1-<4-<(8-chlorooctyl)oxy>phenyl>-2-phenyl-1-butanone | 154287-31-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 1-<4-<(8-chlorooctyl)oxy>phenyl>-2-phenyl-1-butanone
• 英文别名: 1-(4-(8-Chlorooctoxy)phenyl)-2-phenyl-1-butanone；1-[4-(8-chlorooctoxy)phenyl]-2-phenylbutan-1-one
• CAS: 154287-31-7
• 化学式: C₂₄H₃₁ClO₂
• 分子量: 386.962
• InChiKey: SUTIFOFNHFROGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  27
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-<4-<(8-chlorooctyl)oxy>phenyl>-2-phenyl-1-butanone 在 盐酸 、 正丁基锂 作用下， 以 乙醇 为溶剂， 反应 18.67h， 生成 (E)-1-{4-[(8-chlorooctyl)oxy]phenyl}-1-(4-iodophenyl)-2-phenyl-1-butene
  参考文献：
  名称：

  Homologs of Idoxifene:  Variation of Estrogen Receptor Binding and Calmodulin Antagonism with Chain Length

  摘要：

  A series of homologs of idoxifene [1a, (E)-1-[4-(N-pyrrolidinoethoxy)phenyl]-1-(4-iodophenyl)-2-phenyl-1-butene] and selected homologs of 4-iodotamoxifen [2a, (E)-1-[4-[N-dimethylamino)-ethoxy]phenyl]-1-(4-iodophenyl)-2-phenyl-1-butene] with the side chain (CH2)(n) varying in length from n = 3 (1b, 2b) to n = 10 (1i, 2i) have been synthesized and tested for antagonism of the calmodulin-dependent activity of cAMP phosphodiesterase and for binding affinity to rat uterine estrogen receptor. Compared with 1a (IC50 = 1.5 mu M), the homologs showed a progressive increase in calmodulin antagonism with a maximum inhibition at n = 7-9 (1f-h) (IC50 = 0.2 mu M), declining at n = 10 (1i) to IC50 = 1.6 mu M. In the pyrrolidino series, estrogen receptor binding affinity peaked at n = 3 (1b, RBA = 23; estradiol = 100), declining by n = 10 (1i) to RBA = 0.4, but the homolog n = 8 (1g, RBA = 3.5) was still comparable to tamoxifen (RBA = 3.9). A similar pattern of activity was seen for the dimethylamino counterparts. These compounds represent a new class of antiestrogens with potent calmodulin antagonism.

  DOI：

  10.1021/jm9505472
• 作为产物：
  描述：

  1,8-二氯辛烷 在 sodium hydroxide 、 四丁基硫酸氢铵 、 三氟乙酸酐 作用下， 反应 32.0h， 生成 1-<4-<(8-chlorooctyl)oxy>phenyl>-2-phenyl-1-butanone
  参考文献：
  名称：

  Homologs of Idoxifene:  Variation of Estrogen Receptor Binding and Calmodulin Antagonism with Chain Length

  摘要：

  A series of homologs of idoxifene [1a, (E)-1-[4-(N-pyrrolidinoethoxy)phenyl]-1-(4-iodophenyl)-2-phenyl-1-butene] and selected homologs of 4-iodotamoxifen [2a, (E)-1-[4-[N-dimethylamino)-ethoxy]phenyl]-1-(4-iodophenyl)-2-phenyl-1-butene] with the side chain (CH2)(n) varying in length from n = 3 (1b, 2b) to n = 10 (1i, 2i) have been synthesized and tested for antagonism of the calmodulin-dependent activity of cAMP phosphodiesterase and for binding affinity to rat uterine estrogen receptor. Compared with 1a (IC50 = 1.5 mu M), the homologs showed a progressive increase in calmodulin antagonism with a maximum inhibition at n = 7-9 (1f-h) (IC50 = 0.2 mu M), declining at n = 10 (1i) to IC50 = 1.6 mu M. In the pyrrolidino series, estrogen receptor binding affinity peaked at n = 3 (1b, RBA = 23; estradiol = 100), declining by n = 10 (1i) to RBA = 0.4, but the homolog n = 8 (1g, RBA = 3.5) was still comparable to tamoxifen (RBA = 3.9). A similar pattern of activity was seen for the dimethylamino counterparts. These compounds represent a new class of antiestrogens with potent calmodulin antagonism.

  DOI：

  10.1021/jm9505472

文献信息

• Substituted 1,1,2-triphenylbutenes and their use in the treatment of
  申请人：British Technology Group Limited

  公开号：US05589500A1

  公开（公告）日：1996-12-31

  Compounds of the general formula (2) ##STR1## wherein n is an integer of from 3 to 10, the iodo substituent is in the 3- or 4-position and R.sup.1 and R.sup.2, which may be the same or different, represent C.sub.1-3 alkyl, especially methyl or ethyl, groups or R.sup.l represents a hydrogen atom and R.sup.2 a C.sub.1-3 alkyl group or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached represent a saturated heterocyclic group, especially a pyrrolidino group, in the form of their free bases or pharmaceutically acceptable acid addition salts are potent anti-oestrogenic compounds useful for treatment of oestrogen-dependent cancers, especially breast cancers. Compounds where the iodine atom is radioisotopic are useful in radiotherapy or gamma ray imaging of these cancers.

  通式（2）中的化合物##STR1##其中n为3至10的整数，碘取代基位于3-或4-位置，R.sup.1和R.sup.2（可能相同也可能不同）代表C.sub.1-3烷基，尤其是甲基或乙基基团，或者R.sup.l代表氢原子，R.sup.2代表C.sub.1-3烷基基团，或者R.sup.1和R.sup.2与它们连接的氮原子一起代表饱和杂环基团，尤其是吡咯啉基团，以其自由碱或药学上可接受的酸盐形式为治疗雌激素依赖性癌症，尤其是乳腺癌的有效抗雌激素化合物。碘原子是放射性同位素的化合物可用于这些癌症的放射治疗或γ射线成像。
• SUBSTITUTED 1,1,2-TRIPHENYLBUTENES AND THEIR USE IN THE TREATMENT AND DIAGNOSIS OF CANCER
  申请人：BRITISH TECHNOLOGY GROUP LTD

  公开号：EP0638064B1

  公开（公告）日：1997-08-13
• US5589500A
  申请人：——

  公开号：US5589500A

  公开（公告）日：1996-12-31
• [EN] SUBSTITUTED 1,1,2-TRIPHENYLBUTENES AND THEIR USE IN THE TREATMENT AND DIAGNOSIS OF CANCER<br/>[FR] 1,1,2-triphénylbutènes substitués et leur utilisation dans le traitement et le diagnostic du cancer.
  申请人：BRITISH TECHNOLOGY GROUP LTD

  公开号：WO1993022275A1

  公开（公告）日：1993-11-11

  (EN) Compounds of general formula (2) wherein n is an integer of from 3 to 10, the iodo substituent is in the 3- or 4- position and R1 and R2, which may be the same or different, represent C1-3 alkyl, especially methyl or ethyl, groups or R1 represents a hydrogen atom and R2 a C1-3 alkyl group or R1 and R2 together with the nitrogen atom to which they are attached represent a saturated heterocyclic group, especially a pyrrolidino group, in the form of their free bases or pharmaceutically acceptable acid addition salts are potent anti-oestrogenic compounds useful for treatment of oestrogen-dependent cancers, especially breast cancers. Compounds where the iodine atom is radioisotopic are useful in radiotherapy or gamma ray imaging of these cancers.(FR) Cette invention décrit des composés de formule (2). Dans cette formule, n représente un entier compris entre 3 et 10, le substituant iodo se trouve en position 3 ou 4 et R1 et R2 qui peuvent être identiques ou différents représentent des groupes alkyle C1-3, plus particulièrement méthyle ou éthyle, ou bien R1 représente un atome d'hydrogène et R2 représente un groupe alkyle C1-3, ou encore R1 et R2 représentent avec l'atome d'azote sur lequel ils sont fixés un groupe hétérocyclique saturé plus spécifiquement un groupe pyrrolidino. Sous forme de leur bases libres ou de leurs sels d'addition acides pharmaceutiquement acceptables, ces composés sont de puissants composés anti-÷strogènes utiles pour traiter les cancers dépendant des ÷strogènes, notamment les cancers du sein. Des composés dans lesquels l'atome d'iode est radio-isotopique sont utiles en radiothérapie ou pour effectuer l'imagerie par rayons gamma de ces cancers.
• Homologs of Idoxifene:  Variation of Estrogen Receptor Binding and Calmodulin Antagonism with Chain Length
  作者：Ian R. Hardcastle、Martin G. Rowlands、Rachel M. Grimshaw、John Houghton、Michael Jarman、Andrew Sharff、Stephen Neidle

  DOI：10.1021/jm9505472

  日期：1996.1.1

  A series of homologs of idoxifene [1a, (E)-1-[4-(N-pyrrolidinoethoxy)phenyl]-1-(4-iodophenyl)-2-phenyl-1-butene] and selected homologs of 4-iodotamoxifen [2a, (E)-1-[4-[N-dimethylamino)-ethoxy]phenyl]-1-(4-iodophenyl)-2-phenyl-1-butene] with the side chain (CH2)(n) varying in length from n = 3 (1b, 2b) to n = 10 (1i, 2i) have been synthesized and tested for antagonism of the calmodulin-dependent activity of cAMP phosphodiesterase and for binding affinity to rat uterine estrogen receptor. Compared with 1a (IC50 = 1.5 mu M), the homologs showed a progressive increase in calmodulin antagonism with a maximum inhibition at n = 7-9 (1f-h) (IC50 = 0.2 mu M), declining at n = 10 (1i) to IC50 = 1.6 mu M. In the pyrrolidino series, estrogen receptor binding affinity peaked at n = 3 (1b, RBA = 23; estradiol = 100), declining by n = 10 (1i) to RBA = 0.4, but the homolog n = 8 (1g, RBA = 3.5) was still comparable to tamoxifen (RBA = 3.9). A similar pattern of activity was seen for the dimethylamino counterparts. These compounds represent a new class of antiestrogens with potent calmodulin antagonism.