AR091381A1 - Inhibidores de la neprilisina - Google Patents

Inhibidores de la neprilisina

Info

Publication number
AR091381A1
AR091381A1 ARP130102017A AR091381A1 AR 091381 A1 AR091381 A1 AR 091381A1 AR P130102017 A ARP130102017 A AR P130102017A AR 091381 A1 AR091381 A1 AR 091381A1
Authority
AR
Argentina
Prior art keywords
alkyl
chrd
chrcoc
nhc
formula
Prior art date
Application number
Other languages
English (en)
Inventor
d hughes Adam
Fleury Melissa
Original Assignee
Theravance Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Theravance Inc filed Critical Theravance Inc
Publication of AR091381A1 publication Critical patent/AR091381A1/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C229/22—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated the carbon skeleton being further substituted by oxygen atoms
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4155—1,2-Diazoles non condensed and containing further heterocyclic rings
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4192—1,2,3-Triazoles
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4196—1,2,4-Triazoles
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/18—One oxygen or sulfur atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D231/18—One oxygen or sulfur atom
    • C07D231/20—One oxygen atom attached in position 3 or 5
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
    • C07D249/12—Oxygen or sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/16—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
    • C07D249/18—Benzotriazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D253/00—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00
    • C07D253/08—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
    • C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D257/04—Five-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
    • C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D263/36—One oxygen atom
    • C07D263/38—One oxygen atom attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • 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
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6503—Five-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • 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
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6503—Five-membered rings
    • C07F9/65031—Five-membered rings having the nitrogen atoms in the positions 1 and 2

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Cardiology (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Steroid Compounds (AREA)

Abstract

Los compuestos que se describen en la presente son prodrogas de compuestos que presentan actividad de inhibición sobre la neprilisina. Composiciones farmacéuticas que comprenden compuestos como los que se han descripto. Métodos para usar estos compuestos. Procesos e intermediarios para elaborarlos. Reivindicación 1: Un compuesto caracterizado porque es de fórmula (1) donde: (i) Rᵃ es H; Rᵇ es Cl: X es un resto de formula (2); y R² es H, R⁴ es -OH, y R⁷ se selecciona entre -CH₂CF₃, -(CH₂)₂CF₃, -CH₂CF₂CH₃, -CH₂CF₂CF₃, -C(CH₃)(CF₃)₂, -CH(CH₂CH₃)CF₃, -CH(CH₃)CF₂CF₃, -(CH₂)₂₋₃OH, -CH₂CH(NH₂)COOCH₃, -(CH₂)₂OCH₃, CHRᶜOC(O)alquilo C₁₋₄, -CHRᶜOC(O)O-alquilo C₂₋₄, -CHRᶜOC(O)O-ciclohexilo, -alquilen C₂₋₄-N(CH₃)₂, -CH₂OC(O)CHRᵈ-NH₂, -CH₂OC(O)CHRᵈ-NHC(O)O-alquilo C₁₋₆, bencilo, y un resto de la formula (3); o R² es H, R⁴ se selecciona entre -O-bencilo, -OCHRᶜOC(O)alquilo C₁₋₄, -OCH₂OC(O)CHRᵈ-NH₂, y -OCH₂OC(O)CHRᵈ-NHC(O)O-alquilo C₁₋₄, y R⁷ se selecciona entre H y -CH₂OC(O)CH₃; o R² se selecciona entre -C(O)-alquilo C₁₋₆, C₍O₎CHRᵈ-NH₂, C(O)CHRᵈ-NHC(O)O-alquilo C₁₋₆, y P(O)(ORᵉ)₂, R⁴ es -OH, y R⁷ es H; o (ii) Rᵃ es H; Rᵇ es Cl; X es el resto de formula (4); y R² es H, R³ es -OH y R⁷ se selecciona entre -CH₂CF₃, -(CH₂)₂CF₃, -CH₂CF₂CH₃, -CH₂CF₂CF₃, -C(CH₃)(CF₃)₂, -CH(CH₂CH₃)CF₃, -CH(CH₃)CF₂CF₃, -(CH₂)₂₋₃OH, -CH₂CH(NH₂)COOCH₃, -(CH₂)₂OCH₃, CHRᶜOC(O)-alquilo C₁₋₄, -CHRᶜOC(O)O-alquilo C₂₋₄, -CHRᶜOC(O)O-ciclohexilo, -alquilen C₂₋₄-N(CH₃)₂, -CH₂OC(O)CHRᵈ-NH₂, CH₂OC(O)CHRᵈ-NHC(O)O-alquilo C₁₋₆, bencilo, y el compuesto de fórmula (3); o R³ se selecciona entre -OC(O)CH₂CH₃, -OC(O)CH₂CH(CH₃)₂, -OC(O)-fenilo, OCH₂OC(O)CHRᵈ-NH₂, y OCH₂OC(O)CHRᵈ-NHC(O)O-alquilo C₁₋₆, y R⁷ es H; o R² se selecciona entre -C(O)-alquilo C₁₋₆, -C(O)CHRᵈ-NH₂, -C(O)CHRᵈ-NHC(O)O-alquilo C₁₋₆, y -P(O)(ORᵉ)₂, R³ es -OH, y R⁷ es H; o (iii) Rᵃ es H; Rᵇ es Cl; X es el resto de formula (5); o R² es H, R³ es -OH y R⁷ se selecciona entre -CH₂CH₃, -CH₂CH(CH₃)₂, -CH₂CF₃, -(CH₂)₂CF₃, -CH₂CF₂CH₃, -CH₂CF₂CF₃, -C(CH₃)(CF₃)₂, -CH(CH₂CH₃)CF₃, -CH(CH₃)CF₂CF₃, -(CH₂)₂₋₃OH, -CH₂CH(NH₂)COOCH₃, -(CH₂)₂OCH₃, -CHRᶜOC(O)alquilo C₁₋₄, -CHRᶜOC(O)O-alquilo C₂₋₄, -CHRᶜOC(O)O-ciclohexilo, -alquilen C₂₋₄-N(CH₃)₂, -CH₂OC(O)CHRᵈ-NH₂, -CH₂OC(O)CHRᵈ-NHC(O)O-alquilo C₁₋₄, bencilo, y un resto de formula (3); o R² es H, R³ se selecciona entre -OC(O)CH₂CH₃, -OC(O)CH₂CH(CH₃)₂, -OC(O)-fenilo, OCH₂OC(O)CHRᵈ-NH₂, y OCH₂OC(O)CHRᵈ-NHC(O)O-alquilo C₁₋₆, y R⁷ es H; o R² se selecciona entre -C(O)-alquilo C₁₋₆, -C(O)CHRᵈ-NH₂, -C(O)CHRᵈ-NHC(O)O-alquilo C₁₋₆, y -P(O)(ORᵉ)₂, R³ es -OH, y R⁷ es H; o (iv) Rᵃ es F; Rᵇ es Cl; X es un resto de formula (6); y R² es H y R⁷ se selecciona entre H, -CH₂CH₃, -CH₂CF₃, -(CH₂)₂CF₃, -CH₂CF₂CH₃, -CH₂CF₂CF₃, -C(CH₃)(CF₃)₂, -CH(CH₂CH₃)CF₃, -CH(CH₃)CF₂CF₃, -(CH₂)₂₋₃OH, -CH₂CH(NH₂)COOCH₃, -(CH₂)₂OCH₃, CHRᶜOC(O)alquilo C₁₋₄, -CHRᶜOC(O)O-alquilo C₂₋₄, -CHRCOC(O)O-ciclohexilo, -alquilen C₂₋₄-N(CH₃)₂, -CH₂OC(O)CHRᵈ-NH₂, -CH₂OC(O)CHRᵈ-NHC(O)O-alquilo C₁₋₆, bencilo, y el resto de formula (3); o R² se selecciona entre -C(O)-alquilo C₁₋₆, C₍O₎CHRᵈ-NH₂, C(O)CHRᵈ-NHC(O)O-alquilo C₁₋₆, y -P(O)(ORᵉ)₂, y R⁷ es H; o (v) Rᵃ es H; Rᵇ es Cl; X es el resto de formula (7); y es H y R⁷ se selecciona entre H, -CH₂CH₃, -CH₂CF₃, -(CH₂)₂CF₃, -CH₂CF₂CH₃, -CH₂CF₂CF₃, -C(CH₃)(CF₃)₂, -CH(CH₂CH₃)CF₃, -CH(CH₃)CF₂CF₃, -(CH₂)₂₋₃OH, -CH₂CH(NH₂)COOCH₃, -(CH₂)₂OCH₃, CHRᶜOC(O)alquilo C₁₋₄, -CHRᶜOC(O)O-alquilo C₂₋₄, CHRᶜOC(O)O-ciclohexilo, -alquilen C₂₋₄-N(CH₃)₂, -CH₂OC(O)CHRᵈ-NH₂, CH₂OC(O)CHRCINHC(O)O-alquilo C₁₋₆, bencilo, y el resto de fórmula (3); o R² se selecciona entre -C(O)-alquilo C₁₋₆, C₍O₎CHRᵈ-NH₂, C(O)CHRᵈ-NHC(O)O-alquilo C₁₋₆, y -P(O)(ORᵉ)₂, y R⁷ es H; o (vi) Rᵃ es H; Rᵇ es Cl; X es el compuesto de formula (8); y R² es H y R⁷ se selecciona entre H, -CH₂CH₃, -CH₂CF₃, -(CH₂)₂CF₃, -CH₂CF₂CH₃, -CH₂CF₂CF₃, -C(CH₃)(CF₃)₂, -CH(CH₂CH₃)CF₃, -CH(CH₃)CF₂CF₃, -(CH₂)₂₋₃OH, -CH₂CH(NH₂)COOCH₃, -(CH₂)₂OCH₃, CHRᶜOC(O)alquilo C₁₋₄, -CHRᶜOC(O)O-alquilo C₂₋₄, -CHRCOC(O)O-ciclohexilo, -alquilen C₂₋₄-N(CH₃)₂, -CH₂OC(O)CHRᵈ-NH₂, CH₂OC(O)CHRᵈ-NHC(O)O-alquilo C₁₋₆, bencilo, y el resto de fórmula (3); o R² se selecciona entre -C(O)-alquilo C₁₋₆, C₍O₎CHRᵈ-NH₂, C(O)CHRᵈ-NHC(O)O-alquilo C₁₋₆, y -P(O)(ORᵉ)₂, y R⁷ es H; o (vii) Rᵃ es H; Rᵇ es Cl; X es el resto de fórmula (9); R es H o -CH₃ y R² es H y R⁷ se selecciona entre -CH₂CH₃, -CH₂CF₃, -(CH₂)₂CF₃, -CH₂CF₂CH₃, -CH₂CF₂CF₃, -C(CH₃)(CF₃)₂, -CH(CH₂CH₃)CF₃, -CH(CH₃)CF₂CF₃, -(CH₂)₂₋₃OH, -CH₂CH(NH₂)COOCH₃, -(CH₂)₂OCH₃, CHRᶜOC(O)alquilo C₁₋₄, -CHROOC(O)O-alquilo C₂₋₄, CHRCOC(O)O-ciclohexilo, -alquilen C₂₋₄-N(CH₃)₂, -CH₂OC(O)CHRᵈ-NH₂, -CH₂OC(O)CHRᵈ-NHC(O)O-alquilo C₁₋₆, bencilo, y el resto de fórmula (3); o R² se selecciona entre -C(O)-alquilo C₁₋₆, C₍O₎CHRᵈ-NH₂, C(O)CHRᵈ-NHC(O)O-alquilo C₁₋₆, y -P(O)(ORᵉ)₂, y R⁷ es H; o viii) Rᵃ es F; Rᵇ es Cl; X es el resto de fórmula (10) u (11); y R² es H, R⁴ es -OH, y R⁷ se selecciona entre -CH₂CH₃, -CH₂CF₃, -(CH₂)₂CF₃, -CH₂CF₂CH₃, -CH₂CF₂CF₃, -C(CH₃)(CF₃)₂, -CH(CH₂CH₃)CF₃, -CH(CH₃)CF₂CF₃, -(CH₂)₂₋₃OH, -CH₂CH(NH₂)COOCH₃, -(CH₂)₂OCH₃, CHRᶜOC(O)alquilo C₁₋₄, -CHRᶜOC(O)O-alquilo C₂₋₄, CHRᶜOC(O)O-ciclohexilo, -alquilen C₂₋₄-N(CH₃)₂, -CH₂OC(O)CHRᵈ-NH₂, -CH₂OC(O)CHRᵈ-NHC(O)O-alquilo C₁₋₆, bencilo, y el resto de fórmula (3); o R² es H, R⁴ se selecciona entre -O-bencilo, OCHRᶜOC(O)alquilo C₁₋₄, -OCH₂OC(O)CH[CH(CH₃)₂]NH₂, -OCH₂OC(O)CH[CH(CH₃)₂]-NHC(O)OCH₃ y el compuesto de fórmula (12), y R⁷ es H; o R² se selecciona entre -C(O)-alquilo C₁₋₆, C₍O₎CHRᵈ-NH₂, -C(O)CHRᵈ-NHC(O)O-alquilo C₁₋₆, y -P(O)(ORᵉ)₂, R⁴ es -OH, y R⁷ es H; o (ix) Rᵃ es H; Rᵇ es Cl; X es el resto de fórmula (13); y R² es H y R⁷ se selecciona entre -CH₂CH₃, -CH₂CF₃, -(CH₂)
ARP130102017 2012-06-08 2013-06-07 Inhibidores de la neprilisina AR091381A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201261657229P 2012-06-08 2012-06-08
US201361773969P 2013-03-07 2013-03-07

Publications (1)

Publication Number Publication Date
AR091381A1 true AR091381A1 (es) 2015-01-28

Family

ID=48626696

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP130102017 AR091381A1 (es) 2012-06-08 2013-06-07 Inhibidores de la neprilisina

Country Status (28)

Country Link
US (6) US9108934B2 (es)
EP (2) EP3199517B1 (es)
JP (2) JP6162230B2 (es)
KR (1) KR102102197B1 (es)
CN (1) CN104350042B (es)
AR (1) AR091381A1 (es)
AU (1) AU2013271537B2 (es)
BR (1) BR112014030743B1 (es)
CA (1) CA2876024C (es)
DK (1) DK2864292T3 (es)
ES (2) ES2632600T3 (es)
HR (1) HRP20171037T1 (es)
HU (1) HUE032802T2 (es)
IL (1) IL235737B (es)
LT (1) LT2864292T (es)
ME (1) ME02698B (es)
MX (1) MX356260B (es)
NZ (2) NZ702749A (es)
PH (1) PH12014502733A1 (es)
PL (1) PL2864292T3 (es)
PT (1) PT2864292T (es)
RS (1) RS55967B1 (es)
RU (1) RU2663618C2 (es)
SG (2) SG11201408094YA (es)
SI (1) SI2864292T1 (es)
TW (2) TWI583671B (es)
WO (1) WO2013184934A1 (es)
ZA (1) ZA201408634B (es)

Families Citing this family (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX2013006805A (es) 2010-12-15 2013-07-29 Theravance Inc Inhibidores de la neprilisina.
ES2548887T3 (es) 2010-12-15 2015-10-21 Theravance Biopharma R&D Ip, Llc Inhibidores de neprilisina
JP5959065B2 (ja) 2011-02-17 2016-08-02 セラヴァンス バイオファーマ アール＆ディー アイピー， エルエルシー ネプリライシン阻害剤としての置換アミノ酪酸誘導体
EP2675792B1 (en) 2011-02-17 2016-01-06 Theravance Biopharma R&D IP, LLC Substituted aminobutyric derivatives as neprilysin inhibitors
WO2012166387A1 (en) 2011-05-31 2012-12-06 Theravance, Inc. Neprilysin inhibitors
TWI560172B (en) 2011-11-02 2016-12-01 Theravance Biopharma R&D Ip Llc Neprilysin inhibitors
HUE032802T2 (hu) 2012-06-08 2017-10-30 Theravance Biopharma R&D Ip Llc Neprilizininhibitorok
ES2710932T3 (es) 2012-06-08 2019-04-29 Theravance Biopharma R&D Ip Llc Inhibidores de neprilisina
RU2650114C2 (ru) 2012-08-08 2018-04-09 ТЕРЕВАНС БАЙОФАРМА Ар энд Ди АйПи, ЭлЭлСи Ингибиторы неприлизина
JP2016512195A (ja) 2013-03-05 2016-04-25 セラヴァンス バイオファーマ アール＆ディー アイピー， エルエルシー ネプリライシン阻害剤
MX2016009760A (es) 2014-01-30 2016-11-08 Theravance Biopharma R&D Ip Llc Inhibidores de neprilisina.
SG11201606057PA (en) * 2014-01-30 2016-08-30 Theravance Biopharma R&D Ip Llc 5-biphenyl-4-heteroarylcarbonylamino-pentanoic acid derivatives as neprilysin inhibitors
CN105338467B (zh) * 2014-08-07 2019-04-02 电信科学技术研究院 一种设备到设备通信中数据接收方法、发送方法及设备
CN104592163B (zh) * 2015-01-08 2016-08-24 爱斯特（成都）生物制药有限公司 一种手性2-苯基吡咯烷的合成方法
BR112017017317B1 (pt) 2015-02-11 2023-02-14 Theravance Biopharma R&D Ip, Llc Composto, forma cristalina, composições farmacêuticas, forma de dosagem oral ou intravenosa, processos para a preparação do composto ou da forma cristalina e uso
PT3259255T (pt) 2015-02-19 2021-01-26 Theravance Biopharma R&D Ip Llc Ácido (2r,4r)-5-(5¿-cloro-2¿-fluorobifenil-4-il)-2-hidroxi-4-[(5-metiloxazol-2-carbonil)amino]pentanoico
CN108473516B (zh) 2015-12-14 2021-06-18 马克斯·普朗克科学促进协会 3,5-二苯基-二唑化合物的水溶性衍生物
TWI731943B (zh) 2016-03-08 2021-07-01 美商施萬生物製藥研發Ｉｐ有限責任公司 結晶型（2s，4r）－5－（5’－氯－2’－氟－［1，1’－聯苯］－4－基）－2－（乙氧基甲基）－4－（3－羥基異㗁唑－5－甲醯胺基）－2－甲基戊酸及其用途
CN107071636B (zh) * 2016-12-29 2019-12-31 北京小鸟听听科技有限公司 对带麦克风的设备的去混响控制方法和装置
JP6580097B2 (ja) 2017-09-05 2019-09-25 株式会社東芝 面発光量子カスケードレーザ
UY38072A (es) 2018-02-07 2019-10-01 Novartis Ag Compuestos derivados de éster butanoico sustituido con bisfenilo como inhibidores de nep, composiciones y combinaciones de los mismos
JP2022509184A (ja) 2018-11-27 2022-01-20 ノバルティス アーゲー 代謝性障害の処置のためのプロタンパク質コンバターゼスブチリシン／ケキシン９型（ｐｃｓｋ９）阻害剤としての環状ペプチド
UY38485A (es) 2018-11-27 2020-06-30 Novartis Ag Compuestos tetrámeros cíclicos como inhibidores de proproteína convertasa subtilisina/kexina tipo 9 (pcsk9), método de tratamiento, uso y su preparación
US20230089867A1 (en) 2018-11-27 2023-03-23 Novartis Ag Cyclic pentamer compounds as proprotein convertase subtilisin/kexin type 9 (pcsk9) inhibitors for the treatment of metabolic disorder
US11419917B2 (en) * 2020-04-07 2022-08-23 Drora Shevy Treatment for SARS-CoV-2 and other coronaviruses
TW202333563A (zh) 2021-11-12 2023-09-01 瑞士商諾華公司 用於治療疾病或障礙之二胺基環戊基吡啶衍生物
KR102485499B1 (ko) * 2022-07-15 2023-01-09 오가노이드사이언스 주식회사 신장 질환의 치료 또는 예방용 조성물

Family Cites Families (46)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4189604A (en) 1975-07-22 1980-02-19 Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai Bestatin
US4206232A (en) 1976-05-10 1980-06-03 E. R. Squibb & Sons, Inc. Relieving hypertension with carboxyalkylacylamino acids
IL58849A (en) 1978-12-11 1983-03-31 Merck & Co Inc Carboxyalkyl dipeptides and derivatives thereof,their preparation and pharmaceutical compositions containing them
FR2480747A1 (fr) 1980-04-17 1981-10-23 Roques Bernard Derives d'acides amines et leur application therapeutique
US4906615A (en) 1980-12-18 1990-03-06 Schering Corporation Substituted dipeptides as inhibitors of enkephalinases
US4722810A (en) 1984-08-16 1988-02-02 E. R. Squibb & Sons, Inc. Enkephalinase inhibitors
US4939261A (en) 1984-06-08 1990-07-03 Ciba-Geigy Corporation N-substituted butyramide derivatives useful for treatment of conditions responsive to inhibition of enkephalinase
EP0225292A3 (en) 1985-12-06 1988-11-30 Ciba-Geigy Ag Certain n-substituted butyramide derivatives
US4929641B1 (en) 1988-05-11 1994-08-30 Schering Corp Mercapto-acylamino acid antihypertensives
KR880007441A (ko) 1986-12-11 1988-08-27 알렌 제이.스피겔 스피로-치환된 글루타르아미드 이뇨제
FR2623498B1 (fr) 1987-11-24 1990-04-06 Bioprojet Soc Civ Nouveaux composes enantiomeres derives d'amino-acides, leur procede de preparation et leurs applications therapeutiques
GB8820844D0 (en) 1988-09-05 1988-10-05 Pfizer Ltd Therapeutic agents
US5599951A (en) 1989-09-15 1997-02-04 Societe Civile Bioprojet Amino acid derivatives, the process for their preparation and their applications to therapy
US5294632A (en) 1991-05-01 1994-03-15 Ciba-Geigy Corporation Phosphono/biaryl substituted dipetide derivatives
US5155100A (en) 1991-05-01 1992-10-13 Ciba-Geigy Corporation Phosphono/biaryl substituted dipeptide derivatives
US5217996A (en) 1992-01-22 1993-06-08 Ciba-Geigy Corporation Biaryl substituted 4-amino-butyric acid amides
US5508272A (en) 1993-06-15 1996-04-16 Bristol-Myers Squibb Company Compounds containing a fused bicycle ring and processes therefor
DE19510566A1 (de) 1995-03-23 1996-09-26 Kali Chemie Pharma Gmbh Benzazepin-, Benzoxazepin- und Benzothiazepin-N-essigsäurederivate sowie Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende Arzneimittel
JPH11505522A (ja) 1995-04-21 1999-05-21 ノバルティス・アクチエンゲゼルシャフト エンドセリン阻害剤としてのｎ−アロイルアミノ酸アミド
US6660756B2 (en) 2001-03-28 2003-12-09 Pfizer Inc. N-phenpropylcyclopentyl-substituted glutaramide derivatives as inhibitors of neutral endopeptidase
GB0119305D0 (en) 2001-04-12 2001-10-03 Aventis Pharma Gmbh Mercaptoacetylamide derivatives,a process for their preparation and their use
EP1575911B1 (en) * 2002-11-19 2010-01-13 Galderma Research & Development Biaromatic compounds which activate ppar-gamma type receptors and use thereof in cosmetic or pharmaceutical compositions
WO2006027680A1 (en) 2004-09-10 2006-03-16 Pfizer Limited 3-(1-carbamoylcyclohexyl) propionic acid derivatives as inhibitors of neutral endopeptidase enzyme
AR057882A1 (es) 2005-11-09 2007-12-26 Novartis Ag Compuestos de accion doble de bloqueadores del receptor de angiotensina e inhibidores de endopeptidasa neutra
WO2007106708A2 (en) 2006-03-10 2007-09-20 Novartis Ag Combinations of the angiotensin ii antagonist valsartan and the nep inhibitor daglutril
SG185318A1 (en) 2007-01-12 2012-11-29 Novartis Ag Process for preparing 5-biphenyl-4-amino-2-methyl pentanoic acid
TWI448284B (zh) 2007-04-24 2014-08-11 Theravance Inc 雙效抗高血壓劑
PE20091364A1 (es) 2008-01-17 2009-10-13 Novartis Ag Proceso para la preparacion de inhibidores de nep
US20120150643A1 (en) * 2010-12-14 2012-06-14 Moneyhoney Llc System and method for processing remainder amounts of money from gift cards
WO2010136474A2 (en) * 2009-05-28 2010-12-02 Novartis Ag Substituted aminobutyric derivatives as neprilysin inhibitors
UY32662A (es) 2009-05-28 2010-12-31 Novartis Ag Derivados amino-propionicos sustituidos como inhibidores de neprilisina
JO2967B1 (en) 2009-11-20 2016-03-15 نوفارتس ايه جي Acetic acid derivatives of carbamoyl methyl amino are substituted as new NEP inhibitors
BR112012017869A2 (pt) 2010-01-22 2019-09-24 Novartis Ag "intermediários dos inibidores da endopeptidase neutraq e método de preparação dos mesmos"
US8673974B2 (en) 2010-11-16 2014-03-18 Novartis Ag Substituted amino bisphenyl pentanoic acid derivatives as NEP inhibitors
US8993631B2 (en) * 2010-11-16 2015-03-31 Novartis Ag Method of treating contrast-induced nephropathy
MX2013006805A (es) * 2010-12-15 2013-07-29 Theravance Inc Inhibidores de la neprilisina.
ES2548887T3 (es) 2010-12-15 2015-10-21 Theravance Biopharma R&D Ip, Llc Inhibidores de neprilisina
JP5959065B2 (ja) 2011-02-17 2016-08-02 セラヴァンス バイオファーマ アール＆ディー アイピー， エルエルシー ネプリライシン阻害剤としての置換アミノ酪酸誘導体
EP2675792B1 (en) 2011-02-17 2016-01-06 Theravance Biopharma R&D IP, LLC Substituted aminobutyric derivatives as neprilysin inhibitors
CN103582630B (zh) 2011-05-31 2016-08-17 施万生物制药研发Ip有限责任公司 脑啡肽酶抑制剂
WO2012166387A1 (en) 2011-05-31 2012-12-06 Theravance, Inc. Neprilysin inhibitors
CA2835281A1 (en) 2011-05-31 2012-12-06 Theravance, Inc. Neprilysin inhibitors
TWI560172B (en) 2011-11-02 2016-12-01 Theravance Biopharma R&D Ip Llc Neprilysin inhibitors
CA2871292A1 (en) 2012-05-31 2013-12-05 Theravance Biopharma R&D Ip, Llc Nitric oxide donor neprilysin inhibitors
HUE032802T2 (hu) 2012-06-08 2017-10-30 Theravance Biopharma R&D Ip Llc Neprilizininhibitorok
PT3259255T (pt) * 2015-02-19 2021-01-26 Theravance Biopharma R&D Ip Llc Ácido (2r,4r)-5-(5¿-cloro-2¿-fluorobifenil-4-il)-2-hidroxi-4-[(5-metiloxazol-2-carbonil)amino]pentanoico

Also Published As

Publication number Publication date
RU2014153578A (ru) 2016-07-27
KR20150023686A (ko) 2015-03-05
ES2632600T3 (es) 2017-09-14
US9670140B2 (en) 2017-06-06
CN104350042A (zh) 2015-02-11
LT2864292T (lt) 2017-07-10
US20210155576A1 (en) 2021-05-27
AU2013271537B2 (en) 2017-05-11
HUE032802T2 (hu) 2017-10-30
PH12014502733B1 (en) 2015-02-02
US10315984B2 (en) 2019-06-11
US20170355664A1 (en) 2017-12-14
CN104350042B (zh) 2017-05-24
ZA201408634B (en) 2015-12-23
US11174219B2 (en) 2021-11-16
US9108934B2 (en) 2015-08-18
ES2700152T3 (es) 2019-02-14
NZ702749A (en) 2017-01-27
IL235737B (en) 2019-12-31
US20130330366A1 (en) 2013-12-12
MX2014014918A (es) 2015-05-11
KR102102197B1 (ko) 2020-04-20
EP3199517A1 (en) 2017-08-02
JP2017125063A (ja) 2017-07-20
TW201402552A (zh) 2014-01-16
US10829438B2 (en) 2020-11-10
PH12014502733A1 (en) 2015-02-02
TWI644901B (zh) 2018-12-21
PL2864292T3 (pl) 2017-10-31
RS55967B1 (sr) 2017-09-29
US9884807B2 (en) 2018-02-06
RU2663618C2 (ru) 2018-08-07
WO2013184934A1 (en) 2013-12-12
CA2876024A1 (en) 2013-12-12
SG11201408094YA (en) 2015-01-29
EP2864292B1 (en) 2017-04-12
MX356260B (es) 2018-05-21
US20180327350A1 (en) 2018-11-15
NZ723772A (en) 2017-06-30
US20160002148A1 (en) 2016-01-07
EP2864292A1 (en) 2015-04-29
TWI583671B (zh) 2017-05-21
DK2864292T3 (en) 2017-07-31
JP2015525215A (ja) 2015-09-03
BR112014030743B1 (pt) 2022-09-06
PT2864292T (pt) 2017-07-10
EP3199517B1 (en) 2018-09-12
US20200017436A1 (en) 2020-01-16
IL235737A0 (en) 2015-02-01
AU2013271537A1 (en) 2014-12-04
ME02698B (me) 2017-10-20
CA2876024C (en) 2020-04-07
JP6162230B2 (ja) 2017-07-12
TW201726629A (zh) 2017-08-01
BR112014030743A2 (pt) 2017-06-27
SG10201703185VA (en) 2017-05-30
HRP20171037T1 (hr) 2017-10-06
SI2864292T1 (sl) 2017-07-31

Similar Documents

Publication Publication Date Title
AR091381A1 (es) Inhibidores de la neprilisina
AR092073A1 (es) Inhibidores de neprilisina
CO6680699A2 (es) Derivados de amina para el control de plagas
AR090867A1 (es) Compuestos y composiciones plaguicidas y procesos relacionados
CO2017011172A2 (es) Compuestos de 1-ciano-pirrolidina como inhibidores de usp30
AR087193A1 (es) Compuestos fungicidas 2-[2-cloro-4(4-cloro-fenoxi)-fenil]-1-[1,2,4]triazol-1il-etanol alquilo sustituidos
AR107170A1 (es) Compuestos heterocíclicos tricíclicos condesados como inhibidores de integrasa del vih
AR088534A1 (es) Composiciones plaguicidas y procesos relacionados con dichas composiciones
CO2018005848A2 (es) Compuestos de pirazol o sus sales, métodos de preparación de los mismos, composiciones herbicidas y su uso
AR094452A1 (es) COMPUESTOS HETEROCÍCLICOS SUSTITUIDOS CON AMIDA ÚTILES COMO MODULADORES DE LAS RESPUESTAS DE IL-12, IL-23 Y/O INFa
AR103265A1 (es) Compuestos de azolina sustituidos con un sistema de anillos condensado
AR085410A1 (es) Derivados de pirazol heteroaril-sustituidos, composiciones pesticidas que los comprenden y su uso en el control de plagas
AR085004A1 (es) Inhibidores selectivos de glicosidasas y usos de los mismos
AR068075A1 (es) Compuestos de piperazina con accion herbicida. proceso de preparacion
AR066331A1 (es) Piridonacarboxamidas agentes protectores de plantas utiles que contienen a estas y procedimientos para su preparacion y su utilizacion
AR087535A1 (es) Compuestos fungicidas de 1-{2-[2-halo-4-(4-halogen-fenoxi)-fenil]-2-etoxi-etil}-1h-[1,2,4]triazol sustituidos
AR100052A1 (es) Compuestos de diaminotriazina
NI200900037A (es) Derivados de 2-aril-6-fenil-imidazo[1,2-alfa] piridinas, su preparación y su aplicación en terapéutica.
CR20140091A (es) Nuevos derivados dihidroquinolina-2-ona
AR091519A1 (es) Inhibidores pirrolopirazona de tanquirasa
AR074021A1 (es) Compuestos heterociclicos fusionados como moduladores del canal ionico
AR103266A1 (es) Compuestos cíclicos sustituidos con un sistema de anillos condensado para combatir plagas de invertebrados
AR095422A1 (es) Compuestos de piperidina sustituidos y su uso como moduladores de receptores de orexina
AR077080A1 (es) Compuestos de 2,3-dihidro-1h-indeno
AR096613A1 (es) Moduladores de la acetil-coa carboxilasa

Legal Events

Date Code Title Description
FG Grant, registration