S-<4-(9-fluorenylmethoxy)-4-oxobutyl>-L-cysteine | 123963-68-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: S-<4-(9-fluorenylmethoxy)-4-oxobutyl>-L-cysteine
• 英文别名: S-[4-(9-Fluorenylmethoxy)-4-oxobutyl]-L-cysteine；(2R)-2-amino-3-[4-(9H-fluoren-9-ylmethoxy)-4-oxobutyl]sulfanylpropanoic acid
• CAS: 123963-68-8
• 化学式: C₂₁H₂₃NO₄S
• 分子量: 385.484
• InChiKey: ACFFHLZXPYQUHJ-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  二碳酸二叔丁酯 、 S-<4-(9-fluorenylmethoxy)-4-oxobutyl>-L-cysteine 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 5.0h， 生成 N-(tert-butyloxycarbonyl)-S-<4-(9-fluorenylmethoxy)-4-oxobutyl>-L-cysteine
  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
• 作为产物：
  描述：

  9-芴甲醇 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 20.0h， 生成 S-<4-(9-fluorenylmethoxy)-4-oxobutyl>-L-cysteine
  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

• ANE derivatives with novel bridging
  申请人：Bio-Mega Inc.

  公开号：US04891358A1

  公开（公告）日：1990-01-02

  Disclosed herein are derivatives of atrial natriuretic peptides wherein the exocyclic N-terminal peptide segment is deleted and the two cysteinyl residues (at positions 105 and 121) of the natural sequence are replaced with a trivalent unit, --NHCH(CO--)--Q--X--Y--CH.sub.2 CH.sub.2 CO-- wherein Q is methylene, ethylene or CR'R" wherein R' and R" each independently is lower alkyl, X is oxy or thio, and Y is methylene or des-Y. The derivatives may be optionally substituted at various positions including positions 106, 107 and 124. The derivatives possess ANF-like activity and are indicated for treating hypertension and for treating pathological conditions resulting from an imbalance of body fluids and electrolytes.

  本文披露了心房利钠肽的衍生物，其中外环N-末端肽段被删除，天然序列的两个半胱氨酸残基（在105和121位置）被替换为三价单元，--NHCH（CO--）--Q--X--Y--CH.sub.2 CH.sub.2 CO--，其中Q是亚甲基，乙烯或CR'R"，其中R'和R"各自独立地是低碳基，X是氧或硫，Y是亚甲基或去Y。这些衍生物可以在各种位置包括106、107和124位置进行选择性取代。这些衍生物具有类似ANF的活性，并适用于治疗高血压和治疗由体液和电解质失衡引起的病理状况。
• ANF derivatives with novel bridging
  申请人：BIO-MEGA/BOEHRINGER INGELHEIM RESEARCH INC.

  公开号：EP0320967A2

  公开（公告）日：1989-06-21

  Disclosed herein are derivatives of atrial natriuretic peptides of formula 1, wherein the exocyclic N-terminal peptide segment is deleted and the two cysteinyl residues (at positions 105 and 121) of the natural sequence are replaced with a trivalent unit, -NHCH(CO-)-Q-X-Y-CH₂CH₂CO- wherein Q is methylene, ethylene or CR'R" wherein R' and R" each independently is lower alkyl, X is oxy or thio, an Y is methylene or des-Y. The derivatives may be optionally substituted at various positions including positions 106, 107, and 124. The derivatives possess ANF-like activity and are indicated for treating hypertension and for treating pathological conditions resulting from an imbalance of body fluids and electrolytes. Formula 1: wherein Q is is methylene, ethylene or CR'R" wherein R' and R" each independently lower alkyl; R¹ and R⁴ each independently is Phe, 2FPhe, 3FPhe, 4FPhe, 2CF₃Phe, 3CF₃Phe or 4CF₃Phe; R² is Gly, Ala or D-Ala; R³ is Ile or Met; R⁵ is Tyr or des-R⁵; X is oxy or thio; Y is methylene or des-Y; and W is hydroxy, lower alkoxy, amino or lower alkylamino;

  本文公开了式 1 的心房利钠肽衍生物，其中删除了外环 N 端肽段，并用三价单元取代了天然序列的两个半胱氨酰残基（位于 105 和 121 位）、-NHCH(CO-)-Q-X-Y-CH₂CH₂CO-，其中 Q 为亚甲基、亚乙基或 CR'R"，其中 R' 和 R "各自独立地为低级烷基，X 为氧基或硫代，Y 为亚甲基或去乙基。这些衍生物可在不同位置（包括 106、107 和 124 位置）任选被取代。这些衍生物具有类似 ANF 的活性，适用于治疗高血压以及治疗体液和电解质失衡引起的病理状况。 式 1：其中 Q 是亚甲基、亚乙基或 CR'R"，其中 R' 和 R "各自独立地为低级烷基； R¹ 和 R⁴ 各自独立地为 Phe、2FPhe、3FPhe、4FPhe、2CF₃Phe、3CF₃Phe 或 4CF₃Phe； R² 是 Gly、Ala 或 D-Ala； R³ 是 Ile 或 Met； R⁵ 是 Tyr 或 des-R⁵； X 是氧或硫 Y 是亚甲基或 des-Y；以及 W 是羟基、低级烷氧基、氨基或低级烷基氨基；
• 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.