ECSP11011391A - Métodos y productos intermedios para preparar agentes farmacéuticos - Google Patents

Métodos y productos intermedios para preparar agentes farmacéuticos

Info

Publication number
ECSP11011391A
ECSP11011391A ECSP11011391A ECSP11011391A EC SP11011391 A ECSP11011391 A EC SP11011391A EC SP11011391 A ECSP11011391 A EC SP11011391A EC SP11011391 A ECSP11011391 A EC SP11011391A
Authority
EC
Ecuador
Prior art keywords
methods
pharmaceutical agents
intermediate products
prepare pharmaceutical
products
Prior art date
Application number
Other languages
English (en)
Inventor
Eric D Dowdy
Kenneth M Kent
Steven Pfeiffer
Richard Polniaszek
Aaron Cullen
Duong Tran
Zhongxin Zhou
Doug Cordeau
Leah Easton
Richard Yu
Original Assignee
Gilead Sciences Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=42634770&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=ECSP11011391(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Gilead Sciences Inc filed Critical Gilead Sciences Inc
Publication of ECSP11011391A publication Critical patent/ECSP11011391A/es

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D277/00Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/30Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D277/00Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/28Radicals substituted by nitrogen atoms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12Antivirals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/62Preparation of compounds containing amino groups bound to a carbon skeleton by cleaving carbon-to-nitrogen, sulfur-to-nitrogen, or phosphorus-to-nitrogen bonds, e.g. hydrolysis of amides, N-dealkylation of amines or quaternary ammonium compounds
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/68Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton
    • C07C209/70Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by reduction of unsaturated amines
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/34Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfuric acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C307/00Amides of sulfuric acids, i.e. compounds having singly-bound oxygen atoms of sulfate groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C307/02Monoamides of sulfuric acids or esters thereof, e.g. sulfamic acids
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C307/00Amides of sulfuric acids, i.e. compounds having singly-bound oxygen atoms of sulfate groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C307/04Diamides of sulfuric acids
    • C07C307/06Diamides of sulfuric acids having nitrogen atoms of the sulfamide groups bound to acyclic carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • YGENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02PCLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00Technologies relating to chemical industry
    • Y02P20/50Improvements relating to the production of bulk chemicals
    • Y02P20/55Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

La invención proporciona métodos y productos intermedios que son útiles para preparar un compuesto de la fórmula I, y sales de este.
ECSP11011391 2009-04-03 2011-10-12 Métodos y productos intermedios para preparar agentes farmacéuticos ECSP11011391A (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US16649809P 2009-04-03 2009-04-03

Publications (1)

Publication Number Publication Date
ECSP11011391A true ECSP11011391A (es) 2012-03-30

Family

ID=42634770

Family Applications (1)

Application Number Title Priority Date Filing Date
ECSP11011391 ECSP11011391A (es) 2009-04-03 2011-10-12 Métodos y productos intermedios para preparar agentes farmacéuticos

Country Status (27)

Country Link
US (4) US8497396B2 (es)
EP (2) EP3009434A1 (es)
JP (8) JP5612662B2 (es)
KR (3) KR101874557B1 (es)
CN (4) CN107382997B (es)
AP (1) AP2887A (es)
AR (1) AR076027A1 (es)
AU (1) AU2010232559B2 (es)
BR (1) BRPI1012638B8 (es)
CA (4) CA2754698C (es)
CL (1) CL2011002370A1 (es)
CO (1) CO6400216A2 (es)
EA (2) EA022739B1 (es)
EC (1) ECSP11011391A (es)
ES (1) ES2548252T3 (es)
HK (4) HK1166976A1 (es)
IL (4) IL215399A (es)
MX (2) MX338731B (es)
NZ (4) NZ617773A (es)
PE (1) PE20120617A1 (es)
PT (1) PT2414325E (es)
SG (2) SG174585A1 (es)
TW (2) TWI464165B (es)
UA (1) UA108738C2 (es)
UY (1) UY32535A (es)
WO (1) WO2010115000A2 (es)
ZA (1) ZA201107430B (es)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
UA108738C2 (uk) 2009-04-03 2015-06-10 Спосіб одержання інгібітора цитохром р450 монооксигенази та залучені проміжні сполуки
JP2012140390A (ja) * 2011-01-06 2012-07-26 Sumitomo Chemical Co Ltd α−アミノ−γ−ブチロラクトンの製造方法
WO2012151165A1 (en) * 2011-05-02 2012-11-08 Gilead Sciences, Inc. Amorphous solid salts
CN104093702A (zh) 2012-02-03 2014-10-08 吉里德科学公司 用于制备药物试剂的方法和中间体
CN103694196A (zh) * 2012-09-27 2014-04-02 上海迪赛诺化学制药有限公司 细胞色素p450单加氧酶抑制剂中间体及其制法和用途
WO2014047849A1 (zh) * 2012-09-27 2014-04-03 上海迪赛诺化学制药有限公司 细胞色素p450单加氧酶抑制剂中间体及其制法和用途
WO2014057498A2 (en) 2012-10-08 2014-04-17 Mylan Laboratories Ltd. Process for the preparation of cobicistat intermediates
JP2016504364A (ja) * 2012-12-26 2016-02-12 アッシア・ケミカル・インダストリーズ・リミテッド コビシスタット塩
CN104370777A (zh) * 2013-08-13 2015-02-25 上海迪赛诺化学制药有限公司 合成(2r,5r)-1,6-二苯基己烷-2,5-二胺及其盐的中间体及所述中间体的制备方法和应用
EP3073993A1 (en) * 2013-11-29 2016-10-05 Mylan Laboratories Ltd. Amorphous cobicistat solid dispersion
WO2015083066A1 (en) 2013-12-03 2015-06-11 Mylan Laboratories Ltd. Preparation of cobicistat intermediates
CN104193643B (zh) * 2014-09-12 2016-02-10 宁波九胜创新医药科技有限公司 用于合成抗艾滋病药物增强剂cobicistat的中间体
CN104447472A (zh) * 2014-11-06 2015-03-25 江苏森萱医药化工股份有限公司 D)-2-苄基-n,n-二甲基氮杂环丙烷基-1-磺酰胺合成方法
CN104557565B (zh) * 2015-01-08 2016-07-06 浙江工业大学 抗艾滋病药物增强剂Cobicistat关键中间体盐酸盐的制备方法
US10454867B2 (en) * 2015-02-09 2019-10-22 Airwatch Llc Enhanced e-mail delivery to mobile devices
US10351556B2 (en) 2015-02-18 2019-07-16 Msn Laboratories Private Limited Process for the preparation of 1,3-thiazol-5-ylmethyl [(2R,5R)-5-{[(2s)-2-[(methyl{[2-(propan-2-yl)-1,3-thiazol-4YL] methyl} carbamoyl) amino]-4-(morpholin-4-yl)butanoyl]amino)-1,6-diphenylhexan-2-yl]carbamate
CN107674039A (zh) * 2016-08-01 2018-02-09 上海朴颐化学科技有限公司 一种可比西他中间体的制备方法
EP3518935A1 (en) 2016-09-27 2019-08-07 Gilead Sciences, Inc. Therapeutic compositions for treatment of human immunodeficiency virus
CN109912530A (zh) * 2017-12-13 2019-06-21 上海奥博生物医药技术有限公司 一种可比司他原料杂质的制备方法
CN109232301B (zh) * 2018-10-15 2021-01-01 天津希恩思生化科技有限公司 一种四异丙基肼的制备方法
CN110642721B (zh) * 2018-12-21 2022-09-30 安徽贝克生物制药有限公司 盐酸司来吉兰的制备方法
CN110878071A (zh) * 2019-11-21 2020-03-13 华南农业大学 一种α-氨基-γ-丁内酯及其盐的制备方法

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100815412B1 (ko) * 1999-06-04 2008-03-20 아보트 러보러터리즈 개선된 약제학적 제형
US20030153771A1 (en) 2001-09-27 2003-08-14 Kolb Hartmuth C. Large scale synthesis of optically pure aziridines
WO2003106445A1 (en) * 2002-06-12 2003-12-24 Qsi Pharma A/S Compounds and methods for controlling bacterial virulence
CN1989232A (zh) * 2004-07-23 2007-06-27 宝洁公司 用于改善低温下油脂清洁和淀粉污垢清洁效果的液体洗涤剂组合物
US7786153B2 (en) * 2005-03-02 2010-08-31 Abbott Laboratories Inc. Compounds that are useful for improving pharmacokinetics
CA2653374A1 (en) * 2006-07-07 2008-01-24 Manoj C. Desai Modulators of pharmacokinetic properties of therapeutics
ES2779826T3 (es) * 2007-02-23 2020-08-20 Gilead Sciences Inc Moduladores de propiedades farmacocinéticas de agentes terapéuticos
KR20100040896A (ko) * 2007-07-06 2010-04-21 길리애드 사이언시즈, 인코포레이티드 치료제의 약동학적 특성의 조절제
JP5629585B2 (ja) * 2008-01-04 2014-11-19 ギリアード サイエンシーズ, インコーポレイテッド シトクロムp450のインヒビター
JP5722213B2 (ja) 2008-05-02 2015-05-20 ギリアード サイエンシーズ, インコーポレイテッド 医薬薬剤の加工性を改良するための固体担体粒子の使用
UA108738C2 (uk) 2009-04-03 2015-06-10 Спосіб одержання інгібітора цитохром р450 монооксигенази та залучені проміжні сполуки

Also Published As

Publication number Publication date
JP2016128476A (ja) 2016-07-14
NZ708978A (en) 2017-01-27
US8853210B2 (en) 2014-10-07
IL237642A (en) 2017-01-31
AP2887A (en) 2014-05-31
BRPI1012638A2 (pt) 2016-04-05
JP2023002679A (ja) 2023-01-10
AU2010232559A8 (en) 2011-11-10
CA3008903A1 (en) 2010-10-07
AP2011005864A0 (en) 2011-10-31
US20100256366A1 (en) 2010-10-07
JP5612662B2 (ja) 2014-10-22
WO2010115000A3 (en) 2011-09-22
JP2014193897A (ja) 2014-10-09
CA2925137C (en) 2018-07-31
BRPI1012638B8 (pt) 2021-05-25
CN111217808A (zh) 2020-06-02
CA2925137A1 (en) 2010-10-07
SG10201404926UA (en) 2015-02-27
JP6336161B2 (ja) 2018-06-06
IL250068A0 (en) 2017-03-30
WO2010115000A2 (en) 2010-10-07
UY32535A (es) 2010-10-29
IL215399A (en) 2015-11-30
US8497396B2 (en) 2013-07-30
IL237643A (en) 2017-01-31
MX338731B (es) 2016-04-28
CN107382997A (zh) 2017-11-24
NZ726536A (en) 2018-04-27
PT2414325E (pt) 2015-10-29
KR20170043672A (ko) 2017-04-21
HK1166976A1 (zh) 2012-11-16
KR20180077324A (ko) 2018-07-06
BRPI1012638B1 (pt) 2021-04-20
CA3008903C (en) 2021-06-08
CA2754698C (en) 2016-06-07
NZ617773A (en) 2016-02-26
PE20120617A1 (es) 2012-05-26
CA3083433C (en) 2022-08-09
TW201518283A (zh) 2015-05-16
US9115100B2 (en) 2015-08-25
EA022739B1 (ru) 2016-02-29
IL215399A0 (en) 2011-12-29
AU2010232559A1 (en) 2011-10-06
CA2754698A1 (en) 2010-10-07
KR20120006035A (ko) 2012-01-17
JP6491706B2 (ja) 2019-03-27
EP2414325B1 (en) 2015-08-26
JP2012522797A (ja) 2012-09-27
TW201100412A (en) 2011-01-01
TWI464165B (zh) 2014-12-11
JP2018008983A (ja) 2018-01-18
NZ594864A (en) 2014-03-28
ZA201107430B (en) 2012-12-27
JP2020189861A (ja) 2020-11-26
CA3083433A1 (en) 2010-10-07
AU2010232559B2 (en) 2015-06-18
HK1214265A1 (zh) 2016-07-22
MX2011010397A (es) 2011-10-24
US20150005493A1 (en) 2015-01-01
CN104876888A (zh) 2015-09-02
JP2018162274A (ja) 2018-10-18
CN104876888B (zh) 2018-06-15
KR101728375B1 (ko) 2017-04-19
EP2414325A2 (en) 2012-02-08
KR101874557B1 (ko) 2018-07-04
IL237643A0 (en) 2015-04-30
SG174585A1 (en) 2011-10-28
US9428473B2 (en) 2016-08-30
CN107382997B (zh) 2021-02-26
CN102438982A (zh) 2012-05-02
ES2548252T3 (es) 2015-10-15
EP3009434A1 (en) 2016-04-20
HK1245785A1 (zh) 2018-08-31
CN102438982B (zh) 2015-05-06
CL2011002370A1 (es) 2012-05-25
US20140088304A1 (en) 2014-03-27
JP5986599B2 (ja) 2016-09-06
IL237642A0 (en) 2015-04-30
JP6180561B2 (ja) 2017-08-16
UA108738C2 (uk) 2015-06-10
JP2017122107A (ja) 2017-07-13
CO6400216A2 (es) 2012-03-15
AR076027A1 (es) 2011-05-11
EA201590979A1 (ru) 2016-02-29
HK1223912A1 (zh) 2017-08-11
US20160002186A1 (en) 2016-01-07
EA201190179A1 (ru) 2013-01-30

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