ECSP22050936A - Compuestos tric?clicos sustituidos - Google Patents

Compuestos tric?clicos sustituidos

Info

Publication number
ECSP22050936A
ECSP22050936A ECSENADI202250936A ECDI202250936A ECSP22050936A EC SP22050936 A ECSP22050936 A EC SP22050936A EC SENADI202250936 A ECSENADI202250936 A EC SENADI202250936A EC DI202250936 A ECDI202250936 A EC DI202250936A EC SP22050936 A ECSP22050936 A EC SP22050936A
Authority
EC
Ecuador
Prior art keywords
compound
formula
tricyclic compounds
rasopathies
infectious
Prior art date
Application number
ECSENADI202250936A
Other languages
English (en)
Inventor
Manojkumar Shukla
Dagadu Dube
Nilesh Khedkar
Pradip Wagh
Venkata Palle
Samiron Phukan
Ganesh Kakade
Sudhakar Balgude
Milind Sindkhedkar
Sachin Sethi
Rajender Kumar Kamboj
Vikas Tambe
Prathap Nair
Original Assignee
Lupin Ltd
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 Lupin Ltd filed Critical Lupin Ltd
Publication of ECSP22050936A publication Critical patent/ECSP22050936A/es

Links

Classifications

    • 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
    • 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
    • C07D401/04Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/496Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535Heterocyclic 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
    • A61K31/53751,4-Oxazines, e.g. morpholine
    • A61K31/53771,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/70Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
    • 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
    • C07D403/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D413/04Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04Ortho-condensed systems
    • C07D491/044Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10Spiro-condensed systems
    • C07D491/107Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D498/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04Ortho-condensed systems

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

Se divulgan compuestos de f?rmula general (I), su forma tautom?rica, su estereois?mero, su sal farmac?uticamente aceptable, su polimorfo o solvato del mismo, en donde, el anillo A, de R1 a R5, X, Y, m, y n son como se definen en el presente documento, para su uso como inhibidores de SOS1 en el tratamiento de enfermedades o trastornos proliferativos infecciosos y rasopat?as. Tambi?n se divulgan m?todos para sintetizar el compuesto de f?rmula I, composiciones farmac?uticas que contienen el compuesto de f?rmula I, un m?todo para el tratamiento de enfermedades o trastornos proliferativos, infecciosos o rasopat?as, por ejemplo, un c?ncer, administrando dicho compuesto y combinaciones del compuesto de f?rmula I con otros principios activos.
ECSENADI202250936A 2019-11-29 2022-06-28 Compuestos tric?clicos sustituidos ECSP22050936A (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN201921049157 2019-11-29
IN202021035414 2020-08-17

Publications (1)

Publication Number Publication Date
ECSP22050936A true ECSP22050936A (es) 2022-07-29

Family

ID=73856201

Family Applications (1)

Application Number Title Priority Date Filing Date
ECSENADI202250936A ECSP22050936A (es) 2019-11-29 2022-06-28 Compuestos tric?clicos sustituidos

Country Status (27)

Country Link
US (1) US20230013778A1 (es)
EP (1) EP4065575B1 (es)
JP (1) JP2023504113A (es)
KR (1) KR20220110241A (es)
CN (1) CN114746411B (es)
AU (1) AU2020393205A1 (es)
BR (1) BR112022010383A2 (es)
CA (1) CA3154914A1 (es)
CL (1) CL2022001392A1 (es)
CO (1) CO2022008997A2 (es)
CR (1) CR20220312A (es)
DK (1) DK4065575T3 (es)
EC (1) ECSP22050936A (es)
ES (1) ES2982576T3 (es)
FI (1) FI4065575T3 (es)
HR (1) HRP20240547T1 (es)
HU (1) HUE066732T2 (es)
IL (1) IL292721A (es)
LT (1) LT4065575T (es)
MX (1) MX2022006475A (es)
PE (1) PE20221336A1 (es)
PL (1) PL4065575T3 (es)
PT (1) PT4065575T (es)
RS (1) RS65526B1 (es)
SI (1) SI4065575T1 (es)
WO (1) WO2021105960A1 (es)
ZA (1) ZA202206253B (es)

Families Citing this family (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115697994B (zh) * 2020-06-10 2024-08-13 江苏恒瑞医药股份有限公司 稠合喹唑啉类衍生物、其制备方法及其在医药上的应用
AU2021345111A1 (en) 2020-09-15 2023-04-06 Revolution Medicines, Inc. Indole derivatives as Ras inhibitors in the treatment of cancer
CN117561258A (zh) * 2021-03-02 2024-02-13 唯久生物技术(苏州)有限公司 作为sos1抑制剂的新型取代的三环氮杂杂环
CA3213593A1 (en) 2021-03-31 2022-10-06 Sevenless Therapeutics Limited Sos1 inhibitors and ras inhibitors for use in the treatment of pain
TWI807787B (zh) * 2021-04-19 2023-07-01 大陸商昆藥集團股份有限公司 苯並嘧啶三環衍生物及製備方法和應用
CN115490699B (zh) * 2021-06-19 2024-08-09 成都海博为药业有限公司 一种稠环化合物及其药物组合物和用途
WO2023287730A1 (en) * 2021-07-13 2023-01-19 Recurium Ip Holdings, Llc Tricyclic compounds
CN115677699A (zh) * 2021-07-23 2023-02-03 武汉誉祥医药科技有限公司 三并环化合物及其药物组合物和应用
WO2023030216A1 (zh) * 2021-08-30 2023-03-09 浙江海正药业股份有限公司 喹唑啉类衍生物、或其制备方法和用途
AR127308A1 (es) 2021-10-08 2024-01-10 Revolution Medicines Inc Inhibidores ras
AU2022412827A1 (en) 2021-12-17 2024-06-20 Cspc Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd Heterocyclic compound having anti-tumor activity and use thereof
WO2023114954A1 (en) 2021-12-17 2023-06-22 Genzyme Corporation Pyrazolopyrazine compounds as shp2 inhibitors
WO2023134374A1 (zh) * 2022-01-12 2023-07-20 如东凌达生物医药科技有限公司 一类嘧啶并杂环类化合物、制备方法和用途
WO2023135260A1 (en) 2022-01-14 2023-07-20 Jazz Pharmaceuticals Ireland Limited Novel amine-substituted phthalazines and derivatives as sos1 inhibitors
WO2023138691A1 (en) * 2022-01-21 2023-07-27 Shenzhen Ionova Life Science Co., Ltd. Fused heterocyclic compounds as modulators of ras signalling
EP4227307A1 (en) 2022-02-11 2023-08-16 Genzyme Corporation Pyrazolopyrazine compounds as shp2 inhibitors
GB202203976D0 (en) 2022-03-22 2022-05-04 Jazz Pharmaceuticals Ireland Ltd Tricyclic phthalazines and derivatives as sos1 inhibitors
WO2023240263A1 (en) 2022-06-10 2023-12-14 Revolution Medicines, Inc. Macrocyclic ras inhibitors
WO2024211712A1 (en) 2023-04-07 2024-10-10 Revolution Medicines, Inc. Condensed macrocyclic compounds as ras inhibitors
WO2024211663A1 (en) 2023-04-07 2024-10-10 Revolution Medicines, Inc. Condensed macrocyclic compounds as ras inhibitors

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4235871A (en) 1978-02-24 1980-11-25 Papahadjopoulos Demetrios P Method of encapsulating biologically active materials in lipid vesicles
US4501728A (en) 1983-01-06 1985-02-26 Technology Unlimited, Inc. Masking of liposomes from RES recognition
US5019369A (en) 1984-10-22 1991-05-28 Vestar, Inc. Method of targeting tumors in humans
US4837028A (en) 1986-12-24 1989-06-06 Liposome Technology, Inc. Liposomes with enhanced circulation time
AU2003256323A1 (en) 2002-06-26 2004-01-19 Chiron Corporation Sos1 inhibitors
US20070065622A1 (en) 2005-09-22 2007-03-22 Scientific Technologies Incorporated Safety Mat Active Joining Trim
CA2782889C (en) 2009-12-17 2014-08-05 Merck Canada Inc. Aminopyrimidines as syk inhibitors
AU2014227824B2 (en) * 2013-03-15 2018-09-27 Dana-Farber Cancer Institute, Inc. Stabilized SOS1 peptides
WO2016077793A1 (en) 2014-11-14 2016-05-19 Children's Hospital Medical Center Sos1 inhibitors for cancer treatment
CA3014192A1 (en) 2016-02-12 2017-08-17 Forma Therapeutics, Inc. Thienopyridine carboxamides as ubiquitin-specific protease inhibitors
US10898487B2 (en) 2016-12-22 2021-01-26 Boehringer Ingelheim International Gmbh Benzylamino substituted quinazolines and derivatives as SOS1 inhibitors
EP3601267A1 (en) * 2017-03-21 2020-02-05 Bayer Pharma Aktiengesellschaft 2-methyl-quinazolines
CA3085835A1 (en) * 2017-12-21 2019-06-27 Boehringer Ingelheim International Gmbh Novel benzylamino substituted pyridopyrimidinones and derivatives as sos1 inhibitors
EP3781565A1 (en) 2018-04-18 2021-02-24 Bayer Pharma Aktiengesellschaft 2-methyl-aza-quinazolines
AU2020232616A1 (en) 2019-03-01 2021-09-09 Revolution Medicines, Inc. Bicyclic heterocyclyl compounds and uses thereof
CN113767100A (zh) 2019-03-01 2021-12-07 锐新医药公司 双环杂芳基化合物及其用途

Also Published As

Publication number Publication date
PL4065575T3 (pl) 2024-06-24
EP4065575A1 (en) 2022-10-05
LT4065575T (lt) 2024-05-27
ZA202206253B (en) 2023-01-25
CN114746411A (zh) 2022-07-12
AU2020393205A1 (en) 2022-06-30
BR112022010383A2 (pt) 2022-08-23
JP2023504113A (ja) 2023-02-01
CA3154914A1 (en) 2021-06-03
CO2022008997A2 (es) 2022-07-19
RS65526B1 (sr) 2024-06-28
KR20220110241A (ko) 2022-08-05
HUE066732T2 (hu) 2024-09-28
PT4065575T (pt) 2024-05-03
EP4065575B1 (en) 2024-01-31
MX2022006475A (es) 2022-09-07
CN114746411B (zh) 2024-06-25
HRP20240547T1 (hr) 2024-07-05
FI4065575T3 (fi) 2024-05-02
US20230013778A1 (en) 2023-01-19
CL2022001392A1 (es) 2023-03-17
WO2021105960A1 (en) 2021-06-03
DK4065575T3 (da) 2024-04-15
ES2982576T3 (es) 2024-10-16
IL292721A (en) 2022-07-01
PE20221336A1 (es) 2022-09-13
SI4065575T1 (sl) 2024-06-28
CR20220312A (es) 2022-08-05

Similar Documents

Publication Publication Date Title
ECSP22050936A (es) Compuestos tric?clicos sustituidos
ECSP22058816A (es) Compuestos tric?clicos sustituidos
CL2022000271A1 (es) Inhibidores de la fosfatasa shp2 de pirazolo(3,4-b)pirazina.
CL2023002090A1 (es) Inhibidores de kras tricíclicos fusionados
ECSP22046699A (es) Inhibidores de kras g12c
PE20181093A1 (es) Compuestos heterociclicos y usos de los mismos
MX2023000410A (es) Analogos de rapamicina como inhibidores de mtor.
CL2019002777A1 (es) Compuestos que inhiben la proteína mcl-1.
CO2022001094A2 (es) Pirrolo[2,3-b]pirazinas como inhibidores de hpk1 y uso de las mismas
BR112021024131A2 (pt) Derivado de anel inibidor de btk, método de preparação para o mesmo e aplicação farmacêutica do mesmo
DOP2022000194A (es) Compuestos de tetralina y tetrahidroquinolina como inhibidores de hif-2alfa
PE20212303A1 (es) Inhibidores aza-heterobiciclicos de mat2a y metodos de uso en el tratamiento de cancer
PE20211782A1 (es) Compuestos de 5-cloro-2-difluorometoxifenil pirazolopirimidina, composiciones y metodos de uso de los mismos
DOP2024000039A (es) Derivados de quinolina como inhibidores de la integrina alfa4beta7
PE20200341A1 (es) Composiciones y compuestos terapeuticos y metodos para utilizarlos
TN2017000485A1 (en) Tricyclic compounds and their use as phosphodiesterase inhibitors
UY39181A (es) COMPUESTOS Y COMPOSICIONES PARA INHIBIR LA ACTIVIDAD DE HIF2a Y SUS MÉTODOS DE USO
CL2018000856A1 (es) Derivados de éter cíclico de pirazolo[1,5-a]pirimidin-3-carboxiamida.
ECSP22027784A (es) Derivados de 2–azaespiro[3.4]octano como agonistas de m4
CU24543B1 (es) Compuestos bicíclicos 5,6-fusionados y composiciones para el tratamiento de enfermedades parasitarias
ECSP18056196A (es) Derivados de indano
UY39625A (es) Derivados tricíclicos útiles como inhibidores de parp7
CL2022000893A1 (es) Derivados de 2-azaspiro[3,4]octano como agonistas de m4
CO2022006942A2 (es) Compuestos de 1,8-naftiridin-2-ona para el tratamiento de una enfermedad autoinmunitaria
DOP2024000096A (es) Derivados de naftiridinona para el tratamiento de una enfermedad o un trastorno