| 主权项 |
1. A method for prevention or treatment of a pathological condition or symptom in a mammal, wherein the activity of sphingosine 1-phosphate receptors is implicated and agonism of such activity is desired, comprising administering to said mammal an effective amount of a compound of formula (IIa)formula (IIIa, IIIb, IIIc, IIIf, or IIIg)formula (IVa), (IVb) or (IVc)or formula (VIa), (VIb) or (VIc)wherein:
each of X1, X2, X3, X4, X5, and X6, independently, is hydrogen, halo, hydroxy, nitro cyano, alkyl, haloalkyl, cycloalkyl, halocycloalkyl, alkoxy, haloalkoxy, cycloalkoxy, halocycloalkoxy, acyl, aminoacyl, —N(RfRg), —N(Rf)SO2Rg, —SO2Rf, —S(O)2N(RfRg), —CO2Rf, trialkylamino, aryl, or heteroaryl; W is —O—; Cy has the formula:wherein:
Z1 is —CH2CH2—; Z2 is —CH2—; Z3 is a bond; R1a and R1b, independently, are hydrogen, halo, hydroxy, nitro, cyano, —NRfRg, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, alkoxy, cycloalkylalkoxy, cycloalkenylalkoxy, heterocyclylalkoxy, arylalkoxy, heteroarylalkoxy, acyl, cycloalkylacyl, cycloalkenylacyl, heterocyclylacyl, arylacyl, heteroarylacyl, thioalkyl, alkenyl, alkynyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl; or R1a and R1b, when taken together, are C2-C5 alkylene or C2-C5 alkenylene; R2a and R2b, independently, are hydrogen, halo, hydroxy, nitro, cyano, —NRfRg, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, cycloalkylalkyl, cycloalkenylalkyl, heterocyclylalkyl, arylalkyl, heteroarylalkyl, alkoxy, cycloalkylalkoxy, cycloalkenylalkoxy, heterocyclylalkoxy, arylalkoxy, heteroarylalkoxy, acyl, cycloalkylacyl, cycloalkenylacyl, heterocyclylacyl, arylacyl, heteroarylacyl, heteroarylacyl, thioalkyl, alkenyl, alkynyl, cycloalkenyl, heterocyclyl, aryl, or heteroaryl; or R1a and R2a, when taken together, are C1-C5 alkylene or C2-C5 alkenylene;wherein R1a, R1b, R2a, and R2b are each, independently, substituted with 0-5 substituents selected from halo, hydroxy, nitro, cyano, —NRfRg, or CO2Rf;
R3 is -L1-J-L2-T1; L1 is —C(RfRg)—; J is —N(Rf)—; or J is whereineach of D1 and D3, independently, is D2 is —[C(RfRg)]k—, —[C(RfRg)]k—N(Rf)—, —[C(RfRg)]k—O—, —N(Rf)—, or —N(Rf)—[(CRfRg)]k—; andD4 is —[C(RfRg)]m—;wherein k is 1 or 2; and m is 0, 1, 2, or 3;provided that no more than 2 ring atoms of D1-D4 are N or O; L2 is —C(RfRg)—, —C(RfG)—, —C(G)2—, —C(RfRg)—C(RfRg)—, —C(RfRg)—C(RfG)—, —C(RfRg)—C(G)2—, or a bond; T1 is —C(O)(ORf), —C(O)N(Rf)S(O)2Rf, tetrazolyl, —S(O)2ORf, —C(O)NHC(O)—Rf, —Si(O)OH, —B(OH)2, —N(Rf)S(O)2Rf, —S(O)2NRf, —O—P(O)(ORf)ORf, or —P(O)2(ORf); each G, independently, is hydrogen, hydroxy, a halogen, or trifluoromethyl; each Rf, independently, is hydrogen, hydroxy, halo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl or NH2; wherein each of alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocycle are optionally substituted with 1 to 5 substituents independently selected from the group consisting of halo, oxo, —CN, —CHO, —CG3, —OH, —NO2, alkyl, —OCG3, alkoxy, cycloalkoxy, cycloalkenoxy, amino, alkylamino, dialkylamino, acylamino, aminoacyl, alkylsulfonyl, alkylaminosulfonyl, and dialkylaminosulfonyl; and Rg, independently, is hydrogen, hydroxy, halo, alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl; wherein each of alkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl and heterocycle are optionally substituted with 1 to 5 substituents independently selected from the group consisting of halo, oxo, —CN, —CHO, —CG3, —OH, —NO2, alkyl, —OCG3, alkoxy, cycloalkoxy, cycloalkenoxy, amino, alkylamino, dialkylamino, acylamino, aminoacyl, alkylsulfonyl, alkylaminosulfonyl, and dialkylaminosulfonyl; or a pharmaceutically acceptable salt thereof. |
