Z4, Z5 and Z6 represents a nitrogen atom] or a salt thereof, which is useful as an antibacterial agent.

Abstract translation: 公开了由以下通式表示的化合物：其中R 1表示可被取代的芳基或杂环基等; X1表示C2-C4亚烷基等; X2，X3和X5独立地表示NH，键等; X 4表示低级亚烷基，键等; Y1表示可以被取代的二价脂环族烃残基或可以被取代的二价脂环族胺残基; 并且Z 1，Z 2，Z 3，Z 4，Z 5和Z 6独立地表示氮原子，由式CH表示的基团等，条件是Z 3，Z 4，Z 5和Z 6中的至少一个表示氮原子]或 其盐，其可用作抗菌剂。

公开(公告)号：US20090198063A1

公开(公告)日：2009-08-06

申请号：US12302451

申请日：2007-05-24

Applicant: Taro Kiyoto ,  Junichi Ando ,  Tadashi Tanaka ,  Yasuhiro Tsutsui ,  Mai Yokotani ,  Toshiya Noguchi ,  Fumihito Ushiyama ,  Hiroki Urabe ,  Hiromasa Horikiri

Inventor： Taro Kiyoto ,  Junichi Ando ,  Tadashi Tanaka ,  Yasuhiro Tsutsui ,  Mai Yokotani ,  Toshiya Noguchi ,  Fumihito Ushiyama ,  Hiroki Urabe ,  Hiromasa Horikiri

IPC: A61K31/4375 ,  C07D471/04 ,  A61P31/04

CPC classification number: C07D471/04 ,  C07D491/056 ,  C07D519/00 ,  Y02P20/55

Abstract: Disclosed is a compound represented by the general formula: [wherein R1 represents an aryl or heterocyclic group which may be substituted or the like; X1 represents a C2-C4 alkylene group or the like; X2, X3 and X5 independently represent NH, a bond or the like; X4 represents a lower alkylene group, a bond or the like; Y1 represents a bivalent alicyclic hydrocarbon residue which may be substituted or a bivalent alicyclic amine residue which may be substituted; and Z1, Z2, Z3, Z4, Z5 and Z6 independently represent a nitrogen atom, a group represented by the formula: CH, or the like, provided that at least one of Z3, Z4, Z5 and Z6 represents a nitrogen atom] or a salt thereof, which is useful as an antibacterial agent.

Abstract translation: 公开了由以下通式表示的化合物：其中R 1表示可被取代的芳基或杂环基等; X1表示C2-C4亚烷基等; X2，X3和X5独立地表示NH，键等; X 4表示低级亚烷基，键等; Y1表示可以被取代的二价脂环族烃残基或可以被取代的二价脂环族胺残基; 并且Z 1，Z 2，Z 3，Z 4，Z 5和Z 6独立地表示氮原子，由式CH表示的基团等，条件是Z 3，Z 4，Z 5和Z 6中的至少一个表示氮原子]或 其盐，其可用作抗菌剂。

公开(公告)号：US20050203301A1

公开(公告)日：2005-09-15

申请号：US10209078

申请日：2002-08-01

Applicant: Katsuji Ojima ,  Tamotsu Takamatsu ,  Kyoko Taya ,  Taro Kiyoto

Inventor： Katsuji Ojima ,  Tamotsu Takamatsu ,  Kyoko Taya ,  Taro Kiyoto

IPC: A61K31/4709 ,  C07C217/48 ,  C07D209/44 ,  C07D215/56 ,  C07D401/04 ,  C07D471/02 ,  C07D43/02

CPC classification number: C07D401/04 ,  A61K31/4709 ,  C07C217/48 ,  C07D209/44 ,  C07D215/56 ,  C07F5/025 ,  Y02P20/55

Abstract: Process for producing a 7-bromoquinolone-carboxylic acid derivative of the following formula or its salt by reacting a 2,4-dibromo-3-hydroxybenzoic acid ester compound of the formula R7a-x to obtain a 3-alkoxy-2,4-dibromobenzoic acid ester, subjecting the 3-alkoxy-2,4-dibromobenzoic acid ester to elimination reaction of the carboxyl-protecting group to obtain a 3-alkoxy-2,4-dibromobenzoic acid, subjecting the 3-alkoxy-2,4-dibromobenzoic acid to ketoesterification reaction to obtain a 3-alkoxy-2,4-dibromobenyolacetic acid ester, reacting the 3-alkoxy-2,4-dibromobenzoylacetic acid ester with an orthoester or an acetal, then reacting the reaction product with a compound of the formula R2a—NH or its salt to obtain a 2-(3-alkoxy-2,4-dibromobenzoyl)-3-substituted aminoacrylic acid ester and subjecting the 2-(3-alkoxy-2,4-dibromobenzoyl)-3-substituted aminoacrylic acid ester to ring-closing reaction, and products thereof.

Abstract translation: 制备下式的7-溴喹诺酮 - 羧酸衍生物或其盐的方法，其通过使式<β的在线式描述的2,4-二溴-3-羟基苯甲酸酯化合物=“在线式 “end =”lead“？> R 7a -x <？in-line-formula description =”In-line Formulas“end =”tail“？>以获得3-烷氧基-2， 4-二溴苯甲酸酯，使3-烷氧基-2,4-二溴苯甲酸酯与羧基保护基进行消去反应，得到3-烷氧基-2,4-二溴苯甲酸，将3-烷氧基-2,4-二溴苯甲酸 4-二溴苯甲酸进行酮酯化反应，得到3-烷氧基-2,4-二溴苯乙醇酸乙酯，使3-烷氧基-2,4-二溴苯甲酰基乙酸酯与原酸酯或缩醛反应，然后使反应产物与化合物 的式R 2a -NH或其盐，得到2-（3-烷氧基-2,4-二溴苯甲酰基）-3-取代的氨基丙烯酸酯，并使2-（3-烷氧基 - 3,4-二溴苯甲酰基）-3-取代基 叔氨基丙烯酸酯进行闭环反应，及其产物。

公开(公告)号：US08524738B2

公开(公告)日：2013-09-03

申请号：US13463434

申请日：2012-05-03

Applicant: Taro Kiyoto ,  Tadashi Tanaka ,  Yasuhiro Tsutsui ,  Junichi Ando ,  Mai Motono ,  Yasuko Kawaguchi ,  Toshiya Noguchi ,  Yasunobu Ushiki ,  Fumihito Ushiyama ,  Hiroki Urabe

Inventor： Taro Kiyoto ,  Tadashi Tanaka ,  Yasuhiro Tsutsui ,  Junichi Ando ,  Mai Motono ,  Yasuko Kawaguchi ,  Toshiya Noguchi ,  Yasunobu Ushiki ,  Fumihito Ushiyama ,  Hiroki Urabe

IPC: A61K31/47

CPC classification number: C07D405/14 ,  C07D215/227 ,  C07D401/06 ,  C07D401/14 ,  C07D405/12 ,  C07D409/14 ,  C07D413/14 ,  C07D471/04 ,  C07D491/04 ,  C07D495/04 ,  C07D513/04 ,  C07D519/00

Abstract: A nitrogen-containing heterocyclic compound or pharmaceutically acceptable salt thereof represented by the general formula: which have a potent antibacterial activity and a high safety. Thus, the compounds are useful as antibacterial agents against gram-positive bacteria, gram-negative bacteria and drug resistant bacteria.

Abstract translation: 由通式表示的含氮杂环化合物或其药学上可接受的盐，其具有强的抗菌活性和高安全性。 因此，这些化合物可用作抗革兰氏阳性细菌，革兰氏阴性细菌和耐药细菌的抗菌剂。

公开(公告)号：US08367831B2

公开(公告)日：2013-02-05

申请号：US13468140

申请日：2012-05-10

Applicant: Taro Kiyoto ,  Junichi Ando ,  Tadashi Tanaka ,  Yasuhiro Tsutsui ,  Mai Yokotani ,  Toshiya Noguchi ,  Fumihito Ushiyama ,  Hiroki Urabe ,  Hiromasa Horikiri

Inventor： Taro Kiyoto ,  Junichi Ando ,  Tadashi Tanaka ,  Yasuhiro Tsutsui ,  Mai Yokotani ,  Toshiya Noguchi ,  Fumihito Ushiyama ,  Hiroki Urabe ,  Hiromasa Horikiri

IPC: C07D471/04

CPC classification number: C07D471/04 ,  C07D491/056 ,  C07D519/00 ,  Y02P20/55

Abstract: Disclosed is a compound represented by the general formula: wherein R1 represents an aryl or heterocyclic group which may be substituted or the like; X1 represents a C2-C4 alkylene group or the like; X2, X3 and X5 independently represent NH, a bond or the like; X4 represents a lower alkylene group, a bond or the like; Y1 represents a bivalent alicyclic hydrocarbon residue which may be substituted or a bivalent alicyclic amine residue which may be substituted; and Z1, Z2, Z3, Z4, Z5 and Z6 independently represent a nitrogen atom, a group represented by the formula: CH, or the like, provided that at least one of Z3, Z4, Z5 and Z6 represents a nitrogen atom, or a salt thereof, which is useful as an antibacterial agent.

Abstract translation: 公开了由以下通式表示的化合物：其中R1表示可被取代的芳基或杂环基等; X1表示C2-C4亚烷基等; X2，X3和X5独立地表示NH，键等; X 4表示低级亚烷基，键等; Y1表示可以被取代的二价脂环族烃残基或可以被取代的二价脂环族胺残基; 并且Z 1，Z 2，Z 3，Z 4，Z 5和Z 6独立地表示氮原子，由式CH表示的基团等，条件是Z 3，Z 4，Z 5和Z 6中的至少一个表示氮原子，或 其盐，其可用作抗菌剂。

公开(公告)号：US06337399B1

公开(公告)日：2002-01-08

申请号：US09529407

申请日：2000-04-26

Applicant: Minoru Yamada ,  Shoichi Hamamoto ,  Kazuya Hayashi ,  Kazuko Takaoka ,  Hiroko Matsukura ,  Minako Yotsuji ,  Kenji Yonezawa ,  Katsuji Ojima ,  Tamotsu Takamatsu ,  Kyoko Taya ,  Hirohiko Yamamoto ,  Taro Kiyoto ,  Hironori Kotsubo

Inventor： Minoru Yamada ,  Shoichi Hamamoto ,  Kazuya Hayashi ,  Kazuko Takaoka ,  Hiroko Matsukura ,  Minako Yotsuji ,  Kenji Yonezawa ,  Katsuji Ojima ,  Tamotsu Takamatsu ,  Kyoko Taya ,  Hirohiko Yamamoto ,  Taro Kiyoto ,  Hironori Kotsubo

IPC: C07D21516

CPC classification number: C07D401/04 ,  A61K31/4709 ,  C07C217/48 ,  C07D209/44 ,  C07D215/56 ,  C07F5/025 ,  Y02P20/55

Abstract: This invention relates to processes for producing a 7-isoindoline-quinolonecarboxylic acid derivative represented by the general formula [1] which is useful as an antibacterial agent, and an intermediate thereof: wherein R1 represents a hydrogen atom or a carboxyl-protecting group; R2 represents a substituted or unsubstituted alkyl, alkenyl, cycloalkyl, aryl or heterocyclic group; R3 represents at least one group selected from hydrogen atom, halogen atoms, substituted or unsubstituted alkyl, alkenyl, cycloalkyl, aryl, alkoxy or alkylthio groups, nitro group, cyano group, acyl groups, protected or unprotected hydroxyl groups and protected or unprotected or substituted or unsubstituted amino groups; R4 represents at least one group selected from hydrogen atom, halogen atoms, substituted or unsubstituted alkyl, alkenyl, cycloalkyl, aralkyl, aryl, alkoxy or alkylthio groups, protected or unprotected hydroxyl or imino groups, protected or unprotected or substituted or unsubstituted amino groups, alkylidene groups, oxo group and groups each forming a cycloalkane group together with the carbon atom to which R4 bonds; R5 represents a hydrogen atom, an amino-protecting group, a substituted or unsubstituted alkyl, cycloalkyl, alkylsulfonyl, arylsulfonyl, acyl or aryl group; R6 represents a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, alkoxy or alkylthio group, a protected or unprotected hydroxyl or amino group or a nitro group; and A represents CH or C—R7 in which R7 represents a halogen atom, a substituted or unsubstituted alkyl, alkoxy or alkylthio group or a protected or unprotected hydroxyl group, and to a salt of a 7-isoindoline-quinolonecarboxylic acid represented by the general formula [1], a hydrate thereof and a composition comprising them as an active ingredient.