AR033984A1 - Derivados de pirrolidina, procedimiento para su preparacion, composiciones farmaceuticas y el uso de dichos derivados para la fabricacion de medicamentos - Google Patents

Derivados de pirrolidina, procedimiento para su preparacion, composiciones farmaceuticas y el uso de dichos derivados para la fabricacion de medicamentos

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Publication number
AR033984A1
AR033984A1 ARP010103416A ARP010103416A AR033984A1 AR 033984 A1 AR033984 A1 AR 033984A1 AR P010103416 A ARP010103416 A AR P010103416A AR P010103416 A ARP010103416 A AR P010103416A AR 033984 A1 AR033984 A1 AR 033984A1
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AR
Argentina
Prior art keywords
arylcarbonyl
alkyl
arylalkyl
aryl
arylcarbonylalkyl
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ARP010103416A
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English (en)
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Hoffmann La Roche
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Publication date
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Publication of AR033984A1 publication Critical patent/AR033984A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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 linked by a chain containing hetero atoms as chain links
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00Drugs for disorders of the alimentary tract or the digestive system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00Drugs for disorders of the respiratory system
    • A61P11/06Antiasthmatics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00Drugs for disorders of the urinary system
    • A61P13/12Drugs for disorders of the urinary system of the kidneys
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00Drugs for genital or sexual disorders; Contraceptives
    • A61P15/08Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00Drugs for dermatological disorders
    • A61P17/02Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • A61P27/06Antiglaucoma agents or miotics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00Drugs for immunological or allergic disorders
    • A61P37/02Immunomodulators
    • A61P37/06Immunosuppressants, e.g. drugs for graft rejection
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00General protective or antinoxious agents
    • A61P39/06Free radical scavengers or antioxidants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/04Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/06Antiarrhythmics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/10Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • A61P9/12Antihypertensives
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic 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
    • C07D207/04Heterocyclic 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
    • C07D207/10Heterocyclic 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
    • C07D207/12Oxygen or sulfur atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic 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
    • C07D207/04Heterocyclic 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
    • C07D207/10Heterocyclic 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
    • C07D207/16Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/46Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
    • C07D207/48Sulfur atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02Heterocyclic 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
    • C07D413/12Heterocyclic 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Immunology (AREA)
  • Diabetes (AREA)
  • Neurology (AREA)
  • Urology & Nephrology (AREA)
  • Pulmonology (AREA)
  • Hospice & Palliative Care (AREA)
  • Reproductive Health (AREA)
  • Endocrinology (AREA)
  • Neurosurgery (AREA)
  • Ophthalmology & Optometry (AREA)
  • Biomedical Technology (AREA)
  • Psychiatry (AREA)
  • Gynecology & Obstetrics (AREA)
  • Toxicology (AREA)
  • Communicable Diseases (AREA)
  • Emergency Medicine (AREA)
  • Transplantation (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Dermatology (AREA)
  • Oncology (AREA)
  • Pregnancy & Childbirth (AREA)
  • Biochemistry (AREA)

Abstract

Derivados de pirrolidina, que comprenden un compuesto de fórmula general (1) en donde R1 es hidrógeno, alquilcarbonilo o arilcarbonilo; R2 es alquilo, alquilcicloalquilo, alquilcicloalquilalquilo, cicloalquilo, halógenoalquilo, carboxialquilo, aminoalquilo, dialquilaminoalquilo, alcoxialquilo, alcoxicarbonilalquilo, alquinilo, arilo, arilalquilo, arilalquil(alcoxicarbonil)alquilo, arilcarbonilalquilo, ariloxialquilo, arilalquenilo, aril(alcoxicarbonil)alquilo, heteroarilo, heteroarilalquilo, heterociclilo o heterociclilalquilo; A es -C(O)-R3, -CH(OH)-R4, ó -C(O)-NR5R6, en donde R3 y R4 son independientemente del grupo formado por alquilo, arilo, arilalquinilo, arilalquilo y arilalquenilo; R5 es hidrógeno, alquilo, cicloalquilo, cicloalquilalquilo, carboxialquilo, o arilalquilo; R6 es alquilo, alquilcarbonilalquilo, cianoalquilo, hidroxialquilo, hidroxialquil-(hidroxialquilo), alcoxicarbonilalquilo, arilcarbonilalquilo, arilaminocarbonilalquilo, aril(alquil)aminocarbonil-alquilo, aminocarbonillaquilo, arilo, arilalquilo, heteroarilo, heteroarilalquilo, heterociclilo, cicloalquilo, cicloalquilalquilo, o carboxialquilo, o R6 se selecciona del grupo consistente en las fórmulas (2), (3) y (4) o -NR5R6 en -C(O)NR5R6 para A representa un anillo saturado de 5 o 6 miembros, sustituido opcionalmente con carboxi, alquiloxicarbonilo, hidroxi, alcoxicarbonilalcoxi, fenilalquilo o fenilalcoxicarbonilo, R7 es hidrógeno, alquilo, alquenilo, alquiltioalquilo, arilo, heteroarilo, carboxialquilo, carboxi, alcoxicarbonilalquilo, arilalquilo, o heteroarilalquilo; o un compuesto de fórmula 5, R7a es hidrógeno o alquilo; R8 es -OR9 o -NR10R11, en donde R9 es hidrógeno, alquilo, arilalquilo; R10 es hidrógeno o alquilo; y R11 es alquilo, arilo, heteroarilo, arilalquilo, o el grupo -NR10R11 representa un anillo de 5 ó 6 miembros opcionalmente sustituido con carboxi, alquiloxicarbonilo, hidroxi, alcoxicarbonilalcoxi, fenialaquilo o fenilalcoxicarbonilo; R12 es alquilo, arilo, o arilalquilo; Y es -O-, -O-S(O2)-, -O-C(O)- o -O-(C)-NH; m es 0, 1 o 2; X es -SO2, -CO-, -C(O)O-, -SO2NH-, o -C(O)NR13- en donde R13 es hidrógeno, alquilo, arilo o carboxialquilo; y formas diméricas, y/o ésteres farmacéuticamente aceptables, y/o sales farmacéuticamente aceptables, y/o sales farmacéuticamente aceptables de los mismos. Los compuestos son útiles como inhibidores de metaloproteasas, por ej. zinc proteasas, en particular zinc hidrolasas, y son efectivos en el tratamiento de enfermedades asociadas con la vasoconstricción de incidencia creciente. Se describen también un proceso para su preparación, composiciones farmacéuticas y el uso de dichos derivados para la fabricación de medicamentos para la profilaxis y tratamiento de trastornos que están causados por la actividad de la enzima conversora de endotelina (ECE), especialmente isquemia de miocardio, insuficiencia cardíaca congestiva, arritmia, hipertensión, hipertensión pulmonar, asma, vasoespasmo cerebral, hemorragia subaracnoidal, pre-eclampsia, enfermedades del rinón, aterosclerosis, enfermedad de Bueger, artritis de Takayasu, complicaciones diabéticas, cáncer de pulmón, cáncer prostático, trastornos gastroinstestinales, shock endotóxico y septicemia, y para la curación de heridas y control de la menstruación, glaucoma, rechazo de injertos, enfermedades asociadas con indicaciones citostáticas, oftalmológicas y cerebroprotectoras, y protección de órganos.
ARP010103416A 2000-07-19 2001-07-17 Derivados de pirrolidina, procedimiento para su preparacion, composiciones farmaceuticas y el uso de dichos derivados para la fabricacion de medicamentos AR033984A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP00114947 2000-07-19

Publications (1)

Publication Number Publication Date
AR033984A1 true AR033984A1 (es) 2004-01-21

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ARP010103416A AR033984A1 (es) 2000-07-19 2001-07-17 Derivados de pirrolidina, procedimiento para su preparacion, composiciones farmaceuticas y el uso de dichos derivados para la fabricacion de medicamentos

Country Status (16)

Country Link
US (1) US6541638B2 (es)
EP (1) EP1303485A1 (es)
JP (1) JP4068452B2 (es)
KR (1) KR100568841B1 (es)
CN (1) CN1620433A (es)
AR (1) AR033984A1 (es)
AU (1) AU2001270627A1 (es)
BR (1) BR0112580A (es)
CA (1) CA2414311C (es)
GT (1) GT200100145A (es)
MX (1) MXPA03000223A (es)
PA (1) PA8522501A1 (es)
PE (1) PE20020294A1 (es)
UY (1) UY26847A1 (es)
WO (1) WO2002006222A1 (es)
ZA (1) ZA200300167B (es)

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CN100406439C (zh) * 2000-07-19 2008-07-30 霍夫曼-拉罗奇有限公司 作为金属蛋白酶抑制剂的吡咯烷衍生物
RU2290403C2 (ru) 2000-12-28 2006-12-27 Дайити Фармасьютикал Ко., Лтд. Ингибиторы vla-4
DE60336986D1 (de) 2002-03-05 2011-06-16 Sumitomo Chemical Co Verfahren zur herstellung von biarylverbindungen
EP1613269B1 (en) 2003-04-04 2015-02-25 Incyte Corporation Compositions, methods and kits relating to her-2 cleavage
WO2004092164A1 (en) 2003-04-10 2004-10-28 Amgen, Inc. Cyclic amine derivatives and their use in the treatment of inflammation-related disorders mediated by bradykinin
EP1631542A1 (en) 2003-04-10 2006-03-08 Amgen, Inc. Bicyclic compounds having bradykinin receptors affinity and pharmaceutical compositions thereof
ATE388708T1 (de) 2003-06-20 2008-03-15 Amgen Inc Piperazinderivate und anwendungsverfahren
CN1826336B (zh) 2003-07-24 2010-06-02 第一制药株式会社 环己烷羧酸类
CN1294120C (zh) * 2003-10-21 2007-01-10 山东大学 吡咯烷类基质金属蛋白酶抑制剂及其应用
RU2435585C2 (ru) * 2006-04-13 2011-12-10 Актелион Фармасьютиклз Лтд Антагонисты рецептора эндотелина, предназначенные для ранней стадии идиопатического фиброза легких
ES2350548B1 (es) * 2009-06-25 2011-09-29 Institut Univ. De Ciència I Tecnologia, S.A. N-fenil-1-sulfonil-2-pirrolidinacarboxamidas para la identificacion de actividad biologica y farmacologica.
EP2730571A1 (en) * 2012-11-12 2014-05-14 Universitat De Barcelona 1-[1-(benzoyl)-pyrrolidine-2-carbonyl]-pyrrolidine-2-carbonitrile derivatives
WO2017168174A1 (en) 2016-04-02 2017-10-05 N4 Pharma Uk Limited New pharmaceutical forms of sildenafil
JP7163916B2 (ja) * 2017-07-05 2022-11-01 日産化学株式会社 ベンジル化合物
CN110078593A (zh) * 2018-11-15 2019-08-02 南通正达农化有限公司 一种苹果蠹蛾性信息素的合成方法

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CA1283906C (en) * 1983-05-09 1991-05-07 Makoto Sunagawa .beta.-LACTAM COMPOUNDS AND PRODUCTION THEREOF
AU644008B2 (en) * 1990-08-10 1993-12-02 Sumitomo Pharmaceuticals Company, Limited Beta-lactam compounds, and their production and use
JP3091297B2 (ja) * 1992-01-10 2000-09-25 住友製薬株式会社 ピロリジン誘導体およびその製造方法
BR9712792A (pt) * 1996-08-28 1999-12-14 Procter & Gamble Inibidores de metaloprotease bidentada.
IL128666A (en) * 1996-08-28 2005-09-25 Procter & Gamble Substituted cyclic amine metalloprotease inhibitors
EP0998457A4 (en) * 1997-07-10 2010-03-10 CRYSTALLINE FORMS OF INTERMEDIATES OF ANTIBIOTICASE CHAINS
BR9910098A (pt) * 1998-05-01 2000-12-26 Kyoto Pharma Ind Derivados de carbapenem, utilização dos mesmos e compostos intermediários dos mesmos

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AU2001270627A1 (en) 2002-01-30
BR0112580A (pt) 2003-06-17
GT200100145A (es) 2002-05-16
CA2414311C (en) 2008-01-08
EP1303485A1 (en) 2003-04-23
PE20020294A1 (es) 2002-04-17
JP4068452B2 (ja) 2008-03-26
US20020049243A1 (en) 2002-04-25
KR100568841B1 (ko) 2006-04-10
CN1620433A (zh) 2005-05-25
UY26847A1 (es) 2002-01-31
ZA200300167B (en) 2004-04-07
PA8522501A1 (es) 2002-09-17
US6541638B2 (en) 2003-04-01
JP2004504297A (ja) 2004-02-12
CA2414311A1 (en) 2002-01-24
MXPA03000223A (es) 2003-06-06
WO2002006222A1 (en) 2002-01-24
KR20030016416A (ko) 2003-02-26

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