CA2967385C - Methods of manufacturing treprostinil and treprostinil derivative prodrugs - Google Patents

Methods of manufacturing treprostinil and treprostinil derivative prodrugs Download PDF

Info

Publication number
CA2967385C
CA2967385C CA2967385A CA2967385A CA2967385C CA 2967385 C CA2967385 C CA 2967385C CA 2967385 A CA2967385 A CA 2967385A CA 2967385 A CA2967385 A CA 2967385A CA 2967385 C CA2967385 C CA 2967385C
Authority
CA
Canada
Prior art keywords
alkyl
linear
branched
treprostinil
formula
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.)
Active
Application number
CA2967385A
Other languages
English (en)
French (fr)
Other versions
CA2967385A1 (en
Inventor
Vladimir Malinin
Walter Perkins
Franziska LEIFER
Donna M. Konicek
Zhili Li
Adam PLAUNT
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Insmed Inc
Original Assignee
Insmed 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
Application filed by Insmed Inc filed Critical Insmed Inc
Publication of CA2967385A1 publication Critical patent/CA2967385A1/en
Application granted granted Critical
Publication of CA2967385C publication Critical patent/CA2967385C/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C231/00—Preparation of carboxylic acid amides
    • C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/08—Preparation of carboxylic acid esters by reacting carboxylic acids or symmetrical anhydrides with the hydroxy or O-metal group of organic compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/18—Systems containing only non-condensed rings with a ring being at least seven-membered
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/14—All rings being cycloaliphatic
    • C07C2602/24—All rings being cycloaliphatic the ring system containing nine carbon atoms, e.g. perhydroindane

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
CA2967385A 2014-11-18 2015-11-18 Methods of manufacturing treprostinil and treprostinil derivative prodrugs Active CA2967385C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462081515P 2014-11-18 2014-11-18
US62/081,515 2014-11-18
PCT/US2015/061427 WO2016081658A1 (en) 2014-11-18 2015-11-18 Methods of manufacturing treprostinil and treprostinil derivative prodrugs

Publications (2)

Publication Number Publication Date
CA2967385A1 CA2967385A1 (en) 2016-05-26
CA2967385C true CA2967385C (en) 2023-05-16

Family

ID=56014536

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2967385A Active CA2967385C (en) 2014-11-18 2015-11-18 Methods of manufacturing treprostinil and treprostinil derivative prodrugs

Country Status (7)

Country Link
US (5) US10343979B2 (enExample)
EP (2) EP3221291B1 (enExample)
JP (1) JP6866043B2 (enExample)
AU (1) AU2015349969B2 (enExample)
CA (1) CA2967385C (enExample)
ES (1) ES2873873T3 (enExample)
WO (1) WO2016081658A1 (enExample)

Families Citing this family (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3712142B1 (en) 2013-01-11 2022-07-06 Corsair Pharma, Inc. Prodrugs of treprostinil
US9505737B2 (en) 2013-01-11 2016-11-29 Corsair Pharma, Inc. Treprostinil derivative compounds and methods of using same
US9469600B2 (en) 2013-10-25 2016-10-18 Insmed Incorporated Prostacyclin compounds, compositions and methods of use thereof
US10343979B2 (en) 2014-11-18 2019-07-09 Insmed Incorporated Methods of manufacturing treprostinil and treprostinil derivative prodrugs
US9394227B1 (en) 2015-06-17 2016-07-19 Corsair Pharma, Inc. Treprostinil derivatives and compositions and uses thereof
US9643911B2 (en) 2015-06-17 2017-05-09 Corsair Pharma, Inc. Treprostinil derivatives and compositions and uses thereof
WO2017223400A1 (en) * 2016-06-24 2017-12-28 Insmed Incorporated Prostacyclin compounds and compositions for treating sarcoidosis
WO2018058124A1 (en) 2016-09-26 2018-03-29 United Therapeutics Corporation Treprostinil prodrugs
CN119632930A (zh) * 2019-04-29 2025-03-18 英斯梅德股份有限公司 曲前列素前药的干粉组合物及其使用方法
CN114616225A (zh) 2019-08-23 2022-06-10 联合治疗公司 曲前列环素前药
US10781160B1 (en) * 2019-10-04 2020-09-22 Chirogate International Inc. Hexadecyl Treprostinil crystals and methods for preparation thereof
IL296567A (en) 2020-04-17 2022-11-01 United Therapeutics Corp Terfostinil for use in the treatment of interstitial lung disease
AU2021289336B2 (en) 2020-06-09 2025-08-28 Mannkind Corporation Fumaryl diketopiperidine prodrugs of treprostinil
KR102849520B1 (ko) * 2020-12-14 2025-08-25 유나이티드 쎄러퓨틱스 코포레이션 트레프로스티닐 프로드러그로 질환을 치료하는 방법
WO2022187352A1 (en) 2021-03-03 2022-09-09 United Therapeutics Corporation A dry powder composition of trestinil and its prodrug thereof and further comprising comprising (e)-3,6-bis[4-(n-carbonyl-2-propenyl)amidobutyl]-2,5-diketopiperazine (fdkp)
WO2023154705A1 (en) 2022-02-08 2023-08-17 United Therapeutics Corporation Treprostinil iloprost combination therapy
CN121241041A (zh) 2023-01-19 2025-12-30 联合治疗公司 曲前列尼尔类似物及相关制备和使用方法
CN122514512A (zh) 2023-11-09 2026-08-04 联合治疗公司 可用于生产曲前列尼尔的化合物的合成
US20260166056A1 (en) 2024-12-13 2026-06-18 United Therapeutics Corporation Treprostinil formulations and their uses

Family Cites Families (96)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2947526A1 (de) 1978-11-29 1980-06-12 Ono Pharmaceutical Co Prostacyclin-analoge
US4668814A (en) 1984-03-08 1987-05-26 The Upjohn Company Interphenylene carbacyclin derivatives
JPS61289034A (ja) 1985-06-17 1986-12-19 Teijin Ltd イソカルバサイクリン類脂肪乳剤
US4837342A (en) 1986-02-28 1989-06-06 Sagami Chemical Research Center Prostacyclin analogue, and blood circulation improving agent and anti-ulcer composition containing it as active ingredient
GB8814438D0 (en) 1988-06-17 1988-07-20 Wellcome Found Compounds for use in medicine
GB9011588D0 (en) 1990-05-24 1990-07-11 Wellcome Found Prostaglandin analogues for use in medicine
US6165500A (en) 1990-08-24 2000-12-26 Idea Ag Preparation for the application of agents in mini-droplets
CA2056039A1 (en) 1991-01-22 1992-07-23 Philip L. Fuchs Carbacyclin analogs
US5190972A (en) 1992-01-27 1993-03-02 The University Of Melbourne Method of combatting cyclosporine organ toxicity with prostaglandin analogs
CA2091152C (en) 1993-03-05 2005-05-03 Kirsten Westesen Solid lipid particles, particles of bioactive agents and methods for the manfuacture and use thereof
US5576016A (en) 1993-05-18 1996-11-19 Pharmos Corporation Solid fat nanoemulsions as drug delivery vehicles
US6638621B2 (en) 2000-08-16 2003-10-28 Lyotropic Therapeutics, Inc. Coated particles, methods of making and using
US6441245B1 (en) 1997-10-24 2002-08-27 United Therapeutics Corporation Process for stereoselective synthesis of prostacyclin derivatives
ES2214753T3 (es) 1997-11-14 2004-09-16 United Therapeutics Corporation Uso de 9-desoxi-2',9-alfa-metano-3-oxa-4,5,6-trinor-3,7-(1',3'-interfenilen)-13,14-dihidro-prostaglandina f1 para tratar la enfermedad vascular periferica.
EP1043031A4 (en) 1997-12-26 2007-05-02 Astellas Pharma Inc MEDICAL COMPOSITIONS WITH DELAYED ACTIVE INGREDIENTS
JP2002521423A (ja) 1998-07-31 2002-07-16 コリア インスティチュート オブ サイエンス アンド テクノロージ 遺伝子又は薬物運搬体としての脂質エマルジョン及び固形脂質微粒子
US6265495B1 (en) * 1998-09-22 2001-07-24 Nippon Shokubai Co., Ltd. Method for production of esterified product
US6521212B1 (en) 1999-03-18 2003-02-18 United Therapeutics Corporation Method for treating peripheral vascular disease by administering benzindene prostaglandins by inhalation
KR20020012169A (ko) 1999-03-31 2002-02-15 유나이티드 쎄러퓨틱스 코포레이션 프로스타글란딘 화합물, 조성물 및 말초혈관질병 및폐고혈압증의 치료방법
US6242482B1 (en) 2000-06-05 2001-06-05 United Therapeutics Corporation Prostaglandin compounds and derivatives thereof, compositions containing the same and method of using the same for the treatment of congestive heart failure
US6306435B1 (en) 2000-06-26 2001-10-23 Yung Shin Pharmaceutical Industrial Co. Ltd. Oral pharmaceutical preparation embedded in an oily matrix and methods of making the same
WO2003000236A1 (en) 2001-06-23 2003-01-03 Lyotropic Therapeutics, Inc Particles with improved solubilization capacity
US20030108512A1 (en) 2001-12-10 2003-06-12 Robert Shorr Modified prostaglandin compounds and analogs thereof, compositions containing the same useful for the treatment of cancer
US6803386B2 (en) 2002-01-16 2004-10-12 United Therapeutics Corporation Prostacyclin derivative containing compositions and methods of using the same for the treatment of cancer
AU2003258075A1 (en) 2002-08-06 2004-02-23 Lyotropic Therapeutics, Inc. Lipid-drug complexes in reversed liquid and liquid crystalline phases
AU2004240640A1 (en) 2003-05-19 2004-12-02 Baxter International Inc. Solid particles comprising an anticonvulsant or an immunosuppressive coated with one or more surface modifiers
ES2272914T3 (es) 2003-05-20 2007-05-01 Ethypharm Composicion farmaceutica oral de liberacion sostenida.
CN102697790A (zh) 2003-05-22 2012-10-03 联合治疗公司 化合物和释放前列环素类似物的方法
CN1917866B (zh) 2003-12-16 2010-12-15 联合治疗公司 曲前列环素或它的衍生物，或其药学上可接受的盐在制备治疗和预防缺血性损害的药物中的用途
US7199157B2 (en) 2003-12-16 2007-04-03 United Therapeutics Corporation Use of treprostinil to improve kidney functions
DE602005020269D1 (de) 2004-04-12 2010-05-12 United Therapeutics Corp Verwendung von treprostinil zur behandlung von neuropathischen diabetischen fussgeschwüren
GB0416328D0 (en) 2004-07-21 2004-08-25 Univ Cardiff Use of dry powder compositions for pulmonary delivery
CA2574958A1 (en) 2004-07-26 2006-02-09 Cotherix, Inc. Treatment of pulmonary hypertension by inhaled iloprost with a microparticle formulation
EP1806148A4 (en) 2004-10-22 2009-12-02 Ono Pharmaceutical Co THERAPEUTIC PREPARATION FOR INHALATION
US20070178166A1 (en) 2005-12-15 2007-08-02 Acusphere, Inc. Processes for making particle-based pharmaceutical formulations for pulmonary or nasal administration
CA2654492C (en) 2006-05-15 2017-06-27 United Therapeutics Corporation Treprostinil administration using a metered dose inhaler
US20090036465A1 (en) 2006-10-18 2009-02-05 United Therapeutics Corporation Combination therapy for pulmonary arterial hypertension
CA2678258A1 (en) 2007-02-09 2008-08-14 United Therapeutics Corporation Treprostinil treatment for interstitial lung disease and asthma
US20090074828A1 (en) 2007-04-04 2009-03-19 Massachusetts Institute Of Technology Poly(amino acid) targeting moieties
CN103181893A (zh) 2007-09-07 2013-07-03 联合治疗公司 针对革兰氏阴性细菌具有选择性杀菌活性的缓冲液及其使用方法
WO2009078965A1 (en) 2007-12-17 2009-06-25 United Therapeutics Corporation An improved process to prepare treprostinil, the active ingredient in remodulin
JP6219016B2 (ja) 2008-05-08 2017-10-25 ユナイテッド セラピューティクス コーポレーション トレプロスチニル一水和物
WO2009152160A1 (en) 2008-06-10 2009-12-17 Gilead Sciences, Inc. Inhaled carbaprostacyclin and prostacyclin prodrugs for the treatment of pulmonary arterial hypertension
WO2009158010A1 (en) 2008-06-27 2009-12-30 Concert Pharmaceuticals, Inc. Prostacyclin analogs
WO2010039531A1 (en) 2008-09-23 2010-04-08 Resolvyx Pharmaceuticals, Inc. Therapeutic compounds
EP2330893A4 (en) 2008-09-25 2013-01-09 Aradigm Corp DEEP PULMONARY ADMINISTRATION OF TREPROSTINIL
RU2482851C2 (ru) 2009-02-20 2013-05-27 Микро Лабс Лимитед Хранение стабильного продукта простагландина
CN102421288B (zh) 2009-05-07 2015-04-22 联合治疗公司 前列环素类似物的固体剂型
US8519178B2 (en) 2009-06-22 2013-08-27 Johnson Matthey Public Limited Company Method for the purification of prostaglandins
WO2011003058A1 (en) 2009-07-03 2011-01-06 Concert Pharmaceuticals, Inc. Prostacyclin derivatives
AU2010280684B2 (en) 2009-08-07 2016-07-28 Scipharm Sarl Composition for the treatment of cystic fibrosis
GB2486371A (en) 2009-08-21 2012-06-13 Targeted Delivery Technologies Ltd Vesicular formulations
CN101669904B (zh) 2009-09-29 2011-06-22 北京中海康医药科技发展有限公司 一种依前列醇脂质纳米粒及制备方法
US9062094B2 (en) 2010-01-22 2015-06-23 Ascendis Pharma As Dipeptide-based prodrug linkers for aliphatic amine-containing drugs
EP2525829A1 (en) 2010-01-22 2012-11-28 Ascendis Pharma A/S Dipeptide-based prodrug linkers for aromatic amine-containing drugs
KR20160132501A (ko) 2010-03-15 2016-11-18 유나이티드 세러퓨틱스 코오포레이션 폐고혈압의 치료
CN103261142B (zh) 2010-06-03 2014-12-10 联合治疗公司 曲前列环素的制备
WO2011159693A2 (en) 2010-06-15 2011-12-22 United Therapeutics Corporation Oral treatment of digital ischemic lesions
US20120010159A1 (en) 2010-07-09 2012-01-12 United Therapeutics Corporation Combination therapies with cox-2 inhibitors and treprostinil
CA2710726C (en) 2010-07-22 2016-02-23 Alphora Research Inc. Synthesis of treprostinil and intermediates useful therein
WO2012107364A1 (en) 2011-02-07 2012-08-16 Scipharm Sàrl Novel composition for the treatment of cystic fibrosis
JP5780775B2 (ja) 2011-02-18 2015-09-16 株式会社Ｌｔｔバイオファーマ プロスタグランジンｉ２誘導体を含有するナノ粒子
ES2581762T3 (es) 2011-03-02 2016-09-07 United Therapeutics Corporation Síntesis de producto intermedio para la producción de treprostinil
CN103561725B (zh) 2011-03-14 2018-08-31 国立大学法人北海道大学 用于肺递送的载体、导入剂及用途
HK1198628A1 (en) 2011-08-12 2015-05-22 Ascendis Pharma A/S Polymeric hyperbranched carrier-linked prodrugs
BR112014003225A2 (pt) 2011-08-12 2017-03-01 Ascendis Pharma As profármacos de treprostinil ligados a veículo
AU2012296953B2 (en) 2011-08-12 2016-10-20 Ascendis Pharma A/S Sustained release composition of prostacyclin
EP2741779A1 (en) 2011-08-12 2014-06-18 Ascendis Pharma A/S High-loading water-soluble carrier-linked prodrugs
US20140323402A1 (en) 2011-08-12 2014-10-30 Ascendis Phama A/S Protein Carrier-Linked Prodrugs
EP3643306A3 (en) 2011-08-12 2020-08-26 Ascendis Pharma A/S Carrier-linked prodrugs having reversible carboxylic ester linkages
US8524939B2 (en) 2011-08-24 2013-09-03 Chirogate International Inc. Intermediates for the synthesis of benzindene prostaglandins and preparations thereof
US9387214B2 (en) 2012-01-13 2016-07-12 United Therapeutics Corporation Method of identifying therapies for pulmonary hypertension
SI2674413T1 (sl) 2012-06-15 2017-10-30 Scipharm Sarl Postopek za pripravo treprostinila in derivatov le-tega
JP6746313B2 (ja) 2012-08-01 2020-08-26 ユナイテッド セラピューティクス コーポレイション プロスタサイクリン処理された内皮前駆細胞による肺動脈性高血圧症の処置
CN104684561A (zh) 2012-08-01 2015-06-03 联合治疗公司 利用间充质干细胞的肺动脉高血压的治疗
WO2014085813A1 (en) 2012-11-30 2014-06-05 Insmed Incorporated Prostacylin compositions and methods for using the same
KR102466885B1 (ko) 2013-01-09 2022-11-11 유나이티드 세러퓨틱스 코오포레이션 프로스타시클린 및 중간엽 줄기 세포를 사용한 혈관병증의 치료
US9505737B2 (en) 2013-01-11 2016-11-29 Corsair Pharma, Inc. Treprostinil derivative compounds and methods of using same
EP3712142B1 (en) 2013-01-11 2022-07-06 Corsair Pharma, Inc. Prodrugs of treprostinil
WO2014159050A1 (en) 2013-03-14 2014-10-02 United Therapeutics Corporation Solid forms of treprostinil
EP2970081A4 (en) 2013-03-15 2016-10-12 United Therapeutics Corp SALTS OF TREPROSTINIL
WO2014160638A1 (en) 2013-03-25 2014-10-02 United Therapeutics Corporation Process of making prostacyclin compounds with linker thiol and pegylated forms
CA2911172C (en) 2013-04-30 2021-10-19 United Therapeutics Corporation Controlled release pharmaceutical formulations
WO2014203278A2 (en) 2013-06-19 2014-12-24 Msn Laboratories Private Limited NOVEL PROCESS FOR THE PREPARATION OF (1R,2R,3aS,9aS)-[[2,3,3a,4,9,9a-HEXAHYDRO-2-HYDROXY-1-[(3S)-3-HYDROXYOCTYL]-1H-BENZ[f]INDEN-5-YL]OXY]ACETIC ACID
ES2959419T3 (es) 2013-10-11 2024-02-26 Pulmokine Inc Formulaciones secas por aspersión
US9469600B2 (en) 2013-10-25 2016-10-18 Insmed Incorporated Prostacyclin compounds, compositions and methods of use thereof
WO2015138423A1 (en) 2014-03-11 2015-09-17 Insmed Incorporated Prostacylin compositions and methods for using the same
ES2908142T3 (es) 2014-06-13 2022-04-27 United Therapeutics Corp Formulaciones de treprostinil
CN107108427A (zh) 2014-10-20 2017-08-29 联合治疗学有限公司 用于制备前列环素衍生物的中间体的合成
US10343979B2 (en) 2014-11-18 2019-07-09 Insmed Incorporated Methods of manufacturing treprostinil and treprostinil derivative prodrugs
WO2016176555A1 (en) 2015-04-29 2016-11-03 Insmed Incorporated Prostacyclin compounds, compositions and methods of use thereof
EP3452170A4 (en) 2016-05-05 2020-04-01 Liquidia Technologies, Inc. TREPROSTINIL IN POWDER FORM FOR TREATING PULMONAL HYPERTENSION
WO2017223400A1 (en) 2016-06-24 2017-12-28 Insmed Incorporated Prostacyclin compounds and compositions for treating sarcoidosis
WO2018058124A1 (en) 2016-09-26 2018-03-29 United Therapeutics Corporation Treprostinil prodrugs
EP3673895A1 (en) 2018-12-28 2020-07-01 Université Libre de Bruxelles Dry powder inhalation formulation and its use for the therapeutic treatment of lungs
CN119632930A (zh) 2019-04-29 2025-03-18 英斯梅德股份有限公司 曲前列素前药的干粉组合物及其使用方法

Also Published As

Publication number Publication date
AU2015349969B2 (en) 2020-02-06
US20250162982A1 (en) 2025-05-22
AU2015349969A1 (en) 2017-05-25
US20170320813A1 (en) 2017-11-09
ES2873873T3 (es) 2021-11-04
EP3904326A1 (en) 2021-11-03
EP3221291A4 (en) 2018-06-27
JP6866043B2 (ja) 2021-04-28
EP3221291A1 (en) 2017-09-27
US20190337888A1 (en) 2019-11-07
US11148997B2 (en) 2021-10-19
US20220135513A1 (en) 2022-05-05
HK1244783A1 (en) 2018-08-17
US10343979B2 (en) 2019-07-09
WO2016081658A1 (en) 2016-05-26
JP2017535555A (ja) 2017-11-30
CA2967385A1 (en) 2016-05-26
EP3221291B1 (en) 2021-03-31
US20230250051A1 (en) 2023-08-10

Similar Documents

Publication Publication Date Title
US20230250051A1 (en) Methods of manufacturing treprostinil and treprostinil derivative prodrugs
RU2604193C2 (ru) Новое соединение с эффектами тромболизиса, акцептирования свободных радикалов и направленного действия на тромб, а также способ его получения и применение
JP6034802B2 (ja) 大環状ラクタムの調製のための方法および中間体
JP6934011B2 (ja) Ｔｈｒｏｍｂｏｓｐｏｎｄｉｎ １結合ペプチド
CN110627877A (zh) 一种psd-95抑制剂
JP6998878B2 (ja) 環状ポリペプチド、それらを得る方法、及びその治療的使用
KR102258630B1 (ko) 펩티드-올리고우레아 키메라 화합물 및 이의 사용 방법
TW202446783A (zh) 化合物
CA3216095A1 (en) Preparation and application of polypeptide
KR20160016863A (ko) 혈전 용해, 항혈전 및 라디칼 소거능의 3가지 활성을 갖는 신규한 화합물, 및 이의 합성, 나노-구조 및 용도
JP2018531284A6 (ja) 環状ポリペプチド、それらを得る方法、及びその治療的使用
JP2026503110A (ja) インターロイキン－２３受容体の脂質付加ペプチド阻害剤の製剤
JP7804766B2 (ja) ステープルペプチド及びその使用
HK1244783B (en) Methods of manufacturing treprostinil and treprostinil derivative prodrugs
CN102485746B (zh) 具有靶向性溶血栓活性的寡肽、其制备方法和应用
WO2024217443A1 (zh) 一种长效坎普他汀化合物
CN102485745B (zh) 溶血栓寡肽及其制备方法和应用
TWI389899B (zh) 具口服活性之凝血酶抑制劑
CN102485744B (zh) 溶血栓的寡肽化合物及其制备方法和应用
JPS6028992A (ja) ペプチド及びこれを含有する抗精神分裂病薬剤
CN102477073B (zh) 具有溶血栓活性的寡肽及其制备方法和应用
CN102477072A (zh) 用于溶血栓的寡肽化合物及其制备方法和应用
CN102702318A (zh) 具有靶向抗血栓活性的yigskyigsk、制备和应用
MXPA96005426A (en) Derivatives of aminosulphonic acids, use of them in the synthesis of pseudopeptides and procedure for preparation

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20201113

MPN Maintenance fee for patent paid

Free format text: FEE DESCRIPTION TEXT: MF (PATENT, 9TH ANNIV.) - STANDARD

Year of fee payment: 9

U00 Fee paid

Free format text: ST27 STATUS EVENT CODE: A-4-4-U10-U00-U101 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE REQUEST RECEIVED

Effective date: 20241114

U11 Full renewal or maintenance fee paid

Free format text: ST27 STATUS EVENT CODE: A-4-4-U10-U11-U102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE FEE PAYMENT PAID IN FULL

Effective date: 20250529

MPN Maintenance fee for patent paid

Free format text: FEE DESCRIPTION TEXT: MF (PATENT, 10TH ANNIV.) - STANDARD

Year of fee payment: 10

U00 Fee paid

Free format text: ST27 STATUS EVENT CODE: A-4-4-U10-U00-U101 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE REQUEST RECEIVED

Effective date: 20251023

U11 Full renewal or maintenance fee paid

Free format text: ST27 STATUS EVENT CODE: A-4-4-U10-U11-U102 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE FEE PAYMENT PAID IN FULL

Effective date: 20251023