4-(4-((tert-butoxycarbonyl)amino)phenyl)-1-methyl-1H-pyrrole-2-carboxylic acid | 864076-03-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 4-(4-((tert-butoxycarbonyl)amino)phenyl)-1-methyl-1H-pyrrole-2-carboxylic acid
• 英文别名: 4-(4-(Tert-Butoxycarbonylamino)Phenyl)-1-Methyl-1H-Pyrrole-2-Carboxylic Acid；1-methyl-4-[4-[(2-methylpropan-2-yl)oxycarbonylamino]phenyl]pyrrole-2-carboxylic acid
• CAS: 864076-03-9
• 化学式: C₁₇H₂₀N₂O₄
• 分子量: 316.357
• InChiKey: GIFDVQUOPKITFR-UHFFFAOYSA-N

物化性质

• 沸点：
  470.6±45.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  80.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(4-((tert-butoxycarbonyl)amino)phenyl)-1-methyl-1H-pyrrole-2-carboxylic acid 在 四氢吡咯 、 盐酸 、 4-二甲氨基吡啶 、 四(三苯基膦)钯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三苯基膦 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.0h， 生成 (S)-methyl 4-(4-(4-(4-((7-methoxy-5-oxo-2,3,5,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepin-8-yl)oxy)butanamido)phenyl)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxylate
  参考文献：
  名称：

  GC-Targeted C8-Linked Pyrrolobenzodiazepine–Biaryl Conjugates with Femtomolar in Vitro Cytotoxicity and in Vivo Antitumor Activity in Mouse Models

  摘要：

  DNA binding 4-(1-methyl-1H-pyrrol-3-yl)-benzenamine (MPB) building blocks have been developed that span two DNA base pairs with a strong preference for GC-rich DNA. They have been conjugated to a pyrrolo[2,1-c][1,4]benzodiazepine (PBD) molecule to produce C8-linked PBD MPB hybrids that can stabilize GC-rich DNA by up to 13-fold compared to AT-rich DNA. Some have subpicomolar IC50 values in human tumor cell lines and in primary chronic lymphocytic leukemia cells, while being up to 6 orders less cytotoxic in the non-tumor cell line WI38, suggesting that key DNA sequences may be relevant targets in these ultrasensitive cancer cell lines. One conjugate, 7h (KMR-28-39), which has femtomolar activity in the breast cancer cell line MDA-MB-231, has significant dose-dependent antitumor activity in MDA-MB-231 (breast) and MIA PaCa-2 (pancreatic) human tumor xenograft mouse models with insignificant toxicity at therapeutic doses. Preliminary studies suggest that 7h may sterically inhibit interaction of the transcription factor NF-kappa B with its cognate DNA binding sequence.

  DOI：

  10.1021/jm301882a
• 作为产物：
  描述：

  1-(4-bromo-1-methyl-1H-pyrrol-2-yl)-2,2,2-trichloroethan-1-one 在 四(三苯基膦)钯 、 水 、 sodium hydride 、 potassium carbonate 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醇 、 水 、 甲苯 、 mineral oil 为溶剂， 反应 6.7h， 生成 4-(4-((tert-butoxycarbonyl)amino)phenyl)-1-methyl-1H-pyrrole-2-carboxylic acid
  参考文献：
  名称：

  [EN] PYRROLOBENZODIAZEPINES
  [FR] PYRROLOBENZODIAZÉPINES

  摘要：

  发现具有（1-甲基-1H-吡咯-3-基）苯基氨基残基的吡咯苯并二氮杂环烃（PBDs）是具有改善的细胞毒性和DNA结合性能的高效化合物。

  公开号：

  WO2013164593A1

文献信息

• ANTIPROLIFERATIVE COMPOUNDS AND CONJUGATES MADE THEREFROM
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20180110873A1

  公开（公告）日：2018-04-26

  A compound capable of inhibiting cell proliferation, having a structure according to formula (I) wherein the variables in formula (I) are as defined in the specification. Such compounds are useful as anti-cancer agents, especially in antibody-drug conjugates.

  一种能够抑制细胞增殖的化合物，其结构符合以下公式（I） 其中公式（I）中的变量如规范中所定义。这些化合物可用作抗癌药物，特别是在抗体药物结合物中。
• [EN] BENZODIAZEPINE DERIVATIVES<br/>[FR] DÉRIVÉS DE BENZODIAZÉPINE
  申请人：IMMUNOGEN INC

  公开号：WO2019133652A1

  公开（公告）日：2019-07-04

  The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formulae (I), (II) and (III). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

  该发明涉及具有抗增殖活性的新型苯二氮卓衍生物，更具体地涉及具有公式（I）、（II）和（III）的新型苯二氮卓化合物。该发明还提供了与细胞结合剂连接的苯二氮卓化合物的结合物。此外，该发明还提供了使用该发明的化合物或结合物抑制异常细胞生长或治疗哺乳动物增殖性疾病的有效组合物和方法。
• Biaryl Amino Acids and Their Use in Dna Binding Oligomers
  申请人：Howard Wilson Philip

  公开号：US20070249591A1

  公开（公告）日：2007-10-25

  Compounds of formula (1): Z′-CO-A-B—NH-Z (I) wherein: Z is H or an amino protecting group; Z′ is OH, a protected or activated hydroxyl group or Cl; A is an optionally substituted C 5-6 arylene group; and B is an optionally substituted C 5-6 arylene group.

  公式（1）的化合物：Z'-CO-A-B—NH-Z（I），其中：Z为H或氨保护基；Z'为OH，受保护或活化羟基或Cl；A为可选取代的C5-6芳基烃基；B为可选取代的C5-6芳基烃基。
• BIARYL AMINO ACIDS AND THEIR USE IN DNA BINDING OLIGOMERS
  申请人：Howard Philip Wilson

  公开号：US20110160192A1

  公开（公告）日：2011-06-30

  Compounds of formula (I): Z′-CO-A-B—NH-Z (I) wherein: Z is H or an amino protecting group; Z′ is OH, a protected or activated hydroxyl group or Cl; A is an optionally substituted C 5-6 arylene group; and B is an optionally substituted C 5-6 arylene group.

  化合物的化学式(I)：Z'-CO-A-B—NH-Z (I)，其中：Z为氢或氨基保护基；Z'为OH，受保护或活化的羟基或Cl；A为可选取代的C5-6芳基烃基；B为可选取代的C5-6芳基烃基。
• PYRROLOBENZODIAZEPINES
  申请人：UCL BUSINESS PLC

  公开号：US20150126495A1

  公开（公告）日：2015-05-07

  A compound of formula (I) or a salt or solvate thereof, wherein the dotted double bond indicates the presence of a single or double bond between C2 and C3; R 2 is selected from —H, —OH, ═O, ═CH 2 , —CN, —R, OR, halo, dihalo, ═CHR, ═CHRR′, —O—SO 2 —R, CO 2 R and COR; R 7 is selected from H, R, OH, OR, SH, SR, NH 2 , NHR, NRR′, nitro, Me 3 Sn and halo; where R and R′ are independently selected from optionally substituted C 1-7 alkyl, C 3-20 heterocyclyl and C 5-20 aryl groups; R 10 and R 11 either together form a double bond, or are selected from H and QR Q respectively, where Q is selected from O, S and NH and R Q is H or C 1-7 alkyl or H and SO x M, where x is 2 or 3, and M is a monovalent pharmaceutically acceptable cation; A is selected from (A1), (A2), (A3), (A4) or (A5) where X 1 and Y 1 are selected from: CH and NH; CH and NMe; N and NMe; CH and S; N and S; N and O; and CH and O, respectively; X 2 and Y 2 are selected from: CH and NH; CH and NMe; N and NMe; CH and S; N and S; N and O; and CH and O, respectively; Z 1 is selected from O and S; Z 2 is selected from CH and N; F is selected from a single bond and -(E-F 1 ) m -; each E is independently selected from a single bond, and —C(═O)—NH—; each F 1 is independently a C 3-20 heteroarylene group; m is 1, 2 or 3; G is selected from hydrogen, C 1-4 alkyl, —C(═O)—O—C 1-4 alkyl, —(CH 2 ) n —C 3-20 heterocycloalkyl, and —O—(CH 2 ) n —C 3-20 heterocycloalkyl group; each n is 0-4; provided that A2 is not A2′, where X 1 and Y 1 of A2′ are selected from: CH and NMe; COH and NMe; CH and S; N and NMe; N and S, respectively; and provided that A3 is not A3′, where X 2 and Y 2 of A3′ are selected from: CH and NMe; COH and NMe; CH and S; N and NMe; N and S, respectively; B is either a single bond or (B1), where X and Y of B1 are selected from: CH and NMe; COH and NMe; CH and S; N and NMe; N and S, respectively; and R 1 is C 1-4 alkyl.

  化合物的化学式为（I）或其盐或溶剂化物，其中点虚线表示C2和C3之间存在单键或双键；R2选择自-H，-OH，═O，═CH2，-CN，-R，OR，卤素，二卤代基，═CHR，═CHRR′，-O-SO2-R，CO2R和COR；R7选择自H，R，OH，OR，SH，SR，NH2，NHR，NRR'，硝基，Me3Sn和卤素；其中R和R'分别选择自可选取的取代的C1-7烷基，C3-20杂环基和C5-20芳基；R10和R11要么共同形成双键，要么选择自H和QRQ，其中Q选择自O，S和NH，RQ是H或C1-7烷基或H和SOxM，其中x为2或3，M是单价的药用可接受阳离子；A选择自（A1），（A2），（A3），（A4）或（A5），其中X1和Y1选择自：CH和NH；CH和NMe；N和NMe；CH和S；N和S；N和O；和CH和O，依此类推；X2和Y2选择自：CH和NH；CH和NMe；N和NMe；CH和S；N和S；N和O；和CH和O，依此类推；Z1选择自O和S；Z2选择自CH和N；F选择自单键和-(E-F1)m-；每个E独立选择自单键和-C(═O)-NH-；每个F1独立为C3-20杂环芳烃基；m为1、2或3；G选择自氢、C1-4烷基、-C(═O)-O-C1-4烷基、-( )n-C3-20杂环烷基和-O-( )n-C3-20杂环烷基；每个n为0-4；提供A2不是A2'，其中A2'的X1和Y1选择自：CH和NMe；COH和NMe；CH和S；N和NMe；N和S，依此类推；并且提供A3不是A3'，其中A3'的X2和Y2选择自：CH和NMe；COH和NMe；CH和S；N和NMe；N和S，依此类推；B要么是单键，要么是（B1），其中B1的X和Y选择自：CH和NMe；COH和NMe；CH和S；N和NMe；N和S，依此类推；R1是C1-4烷基。