KR20110095881A - 유기 화합물 - Google Patents
유기 화합물 Download PDFInfo
- Publication number
- KR20110095881A KR20110095881A KR1020117013115A KR20117013115A KR20110095881A KR 20110095881 A KR20110095881 A KR 20110095881A KR 1020117013115 A KR1020117013115 A KR 1020117013115A KR 20117013115 A KR20117013115 A KR 20117013115A KR 20110095881 A KR20110095881 A KR 20110095881A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- aryl
- disease
- heteroaryl
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- OOOBGFAUGXVKGI-UHFFFAOYSA-N 5,6-dihydropyrazolo[3,4-d]pyrimidin-4-one Chemical compound O=C1NCN=C2N=NC=C12 OOOBGFAUGXVKGI-UHFFFAOYSA-N 0.000 claims abstract description 5
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Classifications
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Landscapes
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| EP2081431B1 (en) * | 2006-11-13 | 2013-01-16 | Intra-Cellular Therapies, Inc. | Organic compounds |
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| ES2588238T3 (es) * | 2007-12-06 | 2016-10-31 | Intra-Cellular Therapies, Inc. | Derivados de pirazolopirimidin-4,6-diona y su uso como producto farmacéutico |
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| US8633180B2 (en) | 2008-12-06 | 2014-01-21 | Intra-Cellular Therapies, Inc. | Organic compounds |
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| BR112014012444B1 (pt) | 2011-11-23 | 2021-12-14 | Therapeuticsmd, Inc | Composição farmacêutica compreendendo estradiol solubilizado, progesterona e um agente de solubilização, bem como usos desta para tratar um sintoma relacionado à menopausa em uma mulher |
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| US10806740B2 (en) | 2012-06-18 | 2020-10-20 | Therapeuticsmd, Inc. | Natural combination hormone replacement formulations and therapies |
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| US20150196640A1 (en) | 2012-06-18 | 2015-07-16 | Therapeuticsmd, Inc. | Progesterone formulations having a desirable pk profile |
| US10806697B2 (en) | 2012-12-21 | 2020-10-20 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| AR091507A1 (es) | 2012-06-21 | 2015-02-11 | Intra Cellular Therapies Inc | SALES DE (6aR,9aS)-5,6a,7,8,9,9a-HEXAHIDRO-5-METIL-3-(FENILAMINO)-2-((4-(6-FLUOROPIRIDIN-2-IL)FENIL)METIL)-CICLOPENT[4,5]IMIDAZO[1,2-a]PIRAZOLO[4,3-e]PIRIMIDIN-4(2H)-ONA |
| US10537581B2 (en) | 2012-12-21 | 2020-01-21 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| US10471072B2 (en) | 2012-12-21 | 2019-11-12 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| US11246875B2 (en) | 2012-12-21 | 2022-02-15 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| US11266661B2 (en) | 2012-12-21 | 2022-03-08 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| US9180091B2 (en) | 2012-12-21 | 2015-11-10 | Therapeuticsmd, Inc. | Soluble estradiol capsule for vaginal insertion |
| US10568891B2 (en) | 2012-12-21 | 2020-02-25 | Therapeuticsmd, Inc. | Vaginal inserted estradiol pharmaceutical compositions and methods |
| WO2014127331A1 (en) | 2013-02-17 | 2014-08-21 | Intra-Cellular Therapies, Inc. | Novel uses |
| EP3479825B1 (en) | 2013-03-15 | 2021-02-17 | Intra-Cellular Therapies, Inc. | Pde1 inhibitors for use in the treatment and/or prevention of cns or pns diseases or disorders |
| US9598426B2 (en) | 2013-03-15 | 2017-03-21 | Intra-Cellular Therapies, Inc. | Organic compounds |
| EP3702358A1 (en) * | 2013-06-21 | 2020-09-02 | Intra-Cellular Therapies, Inc. | Process for preparing salts of a known pde1 inhibitor |
| EP3091983B1 (en) | 2014-01-08 | 2019-10-02 | Intra-Cellular Therapies, Inc. | Pharmaceutical compositions comprising a pde-1 inhibitor and a pde-2 inhibitor |
| RU2016143081A (ru) | 2014-05-22 | 2018-06-26 | Терапьютиксмд, Инк. | Натуральные комбинированные гормонозаместительные составы и терапии |
| WO2015196186A1 (en) | 2014-06-20 | 2015-12-23 | Intra-Cellular Therapies, Inc. | Organic compounds |
| AU2015296609A1 (en) | 2014-07-29 | 2016-12-22 | Therapeuticsmd, Inc. | Transdermal cream |
| US10285992B2 (en) | 2014-08-07 | 2019-05-14 | Intra-Cellular Therapies, Inc. | Combinations of PDE1 inhibitors and NEP inhibitors and associated methods |
| JP6591530B2 (ja) | 2014-08-07 | 2019-10-16 | 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 |
| US9546175B2 (en) | 2014-08-07 | 2017-01-17 | Intra-Cellular Therapies, Inc. | Organic compounds |
| ES2857567T3 (es) | 2014-09-17 | 2021-09-29 | Intra Cellular Therapies Inc | Derivados de 7,8-dihidro-[2h]-imidazo-[1,2-a]pirazolo[4,3-e]pirimidin-4(5h)-ona como inhibidores de fosfodiesterasa 1 (PDE1) para tratar enfermedades, trastornos o lesiones del sistema nervioso central (SNC) |
| MX371158B (es) | 2014-12-06 | 2020-01-20 | Intra Cellular Therapies Inc | Compuestos inhibidores de pde2. |
| AU2015357498B2 (en) | 2014-12-06 | 2019-09-12 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US10328087B2 (en) | 2015-07-23 | 2019-06-25 | Therapeuticsmd, Inc. | Formulations for solubilizing hormones |
| JP2019510039A (ja) | 2016-03-28 | 2019-04-11 | 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． | 新規組成物および方法 |
| KR20180126582A (ko) | 2016-04-01 | 2018-11-27 | 쎄러퓨틱스엠디, 인코퍼레이티드 | 스테로이드 호르몬 약제학적 조성물 |
| WO2017173044A1 (en) | 2016-04-01 | 2017-10-05 | Therapeuticsmd Inc. | Steroid hormone compositions in medium chain oils |
| EP3970719A1 (en) | 2016-09-12 | 2022-03-23 | Intra-Cellular Therapies, Inc. | Pde1 inhibitor for use in a method of treatment or prophylaxis of inflammation and/or an inflammatory disease or disorder |
| US11839614B2 (en) | 2018-01-31 | 2023-12-12 | Intra-Cellular Therapies, Inc. | Methods for treating or mitigating cardiotoxicity characterized by inhibition of adenosine A2 signaling and/or adenosine A2 receptor expression |
| EP3802545A4 (en) | 2018-05-25 | 2022-03-16 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US11628171B2 (en) | 2019-03-13 | 2023-04-18 | Children's Medical Center Corporation | Method for treating brain or nerve injury |
| WO2020210614A1 (en) | 2019-04-12 | 2020-10-15 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US12410175B2 (en) | 2019-09-03 | 2025-09-09 | Intra-Cellular Therapies, Inc. | Compounds |
| US11633405B2 (en) | 2020-02-07 | 2023-04-25 | Therapeuticsmd, Inc. | Steroid hormone pharmaceutical formulations |
| WO2021226407A1 (en) | 2020-05-06 | 2021-11-11 | Intra-Cellular Therapies, Inc. | Free base crystals |
| US12364695B2 (en) | 2020-06-02 | 2025-07-22 | Intra-Cellular Therapies, Inc. | Methods of treating inflammatory disease |
Family Cites Families (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4666908A (en) | 1985-04-05 | 1987-05-19 | Warner-Lambert Company | 5-Substituted pyrazolo[4,3-d]pyrimidine-7-ones and methods of use |
| IL98559A0 (en) | 1990-06-21 | 1992-07-15 | Schering Corp | Polycyclic guanine derivatives |
| US5202328A (en) | 1991-03-06 | 1993-04-13 | Merck & Co., Inc. | Substituted fused pyrimidinones |
| US5294612A (en) | 1992-03-30 | 1994-03-15 | Sterling Winthrop Inc. | 6-heterocyclyl pyrazolo [3,4-d]pyrimidin-4-ones and compositions and method of use thereof |
| HUT72640A (en) | 1993-02-26 | 1996-05-28 | Schering Corp | 2-benzyl-polycyclic guanine derivatives, pharmaceutical compositions containing them and process for preparing them |
| GB9315017D0 (en) | 1993-07-20 | 1993-09-01 | Glaxo Lab Sa | Chemical compounds |
| US5824683A (en) | 1995-11-28 | 1998-10-20 | Schering Corporation | 2'- 4'-halo- 1,1'-biphenyl!-4-yl!methyl!-5'-methyl-spiro cyclopentane-1,7' (8'H)- 3H! imidazo 2,1-b!purin!-4' (5'H)-ones |
| SE9701398D0 (sv) | 1997-04-15 | 1997-04-15 | Astra Pharma Prod | Novel compounds |
| IT1291372B1 (it) | 1997-05-21 | 1999-01-07 | Schering Plough S P A | Uso di analoghi eterociclici di 1,2,4-triazolo (1,5-c) pirimidine per la preparazione di medicamenti utili per il trattamento delle malattie |
| US6013621A (en) | 1997-10-17 | 2000-01-11 | The Rockfeller University | Method of treating psychosis and/or hyperactivity |
| GB9722520D0 (en) | 1997-10-24 | 1997-12-24 | Pfizer Ltd | Compounds |
| US6133273A (en) | 1998-05-08 | 2000-10-17 | American Home Products Corporation | Pyrazolopyrimidine-2,4-dione sulfonamides |
| DE19931206A1 (de) | 1999-07-07 | 2001-01-11 | Stief Christian | Arzneimittel zur Erhöhung des cAMP-Spiegels und deren Verwendung |
| YU23802A (sh) | 1999-09-30 | 2004-09-03 | Neurogen Corporation | Određeni alkilen diamin-supstituisani pirazolo/1,5-a/-1,5- piramidini i pirazolo/1,5-a/1,3,5-triazini |
| IL149025A0 (en) | 1999-10-11 | 2002-11-10 | Pfizer | 5-(2-substituted-5-heterocyclylsulphonylpyrid-3-yl)-dihydropyrazolo [4, 3-d] pyrimidin-7-ones as phosphodiesterase inhibitors |
| TWI265925B (en) | 1999-10-11 | 2006-11-11 | Pfizer | Pyrazolo[4,3-d]pyrimidin-7-ones useful in inhibiting type 5 cyclic guanosine 3',5'-monophosphate phosphodiesterases(cGMP PDE5), process and intermediates for their preparation, their uses and composition comprising them |
| IL139073A0 (en) | 1999-10-21 | 2001-11-25 | Pfizer | Treatment of neuropathy |
| MY125533A (en) | 1999-12-06 | 2006-08-30 | Bristol Myers Squibb Co | Heterocyclic dihydropyrimidine compounds |
| AU2001255849B8 (en) | 2000-04-19 | 2006-04-27 | Lilly Icos, Llc. | PDE-V inhibitors for treatment of Parkinson's Disease |
| WO2002074312A1 (en) | 2001-03-16 | 2002-09-26 | Pfizer Limited | Pyrazolo`4,3-d.pyrimidinone compounds as cgmp pde inhibitors |
| WO2002088079A2 (en) | 2001-05-01 | 2002-11-07 | Bristol-Myers Squibb Company | Dual inhibitors of pde 7 and pde 4 |
| SE0102315D0 (sv) | 2001-06-28 | 2001-06-28 | Astrazeneca Ab | Compounds |
| US6969719B2 (en) | 2001-08-28 | 2005-11-29 | Schering Corporation | Polycyclic guanine phosphodiesterase V inhibitors |
| KR20040066788A (ko) | 2001-08-31 | 2004-07-27 | 더 락커펠러 유니버시티 | 프스포다이에스터레이즈 활성 및 뇌에서프스포다이에스터레이즈 1ｂ 매개되는 신호의 조절 |
| US6943171B2 (en) | 2001-11-09 | 2005-09-13 | Schering Corporation | Polycyclic guanine derivative phosphodiesterase V inhibitors |
| US20050153372A1 (en) | 2002-02-21 | 2005-07-14 | Paul Greengard | Compositions and method for regulation of calcium-dependent signaling in brain |
| GB0230045D0 (en) | 2002-12-23 | 2003-01-29 | Glaxo Group Ltd | Compounds |
| WO2004087906A1 (en) | 2003-03-31 | 2004-10-14 | Pfizer Products Inc. | Crystal structure of 3',5'-cyclic nucleotide phosphodiesterase 1b (pde1b) and uses thereof |
| EP1624893A2 (en) | 2003-04-01 | 2006-02-15 | Applied Research Systems ARS Holding N.V. | Inhibitors of phosphodiesterases in infertility |
| CN1878773A (zh) | 2003-09-05 | 2006-12-13 | 神经能质公司 | 作为crf1受体配位体的杂芳基稠合的吡啶,吡嗪及嘧啶 |
| CN103467471A (zh) * | 2005-06-06 | 2013-12-25 | 武田药品工业株式会社 | 有机化合物 |
| WO2007025103A2 (en) | 2005-08-23 | 2007-03-01 | Intra-Cellular Therapies, Inc. | Organic compounds for treating reduced dopamine receptor signalling activity |
| US9255099B2 (en) | 2006-06-06 | 2016-02-09 | Intra-Cellular Therapies, Inc. | Pyrazolo[3,4-D]pyrimidine-4,6(5H,7H)-diones as phosphodiesterase 1 inhibitors |
| US20070286890A1 (en) * | 2006-06-07 | 2007-12-13 | John Garnett Walt | Eyelash applicator and method |
| EP2081431B1 (en) | 2006-11-13 | 2013-01-16 | Intra-Cellular Therapies, Inc. | Organic compounds |
| WO2008070095A1 (en) | 2006-12-05 | 2008-06-12 | Intra-Cellular Therapies, Inc. | Novel uses |
| ES2588238T3 (es) | 2007-12-06 | 2016-10-31 | Intra-Cellular Therapies, Inc. | Derivados de pirazolopirimidin-4,6-diona y su uso como producto farmacéutico |
| CN104370920A (zh) | 2007-12-06 | 2015-02-25 | 武田药品工业株式会社 | 有机化合物 |
| US8927556B2 (en) | 2008-12-06 | 2015-01-06 | Intra-Cellular Therapies, Inc. | 1H-pyrrolo[3,4-D]pyrimidin-2(6H)-one compounds |
| US8633180B2 (en) | 2008-12-06 | 2014-01-21 | Intra-Cellular Therapies, Inc. | Organic compounds |
| JP5710493B2 (ja) | 2008-12-06 | 2015-04-30 | 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 |
| ES2638912T3 (es) * | 2008-12-06 | 2017-10-24 | Intra-Cellular Therapies, Inc. | Compuestos orgánicos |
| EP2358204B1 (en) | 2008-12-06 | 2015-08-05 | Intra-Cellular Therapies, Inc. | 4,5,7,8-tetrahydro-4-oxo-2H-imidazo[1,2-a]pyrrolo[3,4-e]pyrimidine compounds as PDE1 inhibitors. |
| JP5813511B2 (ja) | 2008-12-06 | 2015-11-17 | 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 |
| JP2012518685A (ja) | 2009-02-25 | 2012-08-16 | イントラ−セルラー・セラピーズ・インコーポレイテッド | 眼障害のためのｐｄｅ１阻害剤 |
| 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 |
| US8858911B2 (en) | 2009-10-08 | 2014-10-14 | Intra-Cellular Therapies, Inc. | Phosphodiesterase 1-targeting tracers and methods |
| EP2576551A4 (en) | 2010-05-31 | 2014-04-16 | Intra Cellular Therapies Inc | ORGANIC CONNECTIONS |
| EP2575817A4 (en) | 2010-05-31 | 2014-01-08 | Intra Cellular Therapies Inc | ORGANIC CONNECTIONS |
| TW201206937A (en) | 2010-05-31 | 2012-02-16 | Intra Cellular Therapies Inc | Organic compounds |
| WO2011153135A1 (en) | 2010-05-31 | 2011-12-08 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US10561656B2 (en) * | 2011-06-10 | 2020-02-18 | Intra-Cellular Therapies, Inc. | Organic compounds |
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| CN102231953A (zh) | 2011-11-02 |
| US20160083390A1 (en) | 2016-03-24 |
| ES2638912T3 (es) | 2017-10-24 |
| CL2011001263A1 (es) | 2011-11-18 |
| US20110245214A1 (en) | 2011-10-06 |
| CR20110312A (es) | 2011-10-28 |
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| BRPI0922348A2 (pt) | 2015-08-11 |
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| EA201170770A1 (ru) | 2012-02-28 |
| ZA201103631B (en) | 2013-05-29 |
| CA2740391A1 (en) | 2010-06-10 |
| DOP2011000173A (es) | 2011-10-31 |
| PE20110922A1 (es) | 2012-01-22 |
| US8536159B2 (en) | 2013-09-17 |
| EP2367429A4 (en) | 2012-06-06 |
| SG171775A1 (en) | 2011-07-28 |
| AU2009322901A1 (en) | 2010-06-10 |
| US20140005155A1 (en) | 2014-01-02 |
| WO2010065149A1 (en) | 2010-06-10 |
| EP2367429B1 (en) | 2017-06-07 |
| MA32938B1 (fr) | 2012-01-02 |
| EP2367429A1 (en) | 2011-09-28 |
| ECSP11011184A (es) | 2011-10-31 |
| MX2011005933A (es) | 2011-12-16 |
| JP5778582B2 (ja) | 2015-09-16 |
| TN2011000246A1 (en) | 2012-12-17 |
| IL213314A0 (en) | 2011-07-31 |
| JP2012510993A (ja) | 2012-05-17 |
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