tert-butyl (6S,6aS)-3-[[3-[[(6S,6aS)-2-methoxy-5-[(2-methylpropan-2-yl)oxycarbonyl]-6-(oxan-2-yloxy)-11-oxo-6a,7,8,9-tetrahydro-6H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxymethyl]-5-methylphenyl]methoxy]-2-methoxy-6-(oxan-2-yloxy)-11-oxo-6a,7,8,9-tetrahydro-6H-pyrrolo[2,1-c][1,4]benzodiazepine-5-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: tert-butyl (6S,6aS)-3-[[3-[[(6S,6aS)-2-methoxy-5-[(2-methylpropan-2-yl)oxycarbonyl]-6-(oxan-2-yloxy)-11-oxo-6a,7,8,9-tetrahydro-6H-pyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxymethyl]-5-methylphenyl]methoxy]-2-methoxy-6-(oxan-2-yloxy)-11-oxo-6a,7,8,9-tetrahydro-6H-pyrrolo[2,1-c][1,4]benzodiazepine-5-carboxylate
• 化学式: C₅₅H₇₂N₄O₁₄
• 分子量: 1013.2
• InChiKey: CVJZVNRVLTYMAI-UIBPMHNZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  73
• 可旋转键数：
  16
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  174
• 氢给体数：
  0
• 氢受体数：
  14

文献信息

• [EN] PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF<br/>[FR] PYRROLOBENZODIAZÉPINES ET LEURS CONJUGUÉS
  申请人：SPIROGEN SARL

  公开号：WO2014140862A2

  公开（公告）日：2014-09-18

  A conjugate of formula A wherein: D represents either group D1 or D2 the dotted line indicates the optional presence of a double bond between C2 and C3; when there is a double bond present between C2 and C3, R2 is selected from the group consisting of: (ia) C5-10 aryl group, optionally substituted by one or more substituents selected from the group comprising: halo, nitro, cyano, ether, carboxy, ester, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene; (ib) C1-5 saturated aliphatic alkyl; (ic) C3-6 saturated cycloalkyl; (id) wherein each of R31, R32 and R33 a, re independently selected from H, C1-3 saturated alkyl, C2-3 alkenyl, C2-3 alkynyl and cyclopropyl, where the total number of carbon atoms in the R2 group is no more than 5; (ie) wherein one of R35a and R35b is H and the other is selected from: phenyl, which phenyl is optionally substituted by a group selected from halo, methyl, methoxy; pyridyl; and thiophenyl; and (if) where R34 is selected from: H; C1-3 saturated alkyl; C2-3 alkenyl; C2-3 alkynyl; cyclopropyl; phenyl, which phenyl is optionally substituted by a group selected from halo, methyl, methoxy; pyridyl; and thiophenyl; (ig) halo; when there is a single bond present between C2 and C3, where R36a and R36b are independently selected from H, F, C1-4 saturated alkyl, C2-3 alkenyl, which alkyl and alkenyl groups are optionally substituted by a group selected from C1-4 alkyl amido and C1-4 alkyl ester; or, when one of R16a and R16b is H, the other is selected from nitrile and a C1-4 alkyl ester; D' represents either group D'1 or D2: wherein the dotted line indicates the optional presence of a double bond between C2' and C3'; 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 formulae A1, A2, A3, A4, A5 and A6. L is a linker connected to a cell binding agent; CBA is the cell binding agent; n is an integer selected in the range of 0 to 48; RA4 is a C1-6 alkylene group; either (a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl; or (b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or (c) R10 is H and R11 is OSOzM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation; R and R' are each independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups, and optionally in relation to the group NRR', R and R' together with the nitrogen atom to which they are attached form an optionally substituted 4-, 5-, 6- or 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 T and T' are independently selected from a single bond or a C1-9 alkylene, which chain may be interrupted by one or more heteroatoms e.g. O, S, N(H), NMe, provided that the number of atoms in the shortest chain of atoms between X and X' is 3 to 12 atoms; and X and X' are independently selected from O, S and N(H); except that there cannot be double bonds between both C2 and C3 and C2' and C3'.