NO330862B1 - Tizolidinon-vinylkondenserte benzenderivater, fremgangsmate for fremstilling derav og anvendelse derav for fremstilling av medikamenter og farmasoytisk sammensetning innholdende samme - Google Patents
Tizolidinon-vinylkondenserte benzenderivater, fremgangsmate for fremstilling derav og anvendelse derav for fremstilling av medikamenter og farmasoytisk sammensetning innholdende samme Download PDFInfo
- Publication number
- NO330862B1 NO330862B1 NO20050654A NO20050654A NO330862B1 NO 330862 B1 NO330862 B1 NO 330862B1 NO 20050654 A NO20050654 A NO 20050654A NO 20050654 A NO20050654 A NO 20050654A NO 330862 B1 NO330862 B1 NO 330862B1
- Authority
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- Norway
- Prior art keywords
- dione
- thiazolidin
- thiazolidine
- ylmethylene
- methylene
- Prior art date
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- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title claims abstract description 36
- 229920002554 vinyl polymer Polymers 0.000 title claims abstract description 7
- 238000000034 method Methods 0.000 title claims description 73
- 238000002360 preparation method Methods 0.000 title claims description 47
- 239000003814 drug Substances 0.000 title claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 12
- 229940079593 drug Drugs 0.000 title claims description 8
- 238000011282 treatment Methods 0.000 claims abstract description 23
- 238000011321 prophylaxis Methods 0.000 claims abstract description 15
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- 231100000516 lung damage Toxicity 0.000 claims abstract description 9
- 150000001875 compounds Chemical class 0.000 claims description 153
- -1 dihydrobenzodioxin Chemical group 0.000 claims description 124
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims description 67
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 claims description 35
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 claims description 35
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 26
- 230000000694 effects Effects 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical group 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 13
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- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 9
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- 239000003085 diluting agent Substances 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 7
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- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
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- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical group C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims description 4
- VRUPOBLKXUKQDP-UHFFFAOYSA-N 5-[(2-fluoro-1-benzofuran-6-yl)methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2OC(F)=CC2=CC=C1C=C1SC(=O)NC1=O VRUPOBLKXUKQDP-UHFFFAOYSA-N 0.000 claims description 4
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 4
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- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
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- 125000002757 morpholinyl group Chemical group 0.000 claims description 4
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- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims description 4
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
- 229910052727 yttrium Inorganic materials 0.000 claims description 4
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 3
- UOEYYZINJAEXJM-UHFFFAOYSA-N 3-[5-[(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-1-benzofuran-3-yl]-n-ethyl-n-(2-hydroxyethyl)prop-2-enamide Chemical compound C1=C2C(C=CC(=O)N(CCO)CC)=COC2=CC=C1C=C1SC(=O)NC1=O UOEYYZINJAEXJM-UHFFFAOYSA-N 0.000 claims description 3
- KTZAPRYDZSOKAY-UHFFFAOYSA-N 5-[(4-methoxyquinazolin-6-yl)methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=C2C(OC)=NC=NC2=CC=C1C=C1SC(=O)NC1=O KTZAPRYDZSOKAY-UHFFFAOYSA-N 0.000 claims description 3
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- XJLSEXAGTJCILF-UHFFFAOYSA-N nipecotic acid Chemical compound OC(=O)C1CCCNC1 XJLSEXAGTJCILF-UHFFFAOYSA-N 0.000 claims description 3
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- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 3
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Classifications
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EP02100798 | 2002-07-10 | ||
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PCT/EP2003/050302 WO2004007491A1 (en) | 2002-07-10 | 2003-07-10 | Azolidinone-vinyl fused-benzene derivatives |
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EP (1) | EP1549644A1 (de) |
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US6667300B2 (en) | 2000-04-25 | 2003-12-23 | Icos Corporation | Inhibitors of human phosphatidylinositol 3-kinase delta |
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EP1581529A1 (de) * | 2002-12-20 | 2005-10-05 | Warner-Lambert Company | Benzoxazine und derivate davon alsinhibitoren von pi3ks |
WO2005007141A2 (en) * | 2003-07-11 | 2005-01-27 | Proteologics, Inc. | Ubiquitin ligase inhibitors and methods related thereto |
DE602004022170D1 (de) * | 2003-07-28 | 2009-09-03 | Merck Serono Sa Coinsins | 2-imino-4-(thio)oxo-5-polycyclovinylazoline zur verwendung als pi3-kinase-inhibtoren |
RU2379299C2 (ru) | 2003-11-21 | 2010-01-20 | Актелион Фармасьютиклз Лтд | Производные 5-(бенз-(z)-илиден)тиазолидин-4-она и их применение в качестве иммуносупрессорных агентов |
USRE43833E1 (en) | 2003-11-21 | 2012-11-27 | Actelion Pharmaceuticals Ltd. | Thiazolidin-4-one derivatives |
US20070249599A1 (en) * | 2004-02-25 | 2007-10-25 | Duffy Kevin J | Novel Chemical Compounds |
WO2005100331A2 (en) * | 2004-04-14 | 2005-10-27 | Ranbaxy Laboratories Limited | Antidiabetic agents |
WO2005113554A2 (en) | 2004-05-13 | 2005-12-01 | Icos Corporation | Method of preparing 3-phenyl-2-[9h-purin-6-ylamino)-methyl]-3h-quinazolin-4-one and substituted and related compounds |
US20060019975A1 (en) * | 2004-07-23 | 2006-01-26 | Pfizer Inc | Novel piperidyl derivatives of quinazoline and isoquinoline |
MX2007002604A (es) * | 2004-09-03 | 2007-04-25 | Applied Research Systems | Azolidinonas de piridina metileno y uso de las mismas. |
US7253285B2 (en) * | 2004-09-17 | 2007-08-07 | Hoffmann-La Roche Inc. | Thiazolinone 4-monosubstituted quinolines |
US7241893B2 (en) * | 2004-09-17 | 2007-07-10 | Hoffman-La Roche Inc. | Thiazolinone 2-substituted quinolines |
CA2579279C (en) | 2004-10-07 | 2013-10-01 | Boehringer Ingelheim International Gmbh | Tricyclic thiazole derivatives as pi3 kinases |
BRPI0517416A (pt) * | 2004-10-12 | 2008-10-07 | Serono Lab | inibidores de pi3 quinase gama para o tratamento de anemia |
BRPI0518164A (pt) * | 2004-10-14 | 2008-11-04 | Hoffmann La Roche | quinazolinilmetilenotiazolinonas como inibidores de cdk1 |
ES2301066T3 (es) * | 2004-10-14 | 2008-06-16 | F. Hoffmann-La Roche Ag | Nuevas azaindol-tiazolinonas como agentes anti-cancerosos. |
AU2005293835A1 (en) * | 2004-10-14 | 2006-04-20 | F. Hoffmann-La Roche Ag | 1,5-Naphthyridine azolidinones having CDK1 antiproliferative activity |
US7304074B2 (en) * | 2005-04-05 | 2007-12-04 | Hoffmann-La Roche Inc. | Substituted 1,5-naphthyridine azolinones |
JP5226513B2 (ja) | 2005-08-26 | 2013-07-03 | メルク セローノ ソシエテ アノニム | ピラジン誘導体及びその使用 |
CA2618489A1 (en) * | 2005-09-07 | 2007-03-15 | Laboratoires Serono S.A. | Pi3k inhibitors for the treatment of endometriosis |
CN101300047A (zh) * | 2005-09-07 | 2008-11-05 | 雪兰诺实验室有限公司 | Pi3k抑制剂用于子宫内膜异位症的治疗 |
KR100814109B1 (ko) | 2006-01-09 | 2008-03-14 | 한국생명공학연구원 | 로다닌 유도체, 이의 제조방법 및 이를 유효성분으로함유하는 약학적 조성물 |
US7517995B2 (en) | 2006-04-06 | 2009-04-14 | Boehringer Ingelheim International Gmbh | Thiazolyl-dihydro-cyclopentapyrazole |
US7691868B2 (en) | 2006-04-06 | 2010-04-06 | Boehringer Ingelheim International Gmbh | Thiazolyl-dihydro-quinazoline |
AR060391A1 (es) * | 2006-04-11 | 2008-06-11 | Smithkline Beecham Corp | Compuestos de quinolin tiazolidinadiona, sustituidos con heterociclos, composiciones farmaceuticas que los contienen y usos para preparar medicamentos que inhiben la actividad de pi3 quinasas. |
CA2650290C (en) | 2006-04-26 | 2015-11-17 | Genentech, Inc. | Pharmaceutical compounds |
WO2008014219A2 (en) * | 2006-07-24 | 2008-01-31 | Smithkline Beecham Corporation | Thiozolidinedione derivatives as p13 kinase inhibitors |
CN101541772B (zh) | 2006-11-23 | 2013-04-17 | 埃科特莱茵药品有限公司 | 一种制备2-亚氨基-四氢噻唑-4-酮衍生物的新方法 |
US8912340B2 (en) | 2006-11-23 | 2014-12-16 | Actelion Pharmaceuticals Ltd. | Process for the preparation of 2-imino-thiazolidin-4-one derivatives |
KR101460816B1 (ko) | 2006-12-07 | 2014-11-12 | 에프. 호프만-라 로슈 아게 | 포스포이노시타이드 3-키나제 억제제 화합물 및 그의 사용 방법 |
JPWO2008093737A1 (ja) | 2007-01-31 | 2010-05-20 | 大日本住友製薬株式会社 | アミド誘導体 |
WO2008101979A1 (en) | 2007-02-22 | 2008-08-28 | Merck Serono S.A. | Quinoxaline compounds and use thereof |
US20080255115A1 (en) * | 2007-04-11 | 2008-10-16 | Michael Gerard Darcy | Thiazolidinedione derivatives as pi3 kinase inhibitors |
ITFI20070097A1 (it) * | 2007-04-20 | 2008-10-21 | Antonio Guarna | Molecole eterocicliche contenenti il nucleo della morfolina loro preparazione ed uso. |
TW200902008A (en) * | 2007-05-10 | 2009-01-16 | Smithkline Beecham Corp | Quinoxaline derivatives as PI3 kinase inhibitors |
PE20090717A1 (es) | 2007-05-18 | 2009-07-18 | Smithkline Beecham Corp | Derivados de quinolina como inhibidores de la pi3 quinasa |
WO2008148023A2 (en) * | 2007-05-23 | 2008-12-04 | Medical College Of Georgia Research Institute, Inc. | Compositions and methods for treating neurological disorders |
US7928140B2 (en) | 2007-08-02 | 2011-04-19 | Amgen Inc. | Benzothiazole PI3 kinase modulators for cancer treatment |
ES2399774T3 (es) | 2007-09-24 | 2013-04-03 | Genentech, Inc. | Compuestos de tiazolopirimidina inhibidores de PI3K y métodos de uso |
US7820665B2 (en) | 2007-12-19 | 2010-10-26 | Amgen Inc. | Imidazopyridazine inhibitors of PI3 kinase for cancer treatment |
JP5421925B2 (ja) | 2007-12-19 | 2014-02-19 | ジェネンテック, インコーポレイテッド | 5−アニリノイミダゾピリジン及び使用の方法 |
KR20100099185A (ko) | 2007-12-21 | 2010-09-10 | 제넨테크, 인크. | 아자인돌리진 및 이용 방법 |
UY31952A (es) | 2008-07-02 | 2010-01-29 | Astrazeneca Ab | 5-metilideno-1,3-tiazolidina-2,4-dionas sustituidas como inhibidores de quinasa pim |
US20100202963A1 (en) | 2008-11-13 | 2010-08-12 | Gallatin W Michael | Therapies for hematologic malignancies |
US9492449B2 (en) | 2008-11-13 | 2016-11-15 | Gilead Calistoga Llc | Therapies for hematologic malignancies |
RU2683325C2 (ru) | 2009-02-05 | 2019-03-28 | Иммьюноджен, Инк. | Новые производные бензодиазепина |
JP5667086B2 (ja) | 2009-02-12 | 2015-02-12 | メルク セローノ ソシエテ アノニム | 2−モルホリノ−ピリド[3,2−d]ピリミジン |
KR101781654B1 (ko) | 2009-03-12 | 2017-09-25 | 제넨테크, 인크. | 조혈 악성종양의 치료를 위한 포스포이노시티드 3-키나제 억제제 화합물 및 화학요법제의 조합물 |
NZ595307A (en) | 2009-03-24 | 2013-11-29 | Gilead Calistoga Llc | Atropisomers of 2-purinyl-3-tolyl-quinazolinone derivatives and methods of use |
US8546409B2 (en) | 2009-04-20 | 2013-10-01 | Gilead Calistoga Llc | Methods of treatment for solid tumors |
WO2010146059A2 (en) | 2009-06-16 | 2010-12-23 | F. Hoffmann-La Roche Ag | Biomarkers for igf-1r inhibitor therapy |
CN102647987A (zh) | 2009-07-21 | 2012-08-22 | 吉里德卡利斯托加公司 | 使用pi3k抑制剂治疗肝脏障碍 |
NZ599090A (en) | 2009-09-28 | 2014-02-28 | Hoffmann La Roche | Benzoxepin pi3k inhibitor compounds and methods of use |
JPWO2011048936A1 (ja) | 2009-10-19 | 2013-03-07 | 大正製薬株式会社 | アミノチアゾール誘導体 |
WO2011049625A1 (en) | 2009-10-20 | 2011-04-28 | Mansour Samadpour | Method for aflatoxin screening of products |
SG10201500895XA (en) | 2009-11-05 | 2015-04-29 | Rhizen Pharmaceuticals Sa | Chromen-4-one Derivatives As Kinase Modulators |
ES2607952T3 (es) | 2009-11-13 | 2017-04-04 | Merck Serono S.A. | Derivados tricíclicos de Pirazol Amina |
PL2509602T3 (pl) | 2009-12-04 | 2017-08-31 | Senhwa Biosciences, Inc. | Pirazolopirymidyny i podobne heterocykle jako inhibitory ck2 |
CA2789629A1 (en) | 2010-02-10 | 2011-08-18 | Immunogen, Inc. | Cd20 antibodies and uses thereof |
WO2011149841A1 (en) | 2010-05-25 | 2011-12-01 | Janssen Pharmaceutica Nv | SUBSTITUTED THIAZOLIDINEDIONE INDAZOLES, INDOLES AND BENZOTRIAZOLES AS ESTROGEN-RELATED RECEPTOR-α MODULATORS |
CN103108873A (zh) * | 2010-07-16 | 2013-05-15 | 皮拉马尔企业有限公司 | 作为激酶抑制剂的取代的咪唑并喹啉衍生物 |
US8609672B2 (en) | 2010-08-27 | 2013-12-17 | University Of The Pacific | Piperazinylpyrimidine analogues as protein kinase inhibitors |
CN107335061B (zh) | 2011-02-15 | 2021-09-07 | 伊缪诺金公司 | 细胞毒性苯并二氮杂䓬衍生物 |
MY168757A (en) | 2011-05-04 | 2018-12-04 | Rhizen Pharmaceuticals S A | Novel compounds as modulators of protein kinases |
CN102432544B (zh) * | 2011-11-17 | 2014-05-21 | 天津医科大学 | 5-取代苄亚甲基咪唑烷-2,4-二酮类衍生物及其应用 |
EP2834241B1 (de) | 2012-03-05 | 2020-11-18 | Gilead Calistoga LLC | Polymorphe formen von (s)-2-(1-(9h-purin-6-ylamino) propyl)-5-fluor-3-phenylchinazolin-4(3h)-one |
US8940742B2 (en) * | 2012-04-10 | 2015-01-27 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
KR101909801B1 (ko) | 2012-06-08 | 2018-10-18 | 에프. 호프만-라 로슈 아게 | 암의 치료를 위한 포스포이노시타이드 3 키나제 억제제 화합물 및 화학치료제의 돌연변이체 선택성 및 조합물 |
CA2876995C (en) | 2012-07-04 | 2020-10-06 | Rhizen Pharmaceuticals Sa | Novel selective pi3k delta inhibitors |
WO2014021337A1 (ja) * | 2012-07-30 | 2014-02-06 | 国立大学法人京都大学 | 精神神経疾患又は悪性腫瘍に関する化合物及び医薬組成物 |
PT2885266T (pt) | 2012-08-17 | 2020-05-29 | Actelion Pharmaceuticals Ltd | Processo para a preparação de (2z,5z)-5-(3-cloro-4-((r)-2,3-di-hidropropoxi)benzilideno)-2-(propilimino)-3-(o-tolil)tiazolidin-4-ona e intermediário utilizado no referido processo |
EP2887965A1 (de) | 2012-08-22 | 2015-07-01 | ImmunoGen, Inc. | Zytotoxische benzodiazepin-derivate |
US9901647B2 (en) | 2013-02-28 | 2018-02-27 | Immunogen, Inc. | Conjugates comprising cell-binding agents and cytotoxic agents |
JP6494533B2 (ja) | 2013-02-28 | 2019-04-03 | イミュノジェン・インコーポレーテッド | 細胞結合剤及び細胞毒性剤としてのマイタンシノイドを含む複合体 |
JP6378918B2 (ja) * | 2013-04-03 | 2018-08-22 | 株式会社ヤクルト本社 | チアゾリジン誘導体又はその塩を有効成分とするPim阻害剤 |
WO2014194030A2 (en) | 2013-05-31 | 2014-12-04 | Immunogen, Inc. | Conjugates comprising cell-binding agents and cytotoxic agents |
CN103396376B (zh) * | 2013-07-31 | 2016-08-10 | 杨文茂 | 一种抗菌抗癌活性化合物 |
SG10201902074UA (en) | 2013-10-04 | 2019-04-29 | Infinity Pharmaceuticals Inc | Heterocyclic compounds and uses thereof |
ES2752552T3 (es) | 2013-12-20 | 2020-04-06 | Gilead Calistoga Llc | Métodos de proceso para inhibidores de fosfatidilinositol 3-quinasa |
WO2015095605A1 (en) | 2013-12-20 | 2015-06-25 | Gilead Calistoga Llc | Polymorphic forms of a hydrochloride salt of (s) -2-(9h-purin-6-ylamino) propyl) -5-fluoro-3-phenylquinazolin-4 (3h) -one |
CA2943075C (en) | 2014-03-19 | 2023-02-28 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds for use in the treatment of pi3k-gamma mediated disorders |
WO2015161016A1 (en) * | 2014-04-17 | 2015-10-22 | Merck Sharp & Dohme Corp. | Bicyclic cgrp receptor antagonists |
SG11201609877XA (en) | 2014-06-13 | 2016-12-29 | Gilead Sciences Inc | Phosphatidylinositol 3-kinase inhibitors |
CN104230915B (zh) * | 2014-08-29 | 2016-08-17 | 南京大学 | 含噻唑烷二酮的苯基哌嗪衍生物及其制备方法与用途 |
WO2016054491A1 (en) | 2014-10-03 | 2016-04-07 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
AR104068A1 (es) | 2015-03-26 | 2017-06-21 | Hoffmann La Roche | Combinaciones de un compuesto inhibidor de fosfoinosítido 3-cinasa y un compuesto inhibidor de cdk4/6 para el tratamiento del cáncer |
US10160761B2 (en) | 2015-09-14 | 2018-12-25 | Infinity Pharmaceuticals, Inc. | Solid forms of isoquinolinones, and process of making, composition comprising, and methods of using the same |
US10759806B2 (en) | 2016-03-17 | 2020-09-01 | Infinity Pharmaceuticals, Inc. | Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as PI3K kinase inhibitors |
WO2017214269A1 (en) | 2016-06-08 | 2017-12-14 | Infinity Pharmaceuticals, Inc. | Heterocyclic compounds and uses thereof |
AU2017321973A1 (en) | 2016-09-02 | 2019-03-07 | Dana-Farber Cancer Institute, Inc. | Composition and methods of treating B cell disorders |
CA3116141C (en) | 2018-12-06 | 2023-09-05 | Daiichi Sankyo Company, Limited | Cycloalkane-1,3-diamine derivative |
CN110330493B (zh) * | 2019-08-23 | 2020-07-24 | 广州麓鹏制药有限公司 | Pim激酶抑制剂、其制备方法、应用、药物及药物组合 |
WO2021133037A1 (ko) * | 2019-12-26 | 2021-07-01 | 연세대학교 산학협력단 | 피롤리딘 유도체 및 이를 포함하는 베타-아밀로이드 또는 타우 단백질 관련 질병의 예방 또는 치료용 약학 조성물 |
CN112266328B (zh) * | 2020-12-09 | 2023-11-03 | 郑州萃智医药科技有限公司 | 3-氟-4-硝基苯甲醛的合成路线及制备方法 |
CN115703771A (zh) * | 2021-08-06 | 2023-02-17 | 纳莹(上海)生物科技有限公司 | 一种荧光染料及其制备方法和用途 |
EP4173674A1 (de) * | 2021-10-26 | 2023-05-03 | Perha Pharmaceuticals | Imidazolonderivate als inhibitoren von proteinkinasen, insbesondere dyrk1a, clk1 und/oder clk4 |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5536429A (en) * | 1978-09-06 | 1980-03-14 | Hamari Yakuhin Kogyo Kk | Preparation of (+)-2-(6-methoxy-2-naphthyl)propionic acid and its intermediate |
JPS5545648A (en) * | 1978-09-29 | 1980-03-31 | Teikoku Hormone Mfg Co Ltd | 2-formyldibenzazepin derivative and its preparation |
JPS6168472A (ja) * | 1984-09-12 | 1986-04-08 | Mitsui Toatsu Chem Inc | 不飽和ヒダントインの製造方法 |
WO1986007056A1 (en) * | 1985-05-21 | 1986-12-04 | Pfizer Inc. | Hypoglycemic thiazolidinediones |
JPS63230689A (ja) | 1987-03-18 | 1988-09-27 | Tanabe Seiyaku Co Ltd | ベンゾオキサジン誘導体 |
IL106877A (en) * | 1992-09-10 | 1998-03-10 | Lilly Co Eli | Rodinin derivatives for use as drugs for the treatment of Alzheimer's disease |
WO1999059586A1 (en) * | 1998-05-19 | 1999-11-25 | Regents Of The University Of California | Thiazolidine and oxazolidine derivatives for the treatment of acute myocardial infarction and inhibition of cardiomyocyte apoptosis |
JP2000095770A (ja) * | 1998-07-22 | 2000-04-04 | Toa Eiyo Ltd | N置換チアゾリジン誘導体及びそれを含有する医薬 |
AU6330999A (en) * | 1998-09-30 | 2000-04-17 | Roche Diagnostics Gmbh | Rhodanine derivatives for the treatment and prevention of metabolic bone disorders |
US6452014B1 (en) | 2000-12-22 | 2002-09-17 | Geron Corporation | Telomerase inhibitors and methods of their use |
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MXPA05000453A (es) | 2005-03-23 |
US7846925B2 (en) | 2010-12-07 |
IL166202A0 (en) | 2006-01-15 |
JP2005538188A (ja) | 2005-12-15 |
RS115904A (en) | 2006-12-15 |
BR0312650A (pt) | 2005-05-03 |
CN1681811B (zh) | 2010-05-26 |
EA200500143A1 (ru) | 2005-08-25 |
JP4782564B2 (ja) | 2011-09-28 |
CN1681811A (zh) | 2005-10-12 |
AU2003255528A1 (en) | 2004-02-02 |
EP1549644A1 (de) | 2005-07-06 |
CA2493843C (en) | 2012-04-17 |
CA2493843A1 (en) | 2004-01-22 |
EA011807B1 (ru) | 2009-06-30 |
PL374718A1 (en) | 2005-10-31 |
NO20050654L (no) | 2005-03-15 |
IL166202A (en) | 2012-02-29 |
US20060122176A1 (en) | 2006-06-08 |
US20090306069A1 (en) | 2009-12-10 |
WO2004007491A1 (en) | 2004-01-22 |
HK1077068A1 (en) | 2006-02-03 |
AU2003255528B2 (en) | 2009-07-16 |
HRP20041207A2 (en) | 2005-04-30 |
BR0312752A (pt) | 2005-04-26 |
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