CN101175757B - 蝶酸及其缀合物的合成和纯化 - Google Patents

蝶酸及其缀合物的合成和纯化 Download PDF

Info

Publication number
CN101175757B
CN101175757B CN2006800162870A CN200680016287A CN101175757B CN 101175757 B CN101175757 B CN 101175757B CN 2006800162870 A CN2006800162870 A CN 2006800162870A CN 200680016287 A CN200680016287 A CN 200680016287A CN 101175757 B CN101175757 B CN 101175757B
Authority
CN
China
Prior art keywords
acid
resorcinolphthalein
conjugate
pteroic
compound
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.)
Expired - Fee Related
Application number
CN2006800162870A
Other languages
English (en)
Chinese (zh)
Other versions
CN101175757A (zh
Inventor
许乐村
I·R·弗拉霍夫
C·P·利蒙
H·K·桑塔普拉姆
李春红
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.)
Endocyte Inc
Original Assignee
Endocyte 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 Endocyte Inc filed Critical Endocyte Inc
Publication of CN101175757A publication Critical patent/CN101175757A/zh
Application granted granted Critical
Publication of CN101175757B publication Critical patent/CN101175757B/zh
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D475/00—Heterocyclic compounds containing pteridine ring systems
    • C07D475/06—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4
    • C07D475/08—Heterocyclic compounds containing pteridine ring systems with a nitrogen atom directly attached in position 4 with a nitrogen atom directly attached in position 2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/20—Antivirals for DNA viruses
    • A61P31/22—Antivirals for DNA viruses for herpes viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • A61P33/12—Schistosomicides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/14—Ectoparasiticides, e.g. scabicides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Virology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Molecular Biology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Pulmonology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
CN2006800162870A 2005-03-16 2006-03-14 蝶酸及其缀合物的合成和纯化 Expired - Fee Related CN101175757B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US66227705P 2005-03-16 2005-03-16
US60/662,277 2005-03-16
PCT/US2006/009153 WO2006101845A2 (en) 2005-03-16 2006-03-14 Synthesis and purification of pteroic acid and conjugates thereof

Publications (2)

Publication Number Publication Date
CN101175757A CN101175757A (zh) 2008-05-07
CN101175757B true CN101175757B (zh) 2012-11-14

Family

ID=36699050

Family Applications (1)

Application Number Title Priority Date Filing Date
CN2006800162870A Expired - Fee Related CN101175757B (zh) 2005-03-16 2006-03-14 蝶酸及其缀合物的合成和纯化

Country Status (5)

Country Link
US (1) US8044200B2 (https=)
EP (1) EP1863816B1 (https=)
JP (1) JP5289935B2 (https=)
CN (1) CN101175757B (https=)
WO (1) WO2006101845A2 (https=)

Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE427948T1 (de) 2001-04-24 2009-04-15 Purdue Research Foundation Folat-mimetika und deren folatrezeptorbindende konjugate
CN101979095A (zh) 2001-05-02 2011-02-23 普渡研究基金会 巨噬细胞介导的疾病的治疗和诊断
US8043603B2 (en) 2002-02-07 2011-10-25 Endocyte, Inc. Folate targeted enhanced tumor and folate receptor positive tissue optical imaging technology
US8043602B2 (en) 2002-02-07 2011-10-25 Endocyte, Inc. Folate targeted enhanced tumor and folate receptor positive tissue optical imaging technology
WO2004069159A2 (en) 2003-01-27 2004-08-19 Endocyte, Inc. Vitamin receptor binding drug delivery conjugates
WO2004110250A2 (en) 2003-05-30 2004-12-23 Purdue Research Foundation Diagnostic method for atherosclerosis
CN101098854B (zh) * 2004-07-23 2012-12-05 恩多塞特公司 二价连接体及其轭合物
CN101175757B (zh) 2005-03-16 2012-11-14 恩多塞特公司 蝶酸及其缀合物的合成和纯化
EP1904183B1 (en) 2005-07-05 2014-10-15 Purdue Research Foundation Pharmaceutical composition for the treatment of osteoarthritis
EP2382995A3 (en) * 2005-08-19 2013-09-25 Endocyte, Inc. Ligand conjugates of Vinca alkaloids, analogs and derivatives
BRPI0615354A2 (pt) * 2005-08-19 2011-05-17 Endocyte, Inc. conjugado de liberação de fármaco de ligação de receptor, composição farmacêutica que o compreende, bem como seu uso
US8795633B2 (en) 2005-09-23 2014-08-05 Purdue Research Foundation Multiphoton in vivo flow cytometry method and device
JP2010509570A (ja) 2006-11-03 2010-03-25 パーデュー・リサーチ・ファウンデーション エクスビボフローサイトメトリーの方法および装置
US8586595B2 (en) 2007-02-07 2013-11-19 Purdue Research Foundation Positron emission tomography imaging method
US20100104626A1 (en) * 2007-02-16 2010-04-29 Endocyte, Inc. Methods and compositions for treating and diagnosing kidney disease
AU2008224988A1 (en) 2007-03-14 2008-09-18 Endocyte, Inc. Binding ligand linked drug delivery conjugates of tubulysins
PT2146944E (pt) 2007-04-11 2014-03-11 Merck & Cie Processo para a preparação de folatos marcados com 18f
WO2008148001A2 (en) 2007-05-25 2008-12-04 Purdue Research Foundation Method of imaging localized infections
US9877965B2 (en) 2007-06-25 2018-01-30 Endocyte, Inc. Vitamin receptor drug delivery conjugates for treating inflammation
CN101784565B (zh) 2007-06-25 2014-12-10 恩多塞特公司 含有亲水性间隔区接头的共轭物
CN101909441B (zh) 2007-10-25 2015-05-13 恩多塞特公司 微管蛋白抑制剂及其制备方法
ES3029483T3 (en) 2008-09-17 2025-06-24 Endocyte Inc Folate receptor binding conjugates of antifolates
BR112012002064A2 (pt) * 2009-07-31 2017-05-09 Endocyte Inc método para determinar se ec145 é indicado para o tratamento de um paciente com um tumor ovariano ou um tumor de pulmão; método para prever uma resposta de um tumor ovariano ou um tumor de pulmão de um paciente a terapia com ec145; método de tratamento de câncer ovariano resistente à platina em um paciente necessitando dele; uso de ec145 em combinação com doxorrubicina lipossômica peguilada; uso de ec145 para a fabricação de um medicamento; método para obter um benefício clínico comparado a tratamento com uma quantidade terapêutica de doxorrubicina lipossômica peguilada no tratamento de câncer ovariano resistente à platina em um paciente necessitando dele; método para selecionar um paciente para tratamento; composição farmacêutica; unidade de dosagem, método para determinar se um paciente com um tumor tem receptores de folato funcionalmente ativos presentes no tumor do paciente; método de tratamento de um tumor epitelial expressando receptor de folato em um paciente necessitando dele; e; método para obter um benefício clínico no tratamento de um tumor epitelial expressando receptor de folato em um paciente necessitando dele
EP2476414B1 (en) * 2009-09-07 2015-03-04 NIPRO Patch Co., Ltd. Transdermally absorbable preparation
US10080805B2 (en) 2012-02-24 2018-09-25 Purdue Research Foundation Cholecystokinin B receptor targeting for imaging and therapy
US20140080175A1 (en) 2012-03-29 2014-03-20 Endocyte, Inc. Processes for preparing tubulysin derivatives and conjugates thereof
BR112015008365A2 (pt) 2012-10-16 2017-07-04 Endocyte Inc composto da fórmula b-l(d)x, ou um sal farmaceuticamente aceitável do mesmo, composição farmacêutica, uso de um composto, composição de forma de dosagem unitária ou dose unitária, composição para tratar um câncer em um paciente, e método para tratar um câncer em um paciente
WO2014149069A1 (en) * 2013-03-15 2014-09-25 Purdue Research Foundation Synthesis and composition of amino acid linking groups conjugated to compounds used for the targeted imaging of tumors
WO2015077303A1 (en) 2013-11-19 2015-05-28 Purdue Research Foundation Patient selection method for inflammation
US10239891B2 (en) * 2017-05-15 2019-03-26 Indicator Systems International, Inc. Compositions to detect remnant cancer cells
WO2018026965A1 (en) 2016-08-02 2018-02-08 Isi Life Sciences, Inc. Compositions and methods for detecting cancer cells in a tissue sample
US20180036312A1 (en) * 2016-08-02 2018-02-08 ISI Life Sciences Inc. Novel Scaffolds for Intracellular Compound Delivery for the Detection of Cancer Cells
CN106420394B (zh) * 2016-10-21 2019-05-10 江南大学 一种增强叶酸光稳定性的方法
US10753942B2 (en) 2017-05-15 2020-08-25 Indicator Systems International, Inc. Methods to detect remnant cancer cells
CN109734717B (zh) * 2019-01-24 2022-03-22 苏州华健瑞达医药技术有限公司 蝶酸新晶型及其制备方法
EP4274619A4 (en) * 2021-01-08 2025-09-24 Lycia Therapeutics Inc BIFUNCTIONAL FOLATE RECEPTOR-BINDING COMPOUNDS
US20250127913A1 (en) * 2021-06-24 2025-04-24 Lycia Therapeutics, Inc. Bifunctional folate receptor binding compounds
CN116218513A (zh) * 2023-03-03 2023-06-06 杭州谱康医学科技有限公司 Fitc标记的荧光微球、制备方法及应用
CN116621838A (zh) * 2023-04-17 2023-08-22 武汉翱飞科技有限公司 一种蝶酸活性酯及其合成方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4337339A (en) * 1979-04-30 1982-06-29 Baker Instruments Corp. Process for preparation of folic acid derivatives

Family Cites Families (118)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2515483A (en) 1946-08-10 1950-07-18 Merck & Co Inc Diacylated pteroic acid and process for preparing same
US2816110A (en) 1956-11-23 1957-12-10 Merck & Co Inc Methods for the production of substituted pteridines
US3392173A (en) 1964-03-09 1968-07-09 Lilly Co Eli Novel acyl derivatives of desacetyl-vincaleukoblastine and processes for their preparation
US3387001A (en) 1964-10-19 1968-06-04 Lilly Co Eli Novel aminoacyl esters of desacetyl vincaleukoblastine
US4203898A (en) 1977-08-29 1980-05-20 Eli Lilly And Company Amide derivatives of VLB, leurosidine, leurocristine and related dimeric alkaloids
US4166810A (en) 1978-04-20 1979-09-04 Eli Lilly And Company Derivatives of 4-desacetyl VLB C-3 carboxyhydrazide
US4639456A (en) 1980-06-10 1987-01-27 Omnichem S.A. Vinblastin-23-oyl amino acid derivatives
US4316885A (en) 1980-08-25 1982-02-23 Ayerst, Mckenna And Harrison, Inc. Acyl derivatives of rapamycin
US4713249A (en) 1981-11-12 1987-12-15 Schroeder Ulf Crystallized carbohydrate matrix for biologically active substances, a process of preparing said matrix, and the use thereof
US5140104A (en) 1982-03-09 1992-08-18 Cytogen Corporation Amine derivatives of folic acid analogs
EP0116208B1 (en) 1982-12-07 1988-03-30 Kyowa Hakko Kogyo Co., Ltd. Mitomycin analogues
US4866180A (en) 1984-02-24 1989-09-12 Bristol-Myers Company Amino disulfide thiol exchange products
JPS60255789A (ja) 1984-06-01 1985-12-17 Kyowa Hakko Kogyo Co Ltd マイトマイシン誘導体，その製造法および抗腫瘍剤
US5266333A (en) 1985-03-06 1993-11-30 American Cyanamid Company Water dispersible and water soluble carbohydrate polymer compositions for parenteral administration of growth hormone
US4650803A (en) 1985-12-06 1987-03-17 University Of Kansas Prodrugs of rapamycin
ZA873600B (en) 1986-05-27 1988-12-28 Lilly Co Eli Immunoglobulin conjugates
US4801688A (en) 1986-05-27 1989-01-31 Eli Lilly And Company Hydrazone immunoglobulin conjugates
DE3750846T2 (de) 1986-08-29 1995-05-11 Kyowa Hakko Kogyo Kk Mitomycin-derivate.
US5094849A (en) 1988-08-08 1992-03-10 Eli Lilly And Company Cytotoxic antibody conjugates of hydrazide derivatized vinca analogs via simple organic linkers
US5006652A (en) 1988-08-08 1991-04-09 Eli Lilly And Company Intermediates for antibody-vinca drug conjugates
US5108921A (en) 1989-04-03 1992-04-28 Purdue Research Foundation Method for enhanced transmembrane transport of exogenous molecules
US5688488A (en) 1989-04-03 1997-11-18 Purdue Research Foundation Composition and method for tumor imaging
US5627165A (en) 1990-06-13 1997-05-06 Drug Innovation & Design, Inc. Phosphorous prodrugs and therapeutic delivery systems using same
US5998603A (en) 1994-09-29 1999-12-07 Isis Pharmaceuticals, Inc. 4'-desmethyl nucleoside analogs, and oligomers thereof
EP0547163B1 (en) 1990-08-29 2002-02-06 Centre Hospitalier Regional De Nantes Protein polyligands joined to a stable protein core
US5221670A (en) 1990-09-19 1993-06-22 American Home Products Corporation Rapamycin esters
US5130307A (en) 1990-09-28 1992-07-14 American Home Products Corporation Aminoesters of rapamycin
US5378696A (en) 1990-09-19 1995-01-03 American Home Products Corporation Rapamycin esters
US5233036A (en) 1990-10-16 1993-08-03 American Home Products Corporation Rapamycin alkoxyesters
US5120842A (en) 1991-04-01 1992-06-09 American Home Products Corporation Silyl ethers of rapamycin
US5100883A (en) 1991-04-08 1992-03-31 American Home Products Corporation Fluorinated esters of rapamycin
US5118678A (en) 1991-04-17 1992-06-02 American Home Products Corporation Carbamates of rapamycin
US5194447A (en) 1992-02-18 1993-03-16 American Home Products Corporation Sulfonylcarbamates of rapamycin
US5138051A (en) 1991-08-07 1992-08-11 American Home Products Corporation Rapamycin analogs as immunosuppressants and antifungals
US5118677A (en) 1991-05-20 1992-06-02 American Home Products Corporation Amide esters of rapamycin
US5169851A (en) 1991-08-07 1992-12-08 American Home Products Corporation Rapamycin analog as immunosuppressants and antifungals
US6335434B1 (en) 1998-06-16 2002-01-01 Isis Pharmaceuticals, Inc., Nucleosidic and non-nucleosidic folate conjugates
US5151413A (en) 1991-11-06 1992-09-29 American Home Products Corporation Rapamycin acetals as immunosuppressant and antifungal agents
US5159079A (en) 1991-12-20 1992-10-27 Eli Lilly And Company 2-piperidones as intermediates for 5-deaza-10-oxo- and 5-deaza-10-thio-5,6,7,8-tetrahydrofolic acids
US6004555A (en) 1992-03-05 1999-12-21 Board Of Regents, The University Of Texas System Methods for the specific coagulation of vasculature
US5302584A (en) 1992-10-13 1994-04-12 American Home Products Corporation Carbamates of rapamycin
US5258389A (en) 1992-11-09 1993-11-02 Merck & Co., Inc. O-aryl, O-alkyl, O-alkenyl and O-alkynylrapamycin derivatives
US5260300A (en) 1992-11-19 1993-11-09 American Home Products Corporation Rapamycin carbonate esters as immuno-suppressant agents
ES2295093T3 (es) 1993-04-23 2008-04-16 Wyeth Conjugados y anticuerpos de rapamicina.
US5391730A (en) 1993-10-08 1995-02-21 American Home Products Corporation Phosphorylcarbamates of rapamycin and oxime derivatives thereof
US5385908A (en) 1993-11-22 1995-01-31 American Home Products Corporation Hindered esters of rapamycin
US5385909A (en) 1993-11-22 1995-01-31 American Home Products Corporation Heterocyclic esters of rapamycin
US5385910A (en) 1993-11-22 1995-01-31 American Home Products Corporation Gem-distributed esters of rapamycin
US5389639A (en) 1993-12-29 1995-02-14 American Home Products Company Amino alkanoic esters of rapamycin
US5417982A (en) 1994-02-17 1995-05-23 Modi; Pankaj Controlled release of drugs or hormones in biodegradable polymer microspheres
IL112873A (en) 1994-03-08 2005-03-20 Wyeth Corp Rapamycin-fkbp12 binding proteins, their isolation and their use
US6171859B1 (en) 1994-03-30 2001-01-09 Mitokor Method of targeting conjugate molecules to mitochondria
US5362718A (en) 1994-04-18 1994-11-08 American Home Products Corporation Rapamycin hydroxyesters
US5463048A (en) 1994-06-14 1995-10-31 American Home Products Corporation Rapamycin amidino carbamates
US5491231A (en) 1994-11-28 1996-02-13 American Home Products Corporation Hindered N-oxide esters of rapamycin
US5547668A (en) 1995-05-05 1996-08-20 The Board Of Trustees Of The University Of Illinois Conjugates of folate anti-effector cell antibodies
US6207157B1 (en) 1996-04-23 2001-03-27 The United States Of America As Represented By The Department Of Health And Human Services Conjugate vaccine for nontypeable Haemophilus influenzae
US6030941A (en) 1996-05-01 2000-02-29 Avi Biopharma, Inc. Polymer composition for delivering substances in living organisms
EP0954340B1 (en) 1996-05-03 2007-06-27 Immunomedics, Inc. Targeted combination immunotherapy of cancer
DE19621133A1 (de) 1996-05-24 1997-11-27 Boehringer Mannheim Gmbh Bestimmungsverfahren mit oligomerisierten Rezeptoren
JP2001501601A (ja) 1996-09-12 2001-02-06 メルク エンド カンパニー インコーポレーテッド 前立腺ガンの治療において有用な共役体
US6056973A (en) 1996-10-11 2000-05-02 Sequus Pharmaceuticals, Inc. Therapeutic liposome composition and method of preparation
US6177404B1 (en) 1996-10-15 2001-01-23 Merck & Co., Inc. Conjugates useful in the treatment of benign prostatic hyperplasia
US6071532A (en) 1996-10-15 2000-06-06 Emory University Synthesis of glycophospholipid and peptide-phospholipid conjugates and uses thereof
US6291673B1 (en) 1997-10-17 2001-09-18 Purdue Research Foundation Folic acid derivatives
GB9723669D0 (en) 1997-11-07 1998-01-07 Univ Aberdeen Skin penetration enhancing components
US6399638B1 (en) 1998-04-21 2002-06-04 Bristol-Myers Squibb Company 12,13-modified epothilone derivatives
US6093382A (en) 1998-05-16 2000-07-25 Bracco Research Usa Inc. Metal complexes derivatized with folate for use in diagnostic and therapeutic applications
US6291684B1 (en) 1999-03-29 2001-09-18 Bristol-Myers Squibb Company Process for the preparation of aziridinyl epothilones from oxiranyl epothilones
ATE340592T1 (de) 1999-04-23 2006-10-15 Alza Corp Konjugate enthaltend eine spaltbare bindung zur anwendung in einem liposom
AUPQ014799A0 (en) 1999-05-04 1999-05-27 Access Pharmaceuticals Australia Pty Limited Amplification of folate-mediated targeting to tumor cells using polymers
AUPQ071299A0 (en) 1999-06-02 1999-06-24 Access Pharmaceuticals Australia Pty Limited Vitamin directed dual targeting therapy
MXPA02003771A (es) 1999-10-15 2005-04-28 Mayo Foundation Conjugados de cobalamina, utiles como agentes para obtencion de imagen y como agentes anti-tumor.
US7067111B1 (en) 1999-10-25 2006-06-27 Board Of Regents, University Of Texas System Ethylenedicysteine (EC)-drug conjugates, compositions and methods for tissue specific disease imaging
CN1441676B (zh) 2000-03-31 2012-08-22 普渡研究基金会 用配体-免疫原缀合物治疗的方法
US6670355B2 (en) 2000-06-16 2003-12-30 Wyeth Method of treating cardiovascular disease
JP2004507465A (ja) 2000-08-11 2004-03-11 ワイス エストロゲン受容体陽性癌腫の治療方法
ATE411321T1 (de) 2000-09-19 2008-10-15 Wyeth Corp Wasserlösliche rapamycin-ester
US6399625B1 (en) 2000-09-27 2002-06-04 Wyeth 1-oxorapamycins
US6399626B1 (en) 2000-10-02 2002-06-04 Wyeth Hydroxyesters of 7-desmethylrapamycin
US6440991B1 (en) 2000-10-02 2002-08-27 Wyeth Ethers of 7-desmethlrapamycin
CA2429722A1 (en) 2000-11-28 2002-06-06 Wyeth Expression analysis of fkbp nucleic acids and polypeptides useful in the diagnosis and treatment of prostate cancer
AR036993A1 (es) 2001-04-02 2004-10-20 Wyeth Corp Uso de agentes que modulan la interaccion entre pd-1 y sus ligandos en la submodulacion de respuestas inmunologicas
WO2002079499A1 (en) 2001-04-02 2002-10-10 Wyeth Pd-1, a receptor for b7-4, and uses therefor
ATE427948T1 (de) 2001-04-24 2009-04-15 Purdue Research Foundation Folat-mimetika und deren folatrezeptorbindende konjugate
US7109165B2 (en) 2001-05-18 2006-09-19 Sirna Therapeutics, Inc. Conjugates and compositions for cellular delivery
MXPA03010909A (es) 2001-06-01 2004-02-17 Bristol Myers Squibb Co Derivados de epotilona.
US20040018203A1 (en) 2001-06-08 2004-01-29 Ira Pastan Pegylation of linkers improves antitumor activity and reduces toxicity of immunoconjugates
UA77200C2 (en) 2001-08-07 2006-11-15 Wyeth Corp Antineoplastic combination of cci-779 and bkb-569
EP1419153A1 (en) 2001-08-22 2004-05-19 Wyeth Rapamycin dialdehydes
DK1419154T3 (da) 2001-08-22 2006-01-09 Wyeth Corp Rapamycin-29-enoler
EP2168598A1 (en) 2001-09-28 2010-03-31 Purdue Research Foundation Method of Treatment Using Ligand-Immunogen Conjugates
GR1004163B (el) 2001-11-01 2003-02-21 Πολυκυκλικα παραγωγα τροποποιησης των οπτικων ιδιοτητων και των ιδιοτητων αντοχης στο πλασμα των πολυμερων λιθογραφιας
US8043602B2 (en) * 2002-02-07 2011-10-25 Endocyte, Inc. Folate targeted enhanced tumor and folate receptor positive tissue optical imaging technology
US7000695B2 (en) 2002-05-02 2006-02-21 Halliburton Energy Services, Inc. Expanding wellbore junction
JP4801348B2 (ja) 2002-05-06 2011-10-26 エンドサイト，インコーポレイテッド ビタミンを標的とした造影剤
US6596757B1 (en) 2002-05-14 2003-07-22 Immunogen Inc. Cytotoxic agents comprising polyethylene glycol-containing taxanes and their therapeutic use
CA2484640C (en) 2002-05-15 2012-01-17 Endocyte, Inc. Vitamin-mitomycin conjugates
DK1523493T3 (da) 2002-07-09 2013-12-02 Alexander Doemling Nye tubulysinanaloge
CA2501752A1 (en) 2002-10-10 2004-04-22 Wyeth Compositions, organisms and methodologies employing a novel human kinase
DE10254439A1 (de) 2002-11-21 2004-06-03 GESELLSCHAFT FüR BIOTECHNOLOGISCHE FORSCHUNG MBH (GBF) Tubulysine, Herstellungsverfahren und Tubulysin-Mittel
EP1578197A4 (en) 2002-11-21 2006-05-17 Wyeth Corp COMPOSITION AND METHOD FOR THE TREATMENT OF LUPUS NEPHRITIS
WO2004069159A2 (en) 2003-01-27 2004-08-19 Endocyte, Inc. Vitamin receptor binding drug delivery conjugates
AR042938A1 (es) 2003-02-06 2005-07-06 Wyeth Corp Uso del cci-779 en el tratamiento de la fibrosis hepatica
ES2702942T3 (es) 2003-04-17 2019-03-06 Alnylam Pharmaceuticals Inc Agentes de ARNi modificados
WO2004101803A2 (en) 2003-05-12 2004-11-25 Wyeth Holdings Corporation Process for producing anticancer agent ll-d45042
EP1646635A1 (en) 2003-07-16 2006-04-19 Wyeth Cci-779 isomer c
JP4227649B2 (ja) 2003-08-07 2009-02-18 ワイス Ｃｃｉ−７７９の位置選択的合成
CN101098854B (zh) 2004-07-23 2012-12-05 恩多塞特公司 二价连接体及其轭合物
EP1791567B1 (en) 2004-08-10 2015-07-29 Alnylam Pharmaceuticals Inc. Chemically modified oligonucleotides
CN101175757B (zh) 2005-03-16 2012-11-14 恩多塞特公司 蝶酸及其缀合物的合成和纯化
ATE460668T1 (de) 2005-03-30 2010-03-15 Purdue Research Foundation Verfahren zur prognose von brustkrebs mittels quantifizierung von zellulären folat vitamin rezeptoren
EP1904183B1 (en) 2005-07-05 2014-10-15 Purdue Research Foundation Pharmaceutical composition for the treatment of osteoarthritis
EP2382995A3 (en) 2005-08-19 2013-09-25 Endocyte, Inc. Ligand conjugates of Vinca alkaloids, analogs and derivatives
BRPI0615354A2 (pt) 2005-08-19 2011-05-17 Endocyte, Inc. conjugado de liberação de fármaco de ligação de receptor, composição farmacêutica que o compreende, bem como seu uso
AR062448A1 (es) 2006-05-25 2008-11-12 Endocyte Inc Conjugados de analogos de aziridinil-epotilona y composiciones farmaceuticas que comprenden los mismos
US20100104626A1 (en) 2007-02-16 2010-04-29 Endocyte, Inc. Methods and compositions for treating and diagnosing kidney disease
AU2008224988A1 (en) 2007-03-14 2008-09-18 Endocyte, Inc. Binding ligand linked drug delivery conjugates of tubulysins

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4337339A (en) * 1979-04-30 1982-06-29 Baker Instruments Corp. Process for preparation of folic acid derivatives

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
John M.Scott.Preparation and Purification of Pteroic Acid from Pteroylglutamic Acid(Folic Acid).《methods in enzymology》.1980,第66卷658页最后一段至660页.. *
John M.Scott.Preparation and Purification of Pteroic Acid from Pteroylglutamic Acid(Folic Acid).《methods in enzymology》.1980,第66卷658页最后一段至660页。.

Also Published As

Publication number Publication date
WO2006101845A3 (en) 2007-03-29
EP1863816A2 (en) 2007-12-12
US8044200B2 (en) 2011-10-25
CN101175757A (zh) 2008-05-07
JP5289935B2 (ja) 2013-09-11
EP1863816B1 (en) 2014-06-25
JP2008538743A (ja) 2008-11-06
WO2006101845A2 (en) 2006-09-28
US20080207625A1 (en) 2008-08-28

Similar Documents

Publication Publication Date Title
CN101175757B (zh) 蝶酸及其缀合物的合成和纯化
CN114456186B (zh) 一种喜树碱类衍生物及其配体-药物偶联物
EP2349274B1 (en) Folate receptor binding conjugates of antifolates
AU2003217676B2 (en) Active agent delivery systems and methods for protecting and administering active agents
US7060708B2 (en) Active agent delivery systems and methods for protecting and administering active agents
ES2552471T3 (es) Conjugados de agonistas de TLR sintéticos y usos de los mismos
US8394813B2 (en) Active agent delivery systems and methods for protecting and administering active agents
US7427600B2 (en) Active agent delivery systems and methods for protecting and administering active agents
CN112138171B (zh) 抗体偶联药物、其中间体、制备方法及应用
JP7103953B2 (ja) 薬物としてアマトキシンの誘導体を有する抗体薬物コンジュゲート
CN109316605B (zh) 叶酸受体结合配体-药物偶联物
JP2009504803A (ja) Ｔｌｒアゴニスト
WO2021208459A1 (zh) 免疫激动剂
EP2029597A2 (en) Purine analogs
CN113941007A (zh) 一种串联的双药物链接组装单元及其应用
JP2008501038A (ja) １０−プロパルギル−１０−デアザアミノプテリンを用いるｔ細胞リンパ腫の治療
US20090306228A1 (en) Active agent delivery systems and methods for protecting and administering active agents
EP4114417A2 (en) Therapeutic agents and conjugates thereof
CN1953989A (zh) 作为细胞抑制剂的在7位与环肽缀合的喜树碱
WO2015125640A1 (ja) カンプトテシン誘導体とｈｓｐ９０阻害剤の結合した高分子化合物及びその用途
CN106456796A (zh) 用于治疗耐药性癌症及用于联合治疗的药物递送缀合物
EP4731673A1 (en) Nectin-4 antibodies and antibody-drug conjugates
CN118697897A (zh) 多肽偶联药物及其制备方法和应用
HK40097818A (zh) 用於癌症的分子成像和免疫治疗的δ -阿片受体靶向试剂
HK1107005A (en) Camptothecin derivatives conjugated in position 20 with integrin antagonists

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20121114