公开(公告)号：US08809371B2

公开(公告)日：2014-08-19

申请号：US13730000

申请日：2012-12-28

申请人： Hideyasu Fujiwara ,  Kimihiko Sato ,  Shinsuke Mizumoto ,  Yuichiro Sato ,  Hideki Kurihara ,  Yohei Kubo ,  Hiyoku Nakata ,  Yasutaka Baba ,  Takashi Tamura ,  Hidenobu Kuniyoshi ,  Shinji Hagiwara ,  Mari Yamamoto

发明人： Hideyasu Fujiwara ,  Kimihiko Sato ,  Shinsuke Mizumoto ,  Yuichiro Sato ,  Hideki Kurihara ,  Yohei Kubo ,  Hiyoku Nakata ,  Yasutaka Baba ,  Takashi Tamura ,  Hidenobu Kuniyoshi ,  Shinji Hagiwara ,  Mari Yamamoto

IPC分类号： C07D213/82

摘要： An object of the present invention is to provide to a compound and a pharmaceutical composition, which have excellent Syk-inhibitory activity. The present invention provides a nicotinamide derivative represented by the following formula (I) (wherein R1 represents a halogen atom; R2 represents a C1-12 alkyl group, a C2-12 alkenyl group, a C2-12 alkynyl group, a C3-8 cycloalkyl group, an aryl group, an ar-C1-6 alkyl group or a heterocyclic group, each optionally having at least one substituent; R3 represents an aryl group or a heterocyclic group each optionally having at least one substituent; and R4 and R5 each independently represent a hydrogen atom; and R2 and R4 may form a cyclic amino group optionally having at least one substituent together with the nitrogen atom to which they bind) or a salt thereof, and a pharmaceutical composition for use in the treatment of a Syk-related disease which comprises the nicotinamide derivative or a salt thereof.

公开(公告)号：US08354426B2

公开(公告)日：2013-01-15

申请号：US12744633

申请日：2008-11-25

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

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

IPC分类号： A61K31/436 ,  A61K31/4353 ,  C07D471/04

CPC分类号： C07D519/00 ,  C07D309/40 ,  C07D491/04

摘要： 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.

摘要翻译： 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：US08772320B2

公开(公告)日：2014-07-08

申请号：US13730000

申请日：2012-12-28

申请人： Hideyasu Fujiwara ,  Kimihiko Sato ,  Shinsuke Mizumoto ,  Yuichiro Sato ,  Hideki Kurihara ,  Yohei Kubo ,  Hiyoku Nakata ,  Yasutaka Baba ,  Takashi Tamura ,  Hidenobu Kuniyoshi ,  Shinji Hagiwara ,  Mari Yamamoto

发明人： Hideyasu Fujiwara ,  Kimihiko Sato ,  Shinsuke Mizumoto ,  Yuichiro Sato ,  Hideki Kurihara ,  Yohei Kubo ,  Hiyoku Nakata ,  Yasutaka Baba ,  Takashi Tamura ,  Hidenobu Kuniyoshi ,  Shinji Hagiwara ,  Mari Yamamoto

IPC分类号： C07D213/82

摘要： An object of the present invention is to provide to a compound and a pharmaceutical composition, which have excellent Syk-inhibitory activity. The present invention provides a nicotinamide derivative represented by the following formula (I) (wherein R1 represents a halogen atom; R2 represents a C1-12 alkyl group, a C2-12 alkenyl group, a C2-12 alkynyl group, a C3-8 cycloalkyl group, an aryl group, an ar-C1-6 alkyl group or a heterocyclic group, each optionally having at least one substituent; R3 represents an aryl group or a heterocyclic group each optionally having at least one substituent; and R4 and R5 each independently represent a hydrogen atom; and R2 and R4 may form a cyclic amino group optionally having at least one substituent together with the nitrogen atom to which they bind) or a salt thereof, and a pharmaceutical composition for use in the treatment of a Syk-related disease which comprises the nicotinamide derivative or a salt thereof.

公开(公告)号：US07977492B2

公开(公告)日：2011-07-12

申请号：US12302375

申请日：2007-05-25

申请人： Kenji Yonezawa ,  Hironori Kotsubo ,  Yasutaka Baba ,  Yukie Tada

发明人： Kenji Yonezawa ,  Hironori Kotsubo ,  Yasutaka Baba ,  Yukie Tada

IPC分类号： C07D261/20

CPC分类号： C07D261/20

摘要： The crystal of 3-{5-[4-(cyclopentyloxy)-2-hydroxybenzoyl]-2-[(3-hydroxy-1,2-benzisoxazol-6-yl)methoxy]phenyl}propionic acid having peaks at the position of 14.0, 16.0, 23.3, 23.7 and 26.3° and the crystal of 3-{5-[4-(cyclopentyloxy)-2-hydroxybenzoyl]-2-[(3-hydroxy-1,2-benzisoxazol-6-yl)methoxy]phenyl}propionic acid having peaks at the position of 14.6, 23.1, 24.7, 25.6 and 26.0° on 2θ of diffraction angle in a powder X-ray diffraction pattern have a small specific volume, are hard to be charged with electricity, are easily handled and are useful for an active pharmaceutical ingredient of excellent anti-rheumatic agents.

摘要翻译： 3- {5- [4-（环戊氧基）-2-羟基苯甲酰基] -2 - [（3-羟基-1,2-苯并异恶唑-6-基）甲氧基]苯基}丙酸的晶体在 14.0,16.0,23.3,23.7和26.3°，3- {5- [4-（环戊氧基）-2-羟基苯甲酰基] -2 - [（3-羟基-1,2-苯并异恶唑-6-基）甲氧基 ]苯基}丙酸在2℃下在14.6,23.1,24.7,25.6和26.0°的位置具有峰; 的粉末X射线衍射图中的衍射角小，比电容小，难以充电，易于处理，可用于优异的抗风湿剂的活性药物成分。

公开(公告)号：US08895585B2

公开(公告)日：2014-11-25

申请号：US13730000

申请日：2012-12-28

申请人： Hideyasu Fujiwara ,  Kimihiko Sato ,  Shinsuke Mizumoto ,  Yuichiro Sato ,  Hideki Kurihara ,  Yohei Kubo ,  Hiyoku Nakata ,  Yasutaka Baba ,  Takashi Tamura ,  Hidenobu Kuniyoshi ,  Shinji Hagiwara ,  Mari Yamamoto

发明人： Hideyasu Fujiwara ,  Kimihiko Sato ,  Shinsuke Mizumoto ,  Yuichiro Sato ,  Hideki Kurihara ,  Yohei Kubo ,  Hiyoku Nakata ,  Yasutaka Baba ,  Takashi Tamura ,  Hidenobu Kuniyoshi ,  Shinji Hagiwara ,  Mari Yamamoto

IPC分类号： C07D213/82

CPC分类号： C07D401/12 ,  C07D213/82 ,  C07D215/40 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D491/048 ,  C07D491/056 ,  C07D491/107 ,  C07D498/04 ,  C07D513/04

摘要： An object of the present invention is to provide to a compound and a pharmaceutical composition, which have excellent Syk-inhibitory activity. The present invention provides a nicotinamide derivative represented by the following formula (I) (wherein R1 represents a halogen atom; R2 represents a C1-12 alkyl group, a C2-12 alkenyl group, a C2-12 alkynyl group, a C3-8 cycloalkyl group, an aryl group, an ar-C1-6 alkyl group or a heterocyclic group, each optionally having at least one substituent; R3 represents an aryl group or a heterocyclic group each optionally having at least one substituent; and R4 and R5 each independently represent a hydrogen atom; and R2 and R4 may form a cyclic amino group optionally having at least one substituent together with the nitrogen atom to which they bind) or a salt thereof, and a pharmaceutical composition for use in the treatment of a Syk-related disease which comprises the nicotinamide derivative or a salt thereof.

摘要翻译： 本发明的目的是提供具有优异的Syk抑制活性的化合物和药物组合物。 本发明提供下述式（I）表示的烟酰胺衍生物（其中，R1表示卤素原子，R2表示C1-12烷基，C2-12烯基，C2-12炔基，C3-8 环烷基，芳基，芳基-C 1-6烷基或杂环基，各自任选具有至少一个取代基; R 3表示各自任选具有至少一个取代基的芳基或杂环基;以及R 4和R 5各自 独立地表示氢原子; R2和R4可以形成任选具有至少一个取代基的环状氨基以及与它们结合的氮原子）或其盐，以及用于治疗Syk- 其包含烟酰胺衍生物或其盐。

公开(公告)号：US20130116430A1

公开(公告)日：2013-05-09

申请号：US13730000

申请日：2012-12-28

申请人： Hideyasu FUJIWARA ,  Kimihiko SATO ,  Shinsuke MIZUMOTO ,  Yuichiro SATO ,  Hideki KURIHARA ,  Yohei KUBO ,  Hiyoku NAKATA ,  Yasutaka BABA ,  Takashi TAMURA ,  Hidenobu KUNIYOSHI ,  Shinji HAGIWARA ,  Mari YAMAMOTO

发明人： Hideyasu FUJIWARA ,  Kimihiko SATO ,  Shinsuke MIZUMOTO ,  Yuichiro SATO ,  Hideki KURIHARA ,  Yohei KUBO ,  Hiyoku NAKATA ,  Yasutaka BABA ,  Takashi TAMURA ,  Hidenobu KUNIYOSHI ,  Shinji HAGIWARA ,  Mari YAMAMOTO

IPC分类号： C07D401/12 ,  C07D401/04 ,  C07D213/82 ,  C07D513/04 ,  C07D413/14 ,  C07D405/14 ,  C07D409/14 ,  C07D417/12 ,  C07D401/14 ,  C07D471/04

CPC分类号： C07D401/12 ,  C07D213/82 ,  C07D215/40 ,  C07D401/04 ,  C07D401/14 ,  C07D405/14 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D491/048 ,  C07D491/056 ,  C07D491/107 ,  C07D498/04 ,  C07D513/04

摘要： An object of the present invention is to provide to a compound and a pharmaceutical composition, which have excellent Syk-inhibitory activity. The present invention provides a nicotinamide derivative represented by the following formula (I) (wherein R1 represents a halogen atom; R2 represents a C1-12 alkyl group, a C2-12 alkenyl group, a C2-12 alkynyl group, a C3-8 cycloalkyl group, an aryl group, an ar-C1-6 alkyl group or a heterocyclic group, each optionally having at least one substituent; R3 represents an aryl group or a heterocyclic group each optionally having at least one substituent; and R4 and R5 each independently represent a hydrogen atom; and R2 and R4 may form a cyclic amino group optionally having at least one substituent together with the nitrogen atom to which they bind) or a salt thereof, and a pharmaceutical composition for use in the treatment of a Syk-related disease which comprises the nicotinamide derivative or a salt thereof.

摘要翻译： 本发明的目的是提供具有优异的Syk抑制活性的化合物和药物组合物。 本发明提供下述式（I）表示的烟酰胺衍生物（其中，R1表示卤素原子，R2表示C1-12烷基，C2-12烯基，C2-12炔基，C3-8 环烷基，芳基，芳基-C 1-6烷基或杂环基，各自任选具有至少一个取代基; R 3表示各自任选具有至少一个取代基的芳基或杂环基;以及R 4和R 5各自 独立地表示氢原子; R2和R4可以形成任选具有至少一个取代基的环状氨基以及与它们结合的氮原子）或其盐，以及用于治疗Syk- 其包含烟酰胺衍生物或其盐。

公开(公告)号：US20100249417A1

公开(公告)日：2010-09-30

申请号：US12744633

申请日：2008-11-25

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

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

IPC分类号： C07D491/056 ,  C07D315/00

CPC分类号： C07D519/00 ,  C07D309/40 ,  C07D491/04

摘要： 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.

摘要翻译： 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：US20090275757A1

公开(公告)日：2009-11-05

申请号：US12302375

申请日：2007-05-25

申请人： Kenji Yonezawa ,  Hironori Kotsubo ,  Yasutaka Baba ,  Yukie Tada

发明人： Kenji Yonezawa ,  Hironori Kotsubo ,  Yasutaka Baba ,  Yukie Tada

IPC分类号： C07D261/20

CPC分类号： C07D261/20

摘要： The crystal of 3-{5-[4-(cyclopentyloxy)-2-hydroxybenzoyl]-2-[(3-hydroxy-1,2-benzisoxazol-6-yl)methoxy]phenyl}propionic acid having peaks at the position of 14.0, 16.0, 23.3, 23.7 and 26.3° and the crystal of 3-{5-[4-(cyclopentyloxy)-2-hydroxybenzoyl]-2-[(3-hydroxy-1,2-benzisoxazol-6-yl)methoxy]phenyl}propionic acid having peaks at the position of 14.6, 23.1, 24.7, 25.6 and 26.0° on 2θ of diffraction angle in a powder X-ray diffraction pattern have a small specific volume, are hard to be charged with electricity, are easily handled and are useful for an active pharmaceutical ingredient of excellent anti-rheumatic agents.

摘要翻译： 3- {5- [4-（环戊氧基）-2-羟基苯甲酰基] -2 - [（3-羟基-1,2-苯并异恶唑-6-基）甲氧基]苯基}丙酸的晶体在 14.0,16.0,23.3,23.7和26.3°，3- {5- [4-（环戊氧基）-2-羟基苯甲酰基] -2 - [（3-羟基-1,2-苯并异恶唑-6-基）甲氧基 ]苯基}丙酸在粉末X射线衍射图中的衍射角度为14.6,23.1,24.7,25.6和26.0°的峰具有小的比容，难以用电充电，容易 并且可用于优异的抗风湿剂的活性药物成分。