ECSP088367A - Derivados de bifenilo y su uso en el tratamiento de la hepatitis c - Google Patents

Derivados de bifenilo y su uso en el tratamiento de la hepatitis c

Info

Publication number
ECSP088367A
ECSP088367A EC2008008367A ECSP088367A ECSP088367A EC SP088367 A ECSP088367 A EC SP088367A EC 2008008367 A EC2008008367 A EC 2008008367A EC SP088367 A ECSP088367 A EC SP088367A EC SP088367 A ECSP088367 A EC SP088367A
Authority
EC
Ecuador
Prior art keywords
hepatitis
treatment
bifenyl
derivatives
variables
Prior art date
Application number
EC2008008367A
Other languages
English (en)
Inventor
Malcom Carter
Neil Mathews
Christopher James Wheelhouse
Alexander James Floyd Thomas
David John Bushnell
James Lumley
James Iain Salter
Christopher John Pilkington
Richard Martyn Angell
Original Assignee
Arrow Therapeutics Ltd
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
Priority claimed from GBGB0518971.7A external-priority patent/GB0518971D0/en
Priority claimed from GB0610663A external-priority patent/GB0610663D0/en
Priority claimed from GB0610664A external-priority patent/GB0610664D0/en
Application filed by Arrow Therapeutics Ltd filed Critical Arrow Therapeutics Ltd
Publication of ECSP088367A publication Critical patent/ECSP088367A/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/75—Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • 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
    • A61P31/12—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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
    • C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
    • C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
    • C07D237/28—Cinnolines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
    • C07D279/12—1,4-Thiazines; Hydrogenated 1,4-thiazines not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
    • C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
    • C07D295/26—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
    • C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
    • C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Virology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Pyridine Compounds (AREA)
  • Indole Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Furan Compounds (AREA)

Abstract

Un compuesto que es un derivado de bifenilo de la fórmula (I) o una sal farmacéuticamente aceptable del mismo, en donde: R1 es un grupo alquilo C1-C6 o una mitad -A1, -L1-A1, -A1-A1/, -L1-A1-A1/, -A1-L1-A1/, -A1-Y1-A1/, -A1-Het1-A1/, -L1-A1-Y1-A1/, -L1-A1-Het1-A1/, -L1-Het1-A1, -L1-Y1-A1, -L1-Y1-Het1-A1, -L1-Het1-Y1-A1, -L1-Y1-Het1-L1/, -A1-Y1-Het1-A1/, -A1-Het1-Y1-A1/, -A1-Het1-L1-A1/, -A1-L1-Het1-A1/ o -L1-Het1-L1/; - A y B son iguales o diferentes y cada uno representa un enlace directo o una mitad -CO-NR/-, -NR/-CO-, -NR/-CO2-, -CO-, -NR/-CO-NR//-, -NR/-S(O)2-, -S(O)2-NR/-, -SO2-, -NR/-, -NR/-CO-CO-, -CO-O-, -O-CO-, -(alquileno C1-C2)-NR/- o -(hidroxialquileno C1-C2)-NR/-, en donde R/ y R// son iguales o diferentes y cada uno representa hidrógeno o alquilo C1-C4; - R2 y R3 son iguales o diferentes y cada uno representa alquilo C1-C4, alcoxi C1-C4, haloalquilo C1-C4, haloalcoxi C1-C4 o halógeno; n y m son iguales o diferentes y cada uno representa 0 ó 1; R4 es un grupo alquilo C1-C6 o una mitad -A4, -L4-A4, -A4-A4/, -L4-A4-A4/, -A4-L4-A4/, -A4-Y4-A4/, -A4-Het4-A4/, -L4-A4-Y4-A4/, -L4-A4-Het4-A4/, -L4-Het4-A4, -L4-Y4-A4, -L4-Y4-Het4-A4, -L4-Het4-Y4-A4, -L4-Y4-Het4-L4/, -A4-Y4-Het4-A4/, -A4-Het4-Y4-A4/, -A4-Het4-L4-A4/, -A4-L4-Het4-A4/ o -L4-Het4-L4/, cada A1, A4, A1/ y A4/ son iguales o diferentes y representan una mitad fenilo, heteroarilo de 5 a 10 miembros, heterocicliclo de 5 a 10 miembros o carbociclilo C3-C8; cada L1 y L4 son iguales o diferentes y representan un grupo alquileno C1-C4 o hidroxialquileno C1-C4; cada Y1 y Y4 son iguales o diferentes y representan -CO-, -SO- o -S(O)2-; cada L1/ y L4/ son iguales o diferentes y representan hidrógeno o un grupo alquilo C1-C4; y cada Het1 y Het4 son iguales o diferentes y representan -O-, -S- o -NR/-, en donde R/ es hidrógeno o un grupo alquilo C1-C4, estando las mitades fenilo, heteroarilo, heterociclilo y carbociclilo en R1 y R4 opcionalmente fusionadas a un anillo fenilo, heteroarilo de 5 a 10 miembros o heterociclilo de 5 a 10 miembros; y estando las mitades fenilo, heteroarilo, heterociclilo y carbociclilo en R1 y R4 no sustituidas o sustituidas por (a) un solo sustituyente no sustituido seleccionado entre -(alquilo C1-C4)-X1, -CO2R/, -SO2NR/R//, -S(O)2-R/, -CONR/R//, -NR/-CO-R///, -NR/-S(O)2-R///, -CO-NR/-(alquilo C1-C4)-NR/R// y -CO-O-(alquilo C1-C4)-NR/R// y/o (b) 1, 2 ó 3 sustituyentes no sustituidos seleccionados entre -(alquilo C1-C4)-X2, halógeno, alquilo C1-C4, alcoxi C1-C4, haloalquilo C1-C4, haloalcoxi C1-C4, hidroxialquilo C1-C4, hidroxi, ciano, nitro y -NR/R//, en donde X1 es -CO2R/, -SO2-R/, -NR/-CO2-R//, -NR/-S(O)2-R///, -CONR/R// o -SO2-NR/R//, cada X2 es igual o diferente y es ciano, nitro o -NR/R//, cada R/ y R// son iguales o diferentes y representan hidrógeno o alquilo C1-C4 y cada R/// es igual o diferente y representa alquilo C1-C4.
EC2008008367A 2005-09-16 2008-04-14 Derivados de bifenilo y su uso en el tratamiento de la hepatitis c ECSP088367A (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB0518971.7A GB0518971D0 (en) 2005-09-16 2005-09-16 Chemical compounds
GB0610663A GB0610663D0 (en) 2006-05-30 2006-05-30 Chemical compounds
GB0610664A GB0610664D0 (en) 2006-05-30 2006-05-30 Chemical compounds

Publications (1)

Publication Number Publication Date
ECSP088367A true ECSP088367A (es) 2008-06-30

Family

ID=37398704

Family Applications (1)

Application Number Title Priority Date Filing Date
EC2008008367A ECSP088367A (es) 2005-09-16 2008-04-14 Derivados de bifenilo y su uso en el tratamiento de la hepatitis c

Country Status (22)

Country Link
US (1) US8008303B2 (es)
EP (1) EP1940786B1 (es)
JP (1) JP2009508835A (es)
KR (1) KR20080050490A (es)
AT (1) ATE478044T1 (es)
AU (2) AU2006290442B2 (es)
BR (1) BRPI0615934A2 (es)
CA (1) CA2621364A1 (es)
CY (1) CY1110835T1 (es)
DE (1) DE602006016313D1 (es)
DK (1) DK1940786T3 (es)
EC (1) ECSP088367A (es)
ES (1) ES2348332T3 (es)
HR (1) HRP20100542T1 (es)
IL (1) IL189694A0 (es)
NO (1) NO20081846L (es)
NZ (1) NZ566276A (es)
PL (1) PL1940786T3 (es)
PT (1) PT1940786E (es)
RS (1) RS51470B (es)
SI (1) SI1940786T1 (es)
WO (1) WO2007031791A1 (es)

Families Citing this family (95)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
UA93548C2 (uk) * 2006-05-05 2011-02-25 Айерем Елелсі Сполуки та композиції як модулятори хеджхогівського сигнального шляху
WO2008021849A2 (en) 2006-08-09 2008-02-21 Smithkline Beecham Corporation Novel compounds as antagonists or inverse agonists at opioid receptors
US8303944B2 (en) 2006-08-11 2012-11-06 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
US7745636B2 (en) 2006-08-11 2010-06-29 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
US7759495B2 (en) 2006-08-11 2010-07-20 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
US8329159B2 (en) 2006-08-11 2012-12-11 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
US7659270B2 (en) 2006-08-11 2010-02-09 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
KR20090060333A (ko) * 2006-09-08 2009-06-11 노파르티스 아게 림프구 상호작용에 의해 매개되는 질환의 치료에 유용한 ｎ-바이아릴 (헤테로)아릴술폰아미드 유도체
US7741347B2 (en) * 2007-05-17 2010-06-22 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
US8629171B2 (en) 2007-08-08 2014-01-14 Bristol-Myers Squibb Company Crystalline form of methyl ((1S)-1-((25)-2-(5-(4'-(2-((25)-1((2S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-2-pyrrolidinyl)-1H-imidazol-2-yl)-1-pyrrolidinyl)carbonyl)-2-methylpropyl)carbamate dihydrochloride salt
US7728027B2 (en) 2007-08-08 2010-06-01 Bristol-Myers Squibb Company Process for synthesizing compounds useful for treating hepatitis C
WO2009034390A1 (en) * 2007-09-14 2009-03-19 Arrow Therapeutics Limited Heterocyclic derivatives and their use in treating hepatitis c
KR20100123717A (ko) 2008-02-12 2010-11-24 브리스톨-마이어스 스큅 컴퍼니 Ｃ형 간염 바이러스 억제제로서의 헤테로시클릭 유도체
US7704992B2 (en) * 2008-02-13 2010-04-27 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
US8147818B2 (en) 2008-02-13 2012-04-03 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
US7906655B2 (en) 2008-08-07 2011-03-15 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
DE102008049675A1 (de) 2008-09-30 2010-04-01 Markus Dr. Heinrich Verfahren zur Herstellung von 3-Aminobiphenylen
US8383094B2 (en) 2008-10-01 2013-02-26 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
US8394968B2 (en) 2009-02-17 2013-03-12 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
TWI438200B (zh) 2009-02-17 2014-05-21 必治妥美雅史谷比公司 Ｃ型肝炎病毒抑制劑
WO2010094977A1 (en) * 2009-02-23 2010-08-26 Arrow Therapeutics Limited Novel biphenyl compounds useful for the treatment of hepatitis c
RU2544010C2 (ru) 2009-02-27 2015-03-10 Энанта Фармасьютикалс, Инк. Ингибиторы вируса гепатита с
US8796466B2 (en) 2009-03-30 2014-08-05 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
TW201038559A (en) 2009-04-09 2010-11-01 Bristol Myers Squibb Co Hepatitis C virus inhibitors
US8143414B2 (en) 2009-04-13 2012-03-27 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
US8211928B2 (en) 2009-05-29 2012-07-03 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
US8138215B2 (en) 2009-05-29 2012-03-20 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
WO2011031934A1 (en) * 2009-09-11 2011-03-17 Enanta Pharmaceuticals, Inc. Hepatitis c virus inhibitors
US20110274648A1 (en) 2009-11-11 2011-11-10 Bristol-Myers Squibb Company Hepatitis C Virus Inhibitors
US20110269956A1 (en) 2009-11-11 2011-11-03 Bristol-Myers Squibb Company Hepatitis C Virus Inhibitors
US20110281910A1 (en) 2009-11-12 2011-11-17 Bristol-Myers Squibb Company Hepatitis C Virus Inhibitors
US8653070B2 (en) 2009-12-14 2014-02-18 Enanta Pharmaceuticals, Inc. Hepatitis C virus inhibitors
US8377980B2 (en) 2009-12-16 2013-02-19 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
US9452980B2 (en) 2009-12-22 2016-09-27 Hoffmann-La Roche Inc. Substituted benzamides
US8362020B2 (en) 2009-12-30 2013-01-29 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
EP2563759B1 (en) * 2010-04-27 2022-04-06 Calcimedica, Inc. Compounds that modulate intracellular calcium
US20130116227A1 (en) * 2010-07-13 2013-05-09 Dainippon Sumitomo Pharma Co., Ltd. Biaryl amide derivative or pharmaceutically acceptable salt thereof
US8921372B2 (en) * 2010-11-04 2014-12-30 Theravance Biopharma R&D Ip, Llc Inhibitors of hepatitis C virus
US8552047B2 (en) 2011-02-07 2013-10-08 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
RU2456266C1 (ru) * 2011-04-06 2012-07-20 Максим Эдуардович Запольский Производные 4,4'-бифениламидов, обладающие фармакологической активностью, и лекарственные средства на их основе
US9546160B2 (en) 2011-05-12 2017-01-17 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
JP2014525425A (ja) * 2011-08-31 2014-09-29 アマケン エンヴェー 新規のｒｏｃｋキナーゼ阻害剤
WO2013030750A1 (en) 2011-09-01 2013-03-07 Lupin Limited Antiviral compounds
SG11201401891RA (en) * 2011-11-03 2014-05-29 Theravance Inc Rod -like hepatitis c virus inhibitors containing the fragement {2- [4- (bi phenyl - 4 - yl) - 1h - imidazo - 2 - yl] pyrrolidine - 1 - carbonlymethyl} amine
BR112014015197A8 (pt) 2011-12-21 2017-06-13 Novira Therapeutics Inc agentes antivirais de hepatite b
US9326973B2 (en) 2012-01-13 2016-05-03 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
AU2013217224B2 (en) 2012-02-10 2017-04-06 Lupin Limited Antiviral compounds with a dibenzooxaheterocycle moiety
SG10201607345YA (en) 2012-03-02 2016-11-29 Ralexar Therapeutics Inc Liver x receptor (lxr) modulators for the treatment of dermal diseases, disorders and conditions
AR091654A1 (es) * 2012-07-02 2015-02-18 Biogen Idec Inc COMPUESTOS QUE CONTIENEN BIARILO COMO AGONISTAS INVERSOS DE RECEPTORES ROR-g
KR102271574B1 (ko) 2012-08-28 2021-07-01 얀센 사이언시즈 아일랜드 언리미티드 컴퍼니 설파모일-아릴아미드 및 b형 간염 치료제로서의 그 용도
WO2014131847A1 (en) 2013-02-28 2014-09-04 Janssen R&D Ireland Sulfamoyl-arylamides and the use thereof as medicaments for the treatment of hepatitis b
US8993771B2 (en) 2013-03-12 2015-03-31 Novira Therapeutics, Inc. Hepatitis B antiviral agents
JP2016521259A (ja) 2013-03-20 2016-07-21 バイエル・ファルマ・アクティエンゲゼルシャフト 置換Ｎ−ビフェニル−３−アセチルアミノ−ベンズアミドおよびＮ−［３−（アセチルアミノ）フェニル］−ビフェニル−カルボキサミドならびにＷｎｔシグナル伝達経路の阻害剤としてのそれらの使用
MX353412B (es) 2013-04-03 2018-01-10 Janssen Sciences Ireland Uc Derivados de n-fenil-carboxamida y su uso como medicamentos para el tratamiento de la hepatitis b.
TWI733288B (zh) 2013-05-17 2021-07-11 愛爾蘭商健生科學愛爾蘭無限公司 胺磺醯基吡咯醯胺衍生物及其作為用於治療ｂ型肝炎藥物的用途
US9717712B2 (en) 2013-07-02 2017-08-01 Bristol-Myers Squibb Company Combinations comprising tricyclohexadecahexaene derivatives for use in the treatment of hepatitis C virus
US20150023913A1 (en) 2013-07-02 2015-01-22 Bristol-Myers Squibb Company Hepatitis C Virus Inhibitors
US9775831B2 (en) 2013-07-17 2017-10-03 Bristol-Myers Squibb Company Combinations comprising biphenyl derivatives for use in the treatment of HCV
HRP20180791T1 (hr) 2013-07-25 2018-09-07 Janssen Sciences Ireland Uc Glioksamid supstituirani derivati pirolamida i njihova uporaba kao lijekova za liječenje hepatitisa b
JP2016532713A (ja) 2013-09-04 2016-10-20 アレクサー セラピューティクス， インク． 肝臓ｘ受容体（ｌｘｒ）調節因子
RS60479B1 (sr) 2013-09-04 2020-08-31 Ellora Therapeutics Inc Modulatori receptora x jetre (lxr)
CA2923712C (en) 2013-10-23 2021-11-02 Janssen Sciences Ireland Uc Carboxamide derivatives and the use thereof as medicaments for the treatment of hepatitis b
CN104725365B (zh) * 2013-12-23 2019-02-26 南京圣和药业股份有限公司 丙型肝炎病毒抑制剂及其应用
US10392349B2 (en) 2014-01-16 2019-08-27 Novira Therapeutics, Inc. Azepane derivatives and methods of treating hepatitis B infections
US9181288B2 (en) 2014-01-16 2015-11-10 Novira Therapeutics, Inc. Azepane derivatives and methods of treating hepatitis B infections
US9169212B2 (en) 2014-01-16 2015-10-27 Novira Therapeutics, Inc. Azepane derivatives and methods of treating hepatitis B infections
CA2936947A1 (en) 2014-02-05 2015-08-13 Novira Therapeutics, Inc. Combination therapy for treatment of hbv infections
TW201620893A (zh) 2014-02-06 2016-06-16 健生科學愛爾蘭無限公司 磺醯胺基吡咯醯胺衍生物及其用作治療ｂ型肝炎之醫藥品的用途
US9400280B2 (en) 2014-03-27 2016-07-26 Novira Therapeutics, Inc. Piperidine derivatives and methods of treating hepatitis B infections
CA2976973A1 (en) 2015-02-20 2016-08-25 Bayer Pharma Aktiengesellschaft N-phenyl-(morpholin-4-yl or piperazinyl)acetamide derivatives and their use as inhibitors of the wnt signalling pathways
JP2018510159A (ja) 2015-03-19 2018-04-12 ノヴィラ・セラピューティクス・インコーポレイテッド アゾカン及びアゾナン誘導体及びｂ型肝炎感染症の治療法
US10875876B2 (en) 2015-07-02 2020-12-29 Janssen Sciences Ireland Uc Cyclized sulfamoylarylamide derivatives and the use thereof as medicaments for the treatment of hepatitis B
WO2017023631A1 (en) 2015-08-06 2017-02-09 Bristol-Myers Squibb Company Hepatitis c virus inhibitors
TW201718496A (zh) 2015-09-29 2017-06-01 諾維拉治療公司 B型肝炎抗病毒劑之晶型
CN108713019B (zh) 2016-03-17 2021-06-15 豪夫迈·罗氏有限公司 具有作为taar的激动剂的活性的5-乙基-4-甲基-吡唑-3-甲酰胺衍生物
AU2017248828A1 (en) 2016-04-15 2018-11-01 Janssen Sciences Ireland Uc Combinations and methods comprising a capsid assembly inhibitor
CN109790143A (zh) 2016-05-10 2019-05-21 C4医药公司 用于靶蛋白降解的胺连接的c3-戊二酰亚胺降解决定子体
CN109641874A (zh) 2016-05-10 2019-04-16 C4医药公司 用于靶蛋白降解的c3-碳连接的戊二酰亚胺降解决定子体
JOP20190024A1 (ar) 2016-08-26 2019-02-19 Gilead Sciences Inc مركبات بيروليزين بها استبدال واستخداماتها
CN110769822A (zh) 2017-06-20 2020-02-07 C4医药公司 用于蛋白降解的n/o-连接的降解决定子和降解决定子体
CN111372585A (zh) 2017-11-16 2020-07-03 C4医药公司 用于靶蛋白降解的降解剂和降解决定子
JP7050165B2 (ja) 2018-02-26 2022-04-07 ギリアード サイエンシーズ， インコーポレイテッド Ｈｂｖ複製阻害剤としての置換ピロリジン化合物
MX2020009531A (es) 2018-03-14 2020-10-05 Janssen Sciences Ireland Unlimited Co Regimen posologico del modulador del ensamblaje de la capside.
KR102835299B1 (ko) 2018-12-04 2025-07-18 브리스톨-마이어스 스큅 컴퍼니 다중 동위원소체 반응 모니터링에 의한 샘플내 보정 곡선을 사용한 분석 방법
CN120698983A (zh) 2018-12-20 2025-09-26 C4医药公司 靶向蛋白降解
WO2020169784A1 (en) 2019-02-22 2020-08-27 Janssen Sciences Ireland Unlimited Company Amide derivatives useful in the treatment of hbv infection or hbv-induced diseases
AR119732A1 (es) 2019-05-06 2022-01-05 Janssen Sciences Ireland Unlimited Co Derivados de amida útiles en el tratamiento de la infección por vhb o de enfermedades inducidas por vhb
EP4048664A1 (en) 2019-10-25 2022-08-31 Gilead Sciences, Inc. Glp-1r modulating compounds
ES3016132T3 (en) 2020-01-29 2025-05-08 Gilead Sciences Inc Glp-1r modulating compounds
EP4247804A1 (en) 2020-11-20 2023-09-27 Gilead Sciences, Inc. Polyheterocyclic glp-1 r modulating compounds
EP4304712A1 (en) 2021-03-11 2024-01-17 Gilead Sciences, Inc. Glp-1r modulating compounds
WO2022192428A1 (en) 2021-03-11 2022-09-15 Gilead Sciences, Inc. Glp-1r modulating compounds
IL306110A (en) 2021-04-21 2023-11-01 Gilead Sciences Inc Carboxy-benzimidazole glp-1r modulating compounds
WO2023158795A1 (en) * 2022-02-18 2023-08-24 Accent Therapeutics, Inc. Inhibitors of rna helicase dhx9 and uses thereof
US20250288577A1 (en) * 2022-04-29 2025-09-18 Cornell University Methods of treating a virus infection and methods of inhibiting viral replication

Family Cites Families (63)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5026940A (en) 1989-09-08 1991-06-25 Catalytica, Inc. Manufacture of 4,4'-diisopropylbiphenyl
GB9119920D0 (en) 1991-09-18 1991-10-30 Glaxo Group Ltd Chemical compounds
US5605919A (en) 1993-02-26 1997-02-25 Takeda Chemical Industries, Ltd. Treatment for viral diseases
JP3894949B2 (ja) 1993-06-30 2007-03-22 ザ、ウェルカム、ファンデーション、リミテッド 抗アテローム性動脈硬化症ジアリール化合物
IL117580A0 (en) 1995-03-29 1996-07-23 Merck & Co Inc Inhibitors of farnesyl-protein transferase and pharmaceutical compositions containing them
WO1997036591A1 (en) 1996-04-03 1997-10-09 Merck & Co., Inc. Inhibitors of farnesyl-protein transferase
US6297239B1 (en) 1997-10-08 2001-10-02 Merck & Co., Inc. Inhibitors of prenyl-protein transferase
WO1999040075A1 (en) 1998-02-05 1999-08-12 Takeda Chemical Industries, Ltd. Sulfonamide derivatives, process for producing the same and utilization thereof
US6586475B1 (en) 1998-11-20 2003-07-01 Takeda Chemical Industries, Ltd. β-amyloid protein production/secretion inhibitors
AUPP818099A0 (en) 1999-01-14 1999-02-11 Fujisawa Pharmaceutical Co., Ltd. New n-containing heterocyclic compounds
ES2316383T3 (es) 1999-09-17 2009-04-16 Millennium Pharmaceuticals, Inc. Benzamidas e inhibidores relacionados del factor xa.
EP1218336A2 (en) 1999-09-20 2002-07-03 Takeda Chemical Industries, Ltd. Melanin concentrating hormone antagonist
WO2001064642A2 (en) 2000-02-29 2001-09-07 Cor Therapeutics, Inc. Benzamides and related inhibitors of factor xa
US6433236B1 (en) * 2000-03-21 2002-08-13 Arteva North America S.A.R.L. Acid catalyzed isomerization of substituted diaryls
AU2001266346A1 (en) * 2000-06-28 2002-01-08 Takeda Chemical Industries Ltd. Biphenyl compound
ATE409181T1 (de) 2001-05-08 2008-10-15 Univ Yale Proteomimetische verbindungen und verfahren
WO2003006628A2 (en) 2001-07-13 2003-01-23 Virtual Drug Development, Inc. Nad synthetase inhibitors and uses thereof
WO2004043335A2 (en) 2001-09-13 2004-05-27 Genesoft, Inc. Methods of treating infection by drug resistant bacteria
GB0124932D0 (en) * 2001-10-17 2001-12-05 Glaxo Group Ltd Chemical compounds
GB0124931D0 (en) * 2001-10-17 2001-12-05 Glaxo Group Ltd Chemical compounds
GB0124928D0 (en) 2001-10-17 2001-12-05 Glaxo Group Ltd Chemical compounds
GB0124941D0 (en) * 2001-10-17 2001-12-05 Glaxo Group Ltd Chemical compounds
GB0124934D0 (en) * 2001-10-17 2001-12-05 Glaxo Group Ltd Chemical compounds
GB0124933D0 (en) * 2001-10-17 2001-12-05 Glaxo Group Ltd Chemical compounds
GB0124938D0 (en) * 2001-10-17 2001-12-05 Glaxo Group Ltd Chemical compounds
CA2473740A1 (en) 2002-01-18 2003-07-31 David Solow-Cordero Methods of treating conditions associated with an edg receptor
ATE375980T1 (de) 2002-02-12 2007-11-15 Smithkline Beecham Corp Nicotinamide und deren verwendung als p38 inhibitoren
GB0209891D0 (en) * 2002-04-30 2002-06-05 Glaxo Group Ltd Novel compounds
AU2003240488A1 (en) * 2002-06-04 2003-12-19 Neogenesis Pharmaceuticals, Inc. Pyrazolo` 1,5a! pyrimidine compounds as antiviral agents
AU2003252478A1 (en) 2002-07-10 2004-02-02 Ono Pharmaceutical Co., Ltd. Ccr4 antagonist and medicinal use thereof
AU2003286876A1 (en) 2002-11-01 2004-06-07 Vertex Pharmaceuticals Incorporated Compositions useful as inhibitors of jak and other protein kinases
US7122557B2 (en) 2003-03-18 2006-10-17 Bristol-Myers Squibb Company Sulfonyl-amidino-containing and tetrahydropyrimidino-containing compounds as factor Xa inhibitors
US20050026844A1 (en) 2003-04-03 2005-02-03 Regents Of The University Of California Inhibitors for the soluble epoxide hydrolase
BRPI0409227C1 (pt) * 2003-04-07 2021-05-25 Axys Pharm Inc composto, composição farmacêutica, uso de um composto e processo para a preparação de um composto de fórmula (i)
GB0308186D0 (en) 2003-04-09 2003-05-14 Smithkline Beecham Corp Novel compounds
GB0308185D0 (en) 2003-04-09 2003-05-14 Smithkline Beecham Corp Novel compounds
TWI376370B (en) * 2003-07-23 2012-11-11 Synta Pharmaceuticals Corp Compounds for inflammation and immune-related uses
EP1687284B1 (en) 2003-07-25 2008-10-29 Novartis AG p-38 KINASE INHIBITORS
US20050054691A1 (en) 2003-08-29 2005-03-10 St. Jude Children's Research Hospital Carboxylesterase inhibitors
WO2005023761A2 (en) 2003-09-11 2005-03-17 Kemia, Inc. Cytokine inhibitors
US20070099938A1 (en) 2003-10-24 2007-05-03 Ono Pharmaceutical Co., Ltd. Antistress drug and medical use thereof
WO2005065361A2 (en) 2003-12-31 2005-07-21 Khosrow Kashfi Compounds and compositions for treating dysproliferative diseases, and methods of use thereof
CA2558585C (en) 2004-02-27 2010-10-12 Amgen Inc. Compounds, pharmaceutical compositions and methods for use in treating metabolic disorders
TW200600492A (en) * 2004-05-18 2006-01-01 Achillion Pharmaceuticals Inc Substituted aryl acylthioureas and related compounds; inhibitors of viral replication
WO2006001958A2 (en) 2004-05-21 2006-01-05 Merck & Co., Inc. Amino cyclopentyl heterocyclic and carbocyclic modulators of chemokine receptor activity
PE20060574A1 (es) * 2004-07-28 2006-06-24 Glaxo Group Ltd Derivados de arilpiperazina sulfonamida como agonistas de los receptores de secretagogos de la hormona del crecimiento (ghs)
ZA200700811B (en) 2004-08-06 2008-10-29 Otsuka Pharma Co Ltd Aromatic compound
EP1809381A2 (en) 2004-10-06 2007-07-25 Recepticon ApS Use of compounds for the prevention of drug-induced cell toxicity
US7381732B2 (en) 2004-10-26 2008-06-03 Bristol-Myers Squibb Company Pyrazolobenzamides and derivatives as factor Xa inhibitors
KR20140018997A (ko) * 2005-01-07 2014-02-13 신타 파마슈티칼스 코프. 염증 및 면역 관련 용도를 위한 화합물
EP1853573A1 (en) * 2005-02-25 2007-11-14 Rigel Pharmaceuticals, Inc. Benzisothiazoles useful for treating or preventing hcv infection
US20060264415A1 (en) 2005-04-01 2006-11-23 Methylgene Inc. Inhibitors of histone deacetylase
WO2007009083A2 (en) 2005-07-12 2007-01-18 Acadia Pharmaceuticals Inc. Compounds with activity at retinoic acid receptors
TW200806641A (en) 2006-01-25 2008-02-01 Synta Pharmaceuticals Corp Substituted aromatic compounds for inflammation and immune-related uses
UY30117A1 (es) 2006-01-31 2007-06-29 Tanabe Seiyaku Co Compuesto amina trisustituido
WO2007103162A2 (en) 2006-03-01 2007-09-13 Samaritan Pharmaceuticals, Inc. Structure based drug design of steroidogenesis inhibitors
KR20090012345A (ko) 2006-05-30 2009-02-03 애로우 쎄라퓨틱스 리미티드 바이페닐 유도체, 및 ｃ형 간염 치료에 있어서의 이들의 용도
UA95978C2 (ru) 2006-10-02 2011-09-26 Оцука Фармас'Ютікел Ко., Лтд. Ингибитор активации stat3/5
WO2008046216A1 (en) 2006-10-18 2008-04-24 Methylgene, Inc. Kinase inhibitors and uses thereof
KR101472765B1 (ko) 2006-12-08 2014-12-15 밀레니엄 파머슈티컬스 인코퍼레이티드 경구용 Ｘａ 인자 억제제를 포함하는 단위 용량 제형 및 경구용 Ｘａ 인자 억제제를 사용하는 혈전증의 치료 방법
US20090016990A1 (en) 2007-01-24 2009-01-15 Alberte Randall S Antimicrobial Compositions
WO2008147864A2 (en) 2007-05-22 2008-12-04 Xenon Pharmaceuticals Inc. Methods of using piperazine compounds in treating sodium channel-mediated diseases or conditions
WO2009034390A1 (en) 2007-09-14 2009-03-19 Arrow Therapeutics Limited Heterocyclic derivatives and their use in treating hepatitis c

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