http://rdf.ncbi.nlm.nih.gov/pubchem/patent/AR-045047-A1

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filingDate 2004-07-08-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationDate 2005-10-12-04:00^^<http://www.w3.org/2001/XMLSchema#date>
publicationNumber AR-045047-A1
titleOfInvention ARILO AND HETEROARILO DERIVATIVES TRISUSTITUIDOS AS MODULATORS OF METABOLISM AND PROFILAXIS AND TREATMENT OF DISORDERS RELATED TO THEMSELVES
abstract The compounds herein are useful in the prophylaxis or treatment of metabolic disorders and complications thereof such as diabetes and obesity. Claim 1: A compound of formula (1) or a salt, hydrate or solvate or N-oxide thereof, in which: A and B are each C1-3 alkylene optionally substituted with 1 to 4 substituents selected from the group consisting in C1-3 alkyl, C1-4 alkoxy, carboxy, cyano, C1-3 haloalkyl and halogen; D is O, S, S (O), S (O) 2, CR2R3 or N-R2; E is N, C or CR4; the double line (from points up and continues down) is a single link when E is N or CR4, or a double link when E is C; V1 is selected from the group consisting of C1-3 alkylene, ethynylene and C1-2 heteroalkylene optionally substituted with 1 to 4 substituents selected from the group consisting of C1-3 alkyl, C1-4 alkoxy, carboxy, cyano, C1-3 haloalkyl and halogen; or V1 is a link; V2 is C3-6 cycloalkylene or C1-3 alkylene where each is optionally substituted with 1 to 4 substituents selected from the group consisting of C1-3 alkyl, C1-4 alkoxy, carboxy, cyano, C1-3 haloalkyl and halogen; or V2 is a link; W is NR5, O, S, S (O), or S (O) 2; or W is absent; Q is NR6, O, S, S (O) or S (O) 2; X is N or CR7; Y is N or CR8; Z is selected from the group consisting of C1-5 acyl, C1-5 alkoxy, C2-6 alkenyl, C1-4 alkoxy, C1-8 alkyl, C1-4 alkylcarboxamide, C2-6 alkynyl, C1-4 alkylthiocarboxamide, C1 alkylsulfonamide -4, alkylsulfinyl 1-4, alkylsulfonyl C1-4, alkylthio C1-4, alkylthioureyl C1-4, alkylureyl C1-4, amino, alkylamino C1-2, dialkylamino C2-4, carbamimidoyl, carbo-alkoxy C1-6, carboxamide , carboxy, cyano, C3-7 cycloalkyl, C4-8 diacylamino, C2-6 dialkylcarboxamide, C2-6 dialkylthiocarboxamide, C2-6 dialkylsulfonamide, C2-6 dialkylsulfonylamino, formyl, C1-4 haloalkoxy. C1-4 haloalkyl, C1-4 haloalkylcarboxamide, C1-4 haloalkylsulfinyl, C1-4 haloalkylsulfonyl, C1-4 haloalkylthio, halogen, aryl, heterocyclic, heteroaryl, hydroxyl, hydroxycarbamimidoyl, hydroxylamino, nitro and tetrazolyl, where C1-8 alkyl, cycloalkyl C3-7, and heterocyclic are each optionally substituted with 1, 2, 3 or 4 groups selected from the group consisting of C1-5 acyl, C1-5 acyloxy, C1-4 alkoxy, C1-7 alkyl, C1-4 alkylcarboxamide , C 1-4 alkylsulfonamide, C 1-4 alkylsulfinyl, C 1-4 alkylsulfonyl, C 1-4 alkylthio, C 1-4 alkylureyl, amino, C 1-2 alkylamino, C 2-4 dialkylamino, C 1-6 carbo alkoxy, carboxyamide, carboxy, cyano, formyl, C1-4 haloalkoxy, C1-4 haloalkylsulfinyl, C1-4 haloalkylsulfonyl, C1-4 haloalkylthio, halogen, hydroxyl, hydroxylamino and nitro, and wherein said C1-7 alkyl is optionally substituted with amino; or Z is a group of the formula (A); wherein R9 is H, C1-8 alkyl or C3-7 cycloalkyl; and R10 is H, nitro or nitrile; Ar1 is aryl or heteroaryl each optionally substituted with R11, R12, R13, R14, and R15; where R11 is selected from the group consisting of C1-5 acyl, C1-6 acylsulfonamide, C1-5 acyloxy, C2-6 alkenyl, C1-4 alkoxy, C1-8 alkyl, C1-4 alkylamino, C1-6 alkylcarboxamide, alkylthiocarboxamide C1-4, C2-6 alkynyl, C1-4 alkylsulfonamide, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, C1-4 alkylthio, C1-4 alkylthioureyl, C1-4 alkylureyl, amino, arylsulfonyl, carbamimidoyl, C1- carboxy alkoxy 6, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C2-6 dialkylcarboxamide, C2-6 dialkylthiocarboxamide, guanidinyl, halogen, C1-4 haloalkoxy, C1-4 haloalkyl, C1- haloalkylsulfinyl 4, C1-4 haloalkylsulfonyl, C1-4 haloalkylthio, heterocyclic, heterocyclic-oxy, heterocyclic-sulfonyl, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, hydroxyl, nitro, oxo-cycloalkyl C4-7, phenyl, sulfonamide, sulfonic acid and thiol, and wherein C1-5 acyl, C1-6 acylsulfonamide, C1-4 alkoxy, C1-8 alkyl, C1-4 alkylamino, alkylsulfonam C 1-6, C 1-4 alkylsulfonyl, C 1-4 alkylthio, arylsulfonyl, carbamimidoyl, C 2-6 dialkylamino, heterocyclic, heterocyclic-carbonyl, heteroaryl, phenoxy and phenyl are optionally substituted with 1 to 5 substituents independently selected from the group consisting of C1-5 acyl, C1-5 acyloxy, C2-6 alkenyl, C1-4 alkoxy, C1-7 alkyl, C1-4 alkylamino, C1-4 alkylcarboxamide, C2-6 alkynyl, C1-4 alkylsulfonamide, C1-4 alkylsulfinyl, C 1-4 alkylsulfonyl, C 1-4 alkylthio, C 1-4 alkylureyl, C 1-6 carboxy alkoxy, carboxamide, carboxy, cyano, C 3-7 cycloalkyl, C 3-7 cycloalkyloxy, C 2-6 dialkylamino, C 2-6 dialkylcarboxamide, halogen, C1-4 haloalkoxy, C1-4 haloalkyl, C1-4 haloalkylsulfinyl, C1-4 haloalkylsulfonyl, C1-4 haloalkylthio, heteroaryl, heterocyclic, hydroxyl, nitro, phenyl, and phosphonooxy, wherein said C1-7 alkyl and C1-4 alkylcarboxamide are each optionally substituted with 1 to 5 substituents selected from the group consisting of alkoxy C1-4 and hydroxy, or R11 is a group of formula (B), in which "p" and "r" are each independently 0.1, 2 or 3; and R16 is H, C1-5 acyl, C2-6 alkenyl, C1-8 alkyl, C1-4 alkylcarboxamide, C2-6 alkynyl, C1-4 alkylsulfonamide, C1-6 carboxy-alkoxy, carboxamide, carboxy, cyano, C3 cycloalkyl -7, C2-6 dialkylcarboxamide, halogen, heteroaryl or phenyl, and where the heteroaryl or phenyl are optionally substituted with 1 to 5 substituents independently selected from the group consisting of C1-4 alkoxy, amino, alkylamino, C1-4, C2 alkynyl -6, C2-8 dialkylamino, halogen, C1-4 haloalkoxy, C1-4 haloalkyl and hydroxyl; and R12, R13, R14 and R15 are each independently selected from the group consisting of C1-5 acyl, C1-5 alkoxy, C2-6 alkenyl, C1-4 alkoxy, C1-8 alkyl, C1-4 alkylcarboxamide, C2 alkynyl -6, C1-4 alkylsulfonamide, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, C1-4 alkylthio, C1-4 alkylureyl, C1-6 carbo alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C2-6 dialkylcarboxamide , halogen, C1-4 haloalkoxy, C1-4 haloalkyl, C1-4 haloalkylsulfinyl, C1-4 haloalkylsulfonyl, C1-4 haloalkylthio, hydroxyl and nitro; or two adjacent groups selected from the group consisting of R12, R13, R14 and R15 together with the atoms to which they are attached form a 5, 6 or 7 membered cycloalkyl, cycloalkenyl or heterocyclic group that is fused with Ar1, where the group 5, 6 or 7 members is optionally substituted with halogen; R1, R7 and R8 are each independently selected from the group consisting of H, C1-5 alkoxy, C2-6 alkenyl, C1-4 alkoxy, C1-8 alkyl, C1-4 alkylcarboxamide, C2-6 alkynyl, C1- alkylsulfonamide 4, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, C1-4 alkylthio, C1-4 alkylureyl, amino, C1-4 alkylamino, C2-8 dialkylamino, carboxamide, cyano, C3-7 cycloalkyl, C2-6 dialkylcarboxamide, C2 dialkylsulfonamide -6, halogen, C1-4 haloalkoxy, C1-4 haloalkyl, C1-4 haloalkylsulfinyl, C1-4 haloalkylsulfonyl, C1-4 haloalkylthio and hydroxyl; R2 is selected from the group consisting of C1-8 alkyl, amino, aryl, carboxamide, carboxy, cyano, C3-6 cycloalkyl, C1-4 haloalkoxy, C1-4 haloalkyl, halogen, heteroaryl and hydroxyl; and wherein C1-8 alkyl, aryl or heteroaryl are optionally substituted with 1 to 5 substituents selected from the group consisting of C1-5 acyl, C1-5 acyloxy, C1-4 alkoxy, C1-8 alkyl, C1-4 alkylamino, alkylcarboxamide C1-4, C 1-4 alkylthiocarboxamide, C 1-4 alkylsulfonamide, C 1-4 alkylsulfinyl, C 1-4 alkylsulfonyl, C 1-4 alkylthio, C 1-4 alkylthioureyl, C 1-4 alkylureyl, amino, carboxyC 1-6 alkoxy, carboxamide, carboxy, cyano, C3-6 cycloalkyl, C3-6 cycloalkyl C1-3 heteroalkylene, C2-8 dialkylamino, C2-6 dialkylcarboxamide, C2-6 dialkylthiocarboxamide, C2-6 dialkylsulfonamide, C1-4 alkylthioureyl, haloC 1-4 haloalkoxy C1-4, C1-4 haloalkylsulfinyl, C1-4 haloalkylsulfonyl, C1-4 haloalkyl, C1-4 haloalkylthio, halogen, heterocyclic, hydroxy, hydroxylamino and nitro; or R2 is -Ar2-Ar3 where Ar2 and r3 are each independently aryl or heteroaryl optionally substituted with 1 to 5 substituents selected from the group consisting of H, C1-5 acyl, C1-5 acyloxy, C1-4 alkoxy, C1 alkyl -8, C 1-4 alkylcarboxamide, C 1-4 alkylthiocarboxamide, C 1-4 alkylsulfinyl, C 1-4 alkylsulfonyl, C 1-4 alkylthio, amino, C 1-4 alkylamino, C 1-6 carbo-alkoxy, carboxamide, carboxy, cyano, C3 cycloalkyl -6, C2-8 dialkylamino, C2-6 dialkylcarboxamide, C1-4 haloalkoxy, C1-4 haloalkyl, halogen, hydroxyl and nitro; or R2 is a group of formula (C); in which: R17 is H, C1-8 alkyl, C3-7 cycloalkyl, aryl, heteroaryl or OR19; and R18 is F, Cl, Br, CN, or NR20R21; where R19 is H, C1-8 alkyl or C3-7 cycloalkyl, and R20 and R21 are each independently H, C1-8 alkyl, C3-7 cycloalkyl, aryl or heteroaryl; or R2 is a group of the formula (D); in which G is i) -C (O) -, - C (O) NR23-, -C (O) O-, -OC (O) NR23-, -NR23C (O) O-, -OC (O ) -, - C (S) -, -C (S) NR23-, -C (S) O-, -OC (S) -, -CR23R24-, -O-, -S-, -S (O) - or S (O) 2- when D is CR2R3, or ii) -CR23R24C (O) -, -C (O) -, -CR23R24C (O) NR25-, -C (O) NR23-, -C (O ) O-, -C (S) -, -C (S) NR23-, -C (S) O-, -CR23R24-, -S (O) 2-, or a link when D is NR2, where R23, R24 and R25 are each independently H or C1-8 alkyl, and R22 is H, C1-8 alkyl, C2-6 alkynyl, C3-7 cycloalkyl, phenyl, heteroaryl, or heterocyclic each optionally substituted with 1 to 5 selected substituents from the group consisting of C1-5 acyl, C1-5 acyloxy, C2-6 alkenyl, C1-4 alkoxy, C1-7 alkyl, C1-4 alkylamino, C1-4 alkylcarboxamide, C1-4 alkylthiocarboxamide, C1-4 alkylsulfonamide, C 1-4 alkylsulfinyl, C 1-4 alkylsulfonyl, C 1-4 alkylthio, C 1-4 alkylthioureyl, C 1-4 alkylureyl, amino, C 1-6 carboxy alkoxy, carboxamide, carboxy, cyano, C 3-7 cycloalkyl, C 2-8 dialkylamino, C2-6 dialkylcarboxamide, C2 dialkylthiocarboxamide -6, C2-6 dialkylsulfonamide, C1-4 alkylthioureyl, C1-4 haloalkoxy, C1-4 haloalkyl, C1-4 haloalkylsulfinyl, C1-4 haloalkylsulfonyl, haloa
priorityDate 2003-07-11-04:00^^<http://www.w3.org/2001/XMLSchema#date>
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