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    • 9. 发明申请
    • DRUG CONJUGATES
    • 药物联合
    • US20080139815A1
    • 2008-06-12
    • US11856317
    • 2007-09-17
    • Iwao Ojima
    • Iwao Ojima
    • C07D213/70C07C323/62C07D305/14
    • C07D305/14A61K47/6803A61K47/6889C07C323/62C07D213/71
    • A compound having the formula Y-A-Z, wherein:A is a 5, 6, or 7 member ring that is monocyclic or is fused to 1 to 3 additional 4 to 8 member rings; wherein ring A and, independently, the fused additional rings are carbocyclic or heterocyclic, and saturated or unsaturated, wherein unsaturated rings are aromatic or non-aromatic; wherein Y and Z are substituents at adjacent positions on ring A;Y represents: Z represents: X and E represent O, S, or NRa or NRb; each of a, b, c, d, e and f independently represents 0 or 1; a+c equals 0, 1, or 2; b+d equals 0, 1, or 2; a+b+c+d+e+f equals 1, 2, or 3; provided that when f is 1, then d is 1, and when d is 0, then f is 0; and when both e and b are 0, then neither R1 nor R2 is chloro or bromo; v represents 0 or 1, provided that when v is 0, then J is hydrogen, a metal ion, or a quaternary ammonium ion, and X is O and G is H;either G is hydrogen, a metal ion, a quaternary ammonium ion, lower alkyl, or comprised of a pharmaceutically active chemical compound or the precursor thereof; or X-G represents a carbonyl-activating group;J is lower alkyl, aryl, heteroaryl, omega-hydroxycarbonyl-(lower alkyl), omega-(lower alkoxy)carbonyl-(lower alkyl), omega-(X-G)-carbonyl-(lower alkyl) group, or comprised of a specific binding agent; and Ra, Rb, R1, R2, R3, R4 are as defined in the specification.
    • 具有式Y-A-Z的化合物,其中:A为5,6或7元环,其为单环或稠合至1至3个另外的4至8个成员环; 其中环A和独立地稠合的另外的环是碳环或杂环的,饱和或不饱和的,其中不饱和环是芳族或非芳族的; 其中Y和Z是环A上相邻位置的取代基; Y表示:Z表示:X和E表示O,S或NR a或NR b。 a,b,c,d,e和f各自独立地表示0或1; a + c等于0,1或2; b + d等于0,1或2; a + b + c + d + e + f等于1,2或3; 条件是当f为1时,d为1,当d为0时,f为0; 当e和b都为0时,R 1和R 2都不是氯或溴; v表示0或1,条件是当v为0时,J为氢,金属离子或季铵离子,X为O且G为H; G是氢,金属离子,季铵离子,低级烷基,或由药物活性化合物或其前体组成; 或X-G表示羰基活化基团; J是低级烷基,芳基,杂芳基,ω-羟基羰基 - (低级烷基),ω-(低级烷氧基)羰基 - (低级烷基),ω-(XG) - 羰基 - (低级烷基) 粘合剂; R 1,R 2,R 1,R 2,R 3,R 3, R 4如本说明书中所定义。