公开(公告)号：US08178681B2

公开(公告)日：2012-05-15

申请号：US11628804

申请日：2005-10-28

申请人： Natsuki Ishizuka ,  Yoshiharu Hiramatsu ,  Yasuhiko Fujii ,  Yoshikazu Fukui

发明人： Natsuki Ishizuka ,  Yoshiharu Hiramatsu ,  Yasuhiko Fujii ,  Yoshikazu Fukui

IPC分类号： C07D221/04 ,  C07D213/62 ,  A61K31/54 ,  A61K31/435

CPC分类号： C07D213/82

摘要： The present invention provides compounds having an agonistic activity to the cannabinoid receptor, which is represented by the formula (I): wherein R1 is optionally substituted C1-C8 alkyl and the like; R2 is C1-C6 alkyl; R3 is C1-C6 alkyl and the like; or R2 and R3 taken together with may form an optionally substituted 5 to 10 membered non-aromatic carbon ring; R4 is hydrogen and the like; G is a group selected from the groups shown by the formula an the like: wherein R5 is hydrogen and the like; X1 is a single bond and the like; X2 is optionally substituted C1-C8 alkylene that may be replaced by one or two groups of —O—, or —N(R6)—, wherein R6 is hydrogen and the like, and the like; X3 is a single bond and the like; a pharmaceutically acceptable salt or a solvate thereof, and pharmaceutical compositions, atopic dermatitis treating agents, and anti-pruritus agents, especially anti-pruritus agents for oral used and for external application, which each contains the said compound as an active ingredient.

摘要翻译： 本发明提供对大麻素受体具有激动作用的化合物，其由式（I）表示：其中R 1为任选取代的C 1 -C 8烷基等; R2是C1-C6烷基; R3是C1-C6烷基等; 或者R 2和R 3与相邻碳原子一起可以形成任选取代的5至10元非芳族碳环; R4是氢等; G是选自下式的基团：其中R5是氢等; X1是单键等; X2是任选取代的C1-C8亚烷基，其可以被一个或两个-O-或-N（R 6） - 基团取代，其中R 6是氢等; X3是单键等; 药学上可接受的盐或其溶剂合物，以及药物组合物，特应性皮炎治疗剂和抗瘙痒剂，特别是用于口服和外用的抗瘙痒剂，其各自含有所述化合物作为活性成分。

公开(公告)号：US20080103139A1

公开(公告)日：2008-05-01

申请号：US11628804

申请日：2005-10-28

申请人： Natsuki Ishizuka ,  Takashi Sasatani ,  Yoshiharu Hiramatsu ,  Masanao Inagaki ,  Masahide Odan ,  Hiroshi Hashizume ,  Susumu Mitsumori ,  Yasuhiko Fujii ,  Yoshikazu Fukui ,  Hideaki Watanabe ,  Jun Sato

发明人： Natsuki Ishizuka ,  Takashi Sasatani ,  Yoshiharu Hiramatsu ,  Masanao Inagaki ,  Masahide Odan ,  Hiroshi Hashizume ,  Susumu Mitsumori ,  Yasuhiko Fujii ,  Yoshikazu Fukui ,  Hideaki Watanabe ,  Jun Sato

IPC分类号： A61K31/5377 ,  C07D221/04 ,  A61K31/435 ,  C07D211/84 ,  A61K31/4412 ,  A61P17/00 ,  C07D401/12 ,  A61K31/496 ,  A61K31/506 ,  C07D413/12

CPC分类号： C07D213/82

摘要： The present invention provides compounds having an agonistic activity to the cannabinoid receptor, which is represented by the formula (I): wherein R1 is optionally substituted C1-C8 alkyl and the like; R2 is C1-C6 alkyl; R3 is C1-C6 alkyl and the like; or R2 and R3 taken together with may form an optionally substituted 5 to 10 membered non-aromatic carbon ring; R4 is hydrogen and the like; G is a group selected from the groups shown by the formula an the like: wherein R5 is hydrogen and the like; X1 is a single bond and the like; X2 is optionally substituted C1-C8 alkylene that may be replaced by one or two groups of —O—, or —N(R6)—, wherein R6 is hydrogen and the like, and the like; X3 is a single bond and the like; a pharmaceutically acceptable salt or a solvate thereof, and pharmaceutical compositions, atopic dermatitis treating agents, and anti-pruritus agents, especially anti-pruritus agents for oral used and for external application, which each contains the said compound as an active ingredient.

摘要翻译： 本发明提供对大麻素受体具有激动作用的化合物，其由式（I）表示：其中R 1是任选取代的C 1 -C 8烷基等; R 2是C 1 -C 6烷基; R 3是C 1 -C 6烷基等; 或R 2和R 3与相邻碳原子一起可以形成任选取代的5至10元非芳族碳环; R 4是氢等; G为选自下式的基团：其中R 5为氢等; X 1是单键等; X 2是任选取代的C 1 -C 8亚烷基，其可以被一个或两个-O-或-N（R 6） - 基团取代，其中R 0 > 6是氢等; X 3是单键等; 其药学上可接受的盐或溶剂合物，以及药物组合物，特应性皮炎治疗剂和抗瘙痒剂，特别是用于口服和外用的抗瘙痒剂，其各自含有所述化合物作为活性成分。

公开(公告)号：US06472389B1

公开(公告)日：2002-10-29

申请号：US09673413

申请日：2000-10-18

申请人： Mitsuaki Ohtani ,  Masahiro Fuji ,  Yoshikazu Fukui ,  Makoto Adachi

发明人： Mitsuaki Ohtani ,  Masahiro Fuji ,  Yoshikazu Fukui ,  Makoto Adachi

IPC分类号： A61K315025

CPC分类号： C07D487/04

摘要： The present invention provides a compound having sPLA2 inhibiting activity. The compound represented by the formula (I): wherein R1 is —(L1)—R6 wherein L1 is a divalent linking group of 1 to 18 atoms or the like, and R6 is a carbocyclic ring substituted by at least one non-interfering substituent or the like; R2 is C1 to C3 alkyl or the like; R3 is —(L2)-(acidic group); R4 and R5 are hydrogen atoms, non-interfering substituents, carbocyclic groups or the like; X is independently oxygen atom of sulfur atom; and RA is —C(═X)—C(═X)—NH2 or the like; the prodrugs thereof, their pharmaceutically acceptable salts, or their solvates, and a composition for inhibiting sPLA2 containing them as effective ingredients.

摘要翻译： 本发明提供具有sPLA2抑制活性的化合物。式（I）表示的化合物：其中R1为 - （L1）-R6，其中L1为1至18个原子的二价连接基团等，R6为 被至少一个非干扰取代基等取代的碳环; R2是C1-C3烷基等; R3是 - （L2） - （酸性基团）; R4和R5是氢原子，非干扰取代基，碳环基团等; X独立地是硫原子的氧原子; RA为-C（= X）-C（= X）-NH 2等; 其前体药物，其药学上可接受的盐或其溶剂合物，以及用于抑制含有它们作为有效成分的sPLA2的组合物。

公开(公告)号：US20080188651A1

公开(公告)日：2008-08-07

申请号：US12006364

申请日：2008-01-02

申请人： Dennis P. Curran ,  Youseung Shin ,  Jean-Hugues Fournier ,  John Mancuso ,  Billy W. Day ,  Arndt Bruckner ,  Yoshikazu Fukui

发明人： Dennis P. Curran ,  Youseung Shin ,  Jean-Hugues Fournier ,  John Mancuso ,  Billy W. Day ,  Arndt Bruckner ,  Yoshikazu Fukui

IPC分类号： C07D225/02 ,  C07D313/04 ,  C07C59/10

CPC分类号： C07C33/02 ,  C07B2200/07 ,  C07C59/10 ,  C07C59/42 ,  C07C69/732 ,  C07C69/734 ,  C07D309/10 ,  C07D309/30 ,  C07D313/00 ,  C07D319/06 ,  C07D407/06 ,  C07F7/1804 ,  Y02P20/55

摘要： Dictyostatin and its analogs show great promise as new anticancer agents. The present invention provides dictyostatin analogs, synthetic intermediates for the synthesis of dictyostatin analogs, and synthetic methods for the synthesis of such analogs and intermediates. Dictyostatin analogs can have the following structure or its enantiomer wherein R1 is H, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, or a halogen atom; R2 is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; Ra, Rb and Rc are independently an alkyl group or an aryl group; Rd is an alkyl group, an aryl group, an alkoxylalkyl group, —RiSiRaRbRc or a benzyl group, wherein Ri is an alkylene group; Re is an alkyl group, an allyl group, a benzyl group, an aryl group, an alkoxy group, or —NRgRh, wherein Rg and Rh are independently H, an alkyl group or an aryl group; R3 is (CH2)n where n is and integer in the range of 0 to 5, —CH2CH(CH3), —CH═CH—, —CH═C(CH3), or —C≡C—; R4 is wherein R23a is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe, R23b is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe, or R23a and R23b together form a portion of six-membered acetal ring incorporating CRtRu; Rt and Ru are independently H, an alkyl group, an aryl group or an alkoxyaryl group; and R5 is H or OR2b, wherein R2b is H, a protecting group, an alkyl group, an aryl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; provided that the compound is not dictyostatin 1.

公开(公告)号：US07321046B2

公开(公告)日：2008-01-22

申请号：US11139949

申请日：2005-05-27

申请人： Dennis P. Curran ,  Youseung Shin ,  Jean-Hugues Fournier ,  John Mancuso ,  Billy W. Day ,  Arndt Bruckner ,  Yoshikazu Fukui

发明人： Dennis P. Curran ,  Youseung Shin ,  Jean-Hugues Fournier ,  John Mancuso ,  Billy W. Day ,  Arndt Bruckner ,  Yoshikazu Fukui

IPC分类号： C07D313/04 ,  C07D313/16

CPC分类号： C07C33/02 ,  C07B2200/07 ,  C07C59/10 ,  C07C59/42 ,  C07C69/732 ,  C07C69/734 ,  C07D309/10 ,  C07D309/30 ,  C07D313/00 ,  C07D319/06 ,  C07D407/06 ,  C07F7/1804 ,  Y02P20/55

摘要： Dictyostatin and its analogs show great promise as new anticancer agents. The present invention provides dictyostatin analogs, synthetic intermediates for the synthesis of dictyostatin analogs, and synthetic methods for the synthesis of such analogs and intermediates. Dictyostatin analogs can have the following structure or its enantiomer wherein R1 is H, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, or a halogen atom; R2 is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; Ra, Rb and Rc are independently an alkyl group or an aryl group; Rd is an alkyl group, an aryl group, an alkoxylalkyl group, —RiSiRaRbRc or a benzyl group, wherein Ri is an alkylene group; Re is an alkyl group, an allyl group, a benzyl group, an aryl group, an alkoxy group, or —NRgRh, wherein Rg and Rh are independently H, an alkyl group or an aryl group; R3 is (CH2)n where n is and integer in the range of 0 to 5, —CH2CH(CH3)—, —CH═CH—, —CH═C(CH3)—, or —C≡C—; R4 is wherein R23a is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; R23b is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe, or R23a and R23b together form a portion of six-membered acetal ring incorporating CRtRu; Rt and Ru are independently H, an alkyl group, an aryl group or an alkoxyaryl group; and R5 is H or OR2b, wherein R2b is H, a protecting group, an alkyl group, an aryl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; provided that the compound is not dictyostatin 1.

公开(公告)号：US20070054902A1

公开(公告)日：2007-03-08

申请号：US10581322

申请日：2004-11-29

申请人： Yoshikazu Fukui ,  Takasi Sasatani ,  Ken-ichi Sasatani ,  Natsuki Ishizuka ,  Toshisada Yano ,  Yasuhiko Kanda ,  Nobuo Chomei

发明人： Yoshikazu Fukui ,  Takasi Sasatani ,  Ken-ichi Sasatani ,  Natsuki Ishizuka ,  Toshisada Yano ,  Yasuhiko Kanda ,  Nobuo Chomei

IPC分类号： A61K31/5383 ,  A61K31/4245 ,  A61K31/42 ,  C07D413/14

CPC分类号： C07D417/12 ,  C07D261/08 ,  C07D261/18 ,  C07D413/04 ,  C07D413/06 ,  C07D413/12

摘要： A compound of formula (I): (wherein R1-R10 are each independently hydrogen, halogen, optionally substituted lower alkyl or the like, X1 is —O—, —S—, —NR11— (wherein R11 is hydrogen, lower alkyl or the like), —CR12R13CO—, —(CR12R13)mO—, —O(CR12R13)m- (wherein R12 and R13 are each independently hydrogen or lower alkyl and m is a integer between 1 and 3) or the like, X2 is a bond, —O—, —S—, —NR14— (wherein R14 is hydrogen, lower alkyl or the like, R14 and R6 can be taken together with the neighboring atom to form a ring) or —CR15R16— (wherein R15 and R16 are each independently hydrogen or lower alkyl, R15 and R6 or R10 can be taken together with the neighboring carbon atom to form a ring, R16 and R9 can be joined together to form a bond), X3 is COOR17, C(═NR17)NR18OR19 or the like), a pharmaceutically acceptable salt or a solvate thereof.

摘要翻译： 式（I）的化合物：其中R 1〜R 10各自独立地为氢，卤素，任选取代的低级烷基等，X 1， / SUP>是-O - ， - S - ， - NR 11 - （其中R 11是氢，低级烷基等），-CR 12 - （CR 12）13 - ， - （CR 12）， - （CR 12） （其中R 12和R 12各自独立地为氢或低级烷基，m为1和...之间的整数） 3）等，X 2是一个键，-O - ， - S-，-NR 14 - （其中R 14是 氢，低级烷基等，R 14和R 6可以与相邻原子一起形成环）或-CR 15 R 16 - （其中R 15和R 16各自独立地是氢或低级烷基，R 15和 R 6或R 10可以与相邻的碳原子一起形成环，R 16和R 9， S 可以连接在一起形成键），X 3是COOR 17，C（-NR 17）NR 18 其药学上可接受的盐或其溶剂化物。

公开(公告)号：US20060025395A1

公开(公告)日：2006-02-02

申请号：US11139949

申请日：2005-05-27

申请人： Dennis Curran ,  Youseung Shin ,  Jean-Hugues Fournier ,  John Mancuso ,  Billy Day ,  Arndt Bruckner ,  Yoshikazu Fukui

发明人： Dennis Curran ,  Youseung Shin ,  Jean-Hugues Fournier ,  John Mancuso ,  Billy Day ,  Arndt Bruckner ,  Yoshikazu Fukui

IPC分类号： A61K31/365 ,  A61K31/16 ,  A61K31/202

CPC分类号： C07C33/02 ,  C07B2200/07 ,  C07C59/10 ,  C07C59/42 ,  C07C69/732 ,  C07C69/734 ,  C07D309/10 ,  C07D309/30 ,  C07D313/00 ,  C07D319/06 ,  C07D407/06 ,  C07F7/1804 ,  Y02P20/55

摘要： Dictyostatin and its analogs show great promise as new anticancer agents. The present invention provides dictyostatin analogs, synthetic intermediates for the synthesis of dictyostatin analogs, and synthetic methods for the synthesis of such analogs and intermediates. Dictyostatin analogs can have the following structure or its enantiomer wherein R1 is H, an alkyl group, an aryl group, an alkenyl group, an alkynyl group, or a halogen atom; R2 is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; Ra, Rb and Rc are independently an alkyl group or an aryl group; Rd is an alkyl group, an aryl group, an alkoxylalkyl group, —RiSiRaRbRc or a benzyl group, wherein Ri is an alkylene group; Re is an alkyl group, an allyl group, a benzyl group, an aryl group, an alkoxy group, or —NRgRh, wherein Rg and Rh are independently H, an alkyl group or an aryl group; R3 is (CH2)n where n is and integer in the range of 0 to 5, —CH2CH(CH3)—, —CH═CH—, —CH═C(CH3)—, or —C≡C—; R4 is wherein R23a is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; R23b is H, a protecting group, an alkyl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe, or R23a and R23b together form a portion of six-membered acetal ring incorporating CRtRu; Rt and Ru are independently H, an alkyl group, an aryl group or an alkoxyaryl group; and R5 is H or OR2b, wherein R2b is H, a protecting group, an alkyl group, an aryl group, a benzyl group, a trityl group, —SiRaRbRc, CH2ORd, or CORe; provided that the compound is not dictyostatin 1.

公开(公告)号：US20120208813A1

公开(公告)日：2012-08-16

申请号：US13407520

申请日：2012-02-28

申请人： Natsuki ISHIZUKA ,  Takashi SASATANI ,  Yoshiharu HIRAMATSU ,  Masanao INAGAKI ,  Masahide ODAN ,  Hiroshi HASHIZUMI ,  Susumu MITSUMORI ,  Yasuhiko FUJII ,  Yoshikazu FUKUI ,  Hideaki WATANABE ,  Jun SATO

发明人： Natsuki ISHIZUKA ,  Takashi SASATANI ,  Yoshiharu HIRAMATSU ,  Masanao INAGAKI ,  Masahide ODAN ,  Hiroshi HASHIZUMI ,  Susumu MITSUMORI ,  Yasuhiko FUJII ,  Yoshikazu FUKUI ,  Hideaki WATANABE ,  Jun SATO

IPC分类号： A61K31/435 ,  C07D495/04 ,  A61K31/4365 ,  A61P17/00 ,  A61K31/496 ,  A61K31/506 ,  C07D413/12 ,  A61K31/5377 ,  C07D221/04 ,  C07D401/12

CPC分类号： C07D213/82

摘要： The present invention provides compounds having an agonistic activity to the cannabinoid receptor, which is represented by the formula (I): wherein R1, R2, R3, R4, and G are defined as herein, a pharmaceutically acceptable salt or a solvate thereof, and pharmaceutical compositions, atopic dermatitis treating agents, and anti-pruritus agents, especially anti-pruritus agents for oral used and for external application, which each contains the said compound as an active ingredient.

摘要翻译： 本发明提供对大麻素受体具有激动作用的化合物，其由式（I）表示：其中R 1，R 2，R 3，R 4和G如本文所定义，其药学上可接受的盐或溶剂合物，以及 药物组合物，特应性皮炎治疗剂和抗瘙痒剂，特别是用于口服和外用的抗瘙痒剂，其各自含有所述化合物作为活性成分。

公开(公告)号：US20050043387A1

公开(公告)日：2005-02-24

申请号：US10947172

申请日：2004-09-23

申请人： Yoshikazu Fukui ,  Makoto Adachi ,  Takashi Sasatani

发明人： Yoshikazu Fukui ,  Makoto Adachi ,  Takashi Sasatani

IPC分类号： A61P5/28 ,  A61P25/00 ,  A61P25/04 ,  A61P25/06 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P43/00 ,  C07D491/06 ,  A61K31/55 ,  A61K31/407 ,  A61K31/454 ,  C07D491/02

CPC分类号： C07D491/06

摘要： Having an affinity against serotonine receptors, compound (I) shown below is useful as a therapeutic agent against various kinds of diseases of central nervous systems. (wherein R1 is hydrogen; R2 is hydrogen or lower alkyl; R3 is hydrogen, —COOR12 and so on; R4 is hydrogen, lower alkyl and so on, or R3 and R4 taken together may form ═O or ═S; R5 is hydrogen, or R3 and R5 taken together may form a bond; R6 is hydrogen, —COOR24 and so on; R7 is hydrogen, halogen, lower alkyl and so on; R8 is hydrogen, lower alkyl, cycloalkyl and so on; R9, R10 and R11 are each independently hydrogen, halogen, lower alkyl and so on)

摘要翻译： 对于5-羟色胺受体具有亲和性，下文所示的化合物（I）可用作抗各种中枢神经系统疾病的治疗剂。 （其中R 1为氢; R 2为氢或低级烷基; R 3为氢，-COOR 12等; R 4为氢，低级烷基等，或R R 3和R 4一起可以形成= O或= S; R 5是氢，或者R 3和R 5一起可以形成键; R 6是氢， COOR 24等; R 7是氢，卤素，低级烷基等; R 8是氢，低级烷基，环烷基等; R 9，R 10和R 10， 11>各自独立地为氢，卤素，低级烷基等）

公开(公告)号：US06858640B2

公开(公告)日：2005-02-22

申请号：US10312818

申请日：2001-09-17

申请人： Yoshikazu Fukui ,  Makoto Adachi ,  Takashi Sasatani

发明人： Yoshikazu Fukui ,  Makoto Adachi ,  Takashi Sasatani

IPC分类号： A61P5/28 ,  A61P25/00 ,  A61P25/04 ,  A61P25/06 ,  A61P25/16 ,  A61P25/18 ,  A61P25/22 ,  A61P25/24 ,  A61P43/00 ,  C07D491/06 ,  A61K31/40 ,  C07D491/044

CPC分类号： C07D491/06

摘要： Having an affinity against serotonine receptors, compound (I) shown below is useful as a therapeutic agent against various kinds of diseases of central nervous systems; (wherein R1 is hydrogen; R2 is hydrogen or lower alkyl; R3 is hydrogen, —COOR12 and so on; R4 is hydrogen, lower alkyl and so on, or R3 and R4 taken together may form ═O or ═S; R5 is hydrogen, or R3 and R5 taken together may form a bond; R6 is hydrogen, —COOR24 and so on; R7 is hydrogen, halogen, lower alkyl and so on; R8 is hydrogen, lower alkyl, cycloalkyl and so on; R9, R10 and R11 are each independently hydrogen, halogen, lower alkyl and so on).

摘要翻译： 对于5-羟色胺受体具有亲和力，下文所示的化合物（I）可用作抗各种中枢神经系统疾病的治疗剂;（其中R 1是氢; R 2是氢或低级烷基; 3>是氢，-COOR 12等; R 4是氢，低级烷基等，或者R 3和R 4一起可以形成= O或= S; R 5 >是氢，或R 3和R 5一起形成键; R 6是氢，-COOR 24等; R 7是氢，卤素，低级烷基等 R 8是氢，低级烷基，环烷基等; R 9，R 10和R 11各自独立地是氢，卤素，低级烷基等）。