N-(tert-butyloxycarbonyl)-S-<4-(9-fluorenylmethoxy)-4-oxobutyl>-L-penicillamine | 123963-65-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: N-(tert-butyloxycarbonyl)-S-<4-(9-fluorenylmethoxy)-4-oxobutyl>-L-penicillamine
• 英文别名: N-(tert-butyloxycarbonyl)-S-[4-(9-fluorenylmethoxy)-4-oxobutyl]-L-penicillamine；(2R)-3-[4-(9H-fluoren-9-ylmethoxy)-4-oxobutyl]sulfanyl-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid
• CAS: 123963-65-5
• 化学式: C₂₈H₃₅NO₆S
• 分子量: 513.655
• InChiKey: CWZCDVCTOHDRFW-XMMPIXPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  L-青霉胺 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 18.0h， 生成 N-(tert-butyloxycarbonyl)-S-<4-(9-fluorenylmethoxy)-4-oxobutyl>-L-penicillamine
  参考文献：
  名称：

  Synthesis and biological activity of atrial natriuretic factor analogs: effect of modifications to the disulfide bridge

  摘要：

  A series of atrial natriuretic factor (ANF) analogues with modifications to the disulfide bridge and lacking the exocyclic N-terminal sequence was synthesized. The native cystine residue was substituted by isofunctional deamino carba, beta,beta-dimethyl carba and dehydro dicarba spanners that bridge residues 106 and 120. The compounds were prepared by segment condensation coupling using the base-labile (9-fluorenylmethyl)carboxyl protecting group. Biological evaluation revealed that the exocyclic N-terminal segment of ANF is not necessary for expression of high biological activity. The compounds retained high affinity for ANF receptors in bovine adrenal zona glomerulosa cells and were found to be potent antihypertensive and diuretic agents, indicating that the native disulfide bridge can be mimicked by isosteric spanning residues. It was noted that the reported analogues, unlike the endogenous hormone, show marked reduced inhibitory activity on PGE1-stimulated aldosterone secretion from adrenal zona glomerulosa cells. This lack of inhibition may be a contributing element to the low saluresis in spite of the high level of diuresis observed with some analogues.

  DOI：

  10.1021/jm00164a031

文献信息

• ANF derivatives with novel bridging
  申请人：BIO-MEGA/BOEHRINGER INGELHEIM RESEARCH INC.

  公开号：EP0320967B1

  公开（公告）日：1993-12-08
• US4891358A
  申请人：——

  公开号：US4891358A

  公开（公告）日：1990-01-02
• Synthesis and biological activity of atrial natriuretic factor analogs: effect of modifications to the disulfide bridge
  作者：John DiMaio、Jorge Jaramillo、Dominik Wernic、Louis Grenier、Ewald Welchner、Julian Adams

  DOI：10.1021/jm00164a031

  日期：1990.2

  A series of atrial natriuretic factor (ANF) analogues with modifications to the disulfide bridge and lacking the exocyclic N-terminal sequence was synthesized. The native cystine residue was substituted by isofunctional deamino carba, beta,beta-dimethyl carba and dehydro dicarba spanners that bridge residues 106 and 120. The compounds were prepared by segment condensation coupling using the base-labile (9-fluorenylmethyl)carboxyl protecting group. Biological evaluation revealed that the exocyclic N-terminal segment of ANF is not necessary for expression of high biological activity. The compounds retained high affinity for ANF receptors in bovine adrenal zona glomerulosa cells and were found to be potent antihypertensive and diuretic agents, indicating that the native disulfide bridge can be mimicked by isosteric spanning residues. It was noted that the reported analogues, unlike the endogenous hormone, show marked reduced inhibitory activity on PGE1-stimulated aldosterone secretion from adrenal zona glomerulosa cells. This lack of inhibition may be a contributing element to the low saluresis in spite of the high level of diuresis observed with some analogues.