Therapeutic uses of tri-aryl acid derivatives

A compound of formula (Ia)

• wherein:
• is quinoxalinyl, quinazolinyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, benzofuranyl, benzothiophenyl, oxazolyl, thiazolyl, oxadiazolyl, isoxazolyl, imidazolyl, pyrazolyl, thiadiazolyl, triazolyl, pyridyl, pyrimidinyl, pyrazinyl or pyridazinyl, which is optionally substituted by one or more ring system substituents;
• is aryl, which is optionally substituted by one or more ring system substituents;
• A is —O—, —S—, —SO—, —SO2—, —NR13—, —C(O)—, —N(R14)C(O)—, —C(O)N(R15)—, —N(R14)C(O)N(R15)—, —C(R14)═N—, a chemical bond,
• B is —O—, —S—, —SO—, —SO2—, ethynylene, —C(O)—, —N(R18)C(O)—, or —C(O)NR18—;
• D is —O—, —S—, —NR19—, a chemical bond, ethynylene, —N(R20)C(O)—, —C(O)—, or —C(O)N(R20)—;
• E is a chemical bond or an ethylene group;
• a is 0–4;
• b is 0–4;
• c is 0–4;
• d is 0–5;
• e is 0–4;
• f is 0–6;
• g is 1–4;
• h is 1–4;
• R1, R3, R5, R7, R9, and R11, are independently hydrogen, halogen, alkyl, carboxyl, alkoxycarbonyl or aralkyl;
• R2, R4, R6, R8, R10 and R12, are independently —(CH2)q—X;
• q is 0–3;
• X is hydrogen, halogen, alkyl, alkenyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, heteroaralkyl, hydroxy, alkoxy, aralkoxy, heteroaralkoxy, carboxyl, alkoxycarbonyl, tetrazolyl, acyl, acylHNSO2—, —SR23, Y1Y2N— or Y3Y4NCO—;
• Y1 and Y2 are independently hydrogen, alkyl, aryl, aralkyl or heteroaralkyl, or one of Y1 and Y2 is hydrogen or alkyl and the other of Y1 and Y2 is acyl or aroyl;
• Y3 and Y4 are independently hydrogen, alkyl, aryl, aralkyl or heteroaralkyl;
• Z is R21O2C—, R21OC—, cyclo-imide, —CN, R21O2SHNCO—, R21O2SHN—, (R21)2NCO—, R21O-2,4-thiazolidinedionyl, or tetrazolyl;
• R′ and R″ are, independently, hydrogen or ring system substituents;
• R21 is hydrogen, alkyl, aryl, cycloalkyl, or aralkyl;
• R13, R19 and R23 are independently R22OC—, R22NHOC—, hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, heteroaralkyl, or aralkyl;
• R14, R15, R16, R18 and R20 are independently hydrogen, alkyl, aralkyl, carbonyl, or alkoxycarbonyl;
• or R14, and R15 taken together with the carbon and nitrogen atoms through which they are linked form a 5 or 6-membered azaheterocyclyl group;
• and
• R22 is hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, heterocyclyl, heteroaralkyl, or aralkyl;
• or
• a pharmaceutically acceptable salt thereof, an N-oxide thereof, a hydrate thereof or a solvate thereof;
• wherein
• “alkyl,” when used to designate an alkyl group per se or when used as an alkyl component of any other group, is an aliphatic hydrocarbon group which is straight or branched having 1 to about 20 carbon atoms and is optionally substituted by one or more alkyl group substituents;
• “aryl” is an aromatic monocyclic or multicyclic ring system of about 6 to about 14 carbon atoms, which is optionally substituted by one or more ring system substituents;
• “heteroaryl” is an aromatic monocyclic or multicyclic ring system of about 5 to about 14 carbon atoms, in which at least one of the carbon atoms in the ring system is replaced by nitrogen, oxygen or sulfur, which is optionally substituted by one or more ring system substituents;
• “heterocyclyl” is a non-aromatic saturated monocyclic or multicyclic ring system of 3 to about 1.0 carbon atoms, in which at least one of the carbon atoms in the ring system is replaced by nitrogen, oxygen or sulfur, which is optionally substituted by one or more ring system substituents;
• “heteroaralkyl” is a heteroaryl-alkyl group, wherein the heteroaryl and alkyl groups are as defined above;
• an “alkyl group substituent” is halo, carboxy, cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aryl, alkoxy, alkoxycarbonyl, aralkoxycarbonyl, heteroaralkoxycarbonyl, or Y1Y2NCO—, wherein Y1 and Y2 are independently hydrogen, alkyl, aryl, aralkyl or heteroaralkyl, or Y1 and Y2 taken together with the nitrogen atom to which Y1 and Y2 are attached form heterocyclyl
• wherein the substituents may contain further alkyl group substituents or ring system substituents as recited herein;
• and
• a “ring system substituent” is alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, heteroaralkyl, hydroxy, alkoxy, aryloxy, aralkoxy, acyl, aroyl, halo, nitro, cyano, carboxy, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, alkylsulfonyl, arylsulfonyl, heteroarylsulfonyl, alkylsulfinyl, arylsulfinyl, heteroarylsulfinyl, alkylthio, arylthio, heteroarylthio, aralkylthio, heteroaralkylthio, fused cycloalkyl, fused cycloalkenyl, fused heterocyclyl, fused heterocyclenyl, arylazo, heteroarylazo, RaRbN—, RcRdNCO—, RcO2CN—, or RcRdNSO2— wherein Ra and Rb are independently hydrogen, alkyl, aryl, aralkyl or heteroaralkyl, or one of Ra and Rb is hydrogen or alkyl and the other of Ra and Rb is aroyl or heteroaroyl, and Rc and Rd are independently hydrogen, alkyl, aryl, heteroaryl, cycloalkyl, cycloalkenyl, heterocyclyl, heterocyclenyl, aralkyl or heteroaralkyl and, where the ring is cycloalkyl, cycloalkenyl, heterocyclyl or heterocyclenyl, the ring system substituent may also include methylene, oxo and thioxo on carbon atoms thereof
• wherein the substituents may contain further alkyl group substituents or ring system substituents as recited herein.