申请人:SmithKline Beecham Corporation
公开号:US06008213A1
公开(公告)日:1999-12-28
Compounds of formula (I) ##STR1## wherein A.sub.1 is C or N; E is a five- or six-membered heteroaromatic or six-membered aromatic ring optionally substituted by R.sup.3 or R.sup.4 ; X.sup.1 --X.sup.2 is CHR.sup.1 --CH, CR.sup.1 .dbd.CH, NR.sup.1 --CH, S(O).sub.u --CH or O--CH; X.sup.3 is CR.sup.5 R.sup.5 ', NR.sup.5, S(O).sub.u or O; R.sup.2 is --OR', --NR'R", --NR'SO.sub.2 R'", --NR'OR', --OCR'.sub.2 C(O)OR', --OCR'.sub.2 OC(O)--R', --OCR'.sub.2 C(O)NR'.sub.2, CF.sub.3 or --COCR'.sub.2 R.sup.2 '; R.sup.3, R.sup.4 and R.sup.7 are independently H, halo, --OR.sup.12, --SR.sup.12, --CN, --NR'R.sup.12, --NO.sub.2, --CF.sub.3, CF.sub.3 S(O).sub.r --, --CO.sub.2 R', --CONR'.sub.2, R.sup.14 --C.sub.0-6 alky-, R.sup.14 --C.sub.1-6 oxoalkyl-, R.sup.14 --C.sub.2-6 alkenyl-, R.sup.14 --C.sub.2-6 alkynyl-, R.sup.14 --C.sub.0-6 alkyloxy-, R.sup.14 --C.sub.0-6 alkylamino- or R.sup.14 --C.sub.0-6 alkyl--S(O).sub.r --; R.sup.6 is W--(CR'.sub.2).sub.q --Z--(CR'R.sup.10)--U--(CR'.sub.2).sub.s --V-- or W'--(CR'.sub.2).sub.q --U--(CR'.sub.2).sub.s -- U and V are absent or CO, CR'.sub.2, C(.dbd.CR.sup.15.sub.2), S(O).sub.n, O, NR.sup.15, CR.sup.15 'OR.sup.15, CR'(OR")CR'.sub.2, CR'.sub.2 CR'(OR") C(O)CR'.sub.2, CR.sup.15.sub.2 C(O), CONR.sup.15, NR.sup.15 CO, OC(O), C(O)O, C(S)O, OC(S), C(S)NR.sup.15, NR.sup.15 C(S), SO.sub.2 NR.sup.15, NR.sup.15 SO.sub.2, N.dbd.N, NR.sup.15 NR.sup.15, NR.sup.15 CR.sup.15.sub.2, NR.sup.15 CR.sup.15.sub.2, CR.sup.15.sub.2 O, OCR.sup.15.sub.2, C$(m)ZC, CR.sup.15 .dbd.CR.sup.15, Het, or Ar, provided that U and V are not simultaneously absent, and W and W' are a nitrogen-containing substituent, and integrin receptor antagonists.
化合物的式子(I)
其中A1为C或N; E为五元或六元杂环芳香或六元芳香环,可选地被R3或R4取代; X1-X2为CHR1-CH,CR1=CH,NR1-CH,S(O)u-CH或O-CH; X3为CR5R5',NR5,S(O)u或O; R2为-OR',-NR'R",-NR'SO2R'",-NR'OR',-OCR'2C(O)OR',-OCR'2OC(O)-R',-OCR'2C(O)NR'2,CF3或-COCR'2R2'; R3,R4和R7独立地为H,卤素,-OR12,-SR12,-CN,-NR'R12,-NO2,-CF3,CF3S(O)r-,-CO2R',-CONR'2,R14-C0-6烷基,R14-C1-6氧代烷基,R14-C2-6烯基,R14-C2-6炔基,R14-C0-6烷氧基,R14-C0-6烷基氨基或R14-C0-6烷基-S(O)r-; R6为W-(CR'2)q-Z-(CR'R10)-U-(CR'2)s-V-或W'-(CR'2)q-U-(CR'2)s- U和V不存在或为CO,CR'2,C(=CR152),S(O)n,O,NR15,CR15'OR15,CR'(OR")CR'2,CR'2CR'(OR")C(O)CR'2,CR152C(O),CONR15,NR15CO,OC(O),C(S)O,OC(S),C(S)NR15,NR15C(S),SO2NR15,NR15SO2,N=DN,NR15NR15,NR15CR152,NR15CR152,CR152O,OCR15'2,C$(m)ZC,CR15=CR15,Het或Ar,前提是U和V不同时不存在,W和W'是含氮取代基,并且是整合素受体拮抗剂。