ES2642586T3 - Compuestos heterocíclicos condensados como moduladores de canales iónicos - Google Patents

Compuestos heterocíclicos condensados como moduladores de canales iónicos Download PDF

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ES2642586T3
ES2642586T3 ES10737724.4T ES10737724T ES2642586T3 ES 2642586 T3 ES2642586 T3 ES 2642586T3 ES 10737724 T ES10737724 T ES 10737724T ES 2642586 T3 ES2642586 T3 ES 2642586T3
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triazolo
phenyl
trifluoromethoxy
pyridine
methyl
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Britton Corkey
Elfatih Elzein
Robert Jiang
Rao Kalla
Tetsuya Kobayashi
Dmitry Koltun
Xiaofen Li
Gregory Notte
Eric Parkhill
Thao Perry
Jeff Zablocki
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Gilead Sciences Inc
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A61P25/08—Antiepileptics; Anticonvulsants
    • 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
    • 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
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems

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Description

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DESCRIPCION
Compuestos heterocfclicos condensados como moduladores de canales ionicos Campo de la invencion
La presente invencion tambien se refiere a nuevos compuestos y a estos compuestos para su uso en el tratamiento de varias patologfas, incluyendo enfermedades cardiovasculares y diabetes. La invencion tambien se refiere a metodos para su preparacion y a composiciones farmaceuticas que contienen dichos compuestos.
Antecedentes
La corriente tardfa de sodio (INaL) es un componente sostenido de la corriente rapida de Na+ de los miocitos cardfacos y las neuronas. Muchas afecciones neurologicas y cardfacas habituales se asocian con una potenciacion anormal (INaL), que contribuye a la patogenia de la disfuncion electrica y contractil en mamfferos. Vease, por ejemplo, Pathophysiology and Pharmacology of the Cardiac "Late Sodium Current", Pharmacology and Therapeutics 119 (2008) 326-339. Por consiguiente, los compuestos farmaceuticos que inhiben selectivamente (INaL) en mamfferos son utiles en el tratamiento de tales patologfas.
Un ejemplo de un inhibidor selectivo de (INaL) es RANEXA®, un compuesto aprobado por la FDA para el tratamiento de la angina de pecho cronica estable. Tambien se ha demostrado que RANEXA® es util para el tratamiento de diversas enfermedades cardiovasculares, incluyendo isquemia, lesion por reperfusion, arritmia y angina inestable, y tambien para el tratamiento de la diabetes. Serfa deseable proporcionar nuevos compuestos que inhiben selectivamente (INaL) en mamfferos y que tienen la misma selectividad sobre la inhibicion maxima de INa como RANEXA®. El documento W02004/020440 desvela di- y trifluoro-triazolo piridinas como compuestos antiinflamatorios. El documento W02009/089027 desvela compuestos triazolo para inhibir la fosfodiesterasa-4. El documento W02009/005675 desvela triazolopiridazinas como inhibidores de la quinasa. El documento W02007/113226 desvela compuestos heteroarilo para el tratamiento de la diabetes mellitus no dependiente de insulina. El documento EP0464572 desvela compuestos heteroarilo que pueden usarse en el control o prevencion de la hipertension y la insuficiencia cardfaca. El documento US4230705 desvela 6-fenil-1,2,4-triazolo[4,3-b]piridazinas para su uso en el tratamiento de la ansiedad. El documento US4654343 desvela N[3-(1,2,4-triazolo[4,3-b]piridazin-6- il)fenil]alcanamidas N-sustituidas, carbamatos y ureas utiles como agentes ansiolfticos o antiepilepticos. "Synthesis of new 1,2,4-triazolo[4,3-b]pyridazines and related compounds", I. Sircar, Journal of Heterociclic Chemistry, Volumen 22, 1 de julio 1985, paginas 1045-1048 desvela la sfntesis de nuevos 6-[4-(1H-imidazol-1-il)fenil]-1,2,4-triazolo[4,3- b]piridazinas.
Sumario de la invencion
Por consiguiente, en realizaciones tfpicas, la presente invencion proporciona nuevos compuestos que funcionan como bloqueantes de canales de sodio tardfos. En realizaciones tfpicas, la invencion proporciona compuestos de Formula I:
imagen1
en la que:
R es arilo o heteroarilo seleccionado de entre el grupo que consiste en:
imagen2
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imagen3
en el que dicho arilo o heteroarilo estan opcionalmente sustituidos con uno, dos o tres sustituyentes seleccionados independientemente de entre el grupo que consiste en hidroxilo, halo, -NO2, CN, -SF5, -Si(CH3)3 - O-CF3, -O-R20, -S-R20, -C(O)-R20, C(O)OH, -N(R20)(R22), -C(O)-N(R20)(R22), -N(R20)-C(O)-R22, -N(R20)-S(-O)2-R26, -S(=O)2-R20, -S(=O)2-N(R20)(R22), alcoxi C1-C3, alquilo C1-4, alquenilo C2-4, alquinilo C2-4, cicloalquilo, heteroarilo y heterociclilo;
en el que dicho alcoxi, alquilo, alquenilo, alquinilo, heteroarilo, cicloalquilo o heterociclilo estan opcionalmente sustituidos con uno, dos o tres sustituyentes seleccionados independientemente de entre hidroxilo, halo, -NO2, - O-CF3, -O-CHF2, fenilo, heterociclilo, heteroarilo, cicloalquilo, -N(R20)(R22), -C(O)-R20, -C(O)-O-R20, -C(O)- N(R20)(R22), -CN y -O-R20,
o en el que R1 esta sustituido con uno, dos o tres sustituyentes seleccionados independientemente de entre
imagen4

Claims (13)

1. Un compuesto de Formula III:
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imagen1
en la que:
R1 es un arilo o un heteroarilo seleccionados de entre el grupo que consiste en:
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imagen2
imagen3
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en los que dichos arilo o heteroarilo estan sustituidos con uno, dos o tres sustituyentes seleccionados independientemente de entre el arupo que consiste en hidroxilo, halo, -NO2, CN, -SF5, -Si(CH3)3 -O-CF3, -O-R20, - S-R20, -C(O)-R20 C(O)OH,-N(R20)(R22), -C(O)-N(R20)(R22), -N(R20)-C(O)-R22, -N(R20)-S(=O)2-R26, -S(=O)2-R20, - S(=O)2-N(R20)(R22), alcoxi C1-C3, alquilo C1.4, alquenilo C2-4, alquinilo C2-4, cicloalquilo, heteroarilo y heterociclilo;
en los que dichos alcoxi, alquilo, alquenilo, alquinilo, heteroarilo, cicloalquilo o heterociclilo estan opcionalmente sustituidos con uno, dos o tres sustituyentes seleccionados independientemente de entre hidroxilo, halo, -NO2, -O-CF3, -O-CHF2, fenilo, heterociclilo, heteroarilo, cicloalquilo, -N(R )(R ), -C(O)-R , - C(O)-O-R20, -C(O)-N(R20)(R22), -CN y -O-R20,
o en los que R1 esta sustituido con uno, dos o tres sustituyentes seleccionados independientemente de entre
imagen4
imagen5
imagen6
imagen7
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imagen8
R2 se selecciona independientemente de entre el grupo que consiste en hidrogeno, alquilo opcionalmente sustituido, amino, alcoxi opcionalmente sustituido, -CF3, -O-CF3, -CN y -N(R20)C(O)-R22;
R3 se selecciona independientemente de entre el grupo que consiste en hidrogeno, alquilo, -CF3, -halo y -O-R24; R4 se selecciona independientemente de entre el grupo que consiste en hidrogeno, hidroxilo, halo, alquilo C1-4, alcoxi C1-C3, -R25-N(R20)(R22), -R25-O-R20, -R25-C(O)-O-R20, -R25-C(O)-N(R20)(R22), -R25-C(O)-O-N(R20)(R22), -R25- N(R20)-C(O)-R22 y -R25-O-C(O)-N(R20)(R22),
en el que dicho alquilo esta opcionalmente sustituido con uno, dos o tres sustituyentes seleccionados independientemente de entre hidroxilo y halo,
Q se selecciona de entre un enlace covalente o alquinileno C2-4;
Ra es hidrogeno, alquilo C1.15, alcoxi C1.4, -C(O)-O-R26, -C(O)-N(R26)(R28), -N(R20)-S(=O)2-R20, cicloalquilo, arilo, heteroarilo y heterociclilo,
en el que dicho alquilo esta opcionalmente sustituido con uno, dos o tres sustituyentes seleccionados independientemente de entre hidroxilo, halo, -NO2, -O-CF3, -O-CHF2, cicloalquilo, -CN y alcoxi C1-4; y dichos alcoxi, cicloalquilo, arilo, heterociclilo o heteroarilo estan opcionalmente sustituidos con uno, dos o tres sustituyentes seleccionados independientemente de entre hidroxilo, halo, -NO2, -O-CF3, -O-CHF2, fenilo, heterociclilo, heteroarilo, cicloalquilo, -N(R20)(R22), -C(O)-R20, -C(O)-O-R20, -C(O)-N(R20)(R22), -CN y -O-R20; o
Ra es -Y-Z-R25-R23-R20, en el que
Y es un enlace covalente o se selecciona de entre alquileno C1-C3 opcionalmente sustituido con uno o dos grupos alquilo C1-C3 o fluor;
Z es alquinileno C2-4, -O-, -S-, -NR", -NR5'-C(O)-, -NR"-C(O)-NR5'- o -C(O)-NR3-, en el que cada R" y R5' es independientemente hidrogeno o alquilo C1-6 inferior; y
adicionalmente, en el que dicho alquilo esta opcionalmente sustituido con uno, dos o tres sustituyentes seleccionados independientemente de entre hidroxilo, halo, -NO2, -O-CF3, -O-CHF2, fenilo, heterociclilo, heteroarilo, cicloalquilo, -N(R20)(R22), -C(O)-R20, -C(O)-O-R20, -C(O)-N(R20)(R22), -CN y -O-R20, o
en la que Ra se selecciona de entre el grupo que consiste en
imagen9
imagen10
imagen11
imagen12
imagen13
imagen14
imagen15
imagen16
imagen17
imagen18
imagen19
imagen20
R20 y R22 se seleccionan independientemente en cada caso de entre el grupo que consiste en hidrogeno, alquilo C1-C15, alquenilo C2-C15, alquinilo C2-C15, cicloalquilo, heterociclilo, arilo y heteroarilo,
5
en el que el alquilo, alquenilo, alquinilo, heterociclilo, arilo y heteroarilo estan opcionalmente sustituidos con uno, dos o tres sustituyentes seleccionados independientemente de entre hidroxilo, halo, alquilo, mono- o diarilamino, alquilo o arilo o heteroarilamida, -NO2, -SO2R26, -CN, alcoxi C1-3, -CF3, -OCF3, arilo, cicloalquilo y heteroarilo; o;
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20 22 20 22 cuando R y R estan unidos a un atomo de nitrogeno comun, R y R pueden unirse para formar un anillo
heterocfclico que, despues, esta opcionalmente sustituido con uno, dos o tres sustituyentes seleccionados
independientemente de entre hidroxilo, halo, alquilo, mono- o dialquilamino, alquilo o arilo o heteroarilamida, -
NO2, -SO2R26, -CN, alcoxi C1-3, -CF3 y -OCF3, arilo y cicloalquilo;
15 R23 es un enlace covalente o se selecciona del grupo que consiste en cicloalquileno, heterociclileno, arileno y
heteroarileno,
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en donde el cicloalquileno, heterociclileno, arileno y heteroarileno estan opcionalmente sustituidos con uno a tres sustituyentes seleccionados independientemente de entre hidroxilo, halo, alquilo, mono- o diarilamino, alquilo o arilo o heteroarilamida, -NO2, -SO2R26, -CN, alcoxi C1-3, -CF3, -OCF3, arilo, cicloalquilo y heteroarilo;
R24 esta en cada caso independientemente seleccionado de entre alquilo o arilo, cualquiera de los cuales puede estar opcionalmente sustituido con 1, 2 o 3 grupos seleccionados independientemente de entre hidroxilo, -OCF3, halo, alcoxi C1-C3, -O-R20 o alquilo opcionalmente sustituido con halo, -NO2, -CF3, -O-CF3, -N(R20)(R22), -C(O)- R20, -C(O)-O-R20, -C(O)-N(R20)(R22), -CN o -O-R20;
R25 es, en cada caso independientemente un enlace covalente o seleccionado de entre alquileno C1-C3 opcionalmente sustituido con uno o dos grupos alquilo C1-C3; y
R26 y R28 se seleccionan independientemente en cada caso de hidrogeno, alquilo o cicloalquilo, en donde el alquilo y cicloalquilo pueden estar ademas sustituidos con de 1 a 3 sustituyentes seleccionados independientemente de entre hidroxilo, halo, alcoxi C1-4, -CF3 y -OCF3;
o una sal, un ester o un solvato farmaceuticamente aceptables de los mismos, con la condicion de que
a. cuando Ra es -Y-Z-R25-R23-R20, Y no es un enlace covalente y Z es -O-, -S-, -C(=O)NR3-, -NR5 -C(O)-, o NR"-, entonces R25 no puede ser un enlace;
b. cuando Ra es -Y-Z-R25-R23-R20,Y es un enlace covalente y Z es -O-, -S- o NR"'-, entonces R25 es un enlace
23 J
covalente y R no es cicloalquileno;
c. cuando Z es -NR5'-C(O)-, entonces Y no es un enlace covalente;
d. R23 y R25 no pueden ser ambos enlaces covalentes; y
e. cuando Q es un enlace y R1 is heteroarilo, entonces el R1 heteroarilo puede no estar sustituido adicionalmente con fenilo; y
f. cuando R es alquilo sustituido, entonces R no es alquilo, cicloalquilo o heterociclilo.
2. El compuesto de la reivindicacion 1, en el que Q es alquinileno C2-4.
3. El compuesto de la reivindicacion 2, seleccionado entre el grupo que consiste en:
3-(trifluorometil)-6-{[4-(trifluorometil)fenil]etinil}[1,2,4]triazolo[4,3-a]pi ridina;
2,2-difluoro-2-(6-{[4-(trifluorometil)fenil]etinil}[1,2,4]triazolo[4,3-a]piridin-3-il)etanol;
3-(1, 1 -difluoro-2-metoxietil)-6-{[4-(trifluorometil)fenil]etinil}[1,2,4]triazolo[4,3-a]pi ridina;
3-fenoxi-6-{[4-(trifluorometil)fenil]etinil}[1,2,4]triazolo[4,3-a]piridina;
3-(1,1-difluoro-2-metoxietil)-6-{[4-(trifluorometoxi)fenil]etinil}[1,2,4]triazolo[4,3-a]piridina; y
3-( 1, 1 -difluoro-2-metoxietil)-6-[(4-fluorofenil)etinil][1,2,4]triazolo[4,3-a]piridina.
4. El compuesto de la reivindicacion 1, en el que R1 es heteroarilo.
5. El compuesto de la reivindicacion 4, seleccionado entre el grupo que consiste en:
6-(6-ciclopropilpi ridin-3-il)-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
6-(2-ciclopropilpi rimidin-5-il)-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 3-(trifluorometil)-6-[6-(trifluorometil)piridin-3-il][1,2,4]triazolo[4,3-a]piridina;
6-[6-(2,2,2-trifluoroetoxi)pi ridin-3-il]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
6-(5-ciclopropil-1,3,4-tiadiazol-2-il)-3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridina; 3-(trifluorometil)-6-[6-(trifluorometil)piridazin-3-il][1,2,4]triazolo[4,3-a]piridina; 3-(trifluorometil)-6-[2-(trifluorometil)pirimidin-5-il][1,2,4]triazolo[4,3-a]piridina; 3-(1,1-difluoro-2-metoxietil)-6-[6-(2,2,2-trifluoroetoxi)piridin-3-il][1,2,4]triazolo[4,3-a]piridina; 6-[6-(ciclopropiloxi)piridin-3-il]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridina;
6-[6-(2,2,2-trifluoroetoxi)pi ridazin-3-il]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 3-[(ciclopropilmetoxi)(difluoro)metil]-6-[6-(trifluorometil)piridin-3-il][1,2,4]triazolo[4,3-a]piridina;
3-{difluoro[(5-fenil-1,2-oxazol-3-il)metoxi]metil}-6-[6-(trifluorometil)piridin-3-il][1,2,4]triazolo[4,3-a]piridina; y 3-{difluoro[(5-fenil-1,2-oxazol-3-il)metoxi]metil}-6-[6-(2,2,2-trifluoroetoxi)pi ridi n-3-il][1,2,4]triazolo[4,3-a]piridina.
6. El compuesto de la reivindicacion 1, en el que Ra es (i) arilo, (ii) -Y-Z-R25-R23-R20, en donde, preferiblemente, Y es -CF2- y Z es O; o
(iii) alquilo C1-15 opcionalmente sustituido con halo, hidroxilo, ciclopropilo, metoxi o amino.
7. El compuesto segun la reivindicacion 6, seleccionado del grupo que consiste en:
(i) 3-fenil-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3- fenil-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-8-amina; 3,6-bis[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina;
4- {6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}bencenosulfonamida;
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N-(4-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}fenil)metanosulfonamida;
4-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}benzamida;
3,3'-[1,2,4]triazolo[4,3-a]piridina-3,6-diildibenzoato de dietilo;
4-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}benzoato de etilo;
3-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}benzoato de etilo; N-(2-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}fenil)metanosulfonamida; N-metil-3-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}benzamida; y N-[5-(trifluorometoxi)-2-{3-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-6-il}fenil]acetamida;
(ii) 3-[difluoro(metoxi)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-[difluoro(2-metoxietoxi)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-{difluoro[(3-metiloxetan-3-il)metoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-{difluoro[(5-metil-1,2,4-oxadiazol-3-il)metoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-[(benciloxi)(difluoro)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina; 3-[difluoro(piridin-4-ilmetoxi)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina;
2- (difluoro{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}metoxi)etanol;
1-(difluoro{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}metoxi)propan-2-ol;
3- {difluoro[(5-metil-1,2-oxazol-3-il)metoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-[difluoro(piridin-3-ilmetoxi)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina;
3-{[(5-ciclopropil-1,2,4-oxadiazol-3-il)metoxi](difluoro)metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-(difluoro{[5-(2-metilpropil)-1,2,4-oxadiazol-3-il]metoxi}metil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-
a]piridina;
3-(difluoro{[5-(propan-2-il)-1,2,4-oxadiazol-3-il]metoxi}metil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3- [difluoro(piridin-2-ilmetoxi)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina;
4- [(difluoro{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridin-3-il}metoxi)metil]quinolina; 3-[(ciclopropilmetoxi)(difluoro)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-{difluoro[(1-fenil-1 H-1,2,3-triazol-4-il)metoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-[difluoro(piridazin-3-ilmetoxi)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-{difluoro[-(4-fluorofenil)etoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-{difluoro[(1-metil-5-fenil-1H-pirazol-3-il)metoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-{[(2,2-difluoro-1,3-benzodioxol-5-il)metoxi](difluoro)metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-{[(2,5-dimetil-1,3-oxazol-4-il)metoxi](difluoro)metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-{difluoro[(5-metil-2-fenil-1,3-oxazol-4-il)metoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-{difluoro[1 -(piridin-2-il)etoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-{[1-(4-clorofenil)etoxi](difluoro)metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-[difluoro(pirimidin-2-ilmetoxi)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-{[1-(2,4-diclorofenil)etoxi](difluoro)metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
1-[(difluoro{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridin-3-il}metoxi)metil]ciclobutanol;
(2S)-2-[(difluoro{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}metoxi)metil]pirrolidina-1-carboxilato de
terc-butilo;
3-{[(5-ciclobutil-1,2,4-oxadiazol-3-il)metoxi](difluoro)metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina; 3-[(difluoro{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridin-3-il}metoxi)metil]benzonitrilo; 3-(difluoro{3-[(2-metoxifenil)sulfanil]-2-metilpropoxi}metil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-[difluoro(1-{3-[4-(trifluorometil)fenil]-1,2-oxazol-5-il}etoxi)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3- a]piridina;
3-(difluoro{2-[4-(4-metoxifenil)piperazin-1-il]etoxi}metil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-{[(3-ciclopropil-1-metil-1H-pirazol-5-il)metoxi](difluoro)metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-
a]piridina;
5- [(difluoro{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridin-3-il}metoxi)metil]quinolina;
3-[1 -(difluoro{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridi n-3-il}metoxi)etil]quinolina;
3-{[2-(2,6-dimetilfenoxi)etoxi](difluoro)metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-{difluoro[(1-fenil-1H-pirazol-4-il)metoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3- [difluoro({2-[4-(trifluorometil)fenil]-1,3-oxazol-4-il}metoxi)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3- a]piridina;
4- [(difluoro{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridin-3-il}metoxi)metil]-2-metilquinolina; 4-[(difluoro{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridin-3-il}metoxi)metil]-2-(trifluorometil)quinolina;
6- [(difluoro{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridin-3-il}metoxi)metil]quinoxalina; 3-[(but-2-in-1-iloxi)(difluoro)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-{[(2,2-difluorociclopropil)metoxi](difluoro)metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-{difluoro[(3-fenilprop-2-i n-1-il)oxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina; 3-{difluoro[(1-metil-1H-benzoimidazol-2-il)metoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-{[(1-bencil-1H-1,2,3-triazol-4-il)metoxi](difluoro)metil}-6-[4-(trifluorometoxi)fenil][1,2,4J]triazolo[4,3-aJ]piridina; 3-{difluoro[(5-fenil-1,2-oxazol-3-il)metoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-{difluoro[(2-fenil-1,3-oxazol-4-il)metoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-{difluoro[(5-metil-2-fenil-2H-1,2,3-triazol-4-il)metoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-{difluoro[(1-metil-1H-pirazo1-3-il)metoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-[{[1-(4-clorofenil)-5-metil-1H-pirazol-3-il]metoxi}(difluoro)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-
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ajpiridina;
3-[(3,3-difenilpropoxi)(difluoro)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-(difluoro{[3-(pirimidin-2-il)bencil]oxi}metil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-(difluoro{[3-(piridin-3-il)bencil]oxi}metil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-{difluoro[(1-metil-1H-indazol-3-il)metoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-(difluoro{[2-(1 H-1,2,4-triazol-1 -il)bencil]oxi}metil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-(difluoro{[2-(2-metil-1H-imidazol-1-il)bencil]oxi}metil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-(difluoro{[2-fenil-5-(trifluorometil)-1,3-oxazol-4-il]metoxi}metil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-
a]piridina;
3-(difluoro{[1-fenil-3-(trifluorometil)-1H-pirazol-4-il]metoxi}metil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-
a]piridina;
3-(difluoro{[6-(1 H-pi razol-1-il)piridin-3-il]metoxi}metil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 6-ciclopropil-2'-[(difluoro{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}metoxi)metil]-3,4'-bipiridina; 3-[{[3-(4-ciclopropil-1H-imidazol-1-il)bencil]oxi}(difluoro)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3- a]piridina;
3-(difluoro{[5-(4-fluorofenil)-1,2-oxazol-3-il]metoxi}metil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-(difluoro{[2-(piperidin-1 -il)piridin-4-il]metoxi}metil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina; 3-{[(2,2-dimetil-2,3-dihidro-1-benzofuran-7-il)metoxi](difluoro)metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3- a]piridina;
3-{[2-(2,6-difluorofenil)etoxi](difluoro)metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-{difluoro[(5-fenil-1,2,4-oxadiazol-3-il)metoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-[{[2-(6-ciclopropilpi ridin-3-il)bencil]oxi}(difluoro)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina; 3-[{[5-(2-clorofenil)-1,2-oxazol-3-il]metoxi}(difluoro)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-(difluoro{[2-(piridin-3-il)bencil]oxi}metil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-(difluoro{[2-(1 H-pi razol-1-il)bencil]oxi}metil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina; 3-(1,1-difluoro-2-metoxietil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina;
2,2-difluoro-2-[6-(4-fenoxifenil)[1,2,4]triazolo[4,3-a]pi ridin-3-il]etanol; 3-(1,1-difluoro-2-metoxietil)-6-(4-fenoxifenil)[1,2,4]triazolo[4,3-a]piridina; 6-[4-(4-clorofenoxi)fenil]-3-(1,1-difluoro-2-metoxietil)[1,2,4]triazolo[4,3-a]piridina; 3-(1,1-difluoro-2-metoxietil)-6-[4-(4-fluorofenoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina; 3-[1,1-difluoro-2-(piridin-3-ilmetoxi)etil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
2- (2,2-difluoro-2-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}etoxi)-N,N-dimetiletanamina; (2,2-difluoro-2-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridi n-3-il}etoxi)acetonitrilo;
1, 1 -difluoro-1-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}propan-2-ol;
1-ciclopropil-2,2-difluoro-2-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridin-3-il}etanol; (2,2-difluoro-2-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}etoxi)acetato de etilo;
3- [1,1 -difluoro-2-(piridin-2-ilmetoxi)etil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
1, 1 -difluoro-2-metil-1-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}propan-2-ol; 3-(1,1-difluoro-2-metoxietil)-6-[3-metil-4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina; 3-{2-[(3,4-difluorobencil)oxi]-1, 1 -difluoroetil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-(difluoro{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}metil)pentan-3-ol; 3-(1,1-difluoro-2-metoxietil)-6-[2-metil-4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina;
1-(2,2-difluoro-2-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}etoxi)-2-metilpropan-2-ol 3-(1,1-difluoro-2-metoxietil)-6-[3-fluoro-4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-(1,1-difluoro-2-metoxietil)-6-(3,5-difluoro-4-fenoxifenil)[1,2,4]triazolo[4,3-a]piridina;
3-(2-{[3-(4-clorofenil)-1,2-oxazol-5-il]metoxi}-1,1-difluoroetil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
1-(2-clorofenoxi)-3-(2,2-difluoro-2-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}etoxi)propan-2-ol; y
1- (2,2-difluoro-2-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}etoxi)-3-(2,5-dimetilfenoxi)propan-2-ol; y
(iii) 7-metil-6-(4-(trifluorometoxi)fenil)-3-(trifluorometil)-[1,2,4]triazolo[4,3-a]piridina; 6-(3-(trifluorometoxi)fenil)-3-(trifluorometil)-[1,2,4]triazolo[4,3-a]piridina;
3-(trifluorometil)-6-[4-(trifluorometil)fenil][1,2,4]triazolo[4,3-a]piridina;
6-(2,4-diclorofenil)-3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridina;
6-[4-(difluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
6-(3-fenoxifenil)-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
6-[4-cloro-3-(trifluorometil)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridina;
6- (4-cloro-3-fluorofenil)-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
7- metil-6-[3-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
6-(4-terc-butilfenil)-3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridina;
3- (trifluorometil)-6-[4-(trimetilsilil)fenil][1,2,4]triazolo[4,3-a]piridina; 6-(4-metoxifenil)-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 6-[4-(2,2,2-trifluoroetoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridina;
4- [3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridin-6-il]benzoato de metilo;
2- {4-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridin-6-il]fenil}propan-2-ol; 4-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridin-6-il]benzonitrilo;
6-[2-(1 H-tetrazol-5-il)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 6-(bifenil-4-il)-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
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6-(1-metil-1H-indazol-5-il)-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
6-[4-(1H-1,2,4-triazol-1-il)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
6-[4-(4-fluorofenoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
6-[4-(4-clorofenoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
2-metil-2-{4-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridin-6-il]fenil}propanonitrilo;
6-[3-metil-4-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
6-[4-(propan-2-ilsulfonil)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
6-[4-(5-metil-1,3,4-oxadiazol-2-il)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 6-[3-(morfolin-4-ilmetil)-4-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 6-(4-etoxifenil)-3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridina; 6-(4-terc-butoxifenil)-3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridina;
6-{3-[(4-metilpiperazin-1 -il)metil]-4-(trifluorometoxi)fenil}-3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridina; N,N-dimetil-1-{2-(trifluorometoxi)-5-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridin-6-il]fenil}metanamina;
2- ({2-(trifluorometoxi)-5-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridin-6-il]bencil}amino)etanol; 6-(4-ciclopropilfenil)-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 6-[4-(pirazin-2-iloxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 6-[4-(piridin-3-iloxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
6- [4-(ciclopropiloxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
8-metil-6-[4-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
7- metoxi-6-[4-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 6-[2-metoxi-4-(trifluorometil)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
3- (trifluorometil)-6-(3,4,5-trimetoxifenil)[1,2,4]triazolo[4,3-a]piridina;
8- (trifluorometoxi)-5-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridin-6-il]quinolina; 6-(3,5-difluoro-4-fenoxifenil)-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 6-[4-(4-fluoro-2-nitrofenoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 6-[4-(2-fluorofenoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 6-[4-(piridin-4-iloxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
N-fenil-4-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridin-6-il]anilina;
N-(2,2,2-trifl uoroetil)-4-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridin-6-il]anilina; 6-[4-(fenilsulfanil)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
4- [3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridin-6-il]-N-(2,2,2-trifluoro-1 -feniletil)anilina; 6-[2-bromo-4-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
6-[2-(2-metoxipirimidi n-5-il)-4-(trifluorometoxi)fenil]-3-(trifl uorometil)[1,2,4]triazolo[4,3-a]piridina; 6-(2-(piridin-3-il)-4-(trifluorometoxi)fenil)-3-(trifluorometil)-[1,2,4]triazolo[4,3-a]pi ridina;
2-(trifluorometoxi)-5-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridin-6-il]anilina; 1-{4-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridin-6-il]fenil}ciclopentanocarbonitrilo; 6-[2-fluoro-4-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridina; 6-[3-fluoro-4-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 6-[4-(ciclopropilmetoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 6-[2-metoxi-4-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 6-[3-(1,3,4-oxadiazol-2-il)-4-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridina; 1-(4-(3-(trifluorometil)-[1,2,4]triazolo[4,3-a]pi ri di n-6-i l)feni l)eta nona;
5- (trifluorometoxi)-8-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridin-6-il]quinolina;
6- [4-(2-metil-1,3-dioxolan-2-il)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 6-[3-cloro-4-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; (2E)-3-{4-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridin-6-il]fenil}but-2-enenitrilo; N-metil-2-(trifluorometoxi)-5-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridin-6-il]benzamida; 6-[2-(2-metoxietoxi)-4-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; {5-(trifluorometoxi)-2-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridin-6-il]fenoxi}acetonitrilo;
6-[3-(3-metil-1,2,4-oxadiazol-5-il)-4-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 6-[4-(trifluorometoxi)-3-(trifl uorometil)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
1 -{4-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridin-6-il]fenil}ciclopropanocarbonitrilo; 6-[2,4-bis(trifluorometil)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
5- metil-6-[4-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina;
6- [4-(2-metoxipropan-2-il)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridina; 6-[2-etoxi-4-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; 6-[2-(propan-2-iloxi)-4-(trifluorometoxi)fenil]-3-(trifluorometil)1,2,4]triazolo[4,3-a]pi ridina;
4- {4-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridin-6-il]fenil}tetrahidro-2H-piran-4-carbonitrilo; 6-{4-[difluoro(piridin-3-il)metoxi]fenil}-3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridina; 6-{4-[difluoro(fenil)metoxi]fenil}-3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridina;
5- cloro-2-({4-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridin-6-il]fenil}amino)benzonitrilo;
5-(metoximetil)-6-[4-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridina; N-metil-N-fenil-4-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridin-6-il]anilina; ({6-[4-(trifluorometoxi)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridin-5-il}metoxi)acetonitrilo; 4-(difluoro{4-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridin-6-il]fenoxi}metil)benzonitrilo; 4-cloro-N-{4-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridin-6-il]fenil}anilina;
5
10
15
20
25
30
35
40
45
50
55
60
4-fluoro-N-{4-[3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridin-6-il]fenil}anilina;
6-[4-(pentafluoro-lambda~6~-sulfanil)fenil]-3-(trifluorometil)[1,2,4]triazolo[4,3-a]piridina; y
6-(2-cloro-4-nitrofenil)-3-(trifluorometil)[1,2,4]triazolo[4,3-a]pi ridina.
8. El compuesto de la reivindicacion 1, en el que R1 es arilo opcionalmente sustituido con halo, hidroxilo, metoxi, etoxi, -OCF3 o amino.
9. El compuesto segun la reivindicacion 8, seleccionado del grupo que consiste en:
acido {6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}acetico;
3-(difluorometil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-(propan-2-il)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina-3-carboxilato de metilo;
N-metil-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina-3-carboxamida;
3-metil-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridin-8-amina;
3-metil-6-[2-metil-4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-8-amina;
N-{3-metil-6-[2-metil-4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-8-il}acetamida;
3-(1-metil-1H-pirazol-4-il)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
N-{3-metil-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-8-il}propanamida;
N-({6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridin-3-il}metil)metanosulfonamida;
3-(difluorometil)-8-metoxi-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-[(benciloxi)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-[(ciclopropilmetoxi)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-[(2,2,2-trifluoroetoxi)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}metanol;
3-fenoxi-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
2,2,2-trifluoro-1-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}etanol;
3-(2-cloro-1,1-difluoroetil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
N,N-dimetil-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-amina;
3-(fenilsulfanil)-6-[4-(trifl uorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina;
3-(ciclopropiletinil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina;
2- metil-4-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}but-3-in-2-ol; N-(2,2-difluoro-2-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}etil)metanosulfonamida; N-(2,2-difluoro-2-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}etil)piridina-2-carboxamida;
3- metoxi-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-(2,2,2-trifluoroetoxi)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 6-[4-(trifluorometoxi)fenil]-3-({[4-(trifluorometil)bencil]oxi}metil)[1,2,4]triazolo[4,3-a]piridina; 3-{[(4-fluorobencil)oxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-{[(2-fluorobencil)oxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 6-[4-(trifluorometoxi)fenil]-3-({[2-(trifluorometil)bencil]oxi}metil)[1,2,4]triazolo4,3-a]pi ridina; 3-{[(2,4-difluorobencil)oxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina; 3-{[(4-clorobencil)oxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-({[4-(trifluorometoxi)bencil]oxi}metil)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina; N-(2,2-difluoro-2-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}etil)benzamida; 3-[(piridin-2-ilmetoxi)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-[(1-feniletoxi)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-{1-[difluoro(piridin-3-il)metoxi]etil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina; 3-{[(2,4-diclorobencil)oxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-{[(2,4-dimetilbencil)oxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-{[(5-metilpiridin-2-il)metoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-[1-(piridin-2-ilmetoxi)etil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 3-{[difluoro(piridin-3-il)metoxi]metil}-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; 6-[4-(trifluorometoxi)fenil]-3-[3-(trifluorometil)fenoxi][1,2,4]triazolo[4,3-a]piridina;
3-(4,4-difluoropiperidin-1 -il)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]pi ridina; 1-(2,2-difluoro-2-{6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridin-3-il}etil)-3-fenilurea; 6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina-3-carboxamida; 3-(2-metilfenoxi)-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina; y 3-[cloro(difluoro)metil]-6-[4-(trifluorometoxi)fenil][1,2,4]triazolo[4,3-a]piridina.
10. Un compuesto de la reivindicacion 1 que es 6-(4-(trifluorometoxi)fenil)-3-(trifluorometil)-[1,2,4]triazolo[4,3- a]piridina, representado por la estructura
imagen21
o una sal farmaceuticamente aceptable del mismo.
5 11. Un compuesto de una cualquiera de las reivindicaciones 1 a 10, para su uso en un metodo para tratar una
patologla en un mamlfero que se puede aliviar mediante tratamiento con un agente capaz de reducir la corriente tardla de sodio.
12. Uso de un compuesto de una cualquiera de las reivindicaciones 1 a 10, para la preparacion de una composicion 10 farmaceutica para tratar una patologla en un mamlfero que se puede aliviar mediante tratamiento con un agente
capaz de reducir la corriente tardla de sodio.
13. El compuesto de la reivindicacion 11 o el uso de la reivindicacion 12, en donde la patologla es una enfermedad cardiovascular seleccionada de una o mas de arritmias auriculares y ventriculares, insuficiencia cardlaca (incluyendo
15 insuficiencia cardlaca congestiva, insuficiencia cardlaca diastolica, insuficiencia cardlaca sistolica, insuficiencia cardlaca aguda), angina de Prinzmetal (variante), anginas estable e inestable, angina inducida por ejercicio, cardiopatla congestiva, isquemia, isquemia recurrente, lesion por reperfusion, infarto de miocardio, slndrome coronario agudo, enfermedad de las arterias perifericas, hipertension pulmonar, claudicacion intermitente; o la patologla es diabetes o neuropatla periferica diabetica; o la patologla da lugar a uno o mas de dolor neuropatico, 20 epilepsia, convulsiones o paralisis.
14. Una composicion farmaceutica que comprende un excipiente farmaceuticamente aceptable y una cantidad terapeuticamente eficaz del compuesto de una cualquiera de las reivindicaciones 1 a 10 o una sal, un ester o un hidrato farmaceuticamente aceptables del mismo.
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