AR097948A1 - Inhibidores de la proteasa de cisteína catepsina - Google Patents

Inhibidores de la proteasa de cisteína catepsina

Info

Publication number
AR097948A1
AR097948A1 ARP140103731A ARP140103731A AR097948A1 AR 097948 A1 AR097948 A1 AR 097948A1 AR P140103731 A ARP140103731 A AR P140103731A AR P140103731 A ARP140103731 A AR P140103731A AR 097948 A1 AR097948 A1 AR 097948A1
Authority
AR
Argentina
Prior art keywords
alkyl
halo
cycloalkyl
optionally substituted
heterocyclyl
Prior art date
Application number
ARP140103731A
Other languages
English (en)
Original Assignee
Merck Sharp & Dohme
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 Merck Sharp & Dohme filed Critical Merck Sharp & Dohme
Publication of AR097948A1 publication Critical patent/AR097948A1/es

Links

Classifications

    • 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
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/0805—Compounds with Si-C or Si-Si linkages comprising only Si, C or H atoms
    • C07F7/0807—Compounds with Si-C or Si-Si linkages comprising only Si, C or H atoms comprising Si as a ring atom
    • 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
    • A61K31/421—1,3-Oxazoles, e.g. pemoline, trimethadione
    • 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
    • A61K31/422—Oxazoles not 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
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not 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
    • A61K31/495—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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/547—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame spiro-condensed or forming part of bridged 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
    • A61K31/695—Silicon compounds
    • 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
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • 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
    • C07D233/56—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 only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • 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
    • C07D263/32—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D417/10—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 carbon chain containing aromatic rings
    • 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
    • C07D417/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/08—Bridged 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
    • C07D513/08—Bridged systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Ophthalmology & Optometry (AREA)
  • Hematology (AREA)
  • Immunology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Obesity (AREA)
  • Cardiology (AREA)
  • Pain & Pain Management (AREA)
  • Diabetes (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Pulmonology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Inhibidores de las catepsinas K, L, S y B, útiles para el tratamiento de enfermedades en la que está indicada una inhibición de la resorción ósea, tales como la osteoporosis. Reivindicación 1: Un compuesto de la fórmula (1), en la que X es oxígeno, azufre o nitrógeno; R¹ es hidrógeno, alquilo C₁₋₆, alquenilo C₂₋₆, cicloalquilo C₃₋₈ o heterociclilo, en el que dichos grupos alquilo y alquenilo están opcionalmente sustituidos con cicloalquilo C₃₋₆, entre uno y seis halo, hidroxi o R⁸; y en la que dichos grupos cicloalquilo y heterociclilo están opcionalmente sustituidos con uno o dos sustituyentes elegidos de entre el grupo que consiste en alquilo C₁₋₆, halo, OR⁶ y ceto; R² es hidrógeno, alquilo C₁₋₆, o alquenilo C₂₋₆, en el que dichos grupos alquilo y alquenilo están opcionalmente sustituidos con cicloalquilo C₃₋₆ entre uno y seis halo o R⁸; o R¹ y R² pueden tomarse junto con el átomo de carbono al que están unidos para formar un anillo cicloalquilo C₃₋₈ o heterociclilo en el que dichos anillos cicloalquilo y heterociclilo están opcionalmente sustituidos con uno o dos sustituyentes elegidos independientemente de entre el grupo que consiste en R⁶, haloalquilo C₁₋₆ y halo; cada R³ se elige independientemente de entre el grupo que consiste en hidrógeno, halo y alquilo C₁₋₂, en el que dicho grupo alquilo está opcionalmente sustituido con entre uno y tres halo; o dos grupos R³ pueden tomarse junto con el átomo de carbono al que están unidos para formar un anillo cicloalquilo C₃₋₄, en el que dicho anillo está opcionalmente sustituido con entre uno y tres halo; R⁴ es hidrógeno, alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₃, NR⁶R⁷, OR⁶, OR⁸ o R⁸ en el que dichos grupos alquilo están opcionalmente sustituidos con entre uno y seis sustituyentes elegidos independientemente de entre el grupo que consiste en OR⁷, halo, hidroxi, ciano y R⁸; R⁵ es hidrógeno, alquilo C₁₋₆, alquenilo C₂₋₆, arilo, heteroarilo, cicloalquilo C₃₋₈, heterociclilo, C(O)NR⁶R⁸, C(O)R⁸, NR⁶C(O)OR⁷ o SOₘR⁶, en el que dichos grupos arilo, heteroarilo, cicloalquilo C₃₋₈ y heterociclilo están opcionalmente sustituidos con entre uno y cinco sustituyentes elegidos independientemente de entre el grupo que consiste en alquilo C₁₋₆, halo, oxo, ciano, haloalquilo C₁₋₆; y SOₘR⁶; R⁶ es hidrógeno o alquilo C₁₋₆ que está opcionalmente sustituido con entre uno y tres sustituyentes elegidos independientemente de entre el grupo que consiste en halo, hidroxi, ciano y O(alquilo C₁₋₆); R⁷ es hidrógeno o alquilo C₁₋₆ que está opcionalmente sustituido con entre uno y tres sustituyentes elegidos independientemente de entre el grupo que consiste en halo, hidroxi, ciano y O(alquilo C₁₋₆); R⁸ es cicloalquilo C₃₋₈, arilo, heteroarilo o heterociclilo, en la que dichos grupos cicloalquilo, arilo, heteroarilo y heterociclilo están opcionalmente sustituidos con entre uno y cuatro sustituyentes elegidos independientemente de entre el grupo que consiste en halo, ciano, oxo, haloalquilo C₁₋₆, R⁶, OR⁶, cicloalquilo C₃₋₆, arilo, heteroarilo, heterociclilo, SOₘR⁶ y SF₅; m es un número entero entre cero y dos; p es un número entero entre cero y dos; o una sal farmacéuticamente aceptable de los mismos.
ARP140103731A 2013-10-08 2014-10-07 Inhibidores de la proteasa de cisteína catepsina AR097948A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US201361888029P 2013-10-08 2013-10-08

Publications (1)

Publication Number Publication Date
AR097948A1 true AR097948A1 (es) 2016-04-20

Family

ID=51842845

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP140103731A AR097948A1 (es) 2013-10-08 2014-10-07 Inhibidores de la proteasa de cisteína catepsina

Country Status (11)

Country Link
US (1) US9458181B2 (es)
EP (1) EP3055314B1 (es)
JP (1) JP6454335B2 (es)
KR (1) KR20160065854A (es)
CN (1) CN105593230B (es)
AR (1) AR097948A1 (es)
AU (1) AU2014332250B2 (es)
CA (1) CA2923272A1 (es)
RU (1) RU2692799C2 (es)
TW (1) TWI656120B (es)
WO (1) WO2015054089A1 (es)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015051479A1 (en) 2013-10-08 2015-04-16 Merck Sharp & Dohme Corp. Cathepsin cysteine protease inhibitors
WO2015120580A1 (en) 2014-02-11 2015-08-20 Merck Sharp & Dohme Corp. Cathepsin cysteine protease inhibitors
AU2018211735B2 (en) * 2017-01-24 2021-08-12 Astellas Pharma Inc. Phenyldifluoromethyl-substituted prolinamide compound
CN109554456A (zh) * 2017-09-26 2019-04-02 深圳先进技术研究院 Gpr1基因在诊断或治疗骨生长或骨质异常疾病的应用
CN107964009A (zh) * 2018-01-21 2018-04-27 吕迎春 一种2-吡啶衍生物取代的咪唑类化合物及其在防治骨质疏松药物中的应用
JP7271566B2 (ja) * 2018-03-28 2023-05-11 ハンリム ファーマシューティカル カンパニー リミテッド ２－シアノピリミジン－４－イル カルバメート誘導体もしくはウレア誘導体またはその塩及びそれを含む医薬組成物
RU2752531C1 (ru) * 2020-06-11 2021-07-29 федеральное государственное автономное образовательное учреждение высшего образования Первый Московский государственный медицинский университет имени И.М. Сеченова Министерства здравоохранения Российской Федерации (Сеченовский университет) (ФГАОУ ВО Первый МГМУ им. И.М. Сеченова Минздрава России (Се Специфические пептидные ингибиторы цистеиновых катепсинов

Family Cites Families (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA777769A (en) 1963-03-18 1968-02-06 H. Roy Clarence Substituted methylene diphosphonic acid compounds and detergent compositions
US4294926A (en) 1979-06-15 1981-10-13 Merck & Co., Inc. Hypocholesteremic fermentation products and process of preparation
US4319039A (en) 1979-06-15 1982-03-09 Merck & Co., Inc. Preparation of ammonium salt of hypocholesteremic fermentation product
US4231938A (en) 1979-06-15 1980-11-04 Merck & Co., Inc. Hypocholesteremic fermentation products and process of preparation
US4444784A (en) 1980-08-05 1984-04-24 Merck & Co., Inc. Antihypercholesterolemic compounds
DK149080C (da) 1980-06-06 1986-07-28 Sankyo Co Fremgangsmaade til fremstilling af derivater af ml-236b-carboxylsyre
JPS5889191A (ja) 1981-11-20 1983-05-27 Sankyo Co Ltd ３−ヒドロキシ−ｍｌ−２３６ｂ誘導体の製造法
FR2531088B1 (fr) 1982-07-29 1987-08-28 Sanofi Sa Produits anti-inflammatoires derives de l'acide methylenediphosphonique et leur procede de preparation
AU570021B2 (en) 1982-11-22 1988-03-03 Novartis Ag Analogs of mevalolactone
US5354772A (en) 1982-11-22 1994-10-11 Sandoz Pharm. Corp. Indole analogs of mevalonolactone and derivatives thereof
US4911165A (en) 1983-01-12 1990-03-27 Ethicon, Inc. Pliabilized polypropylene surgical filaments
US4761406A (en) 1985-06-06 1988-08-02 The Procter & Gamble Company Regimen for treating osteoporosis
US4681893A (en) 1986-05-30 1987-07-21 Warner-Lambert Company Trans-6-[2-(3- or 4-carboxamido-substituted pyrrol-1-yl)alkyl]-4-hydroxypyran-2-one inhibitors of cholesterol synthesis
DE3623397A1 (de) 1986-07-11 1988-01-14 Boehringer Mannheim Gmbh Neue diphosphonsaeurederivate, verfahren zu deren herstellung und diese verbindungen enthaltende arzneimittel
US4885314A (en) 1987-06-29 1989-12-05 Merck & Co., Inc. Novel HMG-CoA reductase inhibitors
US4782084A (en) 1987-06-29 1988-11-01 Merck & Co., Inc. HMG-COA reductase inhibitors
US4820850A (en) 1987-07-10 1989-04-11 Merck & Co., Inc. Process for α-C-alkylation of the 8-acyl group on mevinolin and analogs thereof
CA1339805C (en) 1988-01-20 1998-04-07 Yasuo Isomura (cycloalkylamino)methylenebis(phosphonic acid) and medicines containing the same as an active
US5030447A (en) 1988-03-31 1991-07-09 E. R. Squibb & Sons, Inc. Pharmaceutical compositions having good stability
US5180589A (en) 1988-03-31 1993-01-19 E. R. Squibb & Sons, Inc. Pravastatin pharmaceuatical compositions having good stability
US4916239A (en) 1988-07-19 1990-04-10 Merck & Co., Inc. Process for the lactonization of mevinic acids and analogs thereof
US5118853A (en) 1988-10-13 1992-06-02 Sandoz Ltd. Processes for the synthesis of 3-disubstituted aminoacroleins
US5290946A (en) 1988-10-13 1994-03-01 Sandoz Ltd. Processes for the synthesis of 3-(substituted indolyl-2-yl)propenaldehydes
US4929437A (en) 1989-02-02 1990-05-29 Merck & Co., Inc. Coenzyme Q10 with HMG-CoA reductase inhibitors
US5189164A (en) 1989-05-22 1993-02-23 Sandoz Ltd. Processes for the synthesis of syn-(E)-3,5-dihydroxy-7-substituted hept-6-enoic and heptanoic acids and derivatives and intermediates thereof
US4922007A (en) 1989-06-09 1990-05-01 Merck & Co., Inc. Process for preparing 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid or salts thereof
FI94339C (fi) 1989-07-21 1995-08-25 Warner Lambert Co Menetelmä farmaseuttisesti käyttökelpoisen /R-(R*,R*)/-2-(4-fluorifenyyli)- , -dihydroksi-5-(1-metyylietyyli)-3-fenyyli-4-/(fenyyliamino)karbonyyli/-1H-pyrroli-1-heptaanihapon ja sen farmaseuttisesti hyväksyttävien suolojen valmistamiseksi
US5019651A (en) 1990-06-20 1991-05-28 Merck & Co., Inc. Process for preparing 4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid (ABP) or salts thereof
US5177080A (en) 1990-12-14 1993-01-05 Bayer Aktiengesellschaft Substituted pyridyl-dihydroxy-heptenoic acid and its salts
HU217629B (hu) 1991-12-12 2000-03-28 Novartis Ag. Eljárás fluvasztatint tartalmazó stabilizált gyógyszerkészítmények előállítására
US5298627A (en) 1993-03-03 1994-03-29 Warner-Lambert Company Process for trans-6-[2-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis
TW257765B (es) 1993-08-25 1995-09-21 Merck & Co Inc
US5510517A (en) 1993-08-25 1996-04-23 Merck & Co., Inc. Process for producing N-amino-1-hydroxy-alkylidene-1,1-bisphosphonic acids
WO2001082923A1 (en) 2000-02-14 2001-11-08 Merck & Co., Inc. Estrogen receptor modulators
US6462076B2 (en) * 2000-06-14 2002-10-08 Hoffmann-La Roche Inc. Beta-amino acid nitrile derivatives as cathepsin K inhibitors
DE60120746T2 (de) 2000-11-27 2007-05-24 Merck & Co., Inc. Östrogenrezeptormodulatoren
US7012075B2 (en) * 2001-03-02 2006-03-14 Merck & Co., Inc. Cathepsin cysteine protease inhibitors
SI1482924T1 (sl) * 2002-03-05 2008-12-31 Merck Frosst Canada Ltd Katepsin cistein proteazni inhibitorji
AU2003297363A1 (en) 2002-12-23 2004-07-22 Alcon, Inc. Use of cathepsin k inhibitors for the treatment of glaucoma
WO2005000800A1 (en) * 2003-06-30 2005-01-06 Merck Frosst Canada Ltd. Cathepsin cysteine protease inhibitors
EP1902031B1 (en) * 2005-07-06 2012-04-11 Merck Canada Inc. Cathepsin cysteine protease inhibitors
AU2008269513B2 (en) * 2007-06-26 2011-06-16 Astrazeneca Ab 1-cyanocyclopropyl-derivatives as cathepsin K inhibitors
US7893099B2 (en) * 2009-06-11 2011-02-22 Hoffman-La Roche Inc. Cyclopentane derivatives
US8524710B2 (en) * 2010-11-05 2013-09-03 Hoffmann-La Roche Inc. Pyrrolidine derivatives

Also Published As

Publication number Publication date
JP2016532646A (ja) 2016-10-20
TW201602102A (zh) 2016-01-16
CN105593230B (zh) 2018-07-06
CN105593230A (zh) 2016-05-18
EP3055314B1 (en) 2018-09-12
RU2016116243A3 (es) 2018-06-26
WO2015054089A1 (en) 2015-04-16
RU2692799C2 (ru) 2019-06-27
KR20160065854A (ko) 2016-06-09
CA2923272A1 (en) 2015-04-16
TWI656120B (zh) 2019-04-11
RU2016116243A (ru) 2017-11-14
EP3055314A1 (en) 2016-08-17
AU2014332250A1 (en) 2016-03-10
JP6454335B2 (ja) 2019-01-16
AU2014332250B2 (en) 2018-07-19
US20150099719A1 (en) 2015-04-09
US9458181B2 (en) 2016-10-04

Similar Documents

Publication Publication Date Title
AR097948A1 (es) Inhibidores de la proteasa de cisteína catepsina
AR129635A2 (es) Moduladores de tetrahidropiridopirazina de gpr6
AR103138A1 (es) Compuestos de heteroarilo como inhibidores de la irak y usos de los mismos
AR102177A1 (es) Compuestos de heteroarilo como inhibidores de btk y usos de los mismos
AR092732A1 (es) Compuestos de tetrazolinona y su uso
AR098136A1 (es) Compuestos de heteroarilo como inhibidores de btk y usos de los mismos
AR109788A1 (es) Compuestos de benzo[b]tiofeno como agonistas de sting
AR100809A1 (es) Inhibidores de fosfatidilinositol 3-quinasa
AR095426A1 (es) Inhibidores tripeptídicos de la epoxicetona proteasa
AR106472A1 (es) Inhibidores de acc y usos de los mismos
AR099177A1 (es) Determinadas (2s)-n-[(1s)-1-ciano-2-feniletil]-1,4-oxazepan-2-carboxamidas como inhibidores de dipeptidil peptidasa 1
AR096979A1 (es) Derivados de pirrol, su procedimiento de preparación y las composiciones farmacéuticas que los contienen
AR094170A1 (es) Composiciones pesticidas y procesos relacionados con las mismas
AR097082A1 (es) Compuestos terapéuticamente activos y sus métodos de uso
AR093505A1 (es) Derivados de 5-fluoro-n-(piridin-2-il)piridin-2-amina que contienen un grupo sulfoximina
AR100808A1 (es) Inhibidores de fosfatidilinositol 3-quinasa
AR087870A1 (es) Derivados 5-fluoro pirimidina disustituidos que contienen un grupo sulfoximina
AR092869A1 (es) Alcoxipirazoles como activadores de guanilato ciclasa soluble
AR094300A1 (es) Derivados de quinolonas
AR110298A1 (es) Compuestos de heterociclo tetracíclicos útiles como inhibidores de la integrasa del vih
AR106100A1 (es) Compuestos bicíclicos como inhibidores duales atx / ca
AR118706A2 (es) Compuesto para el control de plagas y vegetación no deseada, procedimiento para prepararlo, composición que lo comprende, y compuesto intermediario relacionado
PE20170303A1 (es) Derivados de la indolizina como inhibidores de las fosfoinositido-3 quinasas
AR101395A1 (es) Derivados de indolizina y su uso en enfermedades neurodegenerativas
AR104880A1 (es) MODULADORES DE ROR GAMMA (RORg)

Legal Events

Date Code Title Description
FB Suspension of granting procedure