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PE20161338A1 - Nuevas heteroarildihidropirimidinas 6-fusionadas para el tratamiento y la profilaxis de la infeccion por virus de la hepatitis b - Google Patents

Nuevas heteroarildihidropirimidinas 6-fusionadas para el tratamiento y la profilaxis de la infeccion por virus de la hepatitis b

Info

Publication number
PE20161338A1
PE20161338A1 PE2016001260A PE2016001260A PE20161338A1 PE 20161338 A1 PE20161338 A1 PE 20161338A1 PE 2016001260 A PE2016001260 A PE 2016001260A PE 2016001260 A PE2016001260 A PE 2016001260A PE 20161338 A1 PE20161338 A1 PE 20161338A1
Authority
PE
Peru
Prior art keywords
treatment
alkyl
methyl
hepatitis
prophylaxis
Prior art date
Application number
PE2016001260A
Other languages
English (en)
Inventor
Lei Guo
taishan Hu
Buyu Kou
Xianfeng Lin
Hong Shen
Wei Zhu
Shixiang Yan
Zhisen Zhang
Weixing Zhang
Mingwei Zhou
Houguang Shi
Original Assignee
Hoffmann La Roche
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 Hoffmann La Roche filed Critical Hoffmann La Roche
Publication of PE20161338A1 publication Critical patent/PE20161338A1/es

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • 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
    • A61K31/395—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
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K31/395—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
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic 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
    • A61P31/20—Antivirals for DNA viruses
    • 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
    • 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
    • C07D417/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems
    • 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
    • A61K31/395—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
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • 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
    • A61K31/395—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
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La presente invencion se refiere a heteroarildihidropirimidinas 6-fusionadas (HAP) de formula (I), sales farmaceuticamente aceptables, enantiomeros o diastereomeros de las mismas donde: R1 es H, halogeno o alquilo C1-6; R2 y R3 son H o halogeno; R4 es alquilo C1-6; R5 es H, hidroxialquilo C1-6, entre otros; R6 es H, alcoxicarbonilo C1-6 o carboxi-CmH2m-; X es carbonilo o sulfonilo; Y es -CH2-, -O-, o -N(R7)-; R7 es H, alquilo C1-6, entre otros; W es -CH2-, -C(alquilo C1-6)2-, -O- o carbonilo; n es 0 o 1 y m es 0 a 7. Son compuestos preferidos: (4R)-4-(2-cloro-4-fluoro-fenil)-6-[(6-oxo-1, 3, 4, 8, 9, 9a-hexahidropirazino[1,2-c][1,3]oxazin-2-il)metil]-2-tiazol-2-il-1,4-dihidropirimidin-5-carboxilato de metilo; (4R)-4-(2-cloro-4-fluoro-fenil)-6-[(4-oxo-6, 7, 9, 9a-tetrahidro-1H-pirazino[2,1-c][1,4]oxazin-8-il)metil]-2-tiazol-2-il-1,4-dihidropirimidin-5-carboxilato de metilo, entre otros. Tambien se refiere a un procedimiento, una composicion y un metodo de tratamiento. Dichas HAP inducen la formacion aberrante de capsides, siendo utiles en el tratamiento del virus de la hepatitis B (VHB)
PE2016001260A 2014-03-07 2015-03-04 Nuevas heteroarildihidropirimidinas 6-fusionadas para el tratamiento y la profilaxis de la infeccion por virus de la hepatitis b PE20161338A1 (es)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
CNPCT/CN2014/073068 2014-03-07
CNPCT/CN2014/083027 2014-07-25
CN2015070895 2015-01-16

Publications (1)

Publication Number Publication Date
PE20161338A1 true PE20161338A1 (es) 2016-12-12

Family

ID=52684200

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2016001260A PE20161338A1 (es) 2014-03-07 2015-03-04 Nuevas heteroarildihidropirimidinas 6-fusionadas para el tratamiento y la profilaxis de la infeccion por virus de la hepatitis b

Country Status (32)

Country Link
US (4) US9233978B2 (es)
EP (1) EP3114128B1 (es)
JP (1) JP6306750B2 (es)
KR (2) KR101933844B1 (es)
CN (3) CN109232613A (es)
AU (1) AU2015226206B2 (es)
BR (1) BR112016020566B1 (es)
CA (1) CA2935811C (es)
CL (1) CL2016002179A1 (es)
CR (1) CR20160337A (es)
DK (1) DK3114128T3 (es)
EA (1) EA030115B9 (es)
ES (1) ES2714110T3 (es)
HK (1) HK1245784A1 (es)
HR (1) HRP20190352T1 (es)
HU (1) HUE041734T2 (es)
IL (1) IL246449B (es)
LT (1) LT3114128T (es)
MA (1) MA39721A (es)
MX (1) MX350439B (es)
MY (1) MY188114A (es)
NZ (1) NZ721520A (es)
PE (1) PE20161338A1 (es)
PH (1) PH12016501631A1 (es)
PL (1) PL3114128T3 (es)
PT (1) PT3114128T (es)
RS (1) RS58384B1 (es)
SG (1) SG11201607332UA (es)
SI (1) SI3114128T1 (es)
TW (2) TWI603972B (es)
UA (1) UA117518C2 (es)
WO (1) WO2015132276A1 (es)

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