JP2004527510A - ＣＧＭＰＰＤＥ阻害剤としてのピラゾロ［４，３−ｄ］ピリミジノン化合物 - Google Patents
ＣＧＭＰＰＤＥ阻害剤としてのピラゾロ［４，３−ｄ］ピリミジノン化合物 Download PDFInfo
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- JP2004527510A JP2004527510A JP2002573019A JP2002573019A JP2004527510A JP 2004527510 A JP2004527510 A JP 2004527510A JP 2002573019 A JP2002573019 A JP 2002573019A JP 2002573019 A JP2002573019 A JP 2002573019A JP 2004527510 A JP2004527510 A JP 2004527510A
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Landscapes
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0106561A GB0106561D0 (en) | 2001-03-16 | 2001-03-16 | Pharmaceutically active compounds |
| GB0106651A GB0106651D0 (en) | 2001-03-16 | 2001-03-16 | Pharmaceutically active compounds |
| PCT/IB2002/000679 WO2002074312A1 (en) | 2001-03-16 | 2002-03-07 | Pyrazolo`4,3-d.pyrimidinone compounds as cgmp pde inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2004527510A true JP2004527510A (ja) | 2004-09-09 |
| JP2004527510A5 JP2004527510A5 (https=) | 2005-08-25 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2002573019A Pending JP2004527510A (ja) | 2001-03-16 | 2002-03-07 | ＣＧＭＰＰＤＥ阻害剤としてのピラゾロ［４，３−ｄ］ピリミジノン化合物 |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP1372656B1 (https=) |
| JP (1) | JP2004527510A (https=) |
| AT (1) | ATE298238T1 (https=) |
| BR (1) | BR0208078A (https=) |
| CA (1) | CA2436911A1 (https=) |
| DE (1) | DE60204760T2 (https=) |
| ES (1) | ES2241994T3 (https=) |
| MX (1) | MXPA03006310A (https=) |
| WO (1) | WO2002074312A1 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009538930A (ja) * | 2006-05-31 | 2009-11-12 | タケダ サン ディエゴ インコーポレイテッド | グルコキナーゼ活性剤としての、インダゾールおよびイソインドール誘導体 |
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| AU2003303041B2 (en) | 2002-12-13 | 2008-07-24 | Warner-Lambert Company Llc | Alpha-2-delta ligand to treat lower urinary tract symptoms |
| BRPI0408500A (pt) * | 2003-03-17 | 2006-03-07 | Pfizer Prod Inc | tratamento do diabetes do tipo 1 com inibidores de pde5 |
| US7141669B2 (en) | 2003-04-23 | 2006-11-28 | Pfizer Inc. | Cannabiniod receptor ligands and uses thereof |
| CA2532965C (en) | 2003-07-22 | 2013-05-14 | Astex Therapeutics Limited | 3, 4-disubstituted 1h-pyrazole compounds and their use as cyclin dependent kinases (cdk) and glycogen synthase kinase-3 (gsk-3) modulators |
| CA2537916A1 (en) * | 2003-09-03 | 2005-03-31 | Neurogen Corporation | 5-aryl-pyrazolo[4,3-d]pyrimidines, pyridines, and pyrazines and related compounds |
| AR054425A1 (es) | 2005-01-21 | 2007-06-27 | Astex Therapeutics Ltd | Sales de adicion de piperidin 4-il- amida de acido 4-(2,6-dicloro-benzoilamino) 1h-pirazol-3-carboxilico. |
| US8404718B2 (en) | 2005-01-21 | 2013-03-26 | Astex Therapeutics Limited | Combinations of pyrazole kinase inhibitors |
| AU2006255028B2 (en) | 2005-06-06 | 2012-04-19 | Intra-Cellular Therapies, Inc. | Organic compounds |
| KR20090042227A (ko) | 2006-06-06 | 2009-04-29 | 인트라-셀룰라 써래피스, 인코퍼레이티드. | 유기 화합물 |
| WO2008070095A1 (en) | 2006-12-05 | 2008-06-12 | Intra-Cellular Therapies, Inc. | Novel uses |
| EP2240028B1 (en) | 2007-12-06 | 2016-07-20 | Intra-Cellular Therapies, Inc. | Pyrazolopyrimidine-4,6-dione derivatives and their use as pharmaceutical |
| EP2367430B1 (en) | 2008-12-06 | 2014-08-13 | Intra-Cellular Therapies, Inc. | Organic compounds |
| KR20110103949A (ko) | 2008-12-06 | 2011-09-21 | 인트라-셀룰라 써래피스, 인코퍼레이티드. | 유기 화합물 |
| JP5778582B2 (ja) | 2008-12-06 | 2015-09-16 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 有機化合物 |
| EP2367431B1 (en) | 2008-12-06 | 2015-08-05 | Intra-Cellular Therapies, Inc. | Organic compounds |
| BRPI0922809A2 (pt) | 2008-12-06 | 2018-05-29 | Intracellular Therapies Inc | compostos orgânicos |
| MA32942B1 (fr) | 2008-12-06 | 2012-01-02 | Intra Cellular Therapies Inc | Composes organiques |
| JP2012513464A (ja) | 2008-12-23 | 2012-06-14 | ザ トラスティーズ オブ コロンビア ユニヴァーシティ イン ザ シティ オブ ニューヨーク | ホスホジエステラーゼ阻害剤及びその使用 |
| JP2012526810A (ja) | 2009-05-13 | 2012-11-01 | イントラ−セルラー・セラピーズ・インコーポレイテッド | 有機化合物 |
| TW201206937A (en) | 2010-05-31 | 2012-02-16 | Intra Cellular Therapies Inc | Organic compounds |
| WO2011153136A1 (en) | 2010-05-31 | 2011-12-08 | Intra-Cellular Therapies, Inc. | Organic compounds |
| EP2576551A4 (en) | 2010-05-31 | 2014-04-16 | Intra Cellular Therapies Inc | ORGANIC CONNECTIONS |
| WO2011153135A1 (en) | 2010-05-31 | 2011-12-08 | Intra-Cellular Therapies, Inc. | Organic compounds |
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| KR102240326B1 (ko) | 2013-03-15 | 2021-04-13 | 인트라-셀룰라 써래피스, 인코퍼레이티드. | 유기 화합물 |
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| EP3157926B1 (en) | 2014-06-20 | 2019-05-15 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US9546175B2 (en) | 2014-08-07 | 2017-01-17 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US10285992B2 (en) | 2014-08-07 | 2019-05-14 | Intra-Cellular Therapies, Inc. | Combinations of PDE1 inhibitors and NEP inhibitors and associated methods |
| US10131671B2 (en) | 2014-08-07 | 2018-11-20 | Intra-Cellular Therapies, Inc. | Organic compounds |
| CA2961212C (en) | 2014-09-17 | 2024-02-06 | Intra-Cellular Therapies, Inc. | Compounds and methods |
| WO2016192083A1 (en) | 2015-06-04 | 2016-12-08 | Merck Sharp & Dohme Corp. | Dihydropyrazolopyrimidinone compounds as pde2 inhibitors |
| US10682354B2 (en) | 2016-03-28 | 2020-06-16 | Intra-Cellular Therapies, Inc. | Compositions and methods |
| JP7134168B6 (ja) | 2016-09-12 | 2024-02-02 | イントラ－セルラー・セラピーズ・インコーポレイテッド | 新規使用 |
| JP7401442B2 (ja) | 2018-01-31 | 2023-12-19 | イントラ－セルラー・セラピーズ・インコーポレイテッド | 新規使用 |
| EP4413980A3 (en) | 2019-09-03 | 2024-10-30 | Intra-Cellular Therapies, Inc. | Novel compounds |
| US12364695B2 (en) | 2020-06-02 | 2025-07-22 | Intra-Cellular Therapies, Inc. | Methods of treating inflammatory disease |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9114760D0 (en) * | 1991-07-09 | 1991-08-28 | Pfizer Ltd | Therapeutic agents |
| GB9311920D0 (en) * | 1993-06-09 | 1993-07-28 | Pfizer Ltd | Therapeutic agents |
-
2002
- 2002-03-07 WO PCT/IB2002/000679 patent/WO2002074312A1/en not_active Ceased
- 2002-03-07 MX MXPA03006310A patent/MXPA03006310A/es unknown
- 2002-03-07 JP JP2002573019A patent/JP2004527510A/ja active Pending
- 2002-03-07 BR BR0208078-8A patent/BR0208078A/pt not_active IP Right Cessation
- 2002-03-07 ES ES02707031T patent/ES2241994T3/es not_active Expired - Lifetime
- 2002-03-07 EP EP02707031A patent/EP1372656B1/en not_active Expired - Lifetime
- 2002-03-07 CA CA002436911A patent/CA2436911A1/en not_active Abandoned
- 2002-03-07 AT AT02707031T patent/ATE298238T1/de not_active IP Right Cessation
- 2002-03-07 DE DE60204760T patent/DE60204760T2/de not_active Expired - Fee Related
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009538930A (ja) * | 2006-05-31 | 2009-11-12 | タケダ サン ディエゴ インコーポレイテッド | グルコキナーゼ活性剤としての、インダゾールおよびイソインドール誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| MXPA03006310A (es) | 2003-09-16 |
| CA2436911A1 (en) | 2002-09-26 |
| BR0208078A (pt) | 2004-03-02 |
| DE60204760T2 (de) | 2006-05-18 |
| EP1372656A1 (en) | 2004-01-02 |
| WO2002074312A1 (en) | 2002-09-26 |
| ES2241994T3 (es) | 2005-11-01 |
| DE60204760D1 (de) | 2005-07-28 |
| EP1372656B1 (en) | 2005-06-22 |
| ATE298238T1 (de) | 2005-07-15 |
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