MA32322B1 - Dérivés d'urée macrocyclique et de sulfamide en tant qu'inhibiteurs de tafia - Google Patents

Dérivés d'urée macrocyclique et de sulfamide en tant qu'inhibiteurs de tafia

Info

Publication number
MA32322B1
MA32322B1 MA33377A MA33377A MA32322B1 MA 32322 B1 MA32322 B1 MA 32322B1 MA 33377 A MA33377 A MA 33377A MA 33377 A MA33377 A MA 33377A MA 32322 B1 MA32322 B1 MA 32322B1
Authority
MA
Morocco
Prior art keywords
tafia inhibitors
sulphonamide derivatives
macrocyclic urea
inhibitors
macrocyclic
Prior art date
Application number
MA33377A
Other languages
Arabic (ar)
English (en)
French (fr)
Inventor
Christopher Kallus
Mark Broenstrup
Andreas Evers
Anja Globisch
Herman Schreuder
Michael Wagner
Original Assignee
Sanofi Aventis
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 Sanofi Aventis filed Critical Sanofi Aventis
Publication of MA32322B1 publication Critical patent/MA32322B1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
    • C07D273/01—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00 having one nitrogen 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
    • 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
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
    • 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
    • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
    • 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
    • A61P27/00—Drugs for disorders of the senses
    • 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
    • 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
    • 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
    • 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
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial 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
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
    • 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
    • A61P9/06—Antiarrhythmics
    • 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
    • C07D267/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D273/00—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00
    • C07D273/02—Heterocyclic compounds containing rings having nitrogen and oxygen atoms as the only ring hetero atoms, not provided for by groups C07D261/00 - C07D271/00 having two nitrogen atoms and only one oxygen atom
    • 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
    • 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
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Obesity (AREA)
  • Epidemiology (AREA)
  • Oncology (AREA)
  • Pulmonology (AREA)
  • Rheumatology (AREA)
  • Vascular Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Urology & Nephrology (AREA)
  • Communicable Diseases (AREA)
  • Child & Adolescent Psychology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Emergency Medicine (AREA)
  • Dermatology (AREA)
  • Endocrinology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
MA33377A 2008-06-06 2010-11-30 Dérivés d'urée macrocyclique et de sulfamide en tant qu'inhibiteurs de tafia MA32322B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP08290520 2008-06-06
PCT/EP2009/003650 WO2009146802A1 (de) 2008-06-06 2009-05-22 Makrocyclische harnstoff- und sulfamidderivate als inhibitoren von tafia

Publications (1)

Publication Number Publication Date
MA32322B1 true MA32322B1 (fr) 2011-05-02

Family

ID=39800716

Family Applications (1)

Application Number Title Priority Date Filing Date
MA33377A MA32322B1 (fr) 2008-06-06 2010-11-30 Dérivés d'urée macrocyclique et de sulfamide en tant qu'inhibiteurs de tafia

Country Status (34)

Country Link
US (5) US8580777B2 (enExample)
EP (1) EP2300462B1 (enExample)
JP (1) JP5531011B2 (enExample)
KR (1) KR101673886B1 (enExample)
CN (1) CN102056922B (enExample)
AR (1) AR072007A1 (enExample)
AU (1) AU2009254257B2 (enExample)
BR (1) BRPI0913349A2 (enExample)
CA (1) CA2726554C (enExample)
CL (1) CL2009001358A1 (enExample)
CO (1) CO6321271A2 (enExample)
CR (1) CR11807A (enExample)
CY (1) CY1115604T1 (enExample)
DK (1) DK2300462T3 (enExample)
DO (1) DOP2010000363A (enExample)
EC (1) ECSP10010655A (enExample)
ES (1) ES2494390T3 (enExample)
HN (1) HN2010002558A (enExample)
HR (1) HRP20140787T1 (enExample)
IL (1) IL209772A (enExample)
MA (1) MA32322B1 (enExample)
MX (1) MX2010012793A (enExample)
NI (1) NI201000203A (enExample)
NZ (1) NZ589671A (enExample)
PL (1) PL2300462T3 (enExample)
PT (1) PT2300462E (enExample)
RU (1) RU2502736C2 (enExample)
SI (1) SI2300462T1 (enExample)
SV (1) SV2010003747A (enExample)
TW (1) TWI455928B (enExample)
UA (1) UA104002C2 (enExample)
UY (1) UY31868A (enExample)
WO (1) WO2009146802A1 (enExample)
ZA (1) ZA201007719B (enExample)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX2010012793A (es) 2008-06-06 2010-12-14 Sanofi Aventis Derivados de urea macrociclicos y de sulfamida como inhibidores de tafia.
CA2727925A1 (en) 2008-06-23 2009-12-30 Astrazeneca Ab New heterocyclic carboxamides for use as thrombin inhibitors
US8354444B2 (en) 2008-09-18 2013-01-15 Hoffmann-La Roche Inc. Substituted pyrrolidine-2-carboxamides
CA2863892C (en) * 2012-03-06 2016-08-30 Pfizer Inc. Macrocyclic derivatives for the treatment of proliferative diseases
RU2015156612A (ru) * 2013-06-10 2017-07-17 Санофи Макроциклические производные мочевины в качестве ингибиторов tafia, их получение и их применение в качестве фармацевтических средств
UY35809A (es) * 2013-11-05 2015-05-29 Bayer Pharma AG (aza)piridopirazolopirimidinonas e indazolopirimidinonas y sus usos
CN103755852B (zh) * 2013-12-18 2015-12-09 湖北大学 线型聚苯乙烯支载(4s)-(4’-氧苄基)-2-正丁基环磺酰胺及其制备方法和用途
CN106631832A (zh) * 2016-10-08 2017-05-10 帕潘纳(北京)科技有限公司 一种氨基醚类化合物的制备方法
US10411291B2 (en) * 2017-03-22 2019-09-10 Nanotek Instruments, Inc. Multivalent metal ion battery having a cathode layer of protected graphitic carbon and manufacturing method

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU667995B2 (en) 1993-02-15 1996-04-18 Bayer Aktiengesellschaft New pseudopeptides having an antiviral action
TW394760B (en) 1993-09-07 2000-06-21 Hoffmann La Roche Novel Carboxamides, process for their preparation and pharmaceutical composition containing the same
US5888971A (en) * 1996-02-20 1999-03-30 Ortho Pharmaceutical Corporation, Inc. Macrocyclic peptides useful in the treatment of thrombin related disorders
AU749132B2 (en) 1997-08-28 2002-06-20 Biovitrum Ab Inhibitors of protein tyrosine phosphatase
US6124278A (en) * 1998-04-03 2000-09-26 The Regents Of The University Of California Acylbenzoxazines for enhancing synaptic response
US6482921B1 (en) 1999-01-28 2002-11-19 Essential Therapeutics, Inc. Uridyl peptide antibiotic (UPA) derivatives, their synthesis and use
DE60042585D1 (de) * 2000-02-29 2009-09-03 Univ Firenze 3-Aza-6,8-dioxabicycloÄ3.2.1Üoctane und Analoga sowie diese enthaltende kombinatorische Bibliotheken
DE102004020186A1 (de) * 2004-04-22 2005-11-17 Aventis Pharma Deutschland Gmbh Heterocyclylessigsäuren als Inhibitoren von TAFla
NZ577312A (en) 2006-12-06 2012-02-24 Sanofi Aventis Urea and sulfamide derivatives as tafia inhibitors
MX2010012793A (es) 2008-06-06 2010-12-14 Sanofi Aventis Derivados de urea macrociclicos y de sulfamida como inhibidores de tafia.

Also Published As

Publication number Publication date
IL209772A (en) 2016-04-21
NI201000203A (es) 2011-09-29
BRPI0913349A2 (pt) 2015-11-24
ECSP10010655A (es) 2011-01-31
RU2010154089A (ru) 2012-07-20
US20110178130A1 (en) 2011-07-21
KR101673886B1 (ko) 2016-11-08
RU2502736C2 (ru) 2013-12-27
IL209772A0 (en) 2011-02-28
ZA201007719B (en) 2011-07-27
CR11807A (es) 2011-02-16
CA2726554C (en) 2015-02-24
SV2010003747A (es) 2011-03-15
MX2010012793A (es) 2010-12-14
AR072007A1 (es) 2010-07-28
HRP20140787T1 (hr) 2014-11-21
US8722655B2 (en) 2014-05-13
WO2009146802A1 (de) 2009-12-10
JP5531011B2 (ja) 2014-06-25
US20140039011A1 (en) 2014-02-06
CL2009001358A1 (es) 2009-11-27
KR20110020795A (ko) 2011-03-03
DK2300462T3 (da) 2014-08-18
HN2010002558A (es) 2012-08-28
AU2009254257B2 (en) 2013-11-21
JP2011521981A (ja) 2011-07-28
EP2300462B1 (de) 2014-05-21
CN102056922B (zh) 2013-11-20
AU2009254257A1 (en) 2009-12-10
HK1152936A1 (en) 2012-03-16
PL2300462T3 (pl) 2014-10-31
US20140206760A1 (en) 2014-07-24
US9688645B2 (en) 2017-06-27
SI2300462T1 (sl) 2014-09-30
TW201008917A (en) 2010-03-01
EP2300462A1 (de) 2011-03-30
NZ589671A (en) 2012-03-30
US9309207B2 (en) 2016-04-12
US20160024033A1 (en) 2016-01-28
TWI455928B (zh) 2014-10-11
DOP2010000363A (es) 2010-12-15
UA104002C2 (ru) 2013-12-25
CA2726554A1 (en) 2009-12-10
US9126955B2 (en) 2015-09-08
UY31868A (es) 2010-01-05
ES2494390T3 (es) 2014-09-15
PT2300462E (pt) 2014-08-05
CN102056922A (zh) 2011-05-11
US8580777B2 (en) 2013-11-12
CO6321271A2 (es) 2011-09-20
US20160251324A1 (en) 2016-09-01
CY1115604T1 (el) 2017-01-04

Similar Documents

Publication Publication Date Title
EA201190158A1 (ru) Производные бензофуранила для применения в качестве ингибиторов глюкокиназы
CR20110077A (es) Derivados de dioxa-biciclo[3.2.1]octano-2,3,4-triol
EA201290191A1 (ru) N1-ПИРАЗОЛОСПИРОКЕТОНОВЫЕ ИНГИБИТОРЫ АЦЕТИЛ-KoA-КАРБОКСИЛАЗЫ
EA201390609A1 (ru) ПРОИЗВОДНЫЕ ГИДАНТОИНА, ПОЛЕЗНЫЕ В КАЧЕСТВЕ ИНГИБИТОРОВ Kv3-КАНАЛОВ
NO20090202L (no) Prolylhydroksylaseinhibitorer
EA201290267A1 (ru) Производные диоксабицикло[3.2.1]октан-2,3,4-триола
EA201100311A1 (ru) Амидные производные гетероарилов и их применение в качестве активаторов глюкокиназы
WO2007150015A3 (en) Method of treatment
EA201270215A1 (ru) Apaf-1 ингибиторные соединения
EA200900798A1 (ru) Производные индол-4-илпиримидинил-2-иламина и их применение в качестве ингибиторов циклинзависимой киназы
EA200901032A1 (ru) Соединения и композиции в качестве модуляторов активности gpr119
UA107115C2 (uk) Тіоацетатні похідіні піридину, композиція на їх основі та їх застосування
DK2150530T3 (da) Substituerede sulfonamid-derivater
WO2009026166A3 (en) Antiinfective flavonol compounds and methods of use thereof
EA201000895A1 (ru) Композиции и способы для лечения лизосомных болезней
DE602006010564D1 (de) Pyridoä2,3-düpyrimidin-2,4-diamin-verbindungen als ptpib-hemmer
ATE462438T1 (de) Verwendung von carrageenan zur behandlung von rhinovirus-infektionen
NO20090764L (no) 4-hydroksytiobenzamidderivater og legemidler
TW200738651A (en) Cyclohexyl sulfonamide derivatives
CY1116840T1 (el) Χρηση 24-norudca
CY1115604T1 (el) Μακροκυκλικα παραγωγα ουριας και σουλφαμιδης ως αναστολεις των ταfια
BRPI0510159A (pt) derivados de imidazol como inibidores de tafia
CL2009001349A1 (es) Compuestos derivados de urea sustituidos con 1,4-dihidroquinolin-4-ona, inhibidores de adn girasa bacteriana y/o topoisomerasa iv bacteriana; composicion farmceutica; util para el tratamiento de una infeccion bacteriana.
EA201170828A1 (ru) Конденсированные гетероциклические производные оксадиазола, подходящие для лечения рассеянного склероза
MX2009005516A (es) Derivados de urea y de sulfamida en calidad de inhibidores de tafia.