AR047462A1 - DERIVATIVES 1,3,5 TRISUBSTITUIDOS OF 4, 5 DIHIDRO - 1H - PIRAZOL THAT HAVE ANTAGONIST ACTIVITY CB1. PHARMACEUTICAL COMPOSITIONS. - Google Patents

DERIVATIVES 1,3,5 TRISUBSTITUIDOS OF 4, 5 DIHIDRO - 1H - PIRAZOL THAT HAVE ANTAGONIST ACTIVITY CB1. PHARMACEUTICAL COMPOSITIONS.

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Publication number
AR047462A1
AR047462A1 ARP050100262A AR047462A1 AR 047462 A1 AR047462 A1 AR 047462A1 AR P050100262 A ARP050100262 A AR P050100262A AR 047462 A1 AR047462 A1 AR 047462A1
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Argentina
Prior art keywords
group
substituted
branched
alkyl
linear
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Spanish (es)
Inventor
Josephus H M Lange
Cornelis G Kruse
Stuivenberg Herman H Van
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Solvay Pharm Bv
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Application filed by Solvay Pharm Bv filed Critical Solvay Pharm Bv
Publication of AR047462A1 publication Critical patent/AR047462A1/en

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Abstract

Los compuestos pertenecen a la categoría de los derivados de pirazol utilizados como antagonistas de CB1. Además, se presenta composiciones farmacéuticas. Reivindicacion 1: Compuestos, caracterizados por la formula general (1), donde: R1 y R2 representan independientemente fenilo, tienilo o piridilo, grupos que pueden estar substituidos con 1, 2 o 3 sustituyentes Y, que pueden ser iguales o diferentes, del grupo formado por alquilo C1-3 o alcoxi C1-3 ramificado o lineal, fenilo, hidroxi, cloro, bromo, fluoro, yodo, trifluorometilo, trifluorometiltio, trifluorometoxi, metilsulfonilo, carboxilo, trifluorometilsulfonilo, ciano, carbamoilo, sulfamoilo y acetilo, o R1 y/o R2 representan naftilo; X representa uno de los subgrupos de formulas (2) o (3), donde: R3 representa un átomo de hidrogeno o un grupo alquilo C1-3 ramificado o lineal; R4 representa un grupo alquilo C1-8 o cicloalquil-(C3-8)-alquilo-(C1-2) ramificado o lineal, alcoxi C1-8 ramificado o lineal, cicloalquilo C3- 8, bicicloalquilo C5-10, tricicloalquilo C6-10, grupos que pueden contener uno o más heteroátomos del grupo (O, N, S) y que pueden estar substituidos con un grupo hidroxi, 1-3 grupos metilo, un grupo etilo o 1-3 átomos de fluor, o R4 representa un grupo fenilo, fenoxi, bencilo, fenetilo o fenilpropilo, opcionalmente substituido sobre su anillo fenilo con 1-3 sustituyentes Y, donde Y tiene el significado precedentemente mencionado, o R4 representa un grupo piridilo o tienilo, o R4 representa un grupo NR5R6 donde: R5 y R6 -conjuntamente con el átomo de nitrogeno al cual están unidos- forman un grupo heterocíclico, monocíclico o bicíclico, saturado o no saturado que tiene 4 a 10 átomos anulares, grupo heterocíclico que contiene uno o dos heteroátomos del grupo (O, N, S) y que puede estar substituido con un grupo alquilo C1-3 ramificado o lineal, fenilo, hidroxi o trifluorometilo o un átomo de fluor; o R3 y R4 -conjuntamente con el átomo de nitrogeno al cual están unidos- forman un grupo heterocíclico, monocíclico o bicíclico, saturado o no saturado que tiene 4 a 10 átomos anulares, grupo heterocíclico que contiene uno o dos heteroátomos del grupo (O, N, S) y que puede estar substituido con un grupo alquilo C1-3 ramificado o lineal, fenilo, amino, hidroxi o trifluorometilo o un átomo de fluor; R7 representa un grupo bencilo, fenilo, tienilo o piridilo, grupos que pueden estar substituidos sobre su anillo aromático con 1, 2, 3 o 4 sustituyentes Y, donde Y tiene el significado precedentemente indicado, que pueden ser iguala o diferentes, o R7 representa alquilo C1-8 ramificado o lineal, alquenilo C3-8, cicloalquilo C3-10, bicicloalquilo C5-10, tricicloalquilo C6-10 o cicloalquenilo C5-8 o R7 representa naftilo o R7 representa un grupo amino o R7 representa un grupo dialquilamino C1-8, un grupo monoalquilamino C1-8 o un grupo heterocíclico, monocíclico o bicíclico, saturado o no saturado que tiene 4 a 10 átomos anulares, grupo heterocíclico que contiene uno o dos átomos de nitrogeno y que puede contener un heteroátomo del grupo (O, S) y que puede estar substituido con un grupo alquilo C1-3 ramificado o lineal, fenilo, hidroxi o trifluorometilo o un átomo de fluor; R8 representa un átomo de hidrogeno o un grupo alquilo C1-3 ramificado o lineal; R9 representa un átomo de hidrogeno o un grupo alquilo C1-8 ramificado o lineal, cicloalquilo C3-8 o heteroalquilo C2-10, grupos que pueden estar substituidos con un grupo ceto, grupo trifluorometilo o un átomo de fluor, o R9 representa un grupo amino, hidroxi, fenoxi o benciloxi o R9 representa un grupo alcoxi C1-8 ramificado o lineal, que puede estar substituido con un grupo hidroxi, un grupo trifluorometilo o un átomo de fluor, o R9 representa un grupo fenilo, bencilo, piridilo, tienilo, piridilmetilo o fenetilo donde los anillos aromáticos pueden estar substituidos con 1, 2 o 3 de los sustituyentes Y, donde Y tiene el significado precedentemente indicado, o R9 representa un grupo NR10R11 con la condicion de que R8 representa un átomo de hidrogeno o un grupo metilo y donde R10 y R11 son iguales o diferentes y representan alquilo C1-4 o trifluoroalquilo C2-4 o R10 y R11 -conjuntamente con el átomo de nitrogeno al cual están ligados- forman un grupo funcional heterocíclico saturado o no saturado que tiene 4 a 8 átomos anulares, grupo funcional heterocíclico que contiene uno o dos átomos del grupo (O, N, S) y que puede estar substituido con un grupo alquilo C1-2 o R8 y R9 -conjuntamente con el átomo de nitrogeno al cual están ligados- forman un grupo funcional heterocíclico, monocíclico o bicíclico, saturado o no saturado que tiene 4 a 10 átomos anulares, grupo funcional heterocíclico que contiene uno o dos átomos del grupo (O, N, S) o un grupo ceto o un grupo -SO2-, grupo funcional que puede estar substituido con un grupo alquilo C1-2, hidroxi, fenilo, metilamino, dimetilamino, acetidinilo, pirrolidinilo, piperidinilo o hexahidro-1H- azepinilo, y todos los estereoisomeros, como así también las sales y prodrogas de los mismos.The compounds belong to the category of pyrazole derivatives used as CB1 antagonists. In addition, pharmaceutical compositions are presented. Claim 1: Compounds, characterized by the general formula (1), wherein: R1 and R2 independently represent phenyl, thienyl or pyridyl, groups which may be substituted with 1, 2 or 3 substituents Y, which may be the same or different, of the group formed by C1-3 alkyl or branched or linear C1-3 alkoxy, phenyl, hydroxy, chloro, bromine, fluoro, iodine, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, methylsulfonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl, or R1 and / or R2 represent naphthyl; X represents one of the subgroups of formulas (2) or (3), where: R3 represents a hydrogen atom or a branched or linear C1-3 alkyl group; R4 represents a C1-8 alkyl or cycloalkyl- (C3-8) -alkyl- (C1-2) branched or linear group, branched or linear C1-8 alkoxy, C3-8 cycloalkyl, C5-10 bicycloalkyl, C6-10 tricycloalkyl , groups that may contain one or more heteroatoms of the group (O, N, S) and that may be substituted with a hydroxy group, 1-3 methyl groups, an ethyl group or 1-3 fluorine atoms, or R4 represents a group phenyl, phenoxy, benzyl, phenethyl or phenylpropyl, optionally substituted on its phenyl ring with 1-3 Y substituents, where Y has the aforementioned meaning, or R4 represents a pyridyl or thienyl group, or R4 represents an NR5R6 group where: R5 and R6 - together with the nitrogen atom to which they are attached - form a heterocyclic, monocyclic or bicyclic, saturated or unsaturated group having 4 to 10 ring atoms, heterocyclic group containing one or two heteroatoms of the group (O, N, S ) and which may be substituted with a branched C1-3 alkyl group or linear, phenyl, hydroxy or trifluoromethyl or a fluorine atom; or R3 and R4 - together with the nitrogen atom to which they are attached - form a heterocyclic, monocyclic or bicyclic, saturated or unsaturated group having 4 to 10 ring atoms, a heterocyclic group containing one or two heteroatoms of the group (O, N, S) and which may be substituted with a branched or linear C1-3 alkyl group, phenyl, amino, hydroxy or trifluoromethyl or a fluorine atom; R7 represents a benzyl, phenyl, thienyl or pyridyl group, groups that may be substituted on its aromatic ring with 1, 2, 3 or 4 substituents Y, where Y has the meaning indicated above, which may be equal or different, or R7 represents C1-8 branched or linear alkyl, C3-8 alkenyl, C3-10 cycloalkyl, C5-10 cycloalkyl, C6-10 tricycloalkyl or C5-8 cycloalkenyl or R7 represents naphthyl or R7 represents an amino group or R7 represents a C1- dialkylamino group 8, a C1-8 monoalkylamino group or a heterocyclic, monocyclic or bicyclic, saturated or unsaturated group having 4 to 10 ring atoms, heterocyclic group containing one or two nitrogen atoms and which may contain a heteroatom of the group (O, S) and which may be substituted with a branched or linear C1-3 alkyl group, phenyl, hydroxy or trifluoromethyl or a fluorine atom; R8 represents a hydrogen atom or a branched or linear C1-3 alkyl group; R9 represents a hydrogen atom or a branched or linear C1-8 alkyl, C3-8 cycloalkyl or C2-10 heteroalkyl group, groups that may be substituted with a keto group, trifluoromethyl group or a fluorine atom, or R9 represents a group amino, hydroxy, phenoxy or benzyloxy or R9 represents a branched or linear C1-8 alkoxy group, which may be substituted with a hydroxy group, a trifluoromethyl group or a fluorine atom, or R9 represents a phenyl, benzyl, pyridyl, thienyl group , pyridylmethyl or phenethyl where the aromatic rings may be substituted with 1, 2 or 3 of the substituents Y, where Y has the meaning indicated above, or R9 represents a group NR10R11 with the proviso that R8 represents a hydrogen atom or a group methyl and where R10 and R11 are the same or different and represent C1-4 alkyl or C2-4 trifluoroalkyl or R10 and R11 - together with the nitrogen atom to which they are linked - form a heterocyclic sat functional group urate or unsaturated having 4 to 8 ring atoms, heterocyclic functional group containing one or two atoms of the group (O, N, S) and which may be substituted with a C1-2 or R8 and R9 alkyl group - together with the Nitrogen atom to which they are linked - they form a heterocyclic, monocyclic or bicyclic, saturated or unsaturated functional group having 4 to 10 ring atoms, heterocyclic functional group containing one or two atoms of the group (O, N, S) or a keto group or a -SO2- group, a functional group that may be substituted with a C1-2 alkyl group, hydroxy, phenyl, methylamino, dimethylamino, acetyridinyl, pyrrolidinyl, piperidinyl or hexahydro-1H-azepinyl, and all stereoisomers, as well also the salts and prodrugs thereof.

ARP050100262 2004-01-30 2005-01-26 DERIVATIVES 1,3,5 TRISUBSTITUIDOS OF 4, 5 DIHIDRO - 1H - PIRAZOL THAT HAVE ANTAGONIST ACTIVITY CB1. PHARMACEUTICAL COMPOSITIONS. AR047462A1 (en)

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Application Number Priority Date Filing Date Title
EP04100338 2004-01-30

Publications (1)

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AR047462A1 true AR047462A1 (en) 2006-01-18

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ARP050100262 AR047462A1 (en) 2004-01-30 2005-01-26 DERIVATIVES 1,3,5 TRISUBSTITUIDOS OF 4, 5 DIHIDRO - 1H - PIRAZOL THAT HAVE ANTAGONIST ACTIVITY CB1. PHARMACEUTICAL COMPOSITIONS.

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CN (1) CN101823999A (en)
AR (1) AR047462A1 (en)
SA (1) SA05250465B1 (en)
TW (1) TW200528442A (en)

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106660968B (en) * 2014-05-09 2020-02-07 美国政府(由卫生和人类服务部的部长所代表) Pyrazole derivatives and their use as cannabinoid receptor mediators

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CN101823999A (en) 2010-09-08
SA05250465B1 (en) 2009-02-04
TW200528442A (en) 2005-09-01

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