BINQING WEI,JOHN A FLYGARE,PHILIP WILSON HOWARD,THOMAS PILLOW
申请号:
BR112015023070
公开号:
BR112015023070A2
申请日:
2014.03.13
申请国别(地区):
BR
年份:
2017
代理人:
摘要:
summary "pyrrolbenzodiazepines and conjugates thereof" conjugated compounds of the general formula (a): wherein: r2 is, where r36a and r36b are independently selected from h, f, C1-4 saturated alkyl, c2-3 alkenyl, whose alkyl and alkenyl groups is optionally substituted by a group selected from C1-C4-alkyl-starch alkyl and C1-4-alkyl ester; or, when one of r36a and r36b is h, the other is selected from a nitril and C1-4 alkyl ester; r6 and r9 are independently selected from h, r, oh, or, sh, sr, nh2, nhr, nrr ', no2, me3sn and halo; r7 is independently selected from h, r, oh, or, sh, sr, nh2, nhr, nrr ', no2, me3sn and halo; y is selected from formulas a1, a2, a3, a4, a5 and a6: 1 is a binder bound to a cell binding agent; cba is the cell binding agent; n is an integer selected from 0 to 48; ra4 is a C1-6 alkylene group; or (a) r10 is h, and r11 is oh, well, where ra is aikyl c 1-4; or (b) r10 and r11 form a carbon-nitrogen double bond between the nitrogen and carbon atoms to which they are attached; or (c) r10 is h and r11 is osozm, where z is 2 or 3, and m is a pharmaceutically acceptable monovalent cation; rer 'are each independently selected from optionally substituted C1-12 alkyl, c3-20 heterocyclyl and c5-20 aryl groups, and optionally with respect to the group nrr', rer 'together with the nitrogen atom to which they are linked form a 4-, 5-, 6- or optionally substituted 7-membered heterocyclic ring; wherein r16, r17, r19, r20, r21 and r22 are as defined for r6, r7, r9, r10, r11 and r2, respectively; wherein z is ch or n; wherein tet 'are independently selected from a single bond or a C1-9 alkylene, wherein the chain may be interrupted by one or more heteroatoms, for example o, s, n (h), nme, provided that the number of atoms in the shortest chain of atoms from x and x is from 3 to 12 atoms of; and x and x 'are independently selected from o, s and n (h).resumo “pirrolbenzodiazepinas e conjugados das mesmas” compostos conjugados de fórmula geral (a): em que: r2