CA2398018C - Gonadotropin-releasing hormone receptor antagonists and methods relating thereto - Google Patents

Gonadotropin-releasing hormone receptor antagonists and methods relating thereto Download PDF

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Publication number
CA2398018C
CA2398018C CA2398018A CA2398018A CA2398018C CA 2398018 C CA2398018 C CA 2398018C CA 2398018 A CA2398018 A CA 2398018A CA 2398018 A CA2398018 A CA 2398018A CA 2398018 C CA2398018 C CA 2398018C
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compound
4alkyl
ome
substituted
halogen
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CA2398018A
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French (fr)
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CA2398018A1 (en
Inventor
Yun-Fei Zhu
Chen Chen
Fabio C. Tucci
Zhiqiang Guo
Timothy D. Gross
Martin Rowbottom
R. Scott Struthers
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Neurocrine Biosciences Inc
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Neurocrine Biosciences Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/60—Three or more oxygen or sulfur atoms
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    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
    • A—HUMAN NECESSITIES
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    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
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    • A—HUMAN NECESSITIES
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    • A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
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    • A—HUMAN NECESSITIES
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    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
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    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A61P5/02—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
    • A61P5/04—Drugs for disorders of the endocrine system of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin for decreasing, blocking or antagonising the activity of the hypothalamic hormones
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    • A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
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    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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  • Anesthesiology (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
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CA2398018A 2000-01-25 2001-01-25 Gonadotropin-releasing hormone receptor antagonists and methods relating thereto Expired - Fee Related CA2398018C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US17793300P 2000-01-25 2000-01-25
US60/177,933 2000-01-25
US23968300P 2000-10-11 2000-10-11
US60/239,683 2000-10-11
PCT/US2001/002740 WO2001055119A2 (en) 2000-01-25 2001-01-25 Gonadotropin-releasing hormone receptor antagonists and methods relating thereto

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Families Citing this family (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK1255738T3 (da) * 2000-01-25 2012-06-25 Neurocrine Biosciences Inc Gonadotropin-frigivende hormonreceptor-antagonister og fremgangsmåder relateret dertil
SE0100567D0 (sv) * 2001-02-20 2001-02-20 Astrazeneca Ab Compounds
MXPA04000985A (es) * 2001-08-02 2005-02-17 Neurocrine Biosciences Inc Piridin-4-onas sustituidas y su uso como antagonistas del receptor de hormona de liberacion de gonadotropina.
US6750350B2 (en) 2001-08-02 2004-06-15 Neurocrine Biosciences, Inc. Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
EP1495768A4 (en) * 2002-04-12 2007-12-05 Takeda Pharmaceutical MEANS FOR THE PREVENTION / TREATMENT OF HITZEWALLUNGEN
ATE557007T1 (de) * 2003-07-07 2012-05-15 Neurocrine Biosciences Inc Arylpyrimidine geeignet zur behandlung von sexualhormonbedingten zuständen wie endometriose, prostatakrebs und dergleichen
DE602004020638D1 (de) * 2003-07-07 2009-05-28 Neurocrine Biosciences Inc Pyrimidin-2,4-dion-derivate als gonadotropin freisetzende hormon-rezeptor-antagonisten
WO2005007165A1 (en) * 2003-07-07 2005-01-27 Neurocrine Biosciences, Inc. Pyrimidine-2, 4-dione derivatives as gonadotropin-releasing hormone receptor antagonists
MXPA06001601A (es) 2003-08-13 2006-08-25 Takeda Pharmaceutical Derivados de 4-pirimidona y su uso como inhibidores de dipeptidilpeptidasa.
CN102127057A (zh) * 2004-03-15 2011-07-20 武田药品工业株式会社 二肽基肽酶抑制剂
US20080262005A1 (en) * 2004-05-14 2008-10-23 Neurocrine Biosciences, Inc. Uracil-Type Gonadotropin-Releasing Hormone Receptor Antagonists and Methods Related Thereto
EP1655288A1 (en) * 2004-11-05 2006-05-10 Institut Pasteur Aryl pyrimidyl compounds, pharmaceutical compositions comprising them, their use as antimicrobial agents
SI1942898T2 (sl) 2005-09-14 2014-08-29 Takeda Pharmaceutical Company Limited Dipeptidil-peptidazni inhibitorji za zdravljenje diabetesa
EP1924567B1 (en) * 2005-09-16 2012-08-22 Takeda Pharmaceutical Company Limited Process for the preparation of pyrimidinedione derivatives
WO2007122634A2 (en) * 2006-04-24 2007-11-01 Jubilant Biosys Limited Pyrimidinediones as tyrosine kinase inhibitors
TW200838536A (en) 2006-11-29 2008-10-01 Takeda Pharmaceutical Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor
AR065948A1 (es) 2007-04-06 2009-07-15 Neurocrine Biosciences Inc Antagonistas del receptor de la hormona liberadora de gonadotropina y procedimientos relacionados con los mismos
CL2008000986A1 (es) 2007-04-06 2008-10-17 Neurocrine Biosciences Inc COMPUESTO DERIVADO DE HETEROCICLOS DE NITROGENO, AGONISTAS DEL RECEPTOR GnRH; COMPOSICION FARMACEUTICA QUE COMPRENDE A DICHO COMPUESTO; Y USO PARA TRATAR UNA AFECCION RELACIONADA CON LAS HORMONAS SEXUALES, ENDOMETRIOSIS, DISMENORREA, ENFERMEDAD DE OV
CA2682400A1 (en) * 2007-04-18 2008-11-06 Kissei Pharmaceutical Co., Ltd. Fused heterocyclic derivative, pharmaceutical composition comprising the derivative, and use of the composition for medical purposes
EP2147922B1 (en) * 2007-04-18 2017-08-02 Kissei Pharmaceutical Co., Ltd. Fused heterocyclic derivative, pharmaceutical composition comprising the derivative, and use of the composition for medical purposes
WO2009062087A1 (en) * 2007-11-07 2009-05-14 Neurocrine Biosciences, Inc. Processes for the preparation of uracil derivatives
DE102008030091B4 (de) * 2008-06-25 2011-03-03 Resprotect Gmbh Uracilderivate und deren Verwendung
CA2736970A1 (en) * 2008-09-12 2010-03-18 Biolipox Ab Pyrimidinone derivatives for use as medicaments
US9034850B2 (en) 2009-11-20 2015-05-19 Sk Chemicals Co., Ltd. Gonadotropin releasing hormone receptor antagonist, preparation method thereof and pharmaceutical composition comprising the same
TW201130854A (en) 2009-12-22 2011-09-16 Bayer Schering Pharma Ag Pyridinone derivatives and pharmaceutical compositions thereof
WO2012175514A1 (en) 2011-06-21 2012-12-27 Bayer Intellectual Property Gmbh Pyridinone derivatives and pharmaceutical compositions thereof
CA2906894A1 (en) 2013-03-15 2014-09-18 Abbvie Inc. Compositions comprising elagolix for use in treating pain associated with endometriosis
US20200113901A1 (en) * 2017-03-31 2020-04-16 Epizyme, Inc. Methods of using ehmt2 inhibitors
EP3612181A4 (en) 2017-04-21 2021-01-06 Epizyme, Inc. Combination therapies with ehmt2 inhibitors
MX2020001877A (es) 2017-08-18 2020-09-14 Abbvie Inc Formulaciones farmacéuticas para tratar la endometriosis, los fibromas uterinos, el síndrome de ovario poliquístico o la adenomiosis.
WO2019036712A1 (en) 2017-08-18 2019-02-21 Abbvie Inc. PHARMACEUTICAL FORMULATIONS FOR THE TREATMENT OF ENDOMETRIOSIS, UTERINE FIBROIDS, POLYKYSTIC OVARY SYNDROME OR ADENOMYOSIS
TW201912157A (zh) 2017-08-18 2019-04-01 美商艾伯維有限公司 治療子宮內膜異位症、子宮纖維瘤、多囊性卵巢症候群及子宮腺肌症之固體醫藥調配物
CN112261942A (zh) 2018-04-19 2021-01-22 艾伯维公司 治疗重度月经出血的方法
IL280135B2 (en) 2018-07-23 2024-06-01 Abbvie Inc Elagolix sodium compositions and processes
MX2021008457A (es) 2019-01-15 2021-10-01 Lupin Inc Composiciones de tipo elagolix deuterado y métodos.
CN111333586A (zh) * 2020-02-19 2020-06-26 诚达药业股份有限公司 一种含有6-甲基尿嘧啶结构化合物的制备方法
CN111333587B (zh) * 2020-04-11 2023-04-07 东莞市东阳光新药研发有限公司 取代的嘧啶-2,4(1h,3h)-二酮衍生物及其用途
CN113527213B (zh) * 2020-04-20 2023-01-03 上海英诺富成生物科技有限公司 促性激素释放激素受体拮抗剂及其用途
FI4122926T3 (fi) * 2021-04-14 2025-07-23 Shionogi & Co Triatsiinijohdannaisia, joilla on viruksien replikaatiota estävää aktiivisuutta, ja niitä käsittävä lääkekoostumus

Family Cites Families (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2631625B1 (fr) * 1988-05-17 1992-10-16 Synthelabo Derives de phenyl-6 piperazinylalkyl-3 1h,3h-pyrimidinedione-2,4, leur preparation et leur application en therapeutique
US5140029A (en) 1989-01-09 1992-08-18 Janssen Pharmaceutica N.V. 2-aminopyrimidinone derivatives
US5476855A (en) * 1993-11-02 1995-12-19 Mahmoud H. el Kouni Enzyme inhibitors, their synthesis and methods for use
UY23948A1 (es) * 1995-02-08 2001-10-25 Takeda Chemical Industries Ltd Derivados de anillos condensados de tiofeno su producción y uso.
EP0828731A1 (en) 1995-06-01 1998-03-18 Takeda Chemical Industries, Ltd. TRICYCLIC DIAZEPINES USEFUL AS GnRH RECEPTOR ANTAGONISTS
ATE201016T1 (de) * 1995-06-09 2001-05-15 Hoffmann La Roche Pyrimidindion-, pyrimidintrion-, triazindion- derivate als alpha-1-adrenergische rezeptorantagonisten
US5859014A (en) 1995-06-09 1999-01-12 Syntex (U.S.A.) Inc. Pyrimidinedione, pyrimidinetrione, triazinedione and tetrahydroquinazolinedione derivatives as α1 -adrenergic receptor antagonists
CN1063446C (zh) 1995-10-19 2001-03-21 武田药品工业株式会社 作为促性腺激素释放激素拮抗剂的噻吩并吡啶衍生物
AU7333496A (en) 1995-10-19 1997-05-07 Takeda Chemical Industries Ltd. Quinoline derivatives as gnrh antagonists
US5780437A (en) 1995-12-14 1998-07-14 Merck & Co., Inc. Antagonists of gonadotropin releasing hormone
EA000992B1 (ru) 1995-12-14 2000-08-28 Мерк Энд Ко., Инк. Антагонисты гормона, высвобождающего гонадотропин
HUP9902121A3 (en) 1995-12-14 2001-05-28 Merck & Co Inc Indole derivatives as antagonists of gonadotropin releasing hormone and pharmaceutical compositions containing them
US5849764A (en) 1995-12-14 1998-12-15 Merck & Co., Inc. Antagonists of gonadotropin releasing hormone
CA2240115A1 (en) 1995-12-14 1997-06-19 Wallace T. Ashton Antagonists of gonadotropin releasing hormone
US6197975B1 (en) 1995-12-14 2001-03-06 Merck & Co. , Inc. Antagonists of gonadotropin releasing hormone
JPH09286786A (ja) * 1996-04-18 1997-11-04 Nippon Paper Ind Co Ltd ピリミジン誘導体及びその抗腫瘍剤としての用途
JP2000511532A (ja) 1996-05-20 2000-09-05 メルク エンド カンパニー インコーポレーテッド 性腺刺激ホルモン放出ホルモンのアンタゴニスト
CA2254768A1 (en) 1996-05-20 1997-11-27 Jinlong Jiang Antagonists of gonadotropin releasing hormone
EP0918522A4 (en) 1996-05-20 1999-08-18 Merck & Co Inc GONADOLIBERIN ANTAGONISTS
WO1997044041A1 (en) 1996-05-20 1997-11-27 Merck & Co., Inc. Antagonists of gonadotropin releasing hormone
JP2002502422A (ja) 1997-06-05 2002-01-22 メルク エンド カンパニー インコーポレーテッド ゴナドトロピン放出ホルモンの拮抗薬
CA2291829A1 (en) 1997-06-05 1998-12-10 Merck & Co., Inc. Antagonists of gonadotropin releasing hormone
AU729752B2 (en) 1997-06-05 2001-02-08 Merck & Co., Inc. Antagonists of gonadotropin releasing hormone
JP2002502427A (ja) 1997-06-05 2002-01-22 メルク エンド カンパニー インコーポレーテッド ゴナドトロピン放出ホルモンの拮抗薬
US6313301B1 (en) 1997-08-13 2001-11-06 Takeda Chemical Industries, Ltd. Thienopyridine derivatives, their intermediates and production thereof
AU1687199A (en) 1997-12-26 1999-07-19 Takeda Chemical Industries Ltd. Nitrogen-containing heterocyclic compounds, their production and use
WO1999051232A1 (en) 1998-04-02 1999-10-14 Merck & Co., Inc. Antagonists of gonadotropin releasing hormone
WO2000029386A1 (en) * 1998-11-12 2000-05-25 Merck & Co., Inc. Pyrimidinedione derivatives useful as alpha 1a adrenoceptor antagonists
MXPA01011634A (es) 1999-05-14 2002-07-30 Neurocrine Biosciences Inc Imidazo- y pirrolo [1,2-a]pirimid-4-onas como antagonistas receptores de la hormona liberadora de gonadotropina.
AU771740B2 (en) * 1999-05-19 2004-04-01 Pharmacia Corporation Substituted polycyclic aryl and heteroaryl uracils as anticoagulative agents
ES1043085Y (es) * 1999-06-03 2001-02-01 Nueva Ceramica Arb Sa Teja planoconvexa
CA2386942A1 (en) 1999-10-15 2001-04-26 Neurocrine Biosciences, Inc. Gonadotropin-releasing hormone receptor antagonists and methods relating thereto
DK1255738T3 (da) * 2000-01-25 2012-06-25 Neurocrine Biosciences Inc Gonadotropin-frigivende hormonreceptor-antagonister og fremgangsmåder relateret dertil
ATE557007T1 (de) * 2003-07-07 2012-05-15 Neurocrine Biosciences Inc Arylpyrimidine geeignet zur behandlung von sexualhormonbedingten zuständen wie endometriose, prostatakrebs und dergleichen
DE602004020638D1 (de) * 2003-07-07 2009-05-28 Neurocrine Biosciences Inc Pyrimidin-2,4-dion-derivate als gonadotropin freisetzende hormon-rezeptor-antagonisten
WO2005007165A1 (en) * 2003-07-07 2005-01-27 Neurocrine Biosciences, Inc. Pyrimidine-2, 4-dione derivatives as gonadotropin-releasing hormone receptor antagonists

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CA2398018A1 (en) 2001-08-02
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AU767585B2 (en) 2003-11-20
US6608197B2 (en) 2003-08-19
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NO20023525L (no) 2002-07-24
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AU3797501A (en) 2001-08-07
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US20040048884A1 (en) 2004-03-11
CY1112815T1 (el) 2016-02-10
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US6872728B2 (en) 2005-03-29
EP1255738A2 (en) 2002-11-13
US7462625B2 (en) 2008-12-09
US20050234082A1 (en) 2005-10-20
EP1255738B1 (en) 2012-03-07
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