ES2319396T3 - Nuevos nitrilos utiles como inhibidores reversibles de cisteina-proteasas. - Google Patents

Nuevos nitrilos utiles como inhibidores reversibles de cisteina-proteasas. Download PDF

Info

Publication number
ES2319396T3
ES2319396T3 ES02741825T ES02741825T ES2319396T3 ES 2319396 T3 ES2319396 T3 ES 2319396T3 ES 02741825 T ES02741825 T ES 02741825T ES 02741825 T ES02741825 T ES 02741825T ES 2319396 T3 ES2319396 T3 ES 2319396T3
Authority
ES
Spain
Prior art keywords
compounds
proteasas
cisteina
nitrils
reversible inhibitors
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
ES02741825T
Other languages
English (en)
Inventor
Eugene R. Boehringer Ingelheim Corp. HICKEY
Younes Boehringer Ingelheim Corp. BEKKALI
Usha R. Boehringer Ingelheim Corp. PATEL
Denice M. Boehringer Ingelheim Corp. SPERO
David S. Boehringer Ingelheim Corp. THOMSON
Erick R. R. Boehringer Ingelheim Corp. YOUNG
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Boehringer Ingelheim Pharmaceuticals Inc
Original Assignee
Boehringer Ingelheim Pharmaceuticals 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 Boehringer Ingelheim Pharmaceuticals Inc filed Critical Boehringer Ingelheim Pharmaceuticals Inc
Application granted granted Critical
Publication of ES2319396T3 publication Critical patent/ES2319396T3/es
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/84—Nitriles
    • 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
    • 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
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • 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
    • A61P11/04—Drugs for disorders of the respiratory system for throat disorders
    • 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
    • A61P11/06—Antiasthmatics
    • 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
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/06—Antipsoriatics
    • 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
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/02—Antiprotozoals, e.g. for leishmaniasis, trichomoniasis, toxoplasmosis
    • A61P33/06—Antimalarials
    • 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
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/08—Antiallergic 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
    • 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
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/24—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton
    • C07C255/29—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton containing cyano groups and acylated amino groups bound to the carbon skeleton
    • 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
    • C07C271/12—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 hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals
    • 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
    • C07C271/26—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
    • C07C271/28—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a non-condensed six-membered aromatic ring
    • 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
    • C07C271/26—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
    • C07C271/30—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a six-membered aromatic ring being part of a condensed ring system
    • 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
    • C07C271/32—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of rings other than six-membered aromatic rings
    • C07C271/34—Esters of carbamic acids having oxygen atoms of carbamate groups bound to carbon atoms of rings other than six-membered aromatic rings with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • 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
    • C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—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 no 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
    • C07D207/16—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
    • 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
    • C07D295/16—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 acylated on ring nitrogen atoms
    • C07D295/18—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 acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
    • C07D295/182—Radicals derived from carboxylic acids
    • C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
    • 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
    • C07D295/16—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 acylated on ring nitrogen atoms
    • C07D295/20—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 acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
    • C07D295/205—Radicals derived from carbonic acid
    • 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
    • C07D295/16—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 acylated on ring nitrogen atoms
    • C07D295/20—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 acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
    • C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/04—One of the condensed rings being a six-membered aromatic ring
    • C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/14—All rings being cycloaliphatic
    • C07C2602/26—All rings being cycloaliphatic the ring system containing ten carbon atoms
    • C07C2602/28—Hydrogenated naphthalenes
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/50—Spiro compounds

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pulmonology (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Immunology (AREA)
  • Neurology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Diabetes (AREA)
  • Dermatology (AREA)
  • Endocrinology (AREA)
  • Urology & Nephrology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Psychiatry (AREA)
  • Otolaryngology (AREA)
  • Vascular Medicine (AREA)
  • Reproductive Health (AREA)
  • Emergency Medicine (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Pain & Pain Management (AREA)

Abstract

Un compuesto de la siguiente fórmula (I) para el uso de medicamento: ** ver fórmula** en la que: Y es R1, R1O-, R1S-, (R1)2N-, (R1)3C-; cada R 1 es con independencia hidrógeno, alquilo C1-10, cicloalquilo C3-8, arilo, bencilo, tetrahidronaftilo, indenilo, indanilo, (alquilsulfonil C1-10)-alquilo C1-10, (cicloalquilsulfonil C3-8)-alquilo C1-10, arilsulfonil-alquilo C1-10, un heterociclilo o heteroarilo elegido entre pirrolidinilo, piperidinilo, morfolinilo, tiomorfolinilo, piperazinilo, indolinilo, piranilo, tetrahidropiranilo, tetrahidrotiopiranilo, tiopiranilo, furanilo, tetrahidrofuranilo, tienilo, pirrolilo, oxazolilo, isoxazolilo, tiazolilo, imidazolilo, piridinilo, pirimidinilo, pirazinilo, piridazinilo, tetrazolilo, pirazolilo, indolilo, benzofuranilo, benzotienilo, dihidrobenzofuranilo, dihidrobenzotienilo, bencimidazolilo, benzotiazolilo, bencisoxazolilo, bencisotiazolilo, quinolinilo, tetrahidroquinolinilo, isoquinolinilo, tetrahidroisoquinolinilo, quinazolinilo, tetrahidroquinazolinilo, benzoxazolilo, 2H-benzo[e][1,3]oxazina y quinoxalinilo, en la que cada R1 está opcionalmente sustituido por uno o más Ra; o R1 es Ra o Rb; cada R a es con independencia hidrógeno, alquilo C1-10, cicloalquilo C3-8, arilo, tetrahidronaftilo, indenilo, indanilo, un heterociclo o heteroarilo elegido entre el grupo formado por pirrolidinilo, piperidinilo, morfolinilo, tiomorfolinilo, piperazinilo, indolinilo, furanilo, tienilo, pirrolilo, oxazolilo, dihidro-oxazolilo, tiazolilo, imidazolilo, triazolilo, tetrazolilo, piridinilo, pirimidinilo, pirazinilo, indolilo, benzofuranilo, benzotienilo, dihidrobenzofuranilo, dihidrobenzotienilo, bencimidazolilo, benzotiazolilo, benzoxazolilo, bencisoxazolilo, quinolinilo, isoquinolinilo, quinazolinilo y quinoxalinilo, alcoxi C1-10, alcanoílo C1-10, alcanoiloxi C1-10, ariloxi, benciloxi, aroílo, (alcoxi C1-10)-carbonilo, ariloxicarbonilo, aroiloxi, heterocicliloxi, heterociclil-alcoxi C1-6, heteroariloxi o heteroaril-alcoxi C1-6, dicho resto heterociclilo o heteroariloxi se elige entre los mencionados en este párrafo, carbamoílo, cuyo átomo de nitrógeno puede estar mono- o di-sustituido con independencia por alquilo C1-10, arilo, pirrolidinilo, piperidinilo, morfolinilo, tiomorfolinilo, piperazinilo, indolinilo, furanilo, tienilo, pirrolilo, oxazolilo, tiazolilo, imidazolilo, triazolilo, tetrazolilo, piridinilo, pirimidinilo, pirazinilo, indolilo, benzofuranilo, benzotienilo, dihidrobenzofuranilo, dihidrobenzotienilo, bencimidazolilo, benzotiazolilo, quinolinilo, isoquinolinilo, quinazolinilo o quinoxalinilo, o R a es mono- o di-(alquil C1-10)-amino, (alcanoil C1-10)-amino, aroilamino, alquiltio C1-10, cuyo átomo de azufre puede estar oxidado a sulfóxido o sulfona, ariltio, cuyo átomo de azufre puede estar oxidado a sulfóxido o sulfona, ureido, cuyo átomo de nitrógeno puede estar sustituido con independencia por uno o más alquilo C1-10, arilo, pirrolidinilo, piperidinilo, morfolinilo, tiomorfolinilo, piperazinilo, indolinilo, furanilo, tienilo, pirrolilo, oxazolilo, tiazolilo, imidazolilo, triazolilo, tetrazolilo, piridinilo, pirimidinilo, pirazinilo, indolilo, benzofuranilo, benzotienilo, dihidrobenzofuranilo, dihidrobenzotienilo, bencimidazolilo, benzotiazolilo, quinolinilo, isoquinolinilo, quinazolinilo o quinoxalinilo, o Ra es (alcoxi C1-10)-carbonilamino, ariloxicarbonilamino, heterociclilcarbonilamino, heteroarilcarbonilamino, (alquil C1-10)-carbamoiloxi, arilcarbamoiloxi, (alquilsulfonil C1-10)-amino, arilsulfonilamino, (alquil C1-10)-aminosulfonilo, arilaminosulfonilo, amino, cuyo átomo de nitrógeno puede estar mono- o di-sustituido con independencia por alquilo C1-10, arilo, pirrolidinilo, piperidinilo, morfolinilo, tiomorfolinilo, piperazinilo, indolinilo, furanilo, tienilo, pirrolilo, oxazolilo, tiazolilo, imidazolilo, triazolilo, tetrazolilo, piridinilo, pirimidinilo, pirazinilo, indolilo, benzofuranilo, benzotienilo, dihidrobenzofuranilo, dihidrobenzotienilo, bencimidazolilo, benzotiazolilo, quinolinilo, isoquinolinilo, quinazolinilo o quinoxalinilo, o Ra es halógeno, hidroxi, oxo, carboxi, ciano, nitro, carboxamida, amidino o guanidino, en la que R a puede estar además opcionalmente sustituido por uno o más R b; Rb es a alquilo grupo C1-6 saturado o insaturado, en el que uno o más átomos de carbono están opcionalmente sustituido por O, N, S(O), S(O)2 o S y en el que el grupo alquilo está sustituido opcionalmente y con independencia por uno o dos grupos oxo, y/o uno o más: -NH 2, alquilo C1-4, arilo, pirrolidinilo, piperidinilo, morfolinilo, tiomorfolinilo, piperazinilo, indolinilo, furanilo, tienilo, pirrolilo, oxazolilo, tiazolilo, imidazolilo, triazolilo, tetrazolilo, piridinilo, pirimidinilo, pirazinilo, indolilo, benzofuranilo, benzotienilo, dihidrobenzofuranilo, dihidrobenzotienilo, bencimidazolilo, benzotiazolilo, quinolinilo, isoquinolinilo, quinazolinilo o quinoxalinilo; o R b es cicloalquilo C3-6, alcoxi C1-6, arilo, ariloxi, benciloxi, halógeno, hidroxi, oxo, carboxi, ciano, nitro, mono (alquil C1-5)-amino, di(alquil C1-5)-amino, carboxamida, amidino o guanidino; R2 y R3 con independencia entre sí son un hidrógeno, cicloalquilo C3-8, aril-alquilo C1-5, arilo, o un resto alquilo C1-10 saturado o insaturado, en el que uno o más átomos de C se han reemplazado opcionalmente por O, NH, S(O), S(O) 2 o S y en el que dicho resto alquilo está sustituido opcionalmente y con independencia por uno o dos grupos oxo, y/o uno o más: -NH2, alquilo C1-4, arilo, pirrolidinilo, piperidinilo, morfolinilo, tiomorfolinilo, piperazinilo, indolinilo, piranilo, tiopiranilo, furanilo, tienilo, pirrolilo, oxazolilo, isoxazolilo, tiazolilo, imidazolilo, piridinilo, pirimidinilo, pirazinilo, indolilo, benzofuranilo, benzotienilo, dihidrobenzofuranilo, dihidrobenzotienilo, bencimidazolilo, benzotiazolilo, quinolinilo, isoquinolinilo, quinazolinilo, benzoxazolilo o quinoxalinilo; en el que cada R 2 y R 3 está sustituido opcionalmente sustituido con independencia por uno o más Rc; o R2 y R3 con independencia entre sí son Rc; R c es alquilo C1-10, cicloalquilo C3-8, arilo, indanilo, indenilo, biciclo[
ES02741825T 2001-06-08 2002-06-05 Nuevos nitrilos utiles como inhibidores reversibles de cisteina-proteasas. Expired - Lifetime ES2319396T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US29686301P 2001-06-08 2001-06-08
US296863P 2001-06-08

Publications (1)

Publication Number Publication Date
ES2319396T3 true ES2319396T3 (es) 2009-05-07

Family

ID=23143883

Family Applications (1)

Application Number Title Priority Date Filing Date
ES02741825T Expired - Lifetime ES2319396T3 (es) 2001-06-08 2002-06-05 Nuevos nitrilos utiles como inhibidores reversibles de cisteina-proteasas.

Country Status (9)

Country Link
US (1) US6982263B2 (es)
EP (1) EP1399431B1 (es)
JP (1) JP4309251B2 (es)
AT (1) ATE423108T1 (es)
CA (1) CA2449192C (es)
DE (1) DE60231207D1 (es)
ES (1) ES2319396T3 (es)
MX (1) MXPA03011113A (es)
WO (1) WO2002100849A2 (es)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004523506A (ja) 2000-12-22 2004-08-05 アクシス・ファーマシューティカルズ・インコーポレイテッド カテプシン阻害剤としての新規な化合物と組成物
US7030116B2 (en) 2000-12-22 2006-04-18 Aventis Pharmaceuticals Inc. Compounds and compositions as cathepsin inhibitors
DE10141650C1 (de) * 2001-08-24 2002-11-28 Lohmann Therapie Syst Lts Transdermales Therapeutisches System mit Fentanyl bzw. verwandten Substanzen
RS19504A (sr) 2001-09-14 2007-02-05 Aventis Pharmaceuticals Inc., Nova jedinjenja i kompozicije kao inhibitori katepsina
HUP0401906A3 (en) 2001-11-14 2008-07-28 Aventis Pharma Inc Novel cathepsin s inhibitors, process for their preparation and pharmaceutical compositions containing them
US7326719B2 (en) * 2003-03-13 2008-02-05 Boehringer Ingelheim Pharmaceuticals, Inc. Cathepsin S inhibitors
US7297714B2 (en) * 2003-10-21 2007-11-20 Irm Llc Inhibitors of cathepsin S
KR20070008517A (ko) * 2003-10-24 2007-01-17 아벤티스 파마슈티칼스 인크. 카텝신 저해물질로서 신규한 케토-옥사디아졸 유도체
FR2866884B1 (fr) * 2004-02-26 2007-08-31 Sanofi Synthelabo Derives d'aryl-et d'heteroaryl-piperidinecarboxylates, leur preparation et leur application en therapeutique
TW200533398A (en) * 2004-03-29 2005-10-16 Bristol Myers Squibb Co Novel therapeutic agents for the treatment of migraine
PE20060213A1 (es) * 2004-04-30 2006-04-24 Irm Llc Compuestos y composiciones como inhibidores de catepsinas
US20090005323A1 (en) * 2005-01-19 2009-01-01 Michael David Percival Cathepsin K Inhibitors and Obesity
US8026365B2 (en) * 2007-05-25 2011-09-27 Hoffman-La Roche Inc. 4,4-disubstituted piperidine derivatives
WO2009054454A1 (ja) * 2007-10-24 2009-04-30 National University Corporation Tokyo Medical And Dental University カテプシン阻害剤を有効成分として含有するＴｏｌｌ様受容体のシグナル伝達の調整剤
US7893099B2 (en) * 2009-06-11 2011-02-22 Hoffman-La Roche Inc. Cyclopentane derivatives
WO2011069149A2 (en) * 2009-12-04 2011-06-09 Dcb-Usa Llc Cathepsin s inhibitors
JP2013531687A (ja) 2010-07-16 2013-08-08 パーデュー、ファーマ、リミテッド、パートナーシップ ナトリウムチャネル遮断剤としてのピリジン化合物
AU2013203824A1 (en) 2012-03-16 2013-10-03 Purdue Pharma L.P. Substituted pyridines and pryimidines as sodium channel blockers
WO2014096941A1 (en) 2012-12-20 2014-06-26 Purdue Pharma L.P. Cyclic sulfonamides as sodium channel blockers
AU2014230814B2 (en) * 2013-03-14 2017-12-21 Boehringer Ingelheim International Gmbh Substituted 2-Aza-bicyclo[2.2.1]heptane-3-carboxylic acid (benzyl-cyano-methyl)-amides inhibitors of Cathepsin C
US10730866B2 (en) 2014-04-07 2020-08-04 Purdue Pharma L.P. Indole derivatives and use thereof

Family Cites Families (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4137070A (en) * 1971-04-16 1979-01-30 Stauffer Chemical Company Herbicide compositions
US4021224A (en) * 1971-12-09 1977-05-03 Stauffer Chemical Company Herbicide compositions
CA1092606A (en) * 1976-10-05 1980-12-30 Herbert Berger 1-(n-acylcarbamoyl)-2-cyano-aziridines and the preparation thereof
DE2731264A1 (de) * 1977-07-11 1979-02-01 Boehringer Mannheim Gmbh Neue 1-acyl-2-cyanaziridine, verfahren zu deren herstellung und diese verbindungen enthaltende pharmazeutische zubereitungen
DE2833986A1 (de) * 1978-08-03 1980-02-21 Boehringer Mannheim Gmbh Immunstimulierende n-substituierte aziridin-2-carbonsaeurederivate, verfahren zu ihrer herstellung sowie arzneimittel, die diese substanzen enthalten
EP0668870A1 (en) 1991-06-14 1995-08-30 Chiron Corporation Inhibitors of picornavirus proteases
WO1994010155A1 (en) 1992-10-23 1994-05-11 Ciba-Geigy Ag 3-aryluracil derivatives and the use thereof for weed control
US5804560A (en) * 1995-01-06 1998-09-08 Sibia Neurosciences, Inc. Peptide and peptide analog protease inhibitors
US5776718A (en) * 1995-03-24 1998-07-07 Arris Pharmaceutical Corporation Reversible protease inhibitors
TW438591B (en) 1995-06-07 2001-06-07 Arris Pharm Corp Reversible cysteine protease inhibitors
FR2740774B1 (fr) * 1995-11-08 1997-12-19 Roussel Uclaf Nouveaux derives d'imidazole n-benzyldioxole, leur procede de preparation, leur application a titre de medicaments, compositions pharmaceutiques et nouvelle utilisation
HUP0004400A3 (en) 1997-11-05 2002-10-28 Novartis Ag Dipeptide nitriles, process for their preparation, pharmaceutical compositions comprising thereof and their use
CO5180541A1 (es) 1998-12-23 2002-07-30 Smithkline Beechman Corp Inhibidores de proteasa del tipo de 1,3-diaminocetonas con anillo de 8-14 miembros
TR200101869T2 (tr) 1998-12-23 2002-01-21 Smithkline Beecham Corporation Proteaz İnhibitörleri.
GB9903548D0 (en) 1999-02-16 1999-04-07 Novartis Ag Organic compounds
JP2002537293A (ja) 1999-02-20 2002-11-05 アストラゼネカ アクチボラグ カテプシンｌおよび／またはカテプシンｓの阻害剤としてのアセタミドアセトニトリル誘導体
WO2000051998A1 (en) * 1999-03-02 2000-09-08 Boehringer Ingelheim Pharmaceuticals, Inc. Compounds useful as reversible inhibitors of cathepsin s
US6506733B1 (en) 1999-03-15 2003-01-14 Axys Pharmaceuticals, Inc. Compounds and compositions as protease inhibitors
GB9907683D0 (en) 1999-04-06 1999-05-26 Synphar Lab Inc Substituted azetidin-2-ones as cysteine protease inhibitors
US6313117B1 (en) 1999-07-30 2001-11-06 Boehringer Ingelheim Pharmaceuticals, Inc. Succinate derivative compounds useful as cysteine protease inhibitors
WO2001017562A1 (fr) 1999-09-02 2001-03-15 Yamanouchi Pharmaceutical Co., Ltd. Agents promoteurs de l'osteogenese
EG24179A (en) 1999-09-07 2008-09-28 Smithkline Beecham Corp Vitronectin receptor antagonists
JP2003527091A (ja) 1999-09-09 2003-09-16 ミレニアム・ファーマシューティカルズ・インコーポレイテッド 新規カルパインプロテアーゼ２６１７６およびその使用
US6420364B1 (en) * 1999-09-13 2002-07-16 Boehringer Ingelheim Pharmaceuticals, Inc. Compound useful as reversible inhibitors of cysteine proteases
AU7490900A (en) 1999-09-16 2001-04-17 Axys Pharmaceuticals, Inc. Chemical compounds and compositions and their use as cathepsin s inhibitors
WO2001077073A1 (en) 2000-04-06 2001-10-18 Merck Frosst Canada & Co. Cathepsin cysteine protease inhibitors
WO2001087828A1 (en) 2000-05-15 2001-11-22 Novartis Ag N-substituted peptidyl nitriles as cysteine cathepsin inhibitors
US7030116B2 (en) 2000-12-22 2006-04-18 Aventis Pharmaceuticals Inc. Compounds and compositions as cathepsin inhibitors
CN1512983A (zh) 2001-06-01 2004-07-14 AXYSҩ�﹫˾ 作为组织蛋白酶s抑制剂的化合物和组合物

Also Published As

Publication number Publication date
US6982263B2 (en) 2006-01-03
JP4309251B2 (ja) 2009-08-05
ATE423108T1 (de) 2009-03-15
EP1399431B1 (en) 2009-02-18
CA2449192C (en) 2010-10-26
DE60231207D1 (de) 2009-04-02
EP1399431A2 (en) 2004-03-24
WO2002100849A3 (en) 2003-10-16
JP2005501017A (ja) 2005-01-13
MXPA03011113A (es) 2004-03-19
CA2449192A1 (en) 2002-12-19
US20030119827A1 (en) 2003-06-26
WO2002100849A2 (en) 2002-12-19

Similar Documents

Publication Publication Date Title
DE60231207D1 (de) Inhibitoren
EP1482924A4 (en) CATHEPSIN-Cysteine PROTEASE INHIBITORS
EA200500472A1 (ru) Ацетил 2-гидрокси-1,3-диаминоалканы
DE69415690D1 (de) (e)-20(22)-dehydrovitamin-d-verbindungen
PT1289972E (pt) Inibidores de serina proteases
BG66103B1 (bg) Кондензирани пиролокарбазоли
MA27608A1 (fr) Derives d'hydroxyethylamine utilises pour le traitement de la maladie d'alzheimer
MY132419A (en) Inhibitors of factor xa and other serine proteases involved in the coagulation cascade
MXPA03011484A (es) Heteroarilos multiciclicos sustituidos con quinuclidinas para el tratamiento de enfermedades.
NO20030895D0 (no) Ny anvendelse av dipeptidyl peptidase IV inhibitorer
WO2004080376A3 (en) Hydroxyethylamine compounds having asp2 inhibitory activity for the treatment of alzheimer’s disease
EA200300970A1 (ru) Энантиоселективный синтез промежуточных соединений для получения азетидинонов
MY137717A (en) Cathepsin cysteine protease inhibitors
NO20073678L (no) Nye fremgangsmater for fremstilling av benzofuran
MXPA03006749A (es) Proceso para la sintesis de compuestos de urea sustituidos con heteroarilo, utiles como agentes antiinflamatorios.
MY158159A (en) Novel fused pyrrolocarbazoles
SG149042A1 (en) Novel fused pyrrolocarbazoles
ATE335730T1 (de) Verfahren zur kontinuierlich betriebenen reindestillation des bei der koppelproduktfreien synthese von propylenoxid anfallenden 1,2- propylenglykols
YU14595A (sh) Postupak za dobijanje epoksida
AU2003230772A8 (en) Cyanamides useful as reversible inhibitors of cysteine proteases
TR200503401T1 (tr) Kuetiapin (Quetiapine) Fumarat'ın yeni polimorfları
BRPI0416678A (pt) pirazolpirimidinas
DK1334096T3 (da) Friedel-Craft-fremgangsmåde til fremstillingen af thioxanthoner
WO2004094441A3 (en) Piperazine containing phosphonic acid compounds as inhibitors of serine proteases
NO20060643L (no) Nye metoder for fremstilling av 2H-kromener