| 主权项 |
1. A compound having the formula (I),their pharmaceutically acceptable salts, pharmaceutically acceptable solvates or stereoisomers thereof, wherein
R1 is independently selected from hydrogen, alkyl, halogen, alkoxy or haloalkoxy; R2 is selected from hydrogen or fluorine; wherein when R2 is hydrogen, R is —NR3R4; and when R2 is fluorine, R is —NR3R4 or —ORx wherein Rx is hydrogen or alkyl; R3 is hydrogen, alkyl, hydroxyalkyl or alkoxyalkyl; R4 is selected from
(i) —(CRyRz)m—
—CN, —(CRyRz)mCOORb, —(CRyRz)mCONRcRd, —(CRyRz)mNReRf, —(CRyRz)mC ORg, —(CRyRz)n—O—(CH2)n—ORh, alkoxy, haloalkoxy, alkoxyalkyl, thiazolyl, 1,3,4-thiadiazolyl, tetrahydro-2H-thiopyranyl, tetrahydro-2H-thiopyran-1-oxide, tetrahydro-2H-thiopyran-1,1-dioxide, tetrahydrothiophene 1,1-dioxide,(ii) cycloalkyl substituted with hydroxyalkyl, hydroxyalkyl and hydroxyl together, —(CRyRz)m—COORb, —CONRcRd, —NReRf, —CORg, optionally substituted heterocyclyl, wherein the optional substituent is selected from alkyl or haloalkyl,(iii) heterocyclyl substituted with haloalkyl, alkyl and haloalkyl together, halogen and haloalkyl together, hydroxyalkyl, —SO2-alkyl, —SO2-aryl, —SO2—NReRf, —CO—NReRf, —COORb, —CORg, aralkyl, —(CRyRz)n—NReRf, optionally substituted heterocyclyl wherein optional substituent is selected from alkyl or SO2—NReRf,(iv) —(CRyRz)m-aryl susbsituted with hydroxyalkyl, —SO2-alkyl, —SO2-aryl, —SO2—NReRf, —CO—NReRf, —COORb, aralkyl, —NR3R4, —(CRyRz)n—NReRf optionally substituted heterocyclyl wherein optional substituent is selected from halogen, hydroxyl or alkyl; halogen and optionally substituted heterocyclyl together,(v) optionally substituted —(CRyRz)n-heterocyclyl, optionally substituted (C7-C12)cycloalkyl, optionally substituted —(CRyRz)n-cycloalkyl, optionally substituted heterocycle containing 3-4 heteroatoms or heterogroups selected from O, S, N, CO, SO or SO2, wherein the optional substituent is selected from cyano, halogen, hydroxy, alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, −COORb, —(CRyRz)n—CONRcRd, —(CRyRz)nNReRf, —SO2Rg or —(CHRj)p—R5,
Provided that when R2 is Fluorine, R4 can alternatively be hydroxyalkyl;Alternatively R3 and R4 together with the nitrogen atom to which they are attached form an optionally susbstituted 3-10 membered heterocyclic ring wherein the optional substituent is selected from hydroxy, cyano, halogen, alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, —COORb, —CONRcRd, —NReRf, —CORg, —O(CH2)o—ORh, —SO2Ri, —(CHRj)p—R5 or heterocyclyl optionally substituted with hydroxyl or alkyl; R5 is independently selected from an optionally substituted group selected from cycloalkyl, aryl, heterocyclyl; wherein the optional substituent is hydroxyl, alkyl, haloalkyl or SO2Rg; Rb is independently selected from hydrogen or alkyl; Rc is independently selected from hydrogen or alkyl; Rd is independently selected from hydrogen, alkyl or alkoxy; Re is independently selected from hydrogen, alkyl or hydroxyalkyl; Rf is independently selected from hydrogen or alkyl; Alternatively Re and Rf, in each occurrence, independent of each other, together with the nitrogen atom to which they are attached form optionally substituted 3-6 membered heterocyclic ring, wherein the optional substituent is selected from hydroxyl, alkyl, acyl, mesyl or COORb; Rg is independently selected from alkyl, aryl, heterocyclyl or —NReRf; Rh is independently represents alkyl; Ri is independently selected from alkyl, aryl or —NReRd; Rj is independently selected from hydrogen or alkyl; Ry is independently selected from hydrogen, hydroxy, hydroxyalkyl, alkyl or aryl; Rz is independently selected from hydrogen or alkyl; m is independently selected from 0, 1, 2, 3 or 4; n is independently selected from 1, 2, 3 or 4; and p is 0, 1, 2, 3 or 4. |
