AR058370A1 - DERIVATIVES OF 4.5- DIHIDRO - (1H) - PIRAZOL AS MODULATORS OF CANNABINOID RECEIVERS CB 1 - Google Patents

DERIVATIVES OF 4.5- DIHIDRO - (1H) - PIRAZOL AS MODULATORS OF CANNABINOID RECEIVERS CB 1

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Publication number
AR058370A1
AR058370A1 ARP060105577A ARP060105577A AR058370A1 AR 058370 A1 AR058370 A1 AR 058370A1 AR P060105577 A ARP060105577 A AR P060105577A AR P060105577 A ARP060105577 A AR P060105577A AR 058370 A1 AR058370 A1 AR 058370A1
Authority
AR
Argentina
Prior art keywords
group
alkyl
substituted
aryl
substituents
Prior art date
Application number
ARP060105577A
Other languages
Spanish (es)
Inventor
Josephus H M Lange
Der Neut Martina A W Van
Bakker Wouter I Iwema
Vliet Bernard J Van
Original Assignee
Solvay Pharm Bv
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 Solvay Pharm Bv filed Critical Solvay Pharm Bv
Publication of AR058370A1 publication Critical patent/AR058370A1/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D231/00Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/06Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member

Abstract

También se refiere a los usos de tales compuestos y composiciones, particularmente su uso en la administracion de ellos a paciente para lograr un efecto terapéutico en desordenes en los cuales están involucrados receptores CB1, o que pueden ser tratados mediante manipulacion de esos receptores. Reivindicacion 1: Compuestos de la formula general (1) en donde R representa un grupo alquilo C2-10, alquenilo C4-10, alquinilo C4-10, heteroalquilo C2-10, cicloalquil C5-8-alquilo C1-5 o heterocicloalquil C5-8-alquilo C1-5 en donde el(los) heteroátomo(s) es(son) N, O o S, los cuales grupos alquilo C2-10, alquenilo C4-10, alquinilo C4-10, heteroalquilo C2-10, cicloalquil C5-8-alquilo C1-5 o heterocicloalquil C5-8-alquilo C1-5 pueden estar sustituidos con 1-5 sustituyentes seleccionados de metilo, etilo, hidroxi, amino o F, o R representa un grupo aril-alquilo C1-3 o aril-heteroalquilo C1-3 en el cual los grupos arilo pueden estar sustituidos con 1-5 sustituyentes Y, los cuales pueden ser los mismos o diferentes, seleccionados del grupo alquilo C1-3 o alcoxi C1-3, hidroxi, halogeno, trifluorometilo, trifluorometiltio, trifluorometoxi, nitro, amino, mono- o dialquil C1-2-amino, mono- o dialquil C1-2-amido, alquilo C1-3- sulfonilo, dimetilsulfamido, alcoxi C1-3-carbonilo, carboxilo, trifluorometilsulfonilo, ciano, carbamoílo, sulfamoílo, fenilo y acetilo, o R representa un grupo ciclopropilo, el cual grupo ciclopropilo puede estar sustituido con 1-5 sustituyentes seleccionado de metilo, etilo, F o con un grupo alquilo C3-5 lineal o ramificado o con un grupo bencilo o arilo, en el cual el grupo arilo o bencilo puede estar sustituido con 1-5 sustituyentes Y; R1 representa H, hidroxi, alcoxi C1-3, acetiloxi o propioniloxi; R2 representa un grupo arilo el cual puede estar sustituido con 1-5 sustituyentes Y, en donde Y tiene los significados anteriormente mencionados; n es 0 o 1; R3 representa un grupo alquilo lineal C3-10, alquilo ramificado C5-10, ciclopropilo, ciclobutilo, ciclopentilo, cicloheptilo o ciclooctilo, bicicloalquilo C5-10, tricicloalquilo C6-10 o tetracicloalquilo C8-11 los cuales grupos pueden estar sustituidos con 1-5 sustituyentes seleccionados de metilo, etilo, hidroxi, amino, F o R3 representa un grupo cicloalquilo C3-8 el cual grupo cicloalquilo C3-8 está sustituido con un grupo arilo, el cual grupo arilo puede estar sustituido con 1-5 sustituyentes Y en donde Y tiene los significados anteriormente mencionados, o R3 representa un grupo 2,2,2-trifluoroetilo o 2-fluoroetilo o R3 representa un grupo ciclohexilo el cual grupo está substituido con 1-5 sustituyentes seleccionados de metilo, etilo, hidroxi, amino o F, o R3 representa un grupo heterocicloalquilo C5- 8, bicicloheteroalquilo C6-10, tricicloheteroalquilo C7-10, los cuales grupos pueden estar sustituidos con 1-5 sustituyentes seleccionados de metilo, etilo, hidroxi, amino o F, o R3 representa un grupo cicloalquil C3-8-alquilo C1-3, bicicloalquil C5- 10-alquilo C1-3, tricicloalquil-C6-10-alquilo C1-3, los cuales grupos pueden estar sustituidos con 1-5 sustituyentes seleccionados de metilo, etilo, hidroxi, amino o F, o R3 representa un grupo heterocicloalquil C3-8-alquilo C1-3 ramificado o lineal, bicicloheteroalquil C5-10-alquilo C1-3, tricicloheteroalquil-C6-10-alquilo C1-3, los cuales grupos pueden estar sustituidos con 1-5 sustituyentes seleccionados de metilo, etilo, hidroxi, amino o F, o R3 representa un grupo arilo, el cual grupo puede estar sustituido con 1-5 sustituyentes Y, en donde Y tiene los significados anteriormente mencionados, o R3 representa un grupo aril-alquilo C1-5 o diaril-alquilo C1-5 en los cuales grupos los anillos fenilo o heteroaromático pueden estar sustituidos con 1-5 sustituyentes Y, en donde Y tiene los significados anteriormente mencionados, o R3 representa un grupo alquenilo C4-8 o alquinilo C4-8 lineales o ramificados, los cuales grupos alquenilo C4-8 o alquinilo C4-8 lineales o ramificados puede estar sustituido con 1-3 átomos de F, o, cuando n = 1, R3representa un grupo heteroalquilo C2-10 ramificado o lineal, que contiene 1-2 heteroátomos seleccionados de N, O o S; R4 representa un átomo de H, alquilo C1-4 o R3 y R4 junto con el átomo de N al cual están unidos forman un grupo monocíclico, bicíclico o tricíclico heterocíclico, saturado o insaturado, no aromático o, parcialmente aromático, que tiene 5 a 11 átomos de anillo, el cual grupo heterocíclico pude estar sustituido con1-5 sustituyentes seleccionados de arilo, aril-alquilo C1-3, diarilmetilo, o Y, en donde Y tiene los significados anteriormente mencionados; A representa un grupo carbonilo (C=O), tiocarbonilo (C=S) o sulfonilo (SO2) con la condicion de que cuando A representa un grupo tiocarbonilo (C=S), n tiene el valor 1, y estereoisomeros, prodrogas y N-oxidos de los mismos, y compuestos de la formula (1) isotopicamente marcados, así como las sales, hidratos, solvatos, complejos y conjugados farmacéuticamente aceptables de dichos compuestos de la formula (1) y sus estereoisomeros, prodrogas, N-oxidos, o análogos isotopicamente marcados.It also refers to the uses of such compounds and compositions, particularly their use in the administration of them to patients to achieve a therapeutic effect in disorders in which CB1 receptors are involved, or which can be treated by manipulation of those receptors. Claim 1: Compounds of the general formula (1) wherein R represents a C2-10 alkyl, C4-10 alkenyl, C4-10 alkynyl, C2-10 heteroalkyl, C5-8 cycloalkyl-C-5- alkyl or C5- heterocycloalkyl group 8-C1-5 alkyl wherein the heteroatom (s) is (are) N, O or S, which groups C2-10 alkyl, C4-10 alkenyl, C4-10 alkynyl, C2-10 heteroalkyl, cycloalkyl C5-8-C1-5 alkyl or heterocycloalkyl C5-8-C1-5 alkyl may be substituted with 1-5 substituents selected from methyl, ethyl, hydroxy, amino or F, or R represents an aryl-C1-3 alkyl group or aryl-C1-3 heteroalkyl in which the aryl groups may be substituted with 1-5 Y substituents, which may be the same or different, selected from the group C1-3alkyl or C1-3alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, mono- or dialkyl C1-2-amino, mono- or dialkyl C1-2-amido, C1-3-sulfonyl alkyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trif luoromethylsulfonyl, cyano, carbamoyl, sulfamoyl, phenyl and acetyl, or R represents a cyclopropyl group, which cyclopropyl group may be substituted with 1-5 substituents selected from methyl, ethyl, F or with a linear or branched C3-5 alkyl group or with a benzyl or aryl group, in which the aryl or benzyl group may be substituted with 1-5 Y substituents; R1 represents H, hydroxy, C1-3 alkoxy, acetyloxy or propionyloxy; R2 represents an aryl group which may be substituted with 1-5 substituents Y, wherein Y has the aforementioned meanings; n is 0 or 1; R3 represents a C3-10 linear alkyl, C5-10 branched alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cycloheptyl or cyclooctyl, C5-10 bicycloalkyl, C6-10 tricycloalkyl or C8-11 tetracycloalkyl group which groups may be substituted with 1-5 Selected substituents of methyl, ethyl, hydroxy, amino, F or R3 represents a C3-8 cycloalkyl group which C3-8 cycloalkyl group is substituted with an aryl group, which aryl group may be substituted with 1-5 Y substituents wherein And it has the aforementioned meanings, or R3 represents a 2,2,2-trifluoroethyl or 2-fluoroethyl group or R3 represents a cyclohexyl group which group is substituted with 1-5 substituents selected from methyl, ethyl, hydroxy, amino or F , or R3 represents a C5-8 heterocycloalkyl, C6-10 bicycloheteroalkyl, C7-10 tricycloheteroalkyl group, which groups may be substituted with 1-5 substituents selected from methyl, ethyl, hydroxy, amino or F, or R3 represents a C 3-8 cycloalkyl-C 1-3 alkyl, C 5-10 cycloalkyl, C 3-10 tricycloalkyl-C 1-3 alkyl group, which groups may be substituted with 1-5 substituents selected from methyl, ethyl , hydroxy, amino or F, or R3 represents a C3-8-branched or linear heterocycloalkyl-C5-10 alkyl-C3-10-C1-3alkyl, tricycloheteroalkyl-C6-10-C1-3alkyl group, which groups can being substituted with 1-5 substituents selected from methyl, ethyl, hydroxy, amino or F, or R3 represents an aryl group, which group may be substituted with 1-5 substituents Y, wherein Y has the aforementioned meanings, or R3 represents an aryl-C1-5 alkyl or diaryl-C1-5 alkyl group in which groups the phenyl or heteroaromatic rings may be substituted with 1-5 substituents Y, wherein Y has the aforementioned meanings, or R3 represents an alkenyl group C4-8 or linear or branched C4-8 alkynyl, which linear or branched C4-8 alkenyl or C4-8 alkynyl groups may be substituted with 1-3 F atoms, or, when n = 1, R3 represents a branched or linear C2-10 heteroalkyl group, containing 1-2 heteroatoms selected from N, O or S; R4 represents an atom of H, C1-4 alkyl or R3 and R4 together with the N atom to which they are attached form a heterocyclic, saturated or unsaturated, non-aromatic or partially aromatic monocyclic, bicyclic or tricyclic group having 5 a 11 ring atoms, which heterocyclic group may be substituted with 1-5 substituents selected from aryl, aryl-C 1-3 alkyl, diarylmethyl, or Y, wherein Y has the aforementioned meanings; A represents a carbonyl (C = O), thiocarbonyl (C = S) or sulfonyl (SO2) group with the proviso that when A represents a thiocarbonyl group (C = S), n has the value 1, and stereoisomers, prodrugs and N-oxides thereof, and compounds of the formula (1) isotopically labeled, as well as pharmaceutically acceptable salts, hydrates, solvates, complexes and conjugates of said compounds of the formula (1) and their stereoisomers, prodrugs, N-oxides , or isotopically labeled analogs.

ARP060105577A 2005-12-20 2006-12-18 DERIVATIVES OF 4.5- DIHIDRO - (1H) - PIRAZOL AS MODULATORS OF CANNABINOID RECEIVERS CB 1 AR058370A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
EP05112482 2005-12-20

Publications (1)

Publication Number Publication Date
AR058370A1 true AR058370A1 (en) 2008-01-30

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ID=35749602

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP060105577A AR058370A1 (en) 2005-12-20 2006-12-18 DERIVATIVES OF 4.5- DIHIDRO - (1H) - PIRAZOL AS MODULATORS OF CANNABINOID RECEIVERS CB 1

Country Status (8)

Country Link
CN (1) CN101341127A (en)
AR (1) AR058370A1 (en)
AT (1) ATE500228T1 (en)
BR (1) BRPI0620035A2 (en)
DE (1) DE602006020489D1 (en)
SA (1) SA06270469B1 (en)
TW (1) TW200730500A (en)
ZA (1) ZA200804926B (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR079935A1 (en) * 2010-01-29 2012-02-29 Abbott Healthcare Products Bv SYNTHESIS OF DERIVATIVES OF PIRAZOLIN CARBOXAMIDINA REPLACED
SG191884A1 (en) * 2011-01-07 2013-08-30 Targacept Inc Nicotinic receptor non-competitive antagonists
CN107417578B (en) * 2017-08-23 2020-02-07 沈阳海诺威医药科技有限公司 N- (3, 5-dimethyl adamantane-1-yl) -N' -substituted phenylurea compound and preparation method and application thereof

Also Published As

Publication number Publication date
BRPI0620035A2 (en) 2011-10-25
DE602006020489D1 (en) 2011-04-14
CN101341127A (en) 2009-01-07
ATE500228T1 (en) 2011-03-15
TW200730500A (en) 2007-08-16
ZA200804926B (en) 2009-04-29
SA06270469B1 (en) 2010-07-25

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