DE69910045D1 - Neue heteroaromatische fructose 1,6-bisphosphatase inhibitoren - Google Patents

Neue heteroaromatische fructose 1,6-bisphosphatase inhibitoren

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Publication number
DE69910045D1
DE69910045D1 DE69910045T DE69910045T DE69910045D1 DE 69910045 D1 DE69910045 D1 DE 69910045D1 DE 69910045 T DE69910045 T DE 69910045T DE 69910045 T DE69910045 T DE 69910045T DE 69910045 D1 DE69910045 D1 DE 69910045D1
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Germany
Prior art keywords
fructose
bisphosphatase inhibitors
new heteroaromatic
heteroaromatic
new
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 - Lifetime
Application number
DE69910045T
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English (en)
Other versions
DE69910045T2 (de
Inventor
Qun Dang
Rao Kasibhatla
Raja Reddy
D Erion
Rami Reddy
Atul Agarwal
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.)
Metabasis Therapeutics Inc
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Metabasis Therapeutics Inc
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Application filed by Metabasis Therapeutics Inc filed Critical Metabasis Therapeutics Inc
Publication of DE69910045D1 publication Critical patent/DE69910045D1/de
Application granted granted Critical
Publication of DE69910045T2 publication Critical patent/DE69910045T2/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
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    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40—Esters thereof
    • C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
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    • A61P3/06—Antihyperlipidemics
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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    • A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
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    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
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    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6536—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and sulfur atoms with or without oxygen atoms, as the only ring hetero atoms
    • C07F9/6539—Five-membered rings
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    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
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    • C07F9/65517—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring condensed with carbocyclic rings or carbocyclic ring systems
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    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
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    • C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
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    • C07F9/6571—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms
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    • C07F9/657181—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and oxygen atoms as the only ring hetero atoms the ring phosphorus atom being bound to at least one carbon atom the ring phosphorus atom and, at least, one ring oxygen atom being part of a (thio)phosphonic acid derivative
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    • C07F9/6578—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having phosphorus atoms, with or without nitrogen, oxygen, sulfur, selenium or tellurium atoms, as ring hetero atoms having phosphorus and sulfur atoms with or without oxygen atoms, as ring hetero atoms
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    • C07F9/65842—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring
    • C07F9/65846—Cyclic amide derivatives of acids of phosphorus, in which one nitrogen atom belongs to the ring the phosphorus atom being part of a six-membered ring which may be condensed with another ring system

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DE69910045T 1998-09-09 1999-09-03 Neue heteroaromatische fructose 1,6-bisphosphatase inhibitoren Expired - Lifetime DE69910045T2 (de)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US13550498P 1998-09-09 1998-09-09
US135504P 1998-09-09
US11107798P 1998-12-07 1998-12-07
US111077P 1998-12-07
PCT/US1999/020346 WO2000014095A1 (en) 1998-09-09 1999-09-03 Novel heteroaromatic inhibitors of fructose 1,6-bisphosphatase

Publications (2)

Publication Number Publication Date
DE69910045D1 true DE69910045D1 (de) 2003-09-04
DE69910045T2 DE69910045T2 (de) 2004-04-22

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DE69910045T Expired - Lifetime DE69910045T2 (de) 1998-09-09 1999-09-03 Neue heteroaromatische fructose 1,6-bisphosphatase inhibitoren

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US (4) US6489476B1 (de)
EP (1) EP1112275B9 (de)
JP (1) JP2002524463A (de)
KR (2) KR20070053264A (de)
CN (1) CN1215076C (de)
AT (1) ATE246197T1 (de)
AU (1) AU761267C (de)
BR (1) BR9913532A (de)
CA (1) CA2343027A1 (de)
CZ (1) CZ297264B6 (de)
DE (1) DE69910045T2 (de)
DK (1) DK1112275T3 (de)
ES (1) ES2204170T3 (de)
HK (1) HK1042496B (de)
HU (1) HUP0103143A3 (de)
NO (1) NO20011174L (de)
NZ (1) NZ510308A (de)
PL (1) PL205184B1 (de)
PT (1) PT1112275E (de)
SK (1) SK286080B6 (de)
WO (1) WO2000014095A1 (de)

Families Citing this family (144)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998039344A1 (en) 1997-03-07 1998-09-11 Metabasis Therapeutics, Inc. Novel purine inhibitors of fructose-1,6-bisphosphatase
US6312662B1 (en) 1998-03-06 2001-11-06 Metabasis Therapeutics, Inc. Prodrugs phosphorus-containing compounds
EP1112275B9 (de) * 1998-09-09 2004-03-10 Metabasis Therapeutics, Inc. Neue heteroaromatische fructose 1,6-bisphosphatase inhibitoren
US6756360B1 (en) * 1998-12-24 2004-06-29 Metabasis Therapeutics, Inc. Combination of FBPase inhibitors and insulin sensitizers for the treatment of diabetes
CA2362805A1 (en) * 1999-03-05 2000-09-08 Metabasis Therapeutics, Inc. Novel phosphorus-containing prodrugs
US7205404B1 (en) * 1999-03-05 2007-04-17 Metabasis Therapeutics, Inc. Phosphorus-containing prodrugs
GB9923078D0 (en) * 1999-09-29 1999-12-01 Phytopharm Plc Sapogenin derivatives and their use
EP1240174A2 (de) * 1999-12-22 2002-09-18 Metabasis Therapeutics, Inc. Neue bisamidat phosphonat prodrogen
JP2003520226A (ja) 2000-01-21 2003-07-02 ノバルティス アクチエンゲゼルシャフト ジペプチジルペプチダーゼ−ｉｖ阻害剤および抗糖尿病薬剤を含む組合せ物
AU4553201A (en) * 2000-03-08 2001-09-17 Metabasis Therapeutics Inc Novel aryl fructose-1,6-bisphosphatase inhibitors
US7563774B2 (en) * 2000-06-29 2009-07-21 Metabasis Therapeutics, Inc. Combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes
BR0112212A (pt) * 2000-07-06 2003-12-30 Metabasis Therapeutics Inc Uma combinação de inibidores de fbpase e agentes antidiabéticos úteis para o tratamento de diabetes
US20070129334A1 (en) * 2001-10-30 2007-06-07 Conforma Therapeutics Corporation Orally Active Purine-Based Inhibitors of Heat Shock Protein 90
EP1504014B1 (de) * 2002-05-13 2015-12-02 Metabasis Therapeutics, Inc. Verfahren zur herstellung zyklischer prodrugs von pmea und pmpa
EP1532157A4 (de) * 2002-05-13 2009-02-25 Metabasis Therapeutics Inc Neue prodrugs von pmea auf phosphonsäurebasis und ihre analoga
EP1535630A1 (de) * 2002-07-23 2005-06-01 Sankyo Company, Limited Mittel zur verhinderung des auftretens von diabetes
MXPA05004504A (es) * 2002-10-31 2005-08-16 Metabasis Therapeutics Inc Nuevos di-esteres de fosfato ciclicos de 1,3-propano-1-aril-dioles y su uso en la preparacion de profarmacos.
US20040254228A1 (en) * 2002-12-20 2004-12-16 Lin Zhao Treatment of chronic heart failure
US20040122067A1 (en) * 2002-12-20 2004-06-24 Lin Zhao Treatment of chronic heart failure
WO2004072051A1 (en) * 2003-02-11 2004-08-26 Vernalis (Cambridge) Limited Isoxazole compounds as inhibitors of heat shock proteins
JP2007512359A (ja) 2003-11-19 2007-05-17 メタバシス・セラピューティクス・インコーポレイテッド 新規なリン含有甲状腺ホルモン様物質
US7129049B2 (en) * 2003-12-22 2006-10-31 Regents Of The University Of Minnesota Method of detecting equine glycogen storage disease IV
DK1700856T3 (en) * 2003-12-26 2015-12-14 Kyowa Hakko Kirin Co Ltd thiazole
EP1732905A1 (de) * 2004-03-31 2006-12-20 Lexicon Genetics Incorporated 2-aminomethylthiazol-5-carbonsäureamide als proteinkinasemodulatoren
JP2007261945A (ja) * 2004-04-07 2007-10-11 Taisho Pharmaceut Co Ltd チアゾール誘導体
CN1964967B (zh) * 2004-06-08 2014-04-16 症变治疗公司 路易斯酸介导的环状酯的合成
BRPI0514372A (pt) * 2004-08-18 2008-06-10 Metabasis Therapeutics Inc inibidores de tiazol de frutose 1, 6-bisfosfatase
TW200633720A (en) * 2004-12-13 2006-10-01 Sankyo Co Medicinal composition for diabetic
TW200633702A (en) * 2004-12-15 2006-10-01 Sankyo Co Medicinal composition containing fbpase inhibitor
WO2008134474A2 (en) 2007-04-27 2008-11-06 The Board Of Trustees Of The University Of Illinois Compositions and methods including cell death inducers and procaspase activation
EP1894930A4 (de) 2005-06-23 2010-06-23 Kyowa Hakko Kirin Co Ltd Thiazolderivat
FR2889190A1 (fr) * 2005-08-01 2007-02-02 Merck Sante Soc Par Actions Si Nouveaux derives d'imidazoles carboxamides comme inhibiteurs de fructose -1,6-biphosphatase et compositions pharmaceutiques les contenant
EP1752450A1 (de) 2005-08-01 2007-02-14 Merck Sante Imidazolderivate als Fruktose-1,6-biphosphataseinhibitoren und pharmazeutische Zusammensetzungen diese enthaltend
CA2622608C (en) 2005-09-14 2014-08-19 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors for treating diabetes
AU2007253753A1 (en) 2006-05-19 2007-11-29 Board Of Trustees Of The University Of Illinois Phosphorous containing compounds including triphenylmethylphosphonate esters for the treatment of melanoma and other cancers
WO2008063842A2 (en) * 2006-11-02 2008-05-29 Aestus Therapeutics, Inc. Methods of treating neuropathic pain with agonists of ppar-gamma
US8222870B2 (en) * 2007-03-07 2012-07-17 O2Micro, Inc Battery management systems with adjustable charging current
US20080218127A1 (en) * 2007-03-07 2008-09-11 O2Micro Inc. Battery management systems with controllable adapter output
US7973515B2 (en) * 2007-03-07 2011-07-05 O2Micro, Inc Power management systems with controllable adapter output
CA2695583A1 (en) 2007-08-13 2009-02-19 Metabasis Therapeutics, Inc. Novel activators of glucokinase
EP2058308A1 (de) 2007-11-12 2009-05-13 Merck Sante Benzimidazoldihydrothiadiazinonderivate als Fructose-1,6-biphosphatase-Hemmer und diese enthaltende pharmazeutische Zusammensetzungen.
US8111038B2 (en) * 2008-06-12 2012-02-07 O2 Micro, Inc Vehicle electronic systems with battery management functions
EP3924343A1 (de) * 2008-09-26 2021-12-22 Merck Sharp & Dohme Corp. Neue, cyclische benzimidazolderivate, die sich als antidiabetische mittel eignen
AU2009307884B2 (en) 2008-10-22 2014-07-31 Merck Sharp & Dohme Corp. Novel cyclic benzimidazole derivatives useful anti-diabetic agents
CN102271511A (zh) 2008-10-29 2011-12-07 默沙东公司 可用作抗糖尿病剂的新颖的环状苯并咪唑衍生物
EP2362731B1 (de) 2008-10-31 2016-04-06 Merck Sharp & Dohme Corp. Neue nützlich anti-diabetische mittel mit zyklische benzimidazol-derivate
JO2870B1 (en) 2008-11-13 2015-03-15 ميرك شارب اند دوهم كورب Amino Tetra Hydro Pirans as Inhibitors of Peptide Dipeptide IV for the Treatment or Prevention of Diabetes
WO2010056717A1 (en) 2008-11-17 2010-05-20 Merck Sharp & Dohme Corp. Substituted bicyclic amines for the treatment of diabetes
JP5896746B2 (ja) 2009-02-09 2016-03-30 ザ ボード オブ トラスティーズ オブ ザ ユニバーシティ オブ イリノイ 個別化された抗癌薬としてのプロカスパーゼ活性化化合物の設計、合成および評価
WO2010093601A1 (en) 2009-02-10 2010-08-19 Metabasis Therapeutics, Inc. Novel sulfonic acid-containing thyromimetics, and methods for their use
EP3366686B9 (de) 2009-03-20 2021-08-04 Metabasis Therapeutics, Inc. Inhibitoren von diacylglycerin-o-acyltransferase 1 (dgat-1) und verwendungen davon
US20120220567A1 (en) 2009-07-23 2012-08-30 Shipps Jr Gerald W Benzo-fused oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors
WO2011011506A1 (en) 2009-07-23 2011-01-27 Schering Corporation Spirocyclic oxazepine compounds as stearoyl-coenzyme a delta-9 desaturase inhibitors
WO2011019538A1 (en) 2009-08-13 2011-02-17 Merck Sharp & Dohme Corp. Substituted cyclopropyl compounds, compositions containing such compounds and methods of treatment
CN102595897A (zh) 2009-09-02 2012-07-18 默沙东公司 作为用于糖尿病的治疗或预防的二肽基肽酶-iv抑制剂的氨基四氢吡喃
WO2011041293A1 (en) 2009-09-30 2011-04-07 Takeda Pharmaceutical Company Limited Pyrazolo [1, 5-a] pyrimidine derivatives as apoptosis signal-regulating kinase 1 inhibitors
CA2787360C (en) 2010-02-03 2019-03-05 Takeda Pharmaceutical Company Limited Pyrrol0[3,2-c]pyridinyl-4-benzamide compounds and their use as apoptosis signal-regulating kinase 1 inhibitors
US8853212B2 (en) 2010-02-22 2014-10-07 Merck Sharp & Dohme Corp Substituted aminotetrahydrothiopyrans and derivatives thereof as dipeptidyl peptidase-IV inhibitors for the treatment of diabetes
JP2013520502A (ja) 2010-02-25 2013-06-06 メルク・シャープ・エンド・ドーム・コーポレイション 有用な抗糖尿病薬である新規な環状ベンズイミダゾール誘導体
US8980929B2 (en) 2010-05-21 2015-03-17 Merck Sharp & Dohme Corp. Substituted seven-membered heterocyclic compounds as dipeptidyl peptidase-iv inhibitors for the treatment of diabetes
WO2012024183A1 (en) 2010-08-18 2012-02-23 Merck Sharp & Dohme Corp. Spiroxazolidinone compounds
WO2012116050A2 (en) * 2011-02-24 2012-08-30 Eternity Bioscience Inc. Phosphorus containing compounds as protein kinase inhibitors
EA201690035A1 (ru) 2011-02-25 2016-05-31 Мерк Шарп Энд Домэ Корп. Новые циклические производные азабензимидазола, используемые в качестве антидиабетических агентов
EP2693882B1 (de) 2011-04-08 2017-06-28 Merck Sharp & Dohme Corp. Substituierte cyclopropylverbindungen, zusammensetzungen mit solchen verbindungen und behandlungsverfahren damit
JP2014518890A (ja) 2011-06-02 2014-08-07 インターベット インターナショナル ベー． フェー． イミダゾール誘導体
WO2012173917A1 (en) 2011-06-16 2012-12-20 Merck Sharp & Dohme Corp. Substituted cyclopropyl compounds, compositions containing such compounds, and methods of treatment
WO2013048916A1 (en) 2011-09-30 2013-04-04 Merck Sharp & Dohme Corp. Substituted cyclopropyl compounds, compositions containing such compounds and methods of treatment
EP2771000B1 (de) 2011-10-24 2016-05-04 Merck Sharp & Dohme Corp. Substituierte piperidinylverbindungen als gpr119-agonisten
WO2013068328A1 (en) 2011-11-07 2013-05-16 Intervet International B.V. Bicyclo [2.2.2] octan-1-ylcarboxylic acid compounds as dgat-1 inhibitors
WO2013068439A1 (en) 2011-11-09 2013-05-16 Intervet International B.V. 4-amino-5-oxo-7,8-dihydropyrimido[5, 4 -f] [1, 4] oxazepine compounds as dgat1 inhibitors
EP2780337B1 (de) 2011-11-15 2017-12-20 Merck Sharp & Dohme Corp. Substituierte cyclopropylverbindungen als gpr119-agonisten
WO2013074581A1 (en) * 2011-11-15 2013-05-23 Weihua Zhang Fructose-1,6-biphosphatases as new targets for diagnosing and treating breast cancer brain metastasis
EP2814485A4 (de) 2012-02-17 2015-08-26 Merck Sharp & Dohme Dipeptidylpeptidase-iv-inhibitoren zur behandlung oder prävention von diabetes
CN104411710A (zh) 2012-04-16 2015-03-11 卡内克制药公司 作为ptp-1b抑制剂前体的稠合的芳族膦酸酯衍生物
WO2014018350A1 (en) 2012-07-23 2014-01-30 Merck Sharp & Dohme Corp. Treating diabetes with dipeptidyl peptidase-iv inhibitors
WO2014022528A1 (en) 2012-08-02 2014-02-06 Merck Sharp & Dohme Corp. Antidiabetic tricyclic compounds
EP2887807B1 (de) 2012-08-22 2019-09-18 Merck Sharp & Dohme Corp. Benzimidazol-hexahydrofuro[3,2-b]furanderivate als amp-aktivierte proteinkinase-aktivatoren
EP2888005B1 (de) 2012-08-22 2019-04-03 Merck Sharp & Dohme Corp. Neuartige azabenzimidazol-hexahydrofuro[3,2-b]furan-derivate
US9527839B2 (en) 2012-08-22 2016-12-27 Merck Sharp & Dohme Corp. Benzimidazole tetrahydropyran derivatives
US9868733B2 (en) 2012-08-22 2018-01-16 Merck Sharp & Dohme Corp. Azabenzimidazole tetrahydrofuran derivatives
WO2014031441A1 (en) 2012-08-22 2014-02-27 Merck Sharp & Dohme Corp. Novel benzimidazole tetrahydrofuran derivatives
EP2888006B1 (de) 2012-08-22 2019-04-24 Merck Sharp & Dohme Corp. Neuartige azabenzimidazol-tetrahydropyran-derivate als ampk aktivatoren
CN103665043B (zh) 2012-08-30 2017-11-10 江苏豪森药业集团有限公司 一种替诺福韦前药及其在医药上的应用
US9453038B2 (en) 2012-12-17 2016-09-27 Merck Sharp & Dohme Corp. Glucokinase activator compounds, compositions containing such compounds, and methods of treatment
EP2970119B1 (de) 2013-03-14 2021-11-03 Merck Sharp & Dohme Corp. Neuartige indolderivate als antidiabetika
WO2015051496A1 (en) 2013-10-08 2015-04-16 Merck Sharp & Dohme Corp. Antidiabetic tricyclic compounds
ES2747973T3 (es) 2013-11-15 2020-03-12 Merck Sharp & Dohme Compuestos tricíclicos antidiabéticos
WO2015089809A1 (en) 2013-12-19 2015-06-25 Merck Sharp & Dohme Corp. Antidiabetic substituted heteroaryl compounds
WO2015112465A1 (en) 2014-01-24 2015-07-30 Merck Sharp & Dohme Corp. Isoquinoline derivatives as mgat2 inhibitors
US10449210B2 (en) 2014-02-13 2019-10-22 Ligand Pharmaceuticals Inc. Prodrug compounds and their uses
US9732103B2 (en) 2014-02-25 2017-08-15 Achillion Pharmaceuticals, Inc. Carbamate, ester, and ketone compounds for treatment of complement mediated disorders
WO2015176267A1 (en) 2014-05-22 2015-11-26 Merck Sharp & Dohme Corp. Antidiabetic tricyclic compounds
JP2017520545A (ja) 2014-07-02 2017-07-27 リガンド・ファーマシューティカルズ・インコーポレイテッド プロドラッグ化合物およびそれらの使用
US10100042B2 (en) 2014-08-08 2018-10-16 Merck Sharp & Dohme Corp. [5,6]—fused bicyclic antidiabetic compounds
EP3177282B1 (de) 2014-08-08 2021-10-06 Merck Sharp & Dohme Corp. Antidiabetische bicyclische verbindungen
US10968193B2 (en) 2014-08-08 2021-04-06 Merck Sharp & Dohme Corp. Antidiabetic bicyclic compounds
MA55068A (fr) 2014-10-24 2022-01-05 Merck Sharp & Dohme Co-agonistes des récepteurs du glucagon et du glp-1
PE20171058A1 (es) 2014-10-31 2017-07-21 Ngm Biopharmaceuticals Inc Composiciones y metodos de uso para tratar trastornos metabolicos
TW201625635A (zh) 2014-11-21 2016-07-16 默沙東藥廠 作為可溶性鳥苷酸環化酶活化劑之三唑并吡基衍生物
EP3303342B1 (de) 2015-05-27 2021-03-17 Merck Sharp & Dohme Corp. Als lösliche guanylat-cyclase-aktivatoren geeignete imidazopyrazinylderivate
US10213429B2 (en) 2015-05-28 2019-02-26 Merck Sharp & Dohme Corp. Imidazo-pyrazinyl derivatives useful as soluble guanylate cyclase activators
AR105808A1 (es) 2015-08-26 2017-11-08 Achillion Pharmaceuticals Inc Compuestos de amida para el tratamiento de trastornos médicos
WO2017035355A1 (en) 2015-08-26 2017-03-02 Achillion Pharmaceuticals, Inc. Ether compounds for treatment of medical disorders
WO2017035405A1 (en) 2015-08-26 2017-03-02 Achillion Pharmaceuticals, Inc. Amino compounds for treatment of immune and inflammatory disorders
WO2017035409A1 (en) 2015-08-26 2017-03-02 Achillion Pharmaceuticals, Inc. Aryl, heteroaryl, and heterocyclic compounds for treatment of immune and inflammatory disorders
EP3340982B1 (de) 2015-08-26 2021-12-15 Achillion Pharmaceuticals, Inc. Verbindungen zur behandlung von immun- und entzündungserkrankungen
WO2017035361A1 (en) 2015-08-26 2017-03-02 Achillion Pharmaceuticals, Inc. Disubstituted compounds for the treatment of medical disorders
WO2017035401A1 (en) 2015-08-26 2017-03-02 Achillion Pharmaceuticals, Inc. Amide compounds for treatment of immune and inflammatory disorders
AR106018A1 (es) 2015-08-26 2017-12-06 Achillion Pharmaceuticals Inc Compuestos de arilo, heteroarilo y heterocíclicos para el tratamiento de trastornos médicos
AR105809A1 (es) 2015-08-26 2017-11-08 Achillion Pharmaceuticals Inc Compuestos para el tratamiento de trastornos médicos
WO2017035351A1 (en) 2015-08-26 2017-03-02 Achillion Pharmaceuticals, Inc. Amino compounds for treatment of medical disorders
WO2017035357A1 (en) * 2015-08-26 2017-03-02 Achillion Pharmaceuticals, Inc. Phosphonate compounds for treatment of medical disorders
JP2018528254A (ja) * 2015-09-22 2018-09-27 バイキング セラピューティクス，インコーポレーテッド グルコース産生阻害物質との併用療法
US10800826B2 (en) 2015-10-05 2020-10-13 Merck Sharp & Dohme Corp. Antibody peptide conjugates that have agonist activity at both the glucagon and glucagon-like peptide 1 receptors
WO2017095724A1 (en) 2015-11-30 2017-06-08 Merck Sharp & Dohme Corp. Aryl sulfonamides as blt1 antagonists
WO2017107052A1 (en) 2015-12-22 2017-06-29 Merck Sharp & Dohme Corp. Soluble guanylate cyclase stimulators
WO2017197555A1 (en) 2016-05-16 2017-11-23 Merck Sharp & Dohme Corp. Fused pyrazine derivatives useful as soluble guanylate cyclase stimulators
WO2017201683A1 (en) 2016-05-25 2017-11-30 Merck Sharp & Dohme Corp. Substituted tetrahydroisoquinoline compounds useful as gpr120 agonists
US10414774B2 (en) 2016-08-15 2019-09-17 Merck Sharp & Dohme Corp. Compound useful for altering the levels of bile acids for the treatment of diabetes and cardiometabolc disease
WO2018034917A1 (en) 2016-08-15 2018-02-22 Merck Sharp & Dohme Corp. Compounds useful for altering the levels of bile acids for the treatment of diabetes and cardiometabolic disease
US11008313B2 (en) 2016-09-20 2021-05-18 Merck Sharp & Dohme Corp. Substituted 1-methyl-1,2,3,4-tetrahydroisoquinoline molecules as PCSK9 allosteric binders
BR112019009731A2 (pt) 2016-11-18 2019-08-13 Merck Sharp & Dohme composto, composição farmacêutica, uso de um composto, e, método de tratamento
WO2018107415A1 (en) 2016-12-15 2018-06-21 Merck Sharp & Dohme Corp. Hydroxy isoxazole compounds useful as gpr120 agonists
WO2018160891A1 (en) 2017-03-01 2018-09-07 Achillion Pharmaceutical, Inc. Pharmaceutical compounds for treatment of medical disorders
WO2018160892A1 (en) 2017-03-01 2018-09-07 Achillion Pharmaceuticals, Inc. Macrocyclic compounds for treatment of medical disorders
KR20240019857A (ko) 2017-03-01 2024-02-14 아칠리온 파르마세우티칼스 인코포레이티드 의학적 장애의 치료를 위한 아릴, 헤테로아릴, 및 헤테로사이클릭 약학적 화합물
WO2018175670A1 (en) 2017-03-22 2018-09-27 The Research Foundation For The State University Of New York Matrix metalloproteinase-9 hemopexin domain inhibitors and methods of treatment using same
WO2019028284A1 (en) 2017-08-02 2019-02-07 Achillion Pharmaceuticals, Inc. THERAPEUTIC REGIMES FOR THE TREATMENT OF NOCTURNAL PAROXYSTIC HEMOGLOBINURIA
US11970482B2 (en) 2018-01-09 2024-04-30 Ligand Pharmaceuticals Inc. Acetal compounds and therapeutic uses thereof
JOP20190150A1 (ar) 2018-06-21 2019-12-21 Merck Sharp & Dohme مركبات مناهضة لـ pcsk9
EP3846803A4 (de) 2018-09-06 2022-08-10 Achillion Pharmaceuticals, Inc. Makrocyclische verbindungen zur behandlung von medizinischen erkrankungen
CA3111810A1 (en) 2018-09-06 2020-03-12 Achillion Pharmaceuticals, Inc. Morphic forms of dancopan
JP2022502500A (ja) 2018-09-25 2022-01-11 アキリオン ファーマシューティカルズ， インコーポレーテッド 補体因子ｄ阻害剤の形態
KR102691198B1 (ko) 2019-03-28 2024-08-05 백동민 로봇청소기 및 그 제어방법
WO2020205688A1 (en) 2019-04-04 2020-10-08 Merck Sharp & Dohme Corp. Inhibitors of histone deacetylase-3 useful for the treatment of cancer, inflammation, neurodegeneration diseases and diabetes
TW202123960A (zh) 2019-08-30 2021-07-01 美商默沙東藥廠 Pcsk9拮抗劑化合物
EP3842061A1 (de) 2019-12-23 2021-06-30 Merck Sharp & Dohme Corp. Geheftete triazol-co-agonisten der glucagon- und glp-1-rezeptoren
EP3842060A1 (de) 2019-12-23 2021-06-30 Merck Sharp & Dohme Corp. Geheftete lactam-co-agonisten der glucagon- und glp-1-rezeptoren
EP3842449A1 (de) 2019-12-23 2021-06-30 Merck Sharp & Dohme Corp. Geklammerte olefin-co-agonisten der glucagon- und glp-1-rezeptoren
AR122092A1 (es) 2020-05-18 2022-08-10 Merck Sharp & Dohme Inhibidores de diacilglicerol o-aciltransferasa 2
AR123700A1 (es) 2020-10-08 2023-01-04 Merck Sharp & Dohme Preparación de derivados de benzoimidazolona como nuevos inhibidores de la diacilglicerol o-aciltransferasa 2
IL310851A (en) 2021-08-19 2024-04-01 Merck Sharp & Dohme Llc Compounds for the treatment of diseases associated with PCSK9 activity
TW202404574A (zh) 2022-06-15 2024-02-01 美商默沙東有限責任公司 用於捕捉介白素-1 β之環狀肽
US20240254114A1 (en) 2022-12-02 2024-08-01 Merck Sharp & Dohme Llc Preparation of fused azole derivatives as novel diacylglyceride 0-acyltransferase 2 inhibitors

Family Cites Families (68)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR34480E (de) 1929-01-17 1929-06-19
US3551422A (en) 1968-03-27 1970-12-29 Stevens & Co Inc J P N-(oxymethyl) derivatives of phosphonopolyamino-s-triazines
US3822296A (en) * 1969-01-23 1974-07-02 Merck & Co Inc 1-trifluoromethyl-1,2-epoxyethyl-1-phosphonic acid and its salts
US3657282A (en) * 1969-01-23 1972-04-18 Merck & Co Inc Carboxyepoxyethyl-1-phosphonic acid and derivatives
GB1343022A (en) 1970-04-19 1974-01-10 British Oxygen Co Ltd Phosphorus-containing guanamines
US4000305A (en) * 1972-09-27 1976-12-28 Imperial Chemical Industries Limited 15-, 16- AND 17-Indolyl or indolinyl nor prostanoic acid derivatives
GB1428137A (en) 1972-09-27 1976-03-17 Ici Ltd Prostanoic acid derivatives
GB1516347A (en) 1975-09-16 1978-07-05 Ici Ltd Process for the preparation of alkylphosphonate esters
US4092323A (en) 1975-09-16 1978-05-30 Imperial Chemical Industries Limited Hydrazine derivatives of pyridyl-ketones
DE2855659A1 (de) 1978-12-22 1980-07-03 Bayer Ag Benzimidazolyl-2-alkan-phosphonsaeuren
ZA81140B (en) 1980-01-10 1982-02-24 Nyegaard & Co As Pyrimidine-2-sulphides and their s-oxides for use in medicine and methods of use therefor,pharmaceutical compositions containing them,processes for their preparation and such compounds when novel per se
FR2531088B1 (fr) 1982-07-29 1987-08-28 Sanofi Sa Produits anti-inflammatoires derives de l'acide methylenediphosphonique et leur procede de preparation
IL77243A (en) 1984-12-21 1996-11-14 Procter & Gamble Pharmaceutical compositions containing geminal diphosphonic acid compounds and certain such novel compounds
US4902679A (en) 1985-12-13 1990-02-20 Norwich Eaton Pharmaceuticals, Inc. Methods of treating diseases with certain geminal diphosphonates
US4968788A (en) 1986-04-04 1990-11-06 Board Of Regents, The University Of Texas System Biologically reversible phosphate and phosphonate protective gruops
DE3770982D1 (de) 1986-04-24 1991-08-01 Fujisawa Pharmaceutical Co Diphosphonsaeure-verbindungen, verfahren zu deren herstellung und sie enthaltende arzneimittel.
JPS636089A (ja) 1986-06-27 1988-01-12 Nippon Shokubai Kagaku Kogyo Co Ltd 石炭−水スラリ−用分散剤
US5091552A (en) 1986-06-30 1992-02-25 Board Of Regents, The University Of Texas System Novel antitumor aldophosphamide analogs
IL84497A (en) 1986-11-21 1994-10-21 Ciba Geigy Ag History 2-) Imidazol-1-yl (ethane-1,1-diphosphonic acid, their preparation and pharmaceutical preparations containing them
JPS63250290A (ja) 1987-04-06 1988-10-18 Matsushita Electric Ind Co Ltd 電子スチルカメラ
US4912175A (en) 1988-08-01 1990-03-27 E. I. Du Pont De Nemours And Company Process for in creasing polyamide molecular weight with P containing catalyst
US4968790A (en) 1988-08-12 1990-11-06 American Cyanamid Company Antidiabetic phosphates
US4943629A (en) * 1988-08-12 1990-07-24 American Cyanamid Company Antidiabetic alpha-substituted phosphonates
WO1990009163A2 (en) * 1989-01-24 1990-08-23 Gensia Pharmaceuticals, Inc. Method and compounds for aica riboside delivery and for lowering blood glucose
US5658889A (en) * 1989-01-24 1997-08-19 Gensia Pharmaceuticals, Inc. Method and compounds for aica riboside delivery and for lowering blood glucose
MX21452A (es) 1989-07-07 1994-01-31 Ciba Geigy Ag Preparaciones farmaceuticas que se administran en forma topica.
DE4029444A1 (de) 1989-09-19 1991-03-28 Ciba Geigy Ag Phosphonyl-enamine als pflanzenwuchsregulatoren
DE59107135D1 (de) * 1990-01-18 1996-02-08 Ciba Geigy Ag Phoshponsäure- und Thionophosphonsäure-Derivate
US5116919A (en) 1990-12-05 1992-05-26 E. I. Du Pont De Nemours And Company Process for increasing the relative viscosity of polyamides with reduced thermal degradation
FI89366C (fi) 1990-12-20 1993-09-27 Leiras Oy Foerfarande foer framstaellning av nya farmakologiskt anvaendbara metylenbisfosfonsyraderivat
US5194616A (en) 1991-01-24 1993-03-16 E. I. Du Pont De Nemours And Company Preparation of 2-(pyridyl)ethyl bis-(trialkyl silyl)phosphonate derivatives
CA2107082A1 (en) 1991-04-27 1992-10-28 Ichiro Mori Triazole compounds
EP0528760A1 (de) 1991-08-09 1993-02-24 Japat Ltd Neue Triazole
US5142000A (en) 1991-08-28 1992-08-25 E. I. Du Pont De Nemours And Company Process for increasing polyamide molecular weight with organophosphonic acid or ester catalysts in the presence of alumina-containing titanium dioxide
US5302586A (en) * 1991-12-19 1994-04-12 G. D. Searle & Co. Phosphonomethyl-imidazo[1,2-a]pyrimidine-2-carboxylic acid compounds for treatment of neurotoxic injury
MX9300141A (es) 1992-01-13 1994-07-29 Smithkline Beecham Corp Compuestos de imidazol novedosos, procedimiento para su preparacion y composiciones farmaceuticas que lo contienen.
GB9202779D0 (en) 1992-02-10 1992-03-25 Ici Plc Novel compounds
CH683996A5 (fr) 1992-03-05 1994-06-30 Symphar Sa Dérivés aminophosphonates substitués, leur procédé de préparation et compositions pharmaceutiques les contenant.
US5731299A (en) 1992-05-29 1998-03-24 The Procter & Gamble Company Phosphonosulfonate compounds, pharmaceutical compositions, and methods for treating abnormal calcium and phosphate metabolism
KR950703539A (ko) * 1992-09-28 1995-09-20 알렌 제이. 스피겔 당뇨병 합병증 치료용 치환된 피리미딘(substituted pyrimidines for control or diabetic complications)
GB2271113A (en) 1992-10-02 1994-04-06 Japat Ltd Triazolyl alkyl phosphates or phosphonates
DE4303648A1 (de) * 1993-02-09 1994-08-11 Basf Ag Verwendung von Aminovinylphosphonsäureestern als Lichtschutzmittel und Stabilisatoren für organisches Material
JPH06298779A (ja) 1993-04-15 1994-10-25 Hoechst Japan Ltd ヘテロ環イミノビスメチレンビスホスホン酸誘導体
ATE199906T1 (de) 1993-06-29 2001-04-15 Mitsubishi Chem Corp Phosphonat-nukleotid ester-derivate
IT1266570B1 (it) 1993-07-30 1997-01-09 Zambon Spa Derivati della propanammide n-eteroaril sostituiti utili nel trattamento delle malattie cardiovascolari
WO1995007920A1 (en) 1993-09-17 1995-03-23 Gilead Sciences, Inc. Nucleotide analogs
US5728650A (en) 1993-10-07 1998-03-17 Zeneca Limited Herbicidal aza bisphosphonic acids and compositions containing the same
GB9324143D0 (en) 1993-11-24 1994-01-12 Schering Agrochemicals Ltd Triazole phosphonate pesticides
DE19501843A1 (de) 1994-12-16 1996-06-20 Bayer Ag Substituierte Sulfonylharnstoffe
DE69624143T2 (de) * 1995-12-27 2003-06-12 Otsuka Pharmaceutical Factory, Inc. Phosphonsaurediester-derivate
AR008789A1 (es) 1996-07-31 2000-02-23 Bayer Corp Piridinas y bifenilos substituidos
US6011049A (en) 1997-02-19 2000-01-04 Warner-Lambert Company Combinations for diabetes
WO1998039344A1 (en) 1997-03-07 1998-09-11 Metabasis Therapeutics, Inc. Novel purine inhibitors of fructose-1,6-bisphosphatase
AU6691498A (en) * 1997-03-07 1998-09-22 Metabasis Therapeutics, Inc. Novel benzimidazole inhibitors of fructose-1,6-bisphosphatase
AU6691798A (en) * 1997-03-07 1998-09-22 Metabasis Therapeutics, Inc. Novel indole and azaindole inhibitors of fructose-1,6-bisphosphatase
WO1999045016A2 (en) 1998-03-06 1999-09-10 Metabasis Therapeutics, Inc. Novel prodrugs for phosphorus-containing compounds
US6312662B1 (en) * 1998-03-06 2001-11-06 Metabasis Therapeutics, Inc. Prodrugs phosphorus-containing compounds
AU3087099A (en) 1998-03-16 1999-10-11 Ontogen Corporation Piperazines as inhibitors of fructose-1,6-bisphosphatase (FBPase)
EP1112275B9 (de) * 1998-09-09 2004-03-10 Metabasis Therapeutics, Inc. Neue heteroaromatische fructose 1,6-bisphosphatase inhibitoren
US6756360B1 (en) 1998-12-24 2004-06-29 Metabasis Therapeutics, Inc. Combination of FBPase inhibitors and insulin sensitizers for the treatment of diabetes
DK1143955T3 (da) 1998-12-24 2005-11-14 Metabasis Therapeutics Inc En kombination af FBPase-inhibitorer og insulinsensibiliseringsmidler til behandling af diabetes
US6284672B1 (en) * 1999-03-02 2001-09-04 Advanced Micro Devices, Inc. Method of forming a super-shallow amorphous layer in silicon
EP1240174A2 (de) 1999-12-22 2002-09-18 Metabasis Therapeutics, Inc. Neue bisamidat phosphonat prodrogen
JP2003520226A (ja) 2000-01-21 2003-07-02 ノバルティス アクチエンゲゼルシャフト ジペプチジルペプチダーゼ−ｉｖ阻害剤および抗糖尿病薬剤を含む組合せ物
AU4553201A (en) 2000-03-08 2001-09-17 Metabasis Therapeutics Inc Novel aryl fructose-1,6-bisphosphatase inhibitors
US7563774B2 (en) 2000-06-29 2009-07-21 Metabasis Therapeutics, Inc. Combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes
BR0112212A (pt) 2000-07-06 2003-12-30 Metabasis Therapeutics Inc Uma combinação de inibidores de fbpase e agentes antidiabéticos úteis para o tratamento de diabetes
BRPI0514372A (pt) 2004-08-18 2008-06-10 Metabasis Therapeutics Inc inibidores de tiazol de frutose 1, 6-bisfosfatase

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ATE246197T1 (de) 2003-08-15
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