9-(碘甲基)-9H-氧杂蒽 | 201851-33-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: 9-(碘甲基)-9H-氧杂蒽
• 英文名称: 9-iodomethyl-9H-xanthene
• 英文别名: 9-(iodomethyl)-9H-xanthene
• CAS: 201851-33-4
• 化学式: C₁₄H₁₁IO
• 分子量: 322.145
• InChiKey: MEVPAWYPDVSDLL-UHFFFAOYSA-N

物化性质

• 沸点：
  364.1±21.0 °C(Predicted)
• 密度：
  1.635±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  9-(碘甲基)-9H-氧杂蒽 在 sodium hydroxide 、 四(三苯基膦)钯 、 铜 、 锌 作用下， 以 乙醇 为溶剂， 生成 (1R,2R)-2-[2-(9H-xanthen-9-yl)acetyl]cyclopropane-1-carboxylic acid
  参考文献：
  名称：

  2-Substituted (2SR)-2-Amino-2-((1SR,2SR)-2-carboxycycloprop-1-yl)glycines as Potent and Selective Antagonists of Group II Metabotropic Glutamate Receptors. 1. Effects of Alkyl, Arylalkyl, and Diarylalkyl Substitution

  摘要：

  In this paper, we describe the synthesis of a series of a-substituted analogues of the potent and selective group II metabotropic glutamate receptor (mGluR) agonist (1S,1'S,2'S)-carboxy-cyclopropylglycine (2, L-CCG 1). Incorporation of a substituent on the amino acid carbon converted the agonist 2 into antagonist. Ail of the compounds were prepared and tested as a series of four isomers, i.e., two racemic diastereomers. We explored alkyl substitution, both normal and terminally branched; phenylalkyl and diphenylalkyl substitution; and a variety of aromatic and carbocyclic surrogates for phenyl. Affinity for group II mGluRs was measured using [H-3]glutamic acid (Glu) binding in rat forebrain membranes. Antagonist activity was confirmed for these compounds by measuring their ability to antagonize (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-induced inhibition of forskolin-stimulated cyclic-AMP in RGT cells transfected with human mGluR2 and mGluR3. We found that while alkyl substitution provided no increase in affinity relative to 2, phenylethyl and diphenylethyl substitution, as in 105 and 109, respectively, were quite beneficial, The affinity of 109 was further enhanced when the two aromatic rings were joined by an oxygen or sulfur atom to form the tricyclic xanthylmethyl and thioxanthylmethyl amino acids 113 and 114, respectively. Amino acid 113, with an IC50 of 0.10 mu M in the [H-3]Glu binding assay, was 52-fold more patent than 2, whose IC50 was 0.47 mu M.

  DOI：

  10.1021/jm970497w
• 作为产物：
  描述：

  9H-氧杂蒽-9-甲醇 在 咪唑 、 三苯基膦二碘化物 作用下， 以 二氯甲烷 为溶剂， 生成 9-(碘甲基)-9H-氧杂蒽
  参考文献：
  名称：

  2-Substituted (2SR)-2-Amino-2-((1SR,2SR)-2-carboxycycloprop-1-yl)glycines as Potent and Selective Antagonists of Group II Metabotropic Glutamate Receptors. 1. Effects of Alkyl, Arylalkyl, and Diarylalkyl Substitution

  摘要：

  In this paper, we describe the synthesis of a series of a-substituted analogues of the potent and selective group II metabotropic glutamate receptor (mGluR) agonist (1S,1'S,2'S)-carboxy-cyclopropylglycine (2, L-CCG 1). Incorporation of a substituent on the amino acid carbon converted the agonist 2 into antagonist. Ail of the compounds were prepared and tested as a series of four isomers, i.e., two racemic diastereomers. We explored alkyl substitution, both normal and terminally branched; phenylalkyl and diphenylalkyl substitution; and a variety of aromatic and carbocyclic surrogates for phenyl. Affinity for group II mGluRs was measured using [H-3]glutamic acid (Glu) binding in rat forebrain membranes. Antagonist activity was confirmed for these compounds by measuring their ability to antagonize (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid-induced inhibition of forskolin-stimulated cyclic-AMP in RGT cells transfected with human mGluR2 and mGluR3. We found that while alkyl substitution provided no increase in affinity relative to 2, phenylethyl and diphenylethyl substitution, as in 105 and 109, respectively, were quite beneficial, The affinity of 109 was further enhanced when the two aromatic rings were joined by an oxygen or sulfur atom to form the tricyclic xanthylmethyl and thioxanthylmethyl amino acids 113 and 114, respectively. Amino acid 113, with an IC50 of 0.10 mu M in the [H-3]Glu binding assay, was 52-fold more patent than 2, whose IC50 was 0.47 mu M.

  DOI：

  10.1021/jm970497w

文献信息

• 2-Substituted (2<i>SR</i>)-2-Amino-2-((1<i>SR</i>,2<i>SR</i>)-2-carboxycycloprop-1-yl)glycines as Potent and Selective Antagonists of Group II Metabotropic Glutamate Receptors. 2. Effects of Aromatic Substitution, Pharmacological Characterization, and Bioavailability
  作者：Paul L. Ornstein、Thomas J. Bleisch、M. Brian Arnold、Joseph H. Kennedy、Rebecca A. Wright、Bryan G. Johnson、Joseph P. Tizzano、David R. Helton、Mary Jeanne Kallman、Darryle D. Schoepp、Marc Hérin

  DOI：10.1021/jm970498o

  日期：1998.1.1

  5-fold increases in affinity. Substitution with p-fluorine, as in 97 (IC50 = 0.022 +/- 0.002), was the exception. Here, a greater increase in affinity was realized than for either the ortho- or meta-substituted analogues; 97 was the most potent compound resulting from monosubstitution of the aromatic. At best, only modest increases in affinity were realized for certain compounds bearing either two chlorines

  在本文中，我们描述了一系列有效的和选择性的II型代谢型谷氨酸受体（mGluR）激动剂（1S，1'S，2'S）-羧基环丙基甘氨酸（2，L-CCG 1）的一系列α-取代类似物的合成。在氨基酸碳上引入取代基将激动剂2转化为拮抗剂。所有化合物均已制备并测试为一系列四个异构体，即两个外消旋非对映异构体。基于对α-苯乙基类似物3亲和力的改善，在本文中，我们探讨了取代对芳环的影响，作为增加与这些化合物对II型mGluRs的亲和力的策略。II组mGluRs的亲和力是使用[3H]谷氨酸（Glu）在大鼠前脑膜中的结合来测量的。通过测量它们在人类mGluR2和mGluR3转染的RGT细胞中拮抗（1S，3R）-1-氨基环戊烷-1,3-二羧酸诱导的福司柯林刺激的环-AMP抑制作用的能力，证实了它们的拮抗活性。3的芳香环上的间位取代基由各种取代基提供，这些取代基分别是给电子（例如甲基，羟基，氨基，甲氧基，苯基，苯氧基
• Pharmaceutical acidic compounds
  申请人：ELI LILLY AND COMPANY LIMITED

  公开号：EP0837061A1

  公开（公告）日：1998-04-22

  Pharmaceutical compounds of the formula in which R1 is Y or Y-C1-6 alkyl, where Y is carboxy, tetrazolyl, -SO2H, -SO3H, -OSO3H, -CONHOH, or -P(OH)OR', -PO(OH)OR'. -OP(OH)OR' or -OPO(OH)OR' where R' is hydrogen, C1-6 alkyl, C2-6 alkenyl or optionally substituted phenyl-C1-6 alkyl, R2, R3 and R4 are each hydrogen, hydroxyl, halo, carboxy, C1-6 alkyl, carboxy-C1-6 alkyl, optionally substituted phenyl, optionally substituted phenyl-C1-6 alkyl or C2-6 alkenyl, X and Z are each hydrogen, C1-6 alkyl, C3-7 cycloalkyl, optionally substituted phenyl, optionally substituted phenyl-C1-6 alkyl, optionally substituted naphthylmethyl, optionally substituted anthracenylmethyl, where R'' and R''' are optionally substituted phenyl, or where n is 0 or 1 to 3, Q is -O-, -NH-, -S-, -SO-, -SO2-, -CH2-, -CH=CH-, -CH2S-, -CH2O-, -CH2CH2- or -CONR'''' where R'''' is hydrogen or C1-6 alkyl, and R5, R6, R7, R8 and R9 are each hydrogen, halo, C1-6 alkyl, C1-6 alkyloxy or hydroxy; provided that one of X and Z is hydrogen, or both of X and Z are hydrogen; or a salt or ester thereof.

  化合物的公式为其中R1是Y或Y-C1-6烷基，其中Y是羧基，四唑基，-SO2H，-SO3H，-OSO3H，-CONHOH，或-P（OH）OR'，-PO（OH）OR'，-OP（OH）OR'或-OPO（OH）OR'，其中R'是氢，C1-6烷基，C2-6烯基或可选取代苯基-C1-6烷基，R2，R3和R4分别是氢，羟基，卤素，羧基，C1-6烷基，羧基-C1-6烷基，可选取代苯基，可选取代苯基-C1-6烷基或C2-6烯基，X和Z分别是氢，C1-6烷基，C3-7环烷基，可选取代苯基，可选取代苯基-C1-6烷基，可选取代萘基甲基，可选取代蒽基甲基，其中R''和R'''是可选取代苯基，或n为0或1至3，Q是-O-，-NH-，-S-，-SO-，-SO2-，-CH2-，-CH=CH-，-CH2S-，-CH2O-，-CH2CH2-或-CO NR''''其中R''''是氢或C1-6烷基，R5，R6，R7，R8和R9分别是氢，卤素，C1-6烷基，C1-6烷氧基或羟基;前提是X和Z中的一个是氢，或X和Z都是氢;或其盐或酯。
• [EN] EXCITATORY AMINO ACID RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RECEPTEURS D'ACIDES AMINES EXCITATEURS
  申请人：ELI LILLY AND COMPANY

  公开号：WO1996007405A1

  公开（公告）日：1996-03-14

  (EN) The present invention provides compounds of formula (I) in which R is as defined in the specification, or a pharmaceutically acceptable metabolically labile ester or amide thereof, or a pharmaceutically acceptable salt thereof, which are useful as antagonists of one or more of the actions of L-glutamate at metabotropic excitatory amino acid receptors.(FR) Cette invention concerne des composés de formule (I), dans laquelle R est tel que défini dans le descriptif, ou un ester ou amide pharmaceutiquement acceptable de ces composés qui est métaboliquement labile, ou encore un sel pharmaceutiquement acceptable de ces composés, qu'on utilise comme antagonistes d'une ou de plusieurs actions du L-glutamate au niveau des récepteurs d'acides aminés excitateurs métabotropiques.

  本发明提供了公式（I）的化合物，其中R如规范中定义，或其药物可接受的代谢易裂解酯或酰胺，或其药物可接受的盐，这些化合物是L-谷氨酸在代谢型兴奋性氨基酸受体上的一个或多个作用的拮抗剂。
• Pharmaceutical substituted propanoic acid derivatives
  申请人：ELI LILLY AND COMPANY LIMITED

  公开号：EP0849263A2

  公开（公告）日：1998-06-24

  A pharmaceutical compound of the formula: in which A is carboxy, tetrazolyl, -SO2H, -SO3H, -OSO3H, -CONHOH, or -P(OH)OR', -PO(OH)OR', -OPO(OH)OR' where R' is hydrogen, C1-6 alkyl, C2-6 alkenyl or optionally substituted phenyl-C1-6 alkyl, B is a bond, C1-6 alkylene or C2-6 alkenylene, R1 is hydrogen, hydroxyl, halo or group of the formula A-B-, X is C1-6 alkylene, C2-6 alkenylene, C2-6 alkynylene or C1-6 alkylene linked through -O-, -S- or -NR"- to Y, where R" is hydrogen or C1-6 alkyl, and Y is (1) in which R2 and R3 are each halo, nitro, nitrile, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl or optionally substituted phenyl, m and n are each 0 to 3, Q is -O-, -S-, -SO-, -SO2-, -CH=CH-, -(CH2)p-,-CONR"'- or -NR"'CO-, where p is 0 to 3 and R"' is hydrogen or C1-6 alkyl, and Z is or (2) in which R2, R3, m, n and Z are as defined above; provided that when Z is X is C1-6 alkylene, C2-6 alkenylene or C2-6 alkynylene; and salts and esters thereof.

  式的药物化合物： 其中 A 是羧基、四唑基、-SO2H、-SO3H、-OSO3H、-CONHOH 或-P(OH)OR'、-PO(OH)OR'、-OPO(OH)OR'，其中 R' 是氢、C1-6 烷基、C2-6 烯基或任选取代的苯基-C1-6 烷基、 B 是键、C1-6 烯基或 C2-6 烯基、 R1 是氢、羟基、卤代或式 A-B- 的基团、 X 是通过 -O-、-S- 或 -NR"- 与 Y 连接的 C1-6 亚烷基、C2-6 亚烯基、C2-6 亚炔基或 C1-6 亚烷基，其中 R" 是氢或 C1-6 烷基、 而 Y 是 (1) 其中 R2 和 R3 分别为卤代、硝基、腈基、C1-6 烷基、C2-6 烯基、C2-6 炔基或任选取代的苯基，m 和 n 分别为 0 至 3，Q 为-O-、-S-、-SO-、-SO2-、-CH=CH-、-(CH2)p-、-CONR"'- 或-NR"'CO-，其中 p 为 0 至 3，R"'为氢或 C1-6 烷基，且 Z 为 或 (2) 其中 R2、R3、m、n 和 Z 如上定义； 但当 Z 为 X 为 C1-6 亚烷基、C2-6 亚烯基或 C2-6 亚炔基； 及其盐类和酯类。
• Synthesis, in vitro pharmacology, and pharmacokinetic profiles of 2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)-ethyl]-1-fluorocyclopropanecarboxylic acid and its 6-heptyl ester, a potent mGluR2 antagonist
  作者：Kazunari Sakagami、Akito Yasuhara、Shigeyuki Chaki、Ryoko Yoshikawa、Yasunori Kawakita、Akio Saito、Takeo Taguchi、Atsuro Nakazato

  DOI：10.1016/j.bmc.2008.02.066

  日期：2008.4

  In this paper, we describe the synthesis of (+)-(1R*,2R*)-2-[(1S*)-1-amino-1-carboxy- 2-(9H-xanthen-9-yl)-ethyl]-1-fluoro-cyclopropanecarboxylic acid (+)-16a, a compound, that is, fluorinated at the alpha position of the carboxylic acid in the cyclopropane ring of a group II mGluRs antagonist, 1 (LY341495), using a previously reported stereoselective cyclopropanation reaction. The fluorinated compound (+)-16a exhibited almost the same affinity (IC50 = 3.49 nM) for mGluR2 as 1 but had a superior pharmacokinetic pro. le. Furthermore, a marked elevation of the plasma levels of (+)-16a was observed following the administration of a prodrug, (+)-17. (C) 2008 Elsevier Ltd. All rights reserved.