公开(公告)号：US06949536B2

公开(公告)日：2005-09-27

申请号：US10771861

申请日：2004-02-03

申请人： Kazuo Ando ,  Tomoki Kato ,  Akiyoshi Kawai ,  Tomomi Nonomura

发明人： Kazuo Ando ,  Tomoki Kato ,  Akiyoshi Kawai ,  Tomomi Nonomura

IPC分类号： A61K31/33 ,  A61K31/4025 ,  A61K31/422 ,  A61K31/425 ,  A61K31/427 ,  A61K31/454 ,  C07D233/00 ,  C07D277/00 ,  C07D333/00

CPC分类号： A61K31/422 ,  A61K31/427 ,  A61K31/454 ,  C07C311/39 ,  C07C317/36 ,  C07D207/325 ,  C07D207/333 ,  C07D401/10 ,  C07D403/10 ,  C07D405/10 ,  C07D409/10 ,  C07D413/10 ,  C07D417/10

摘要： This invention provides a compound of the formula: or its pharmaceutically acceptable salt thereof, wherein A is partially unsaturated or unsaturated five membered heterocyclic, or partially unsaturated or unsaturated five membered carbocyclic, wherein the 4-(sulfonyl)phenyl and the 4-substituted phenyl in the formula (I) are attached to ring atoms of Ring A, which are adjacent to each other; R1 is optionally substituted aryl or heteroaryl, with the proviso that when A is pyrazole, R1 is heteroaryl; R2 is C1-4 alkyl; halo-substituted C1-4 alkyl, C1-4 alkylamino, C1-4 dialkylamino or amino; R3, R4 and R5 are independently hydrogen, halo, C1-4 alkyl, halo-substituted C1-4 alkyl or the like; or two of R3, R4 and R5 are taken together with atoms to which they are attached and form a 4-7 membered ring. R6 and R7 are independently hydrogen, halo, C1-4 alkyl, halo-substituted C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylamino or N,N-di C1-4 alkylamino; and m and n are independently 1, 2, 3 or 4. This invention also provides a pharmaceutical composition useful for the treatment of a medical condition in which prostaglandins are implicated as pathogens.

摘要翻译： 本发明提供下式的化合物或其药学上可接受的盐，其中A是部分不饱和或不饱和的五元杂环或部分不饱和或不饱和的五元碳环，其中4-（磺酰基）苯基和4-取代的苯基 在式（I）中，与环A相邻的环原子相连; R 1是任选取代的芳基或杂芳基，条件是当A是吡唑时，R 1是杂芳基; R 2是C 1-4烷基; 卤素取代的C 1-4烷基，C 1-4烷基氨基，C 1-4烷基氨基或氨基; R 4，R 4和R 5独立地是氢，卤素，C 1-4烷基，卤代 - 取代的C 1-4烷基等; 或者R 3，R 4和R 5中的两个与它们所连接的原子一起形成4-7元环 。 R 6和R 7独立地是氢，卤素，C 1-4烷基，卤素取代的C 1-4烷基， C 1-4烷基，C 1-4烷氧基，C 1-4烷硫基，C 1-4烷基氨基或N，N-二C < 烷基氨基; m和n分别为1,2,3或4.本发明还提供了一种药物组合物，其用于治疗前列腺素涉及病原体的医疗状况。

公开(公告)号：US06727238B2

公开(公告)日：2004-04-27

申请号：US10465767

申请日：2003-06-18

申请人： Kazuo Ando ,  Tomoki Kato ,  Akiyoshi Kawai ,  Tomomi Nonomura

发明人： Kazuo Ando ,  Tomoki Kato ,  Akiyoshi Kawai ,  Tomomi Nonomura

IPC分类号： A61K3133

CPC分类号： A61K31/422 ,  A61K31/427 ,  A61K31/454 ,  C07C311/39 ,  C07C317/36 ,  C07D207/325 ,  C07D207/333 ,  C07D401/10 ,  C07D403/10 ,  C07D405/10 ,  C07D409/10 ,  C07D413/10 ,  C07D417/10

摘要： This invention provides a compound of the formula: or its pharmaceutically acceptable salt thereof, wherein A is partially unsaturated or unsaturated five membered heterocyclic, or partially unsaturated or unsaturated five membered carbocyclic, wherein the 4-(sulfonyl)phenyl and the 4-substituted phenyl in the formula (I) are attached to ring atoms of Ring A, which are adjacent to each other; R1 is optionally substituted aryl or heteroaryl, with the proviso that when A is pyrazole, R1 is heteroaryl; R2 is C1-4 alkyl, halo-substituted C1-4 alkyl, C1-4 alkylamino, C1-4 dialkylamino or amino; R3, R4 and R5 are independently hydrogen, halo,, C1-4 alkyl, halo-substituted C1-4 alkyl or the like; or two of R3, R4 and R5 are taken together with atoms to which they are attached and form a 4-7 membered ring; R6 and R7 are independently hydrogen, halo, C1-4 alkyl, halo-substituted C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylamino or N,N-di C1-4 alkylamino; and m and n are independently 1, 2, 3 or 4. This invention also provides a pharmaceutical composition useful for the treatment of a medical condition in which prostaglandins are implicated as pathogens.

摘要翻译： 本发明提供下式的化合物或其药学上可接受的盐，其中A是部分不饱和或不饱和的五元杂环或部分不饱和或不饱和的五元碳环，其中4-（磺酰基）苯基和4-取代的苯基 在式（I）中，与环A相邻的环原子相连; R 1是任选取代的芳基或杂芳基，条件是当A是吡唑时，R 1是杂芳基; R 2是C 1-4烷基，卤素取代的C 1-4烷基，C 1-4烷基氨基，C 1-4二烷基氨基或氨基; R 3，R 4和R 5独立地是氢，卤素，C 1-4烷基，卤素取代的C 1-4烷基等; 或R 3，R 4和R 5中的两个与它们所连接的原子一起形成4-7元环; R 6和R 7独立地是氢，卤素，C 1-4烷基，卤素取代的C 1-4烷基，C 1-4烷氧基，C 1-4烷硫基，C 1-4烷基氨基或N，N-二C1- 4烷基氨基; 并且m和n独立地为1,2,3或4.本发明还提供了可用于治疗前列腺素作为病原体的医学病症的药物组合物。

公开(公告)号：US06608095B2

公开(公告)日：2003-08-19

申请号：US09841348

申请日：2001-04-24

申请人： Kazuo Ando ,  Tomoki Kato ,  Akiyoshi Kawai ,  Tomomi Nonomura

发明人： Kazuo Ando ,  Tomoki Kato ,  Akiyoshi Kawai ,  Tomomi Nonomura

IPC分类号： A61K3141

CPC分类号： C07D207/335 ,  C07D401/10 ,  C07D403/10 ,  C07D405/10 ,  C07D409/10 ,  C07D413/10 ,  C07D417/10

摘要： This invention provides a compound of the formula: or its pharmaceutically acceptable salt thereof, wherein A is partially unsaturated or unsaturated five membered heterocyclic, or partially unsaturated or unsaturated five membered carbocyclic, wherein the 4-(sulfonyl)phenyl and the 4-substituted phenyl in the formula (I) are attached to ring atoms of Ring A, which are adjacent to each other; R1 is optionally substituted aryl or heteroaryl, with the proviso that when A is pyrazole, R1 is heteroaryl; R2 is C1-4 alkyl, halo-substituted C1-4 alkyl, C1-4 alkylamino, C1-4 dialkylamino or amino; R3, R4 and R5 are independently hydrogen, halo, C1-4 alkyl, halo-substituted C1-4 alkyl or the like; or two of R3, R4 and R5 are taken together with atoms to which they are attached and form a 4-7 membered ring; R6 and R7 are independently hydrogen, halo, C1-4 alkyl, halo-substituted C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylamino or N,N-di C1-4 alkylamino; and m and n are independently 1, 2, 3 or 4. This invention also provides a pharmaceutical composition useful for the treatment of a medical condition in which prostaglandins are implicated as pathogens.

摘要翻译： 本发明提供下式的化合物或其药学上可接受的盐，其中A是部分不饱和或不饱和的五元杂环或部分不饱和或不饱和的五元碳环，其中4-（磺酰基）苯基和4-取代的苯基 在式（I）中，与环A相邻的环原子相连; R1是任选取代的芳基或杂芳基，条件是当A是吡唑时，R 1是杂芳基; R2是C1-4烷基，卤素取代的C1-4烷基，C1-4烷基氨基，C1-4二烷基氨基或氨基; R 3，R 4和R 5独立地为氢，卤素，C 1-4烷基，卤素取代的C 1-4烷基等; 或者R 3，R 4和R 5中的两个与它们所连接的原子一起形成4-7元环; R 6和R 7独立地是氢，卤素，C 1-4烷基，卤素取代的C 1-4烷基，C 1-4烷氧基，C 1-4烷硫基，C 1-4烷基氨基或N，N-二C 1-4烷基氨基; 并且m和n独立地为1,2,3或4.本发明还提供了可用于治疗前列腺素作为病原体的医学病症的药物组合物。

公开(公告)号：US06294558B1

公开(公告)日：2001-09-25

申请号：US09446049

申请日：1999-12-15

申请人： Kazuo Ando ,  Tomoki Kato ,  Akiyoshi Kawai ,  Tomomi Nonomura

发明人： Kazuo Ando ,  Tomoki Kato ,  Akiyoshi Kawai ,  Tomomi Nonomura

IPC分类号： A61K3144

CPC分类号： C07D207/335 ,  C07D401/10 ,  C07D403/10 ,  C07D405/10 ,  C07D409/10 ,  C07D413/10 ,  C07D417/10

摘要： This invention provides a compound of the formula: or its pharmaceutically acceptable salt thereof, wherein A is partially unsaturated or unsaturated five membered heterocyclic, or partially unsaturated or unsaturated five membered carbocyclic, wherein the 4-(sulfonyl)phenyl and the 4-substituted phenyl in the formula (I) are attached to ring atoms of Ring A, which are adjacent to each other; R1 is optionally substituted aryl or heteroaryl, with the proviso that when A is pyrazole, R1 is heteroaryl; R2 is C1-4 alkyl, halo-substituted C1-4 alkyl, C1-4 alkylamino, C1-4 dialkylamino or amino; R3, R4 and R5 are independently hydrogen, halo, C1-4 alkyl, halo-substituted C1-4 alkyl or the like; or two of R3, R4 and R5 are taken together with atoms to which they are attached and form a 4-7 membered ring; R6 and R7 are independently hydrogen, halo, C1-4 alkyl, halo-substituted C1-4 alkyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylamino or N,N-di C1-4 alkylamino; and m and n are independently 1, 2, 3 or 4. This invention also provides a pharmaceutical composition useful for the treatment of a medical condition in which prostaglandins are implicated as pathogens.

摘要翻译： 本发明提供下式的化合物或其药学上可接受的盐，其中A是部分不饱和或不饱和的五元杂环或部分不饱和或不饱和的五元碳环，其中4-（磺酰基）苯基和4-取代的苯基 在式（I）中，与环A相邻的环原子相连; R1是任选取代的芳基或杂芳基，条件是当A是吡唑时，R 1是杂芳基; R 2是C 1-4烷基，卤素取代的C 1-4烷基，C 1-4烷基氨基，C 1-4二烷基氨基或氨基; R 3，R 4和R 5独立地为氢，卤素，C 1-4烷基，卤素取代的C 1-4烷基等; 或者R 3，R 4和R 5中的两个与它们所连接的原子一起形成4-7元环; R 6和R 7独立地是氢，卤素，C 1-4烷基，卤素取代的C 1-4烷基，C 1-4烷氧基，C 1-4烷硫基，C 1-4烷基氨基或N，N-二C 1-4烷基氨基; m和n分别为1,2,3或4.本发明还提供了一种药物组合物，其用于治疗前列腺素涉及病原体的医疗状况。

公开(公告)号：US07141580B2

公开(公告)日：2006-11-28

申请号：US10771696

申请日：2004-02-04

申请人： Kazunari Nakao ,  Yoshiyuki Okumura ,  Miyako Matsumizu ,  Naomi Ueno ,  Yoshinobu Hashizume ,  Tomoki Kato ,  Akiyoshi Kawai ,  Yoriko Miyake ,  Seiji Nukui ,  Katsuhiro Shinjyo ,  Kana Taniguchi

发明人： Kazunari Nakao ,  Yoshiyuki Okumura ,  Miyako Matsumizu ,  Naomi Ueno ,  Yoshinobu Hashizume ,  Tomoki Kato ,  Akiyoshi Kawai ,  Yoriko Miyake ,  Seiji Nukui ,  Katsuhiro Shinjyo ,  Kana Taniguchi

IPC分类号： A61K31/437

CPC分类号： C07D213/75 ,  A61K31/00 ,  A61K31/4178 ,  A61K31/437 ,  A61K31/64 ,  C07D231/12 ,  C07D233/56 ,  C07D235/06 ,  C07D235/08 ,  C07D235/12 ,  C07D235/14 ,  C07D235/16 ,  C07D235/18 ,  C07D235/30 ,  C07D249/08 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D471/04 ,  C07D473/00 ,  C07D491/04 ,  Y02P20/55

摘要： This invention provides a compound of the formula (I): or the pharmaceutically acceptable salts thereof, wherein Y1, Y2, Y3 and Y4 are independently selected from N, CH, etc.; R1 is H, C1-8 alkyl, etc.; Q1 is a 5–12 membered monocyclic or bicyclic aromatic ring optionally containing up to 4 heteroatoms selected from O, N and S, etc.; A is a 5–6 membered monocyclic aromatic ring optionally containing up to 3 heteroatoms selected from O, N and S, etc.; B is C1-6 alkylene optionally substituted with an oxo group, etc.; W is NH, O, etc.; R2 is H, C1-4 alkyl, etc.; Z is a 5–12 membered monocyclic or bicyclic aromatic ring optionally containing up to 3 heteroatoms selected from O, N and S, etc.; L is halo, C1-4 alkyl, etc.; m is 0, 1 or 2; R3 and R4 are independently selected from H and C1-4 alkyl; R5 is H, C1-4 alkyl, etc.; Q2 is a 5–12 membered monocyclic or bicyclic aromatic ring or tricyclic ring optionally containing up to 3 heteroatoms selected from O, N and S, etc. These compounds are useful for the treatment of medical conditions mediated by prostaglamndin such as pain, fever or inflammation, etc. This invention also provides a pharmaceutical composition comprising the above compound.

摘要翻译： 本发明提供式（I）化合物或其药学上可接受的盐，其中Y 1，Y 2，Y 3和 Y 4独立地选自N，CH等; R 1是H，C 1-8烷基等; Q 1是5-12元单环或双环芳族环，任选地含有至多4个选自O，N和S的杂原子等; A是任选含有至多3个选自O，N和S的杂原子的5-6元单环芳环等; B是任选被氧代基取代的C 1-6亚烷基等; W是NH，O等; R 2是H，C 1-4烷基等; Z是任选地含有至多3个选自O，N和S的杂原子的5-12元单环或双环芳环等; L为卤素，C 1-4烷基等; m为0,1或2; R 3和R 4独立地选自H和C 1-4烷基; R 5是H，C 1-4烷基等; Q 2是5-12元单环或双环芳族环或三环，任选地含有至多3个选自O，N和S的杂原子等。这些化合物可用于治疗介导的医学病症 通过前列腺素如疼痛，发烧或炎症等。本发明还提供了包含上述化合物的药物组合物。

公开(公告)号：US06710054B2

公开(公告)日：2004-03-23

申请号：US09977621

申请日：2001-10-15

申请人： Kazunari Nakao ,  Yoshiyuki Okumura ,  Miyako Matsumizu ,  Naomi Ueno ,  Yoshinobu Hashizume ,  Tomoki Kato ,  Akiyoshi Kawai ,  Yoriko Miyake ,  Seiji Nukui ,  Katsuhiro Shinjyo ,  Kana Taniguchi

发明人： Kazunari Nakao ,  Yoshiyuki Okumura ,  Miyako Matsumizu ,  Naomi Ueno ,  Yoshinobu Hashizume ,  Tomoki Kato ,  Akiyoshi Kawai ,  Yoriko Miyake ,  Seiji Nukui ,  Katsuhiro Shinjyo ,  Kana Taniguchi

IPC分类号： A61K31437

CPC分类号： C07D213/75 ,  A61K31/00 ,  A61K31/4178 ,  A61K31/437 ,  A61K31/64 ,  C07D231/12 ,  C07D233/56 ,  C07D235/06 ,  C07D235/08 ,  C07D235/12 ,  C07D235/14 ,  C07D235/16 ,  C07D235/18 ,  C07D235/30 ,  C07D249/08 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D471/04 ,  C07D473/00 ,  C07D491/04 ,  Y02P20/55

摘要： This invention provides a compound of the formula (I): or the pharmaceutically acceptable salts thereof, wherein Y1, Y2, Y3 and Y4 are independently selected from N, CH, etc.; R1 is H, C1-8 alkyl, etc.; Q1 is a 5-12 membered monocyclic or bicyclic aromatic ring optionally containing up to 4 heteroatoms selected from O, N, and S, etc.; A is 5-6 membered monocyclic aromatic ring optionally containing up to 3 heteroatoms selected form O, N and S, etc.; B is C1-6 alkylene optionally substituted with an oxo group, etc.; W is NH, O, etc.; R2 is H, C1-4 alkyl, etc.; Z is a 5-12 membered monocyclic or bicyclic aromatic ring optionally containing up to 3 heteroatoms selected form O, N and S, etc.; L is halo, C1-4 alkyl, etc.; m is 0, 1 or 2; R3 and R4 are independently selected from H and C1-4 alkyl; R5 is H, C1-4 alkyl; etc.; Q2 is a 5-12 membered monocyclic or bicyclic aromatic ring or tricyclic ring optionally containing up to 3 heteroatoms selected from O, N and S, etc. These compounds are useful for the treatment of medical conditions mediated by prostaglamndin such as pain, fever or inflammation, etc. This invention also provides a pharmaceutical composition comprising the above compound.

摘要翻译： 本发明提供式（I）化合物或其药学上可接受的盐，其中Y 1，Y 2，Y 3和Y 4独立地选自N，CH等; R 1是H，C 1-8烷基等; Q 1是任选地含有至多4个选自O，N和S的杂原子的5-12元单环或双环芳环等; A是任选含有至多3个选自O，N和S的杂原子的5-6元单环芳环等; B是任选被氧代基取代的C 1-6亚烷基等; W是NH，O等; R 2是H，C 1-4烷基等; Z是任选地含有至多3个选自O，N和S等的杂原子的5-12元单环或双环芳环; L是卤素，C 1-4烷基等; m为0,1或2; R 3和R 4独立地选自H和C 1-4烷基; R 5是H，C 1-4烷基; 等等。; Q 2是任选地含有至多3个选自O，N和S的杂原子的5-12元单环或双环芳族环或三环，这些化合物可用于治疗由前列腺素介导的医学病症如疼痛 ，发热或炎症等。本发明还提供包含上述化合物的药物组合物。

公开(公告)号：US20070155732A1

公开(公告)日：2007-07-05

申请号：US11556523

申请日：2006-11-03

申请人： Kazunari Nakao ,  Yoshiyuki Okumura ,  Miyako Matsumizu ,  Naomi Ueno ,  Yoshinobu Hashizume ,  Tomoki Kato ,  Akiyoshi Kawai ,  Yoriko Miyake ,  Seiji Nukui ,  Katsuhiro Shinjyo ,  Kana Taniguchi

发明人： Kazunari Nakao ,  Yoshiyuki Okumura ,  Miyako Matsumizu ,  Naomi Ueno ,  Yoshinobu Hashizume ,  Tomoki Kato ,  Akiyoshi Kawai ,  Yoriko Miyake ,  Seiji Nukui ,  Katsuhiro Shinjyo ,  Kana Taniguchi

IPC分类号： A61K31/541 ,  A61K31/5377 ,  A61K31/496 ,  A61K31/4745 ,  C07D471/02

CPC分类号： C07D213/75 ,  A61K31/00 ,  A61K31/4178 ,  A61K31/437 ,  A61K31/64 ,  C07D231/12 ,  C07D233/56 ,  C07D235/06 ,  C07D235/08 ,  C07D235/12 ,  C07D235/14 ,  C07D235/16 ,  C07D235/18 ,  C07D235/30 ,  C07D249/08 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D471/04 ,  C07D473/00 ,  C07D491/04 ,  Y02P20/55

摘要： This invention provides a compound of the formula (I): or the pharmaceutically acceptable salts thereof, wherein Y1, Y2, Y3 and Y4 are independently selected from N, CH, etc.; R1 is H, C1-8 alkyl, etc.; Q1 is a 5-12 membered monocyclic or bicyclic aromatic ring optionally containing up to 4 heteroatoms selected from O, N and S, etc.; A is a 5-6 membered monocyclic aromatic ring optionally containing up to 3 heteroatoms selected from O, N and S, etc.; B is C1-6 alkylene optionally substituted with an oxo group, etc.; W is NH, O, etc.; R2 is H, C1-4 alkyl, etc.; Z is a 5-12 membered monocyclic or bicyclic aromatic ring optionally containing up to 3 heteroatoms selected from O, N and S, etc.; L is halo, C1-4 alkyl, etc.; m is 0, 1 or 2; R3 and R4 are independently selected from H and C1-4 alkyl ; R5 is H, C1-4 alkyl, etc.; Q2 is a 5-12 membered monocyclic or bicyclic aromatic ring or tricyclic ring optionally containing up to 3 heteroatoms selected from O, N and S, etc. These compounds are useful for the treatment of medical conditions mediated by prostaglamadin such as pain, fever or inflammation, etc. This invention also provides a pharmaceutical composition comprising the above compound.

摘要翻译： 本发明提供式（I）化合物或其药学上可接受的盐，其中Y 1，Y 2，Y 3和 Y 4独立地选自N，CH等; R 1是H，C 1-8烷基等; Q 1是5-12元单环或双环芳族环，任选地含有至多4个选自O，N和S的杂原子等; A是任选含有至多3个选自O，N和S的杂原子的5-6元单环芳环等; B是任选被氧代基取代的C 1-6亚烷基等; W是NH，O等; R 2是H，C 1-4烷基等; Z是任选地含有至多3个选自O，N和S的杂原子的5-12元单环或双环芳环等; L为卤素，C 1-4烷基等; m为0,1或2; R 3和R 4独立地选自H和C 1-4烷基; R 5是H，C 1-4烷基等; Q 2是5-12元单环或双环芳族环或三环，任选地含有至多3个选自O，N和S的杂原子等。这些化合物可用于治疗介导的医学病症 通过前列腺炎如疼痛，发热或炎症等。本发明还提供包含上述化合物的药物组合物。

公开(公告)号：US07479564B2

公开(公告)日：2009-01-20

申请号：US11556523

申请日：2006-11-03

申请人： Kazunari Nakao ,  Yoshiyuki Okumura ,  Miyako Matsumizu ,  Naomi Ueno ,  Yoshinobu Hashizume ,  Tomoki Kato ,  Akiyoshi Kawai ,  Yoriko Miyake ,  Seiji Nukui ,  Katsuhiro Shinjyo ,  Kana Taniguchi

发明人： Kazunari Nakao ,  Yoshiyuki Okumura ,  Miyako Matsumizu ,  Naomi Ueno ,  Yoshinobu Hashizume ,  Tomoki Kato ,  Akiyoshi Kawai ,  Yoriko Miyake ,  Seiji Nukui ,  Katsuhiro Shinjyo ,  Kana Taniguchi

IPC分类号： A61K31/4184 ,  C07D235/06

CPC分类号： C07D213/75 ,  A61K31/00 ,  A61K31/4178 ,  A61K31/437 ,  A61K31/64 ,  C07D231/12 ,  C07D233/56 ,  C07D235/06 ,  C07D235/08 ,  C07D235/12 ,  C07D235/14 ,  C07D235/16 ,  C07D235/18 ,  C07D235/30 ,  C07D249/08 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D413/12 ,  C07D417/04 ,  C07D417/12 ,  C07D471/04 ,  C07D473/00 ,  C07D491/04 ,  Y02P20/55

摘要： This invention provides a compound of the formula (I): or the pharmaceutically acceptable salts thereof, wherein Y1, Y2, Y3 and Y4 are independently selected from N, CH, etc.; R1 is H, C1-8 alkyl, etc.; Q1 is a 5-12 membered monocyclic or bicyclic aromatic ring optionally containing up to 4 heteroatoms selected from O, N and S, etc.; A is a 5-6 membered monocyclic aromatic ring optionally containing up to 3 heteroatoms selected from O, N and S, etc.; B is C1-6 alkylene optionally substituted with an oxo group, etc.; W is NH, O, etc.; R2 is H, C1-4 alkyl, etc.; Z is a 5-12 membered monocyclic or bicyclic aromatic ring optionally containing up to 3 heteroatoms selected from O, N and S, etc.; L is halo, C1-4 alkyl, etc.; m is 0, 1 or 2; R3 and R4 are independently selected from H and C1-4 alkyl ; R5 is H, C1-4 alkyl, etc.; Q2 is a 5-12 membered monocyclic or bicyclic aromatic ring or tricyclic ring optionally containing up to 3 heteroatoms selected from O, N and S, etc. These compounds are useful for the treatment of medical conditions mediated by prostaglamadin such as pain, fever or inflammation, etc. This invention also provides a pharmaceutical composition comprising the above compound.

摘要翻译： 本发明提供式（I）化合物或其药学上可接受的盐，其中Y 1，Y 2，Y 3和Y 4独立地选自N，CH等; R1是H，C1-8烷基等; Q1是任选地含有至多4个选自O，N和S的杂原子的5-12元单环或双环芳环; A是任选含有至多3个选自O，N和S的杂原子的5-6元单环芳环等; B是任选被氧代基取代的C 1-6亚烷基等; W是NH，O等; R2是H，C1-4烷基等; Z是任选地含有至多3个选自O，N和S的杂原子的5-12元单环或双环芳环等; L是卤素，C 1-4烷基等; m为0,1或2; R 3和R 4独立地选自H和C 1-4烷基; R5是H，C1-4烷基等; Q2是任选地含有至多3个选自O，N和S等杂原子的5-12元单环或双环芳族环或三环，这些化合物可用于治疗前列腺素介导的医学病症，例如疼痛，发热或 炎症等。本发明还提供包含上述化合物的药物组合物。

公开(公告)号：US06417202B1

公开(公告)日：2002-07-09

申请号：US09214573

申请日：1999-12-10

申请人： Akiyoshi Kawai ,  Makoto Kawai ,  Yoshinori Murata ,  Junji Takada ,  Minoru Sakakibara

发明人： Akiyoshi Kawai ,  Makoto Kawai ,  Yoshinori Murata ,  Junji Takada ,  Minoru Sakakibara

IPC分类号： A61K314427

CPC分类号： C07D401/04 ,  C07D401/14 ,  C07D409/14 ,  C07D491/04 ,  C07D491/10

摘要： The present invention provides a compound of the formula: and its pharmaceutically acceptable salts, wherein R1, R2, R3, R4, R5 and m are as defined in claim 1. The present invention also provides processes for the preparation thereof, the use thereof in treating cytokines mediated diseases and/or cell adhesion molecules (CAMs) mediated diseases and pharmaceutical compositions for use in such therapy.

摘要翻译： 本发明提供下式的化合物及其药学上可接受的盐，其中R 1，R 2，R 3，R 4，R 5和m如权利要求1中所定义。本发明还提供其制备方法， 治疗细胞因子介导的疾病和/或细胞粘附分子（CAM）介导的疾病和用于这种治疗的药物组合物。

公开(公告)号：US6048880A

公开(公告)日：2000-04-11

申请号：US3108

申请日：1998-01-06

申请人： Akiyoshi Kawai ,  Makoto Kawai

发明人： Akiyoshi Kawai ,  Makoto Kawai

IPC分类号： A61K31/44 ,  A61K31/443 ,  A61K31/4433 ,  A61K31/4436 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/5377 ,  A61P1/00 ,  A61P1/04 ,  A61P3/00 ,  A61P3/04 ,  A61P3/08 ,  A61P7/02 ,  A61P9/00 ,  A61P11/00 ,  A61P17/00 ,  A61P19/06 ,  A61P25/04 ,  A61P29/00 ,  A61P31/04 ,  A61P31/12 ,  A61P35/00 ,  A61P37/00 ,  A61P37/02 ,  A61P37/04 ,  A61P37/06 ,  A61P37/08 ,  A61P43/00 ,  C07D405/04 ,  C07D409/04 ,  C07D409/14 ,  C07D411/02 ,  C07D493/04 ,  C07D495/04 ,  C07D405/14

CPC分类号： C07D405/04 ,  C07D409/04 ,  C07D409/14 ,  C07D493/04 ,  C07D495/04

摘要： A compound of the formula: ##STR1## and its pharmaceutically effective salts, wherein R.sup.1 and R.sup.2 are independently selected from the following:(a) hydrogen, halo, R.sup.5 --, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, hydroxy-R.sup.5 --, R.sup.5 --O--R.sup.5 --, or the like; (b) Ar--, Ar--R.sup.5 --, Ar--C.sub.2-6 alkenyl, Ar--C.sub.2-6 alkynyl, Ar--O--, Ar--O--R.sup.5 -- or the like; (c) R.sup.5 --C(O)--, --NO.sub.2, cyano, NH.sub.2 --C(O)--, R.sup.5 --NH--C(O)--, (R.sup.5).sub.2 --N--C(O)--, Ar--C(O)-- or the like; and (d) R.sup.5 --C(O)--NH--, Ar--C(O)--NH-- or the like; wherein Ar is optionally substituted aryl or heteroaryl such as phenyl and pyridyl; and wherein R.sup.5 is optionally halo-substituted C.sub.1-6 alkyl; R.sup.3 is selected from the following: (e) cyano, formyl, tetrazolyl, triazolyl, imidazolyl, oxazolyl, thiazolyl, R.sup.5 --C(O)--, C.sub.2-6 alkenyl-C(O)--, C.sub.2-6 alkynyl-C(O)--, R.sup.5 --C(O)--R.sup.5 --, or the like; (f) R.sup.5 --C(O)--NH--, Ar--C(O)--NH--, or the like; (g) R.sup.5 --S--, R.sup.5 --S(O)--, R.sup.5 --NH--S(O).sub.2 --, or the like; and (h) Ar--C(O)--, Ar--R.sup.5 --C(O)--, Ar--C.sub.2-6 alkenylene-C(O)-- or the like; or two of R.sup.1, R.sup.2 and R.sup.3 together form a group of the formula --A.sup.1 --B.sup.1 --A.sup.2 -- or --A.sup.1 --B.sup.1 --A.sup.3 --B.sup.2 --A.sup.2 -- such as cyclic alkyl optionally substituted with oxo; R.sup.4 is hydrogen, halo, R.sup.5 --C(O)-- and the like; X is O, S, S(O) or S(O).sub.2 ; m is 0, 1, 2, 3 or 4. The present invention also provides processes for the preparation thereof, the use thereof in treating cytokine mediated diseases and/or cell adhesion molecule (CAM) mediated diseases and pharmaceutical compositions for use in such therapy.

摘要翻译： 下式的化合物及其药学上有效的盐，其中R 1和R 2独立地选自以下：（a）氢，卤素，R 5 - ，C 2-6烯基，C 2-6炔基，羟基-R 5 - ，R 5 - O-R 5 - 等; （b）Ar-，Ar-R5-，Ar-C2-6烯基，Ar-C2-6炔基，Ar-O-，Ar-O-R5-等; （C）R 5 -C（O） - ， - O 2，氰基，NH 2 -C（O） - ，R 5 -NH-C（O） - ，（R 5）2-NC（O） ） - 等等; 和（d）R 5 -C（O）-NH-，Ar-C（O）-NH-等; 其中Ar是任选取代的芳基或杂芳基，例如苯基和吡啶基; 并且其中R 5任选为卤素取代的C 1-6烷基; R3选自如下：（e）氰基，甲酰基，四唑基，三唑基，咪唑基，恶唑基，噻唑基，R5-C（O） - ，C2-6烯基-C（O） - ，C2-6炔基-C（ O） - ，R 5 -C（O）-R 5 - 等; （f）R5-C（O）-NH-，Ar-C（O）-NH-等; （g）R5-S-，R5-S（O） - ，R5-NH-S（O）2 - 等; 和（h）Ar-C（O） - ，Ar-R 5 -C（O） - ，Ar-C 2-6亚烯基-C（O） - 等; 或两个R 1，R 2和R 3一起形成式-A1-B1-A2-或-A1-B1-A3-B2-A2-的基团，例如任选被氧代取代的环烷基; R4是氢，卤素，R5-C（O） - 等; X是O，S，S（O）或S（O）2; 本发明还提供其制备方法，其用于治疗细胞因子介导的疾病和/或细胞粘附分子（CAM）介导的疾病的用途和用于这种治疗的药物组合物 。