CN1111127A - 用渥曼青霉素及其类似物抑制磷脂酰肌醇3-激酶 - Google Patents
用渥曼青霉素及其类似物抑制磷脂酰肌醇3-激酶 Download PDFInfo
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- CN1111127A CN1111127A CN94108398A CN94108398A CN1111127A CN 1111127 A CN1111127 A CN 1111127A CN 94108398 A CN94108398 A CN 94108398A CN 94108398 A CN94108398 A CN 94108398A CN 1111127 A CN1111127 A CN 1111127A
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
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- A61K31/365—Lactones
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Furan Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
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| US08/094,279 US5378725A (en) | 1993-07-19 | 1993-07-19 | Inhibition of phosphatidylinositol 3-kinase with wortmannin and analogs thereof |
| US094,279 | 1993-07-19 |
Publications (1)
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|---|---|
| CN1111127A true CN1111127A (zh) | 1995-11-08 |
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| CN94108398A Pending CN1111127A (zh) | 1993-07-19 | 1994-07-18 | 用渥曼青霉素及其类似物抑制磷脂酰肌醇3-激酶 |
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| EP (1) | EP0635268A1 (enExample) |
| JP (1) | JPH0753370A (enExample) |
| KR (1) | KR950002755A (enExample) |
| CN (1) | CN1111127A (enExample) |
| AU (1) | AU678831B2 (enExample) |
| CA (1) | CA2128046A1 (enExample) |
| CZ (1) | CZ283806B6 (enExample) |
| HU (1) | HUT67667A (enExample) |
| IL (1) | IL110325A0 (enExample) |
| NO (1) | NO942641L (enExample) |
| PH (1) | PH30794A (enExample) |
| PL (1) | PL304317A1 (enExample) |
| RU (1) | RU94026082A (enExample) |
| TW (1) | TW287102B (enExample) |
| ZA (1) | ZA945103B (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100369632C (zh) * | 2004-10-14 | 2008-02-20 | 孔庆忠 | 抗癌药物组合物 |
| CN1875959B (zh) * | 2004-10-14 | 2010-05-12 | 孔庆忠 | 一种抗癌药物组合物 |
| CN104774239A (zh) * | 2015-03-13 | 2015-07-15 | 暨南大学 | 多节孢绿胶霉素类化合物及其用途 |
Families Citing this family (66)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5468773A (en) * | 1993-08-25 | 1995-11-21 | Eli Lilly And Company | Methods for inhibiting bone loss and cartilage degradation using wortmannin and its analogs |
| US5504103A (en) * | 1993-08-25 | 1996-04-02 | Eli Lilly And Company | Inhibition of phosphatidylinositol 3-kinase with 17 β-hydroxywortmannin and analogs thereof |
| US7863429B2 (en) * | 1995-12-21 | 2011-01-04 | Qlt Inc. | Treatment of inflammatory diseases including psoriasis |
| US5910417A (en) * | 1996-05-31 | 1999-06-08 | National Jewish Center For Immunology And Respiratory Medicine | Regulation of cytokine production in a hematopoietic cell |
| US7670767B1 (en) | 1997-01-16 | 2010-03-02 | The Regents Of The University Of California | Genetic alterations associated with cancer |
| EP1072273B1 (en) * | 1998-03-24 | 2006-07-26 | Chugai Seiyaku Kabushiki Kaisha | Vascularization inhibitors |
| US6413773B1 (en) * | 1998-06-01 | 2002-07-02 | The Regents Of The University Of California | Phosphatidylinositol 3-kinase inhibitors as stimulators of endocrine differentiation |
| BR9914465A (pt) * | 1998-09-29 | 2001-10-09 | Gamida Cell Ltd | Métodos para controlar a proliferação e a diferenciação de células-tronco e células progenitoras e uma composição farmacêutica para induzir a diferenciação em uma população de células |
| ATE538794T1 (de) * | 1999-01-13 | 2012-01-15 | Bayer Healthcare Llc | Gamma carboxyarylsubstituierte diphenylharnstoffverbindungen als p38 kinasehemmer |
| US8124630B2 (en) | 1999-01-13 | 2012-02-28 | Bayer Healthcare Llc | ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors |
| WO2001024826A2 (en) * | 1999-10-06 | 2001-04-12 | The Brigham And Women's Hospital, Inc. | Inrease of enos activity through activation of the pi3-kinase/akt pathway by estrogens |
| US6667300B2 (en) | 2000-04-25 | 2003-12-23 | Icos Corporation | Inhibitors of human phosphatidylinositol 3-kinase delta |
| US6777439B2 (en) * | 2000-05-30 | 2004-08-17 | Advanced Research & Technology Institute, Inc. | Compositions and methods for identifying agents which modulate PTEN function and PI-3 kinase pathways |
| US7235523B2 (en) * | 2001-04-13 | 2007-06-26 | Children's Hospital Medical Center | Methods for the treatment of hepatic disorders |
| US7371763B2 (en) * | 2001-04-20 | 2008-05-13 | Bayer Pharmaceuticals Corporation | Inhibition of raf kinase using quinolyl, isoquinolyl or pyridyl ureas |
| GB0119865D0 (en) | 2001-08-14 | 2001-10-10 | Cancer Res Campaign Tech | DNA-PK inhibitors |
| GB0119863D0 (en) | 2001-08-14 | 2001-10-10 | Cancer Res Campaign Tech | DNA-PK inhibitors |
| US6703414B2 (en) * | 2001-09-14 | 2004-03-09 | Arizona Board Of Regents On Behalf Of The University Of Arizona | Device and method for treating restenosis |
| US20080108672A1 (en) * | 2002-01-11 | 2008-05-08 | Bernd Riedl | Omega-Carboxyaryl Substituted Diphenyl Ureas As Raf Kinase Inhibitors |
| IL152904A0 (en) * | 2002-01-24 | 2003-06-24 | Gamida Cell Ltd | Utilization of retinoid and vitamin d receptor antagonists for expansion of renewable stem cell populations |
| WO2003062404A1 (en) * | 2002-01-25 | 2003-07-31 | Gamida-Cell Ltd. | Methods of expanding stem and progenitor cells and expanded cell populations obtained thereby |
| MXPA04007832A (es) * | 2002-02-11 | 2005-09-08 | Bayer Pharmaceuticals Corp | Aril-ureas con actividad inhibitoria de angiogenesis. |
| US7049313B2 (en) | 2002-02-25 | 2006-05-23 | Kudos Pharmaceuticals Ltd. | ATM inhibitors |
| WO2004005532A2 (en) * | 2002-07-10 | 2004-01-15 | Massachusetts Institute Of Technology | Solid-phase and solution-phase synthesis of glycosylphosphatidylinositol glycans |
| US20050054097A1 (en) * | 2002-11-17 | 2005-03-10 | Tony Peled | EX-VIVO expansion of hematopoietic system cell populations in mononuclear cell cultures |
| GB0304632D0 (en) * | 2003-02-28 | 2003-04-02 | Proxara Biotechnology Ltd | Method |
| UY28213A1 (es) * | 2003-02-28 | 2004-09-30 | Bayer Pharmaceuticals Corp | Nuevos derivados de cianopiridina útiles en el tratamiento de cáncer y otros trastornos. |
| CA2517959A1 (en) * | 2003-03-07 | 2004-09-16 | Gamida-Cell Ltd. | Expansion of renewable stem cell populations using modulators of pi 3-kinase |
| JP2006524289A (ja) * | 2003-04-23 | 2006-10-26 | ワイス・ホールディングズ・コーポレイション | Ｐｅｇ−ワートマニンコンジュゲート |
| EP1636585B2 (en) * | 2003-05-20 | 2012-06-13 | Bayer HealthCare LLC | Diaryl ureas with kinase inhibiting activity |
| IL161903A0 (en) * | 2003-07-17 | 2005-11-20 | Gamida Cell Ltd | Ex vivo progenitor and stem cell expansion for usein the treatment of disease of endodermally- deri ved organs |
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| US7429660B2 (en) | 2003-08-13 | 2008-09-30 | Kudos Pharmaceuticals Limited | ATM inhibitors |
| WO2005016349A1 (en) * | 2003-08-14 | 2005-02-24 | Icos Corporation | Methods of inhibiting leukocyte accumulation |
| WO2005016348A1 (en) * | 2003-08-14 | 2005-02-24 | Icos Corporation | Method of inhibiting immune responses stimulated by an endogenous factor |
| WO2005113556A1 (en) | 2004-05-13 | 2005-12-01 | Icos Corporation | Quinazolinones as inhibitors of human phosphatidylinositol 3-kinase delta |
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| WO2006030442A2 (en) * | 2004-09-16 | 2006-03-23 | Gamida-Cell Ltd. | Methods of ex vivo progenitor and stem cell expansion by co-culture with mesenchymal cells |
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| MX2007004489A (es) * | 2004-10-13 | 2007-09-21 | Wyeth Corp | Analogos de 17-hidroxiwortamina como inhibidores pi3k. |
| CN101115747A (zh) | 2005-02-09 | 2008-01-30 | 库多斯药物有限公司 | Atm抑制剂 |
| US20080287469A1 (en) * | 2005-02-17 | 2008-11-20 | Diacovo Thomas G | Phosphoinositide 3-Kinase Inhibitors for Inhibiting Leukocyte Accumulation |
| AR053358A1 (es) | 2005-04-15 | 2007-05-02 | Cancer Rec Tech Ltd | Inhibidores de adn - pk |
| JP2008543277A (ja) * | 2005-05-11 | 2008-12-04 | ジェネティック テクノロジーズ リミテッド | 胎児細胞を富化する方法 |
| JP2008545670A (ja) * | 2005-05-27 | 2008-12-18 | バイエル・ヘルスケア・アクチェンゲゼルシャフト | 疾患を処置するためのジアリールウレア類を含む組合せ治療 |
| JP2007063205A (ja) * | 2005-08-31 | 2007-03-15 | Japan Science & Technology Agency | 神経因性疼痛治療剤 |
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| TW200845960A (en) * | 2007-04-05 | 2008-12-01 | Wyeth Corp | Wortmannin-rapalog conjugate and uses thereof |
| US20100109416A1 (en) * | 2008-11-03 | 2010-05-06 | Jones Margaret L | Adjustable safety harness |
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| US9492449B2 (en) | 2008-11-13 | 2016-11-15 | Gilead Calistoga Llc | Therapies for hematologic malignancies |
| US20100233733A1 (en) * | 2009-02-10 | 2010-09-16 | Nodality, Inc., A Delaware Corporation | Multiple mechanisms for modulation of the pi3 kinase pathway |
| BRPI1012333A2 (pt) | 2009-03-24 | 2016-03-29 | Gilead Calistoga Llc | atropisômeros de derivados de 2-purinil-3-tolil-quinazolinonas e métodos de uso |
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| WO2011011550A1 (en) | 2009-07-21 | 2011-01-27 | Calistoga Pharmaceuticals Inc. | Treatment of liver disorders with pi3k inhibitors |
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| EA201691327A1 (ru) | 2012-03-05 | 2017-03-31 | Джилид Калистога Ллс | Полиморфные формы (s)-2-(1-(9h-пурин-6-иламино)пропил)-5-фтор-3-фенилхиназолин-4(3h)-она |
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| AU2014364414A1 (en) | 2013-12-20 | 2016-06-30 | Gilead Calistoga Llc | Polymorphic forms of a hydrochloride salt of (S) -2-(1-(9H-purin-6-ylamino) propyl) -5-fluoro-3-phenylquinazolin-4 (3H) -one |
| CN105849108A (zh) | 2013-12-20 | 2016-08-10 | 吉利德卡利斯托加公司 | 磷脂酰肌醇3-激酶抑制剂的制备方法 |
| CN106459005A (zh) | 2014-06-13 | 2017-02-22 | 吉利德科学公司 | 磷脂酰肌醇3‑激酶抑制剂 |
| CN107058137B (zh) * | 2017-06-14 | 2020-02-07 | 海正药业(杭州)有限公司 | 一种渥曼青霉及其生产渥曼青霉素的方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3668222A (en) * | 1969-05-14 | 1972-06-06 | Sandoz Ltd | 11-desacetoxy-wortmannin |
| US4988682A (en) * | 1989-02-03 | 1991-01-29 | University Of Pittsburgh | Myo-inositol analogs and method for their use |
| JPH0328948A (ja) * | 1989-06-27 | 1991-02-07 | Nec Corp | 入出力制御装置の動作状態情報収集方式 |
-
1993
- 1993-07-19 US US08/094,279 patent/US5378725A/en not_active Expired - Fee Related
- 1993-11-23 TW TW082109883A patent/TW287102B/zh active
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1994
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- 1994-07-13 ZA ZA945103A patent/ZA945103B/xx unknown
- 1994-07-14 IL IL11032594A patent/IL110325A0/xx unknown
- 1994-07-14 CA CA002128046A patent/CA2128046A1/en not_active Abandoned
- 1994-07-14 NO NO942641A patent/NO942641L/no unknown
- 1994-07-15 PH PH48651A patent/PH30794A/en unknown
- 1994-07-15 PL PL94304317A patent/PL304317A1/xx unknown
- 1994-07-15 EP EP94305192A patent/EP0635268A1/en not_active Withdrawn
- 1994-07-18 CN CN94108398A patent/CN1111127A/zh active Pending
- 1994-07-18 JP JP6165068A patent/JPH0753370A/ja active Pending
- 1994-07-18 HU HU9402128A patent/HUT67667A/hu unknown
- 1994-07-18 KR KR1019940017228A patent/KR950002755A/ko not_active Withdrawn
- 1994-07-18 RU RU94026082/14A patent/RU94026082A/ru unknown
- 1994-07-18 AU AU67540/94A patent/AU678831B2/en not_active Ceased
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100369632C (zh) * | 2004-10-14 | 2008-02-20 | 孔庆忠 | 抗癌药物组合物 |
| CN1875959B (zh) * | 2004-10-14 | 2010-05-12 | 孔庆忠 | 一种抗癌药物组合物 |
| CN104774239A (zh) * | 2015-03-13 | 2015-07-15 | 暨南大学 | 多节孢绿胶霉素类化合物及其用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| PH30794A (en) | 1997-10-17 |
| CZ169294A3 (en) | 1995-02-15 |
| AU678831B2 (en) | 1997-06-12 |
| KR950002755A (ko) | 1995-02-16 |
| US5378725A (en) | 1995-01-03 |
| CA2128046A1 (en) | 1995-01-20 |
| ZA945103B (en) | 1996-03-27 |
| NO942641L (no) | 1995-01-20 |
| PL304317A1 (en) | 1995-01-23 |
| RU94026082A (ru) | 1996-05-20 |
| IL110325A0 (en) | 1994-10-21 |
| NO942641D0 (no) | 1994-07-14 |
| AU6754094A (en) | 1995-01-27 |
| HUT67667A (en) | 1995-04-28 |
| JPH0753370A (ja) | 1995-02-28 |
| CZ283806B6 (cs) | 1998-06-17 |
| HU9402128D0 (en) | 1994-09-28 |
| EP0635268A1 (en) | 1995-01-25 |
| TW287102B (enExample) | 1996-10-01 |
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