4-cyano-2-ethylphenyl isocyanate | 959694-33-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-cyano-2-ethylphenyl isocyanate
• 英文别名: 3-Ethyl-4-isocyanatobenzonitrile
• CAS: 959694-33-8
• 化学式: C₁₀H₈N₂O
• 分子量: 172.186
• InChiKey: RGHMZROASUABES-UHFFFAOYSA-N

物化性质

• 沸点：
  298.4±33.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  53.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-cyano-2-ethylphenyl isocyanate 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 作用下， 以 甲苯 为溶剂， 反应 12.0h， 生成 4-[(7R,7aS)-7-hydroxy-1,3-dioxo-5,6,7,7a-tetrahydropyrrolo[1,2-c]imidazol-2-yl]-3-ethylbenzonitrile
  参考文献：
  名称：

  Tandem optimization of target activity and elimination of mutagenic potential in a potent series of N-aryl bicyclic hydantoin-based selective androgen receptor modulators

  摘要：

  Pharmacokinctic studies in cynomolgus monkeys with a novel prototype selective androgen receptor modulator revealed trace amounts of an aniline fragment released through hydrolytic metabolism. This aniline fragment was determined to be mutagenic in an Ames assay. subsequent concurrent optimization for target activity and avoidance of mutagenicity led to the identification of a pharmacologically superior clinical candidate without mutagenic potential. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.076
• 作为产物：
  描述：

  2-乙基苯胺 在 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 盐酸 、 sodium hydroxide 、 溴 、 碳酸氢钠 、 溶剂黄146 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-cyano-2-ethylphenyl isocyanate
  参考文献：
  名称：

  Tandem optimization of target activity and elimination of mutagenic potential in a potent series of N-aryl bicyclic hydantoin-based selective androgen receptor modulators

  摘要：

  Pharmacokinctic studies in cynomolgus monkeys with a novel prototype selective androgen receptor modulator revealed trace amounts of an aniline fragment released through hydrolytic metabolism. This aniline fragment was determined to be mutagenic in an Ames assay. subsequent concurrent optimization for target activity and avoidance of mutagenicity led to the identification of a pharmacologically superior clinical candidate without mutagenic potential. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.076

文献信息

• Imidazolidine Derivatives, Uses Therefor, Preparation Thereof and Compositions Comprising Such
  申请人：Nique Francois

  公开号：US20100063120A1

  公开（公告）日：2010-03-11

  Compounds of formula (I): wherein X is O or S, R 1 is acyl, aldehyde, cycloalkyl, an optionally substituted alkyl, alkenyl or alkynyl, R 2 is H. alkyl, hydroxyalkyl, haloalkyl, alkenyl, or alkynyl; substituted alkyl; alkylcarbonyl; R 3 and R 4 are H, halogen, alkyl, alkenyl, alkynyl, alkoxyl, alkylthio, hydroxyalkyl, haloalkyl, haloalkenyl, or haloalkynyl; or R 3 and R 4 form an, optionally aromatic or heterocyclic, optionally substituted ring, R 5 is H, halogen, trifluoromethyl, —CN, or —NO2; not all of R 3 , R 4 , and R 5 being H, R 6 and R 9 are H, halogen, OH; alkyl. hydroxyalkyl, alkoxyl, thioalkyl, haloalkyl, alkenyl, or alkynyl; R 7 and R 8 are H, halogen, OH, SH; alkoxyl or alkylthio optionally substituted by OH and/or halogen; one of R 7 and R 8 not being H or halogen; or one of R 7 and R 8 is a pharmaceutically acceptable ester or thioester grouping, or R 6 is C 1-3 -alkyl or, together with either R 1 or R 2 , represents C 1-3 alkylene or alkenylene linking group, optionally substituted by methyl, trifluoromethyl, OH, or halogen, and pharmaceutically acceptable salts and esters thereof, are useful as selective androgen modulators.

  式(I)的化合物：其中X为O或S，R1为酰基，醛基，环烷基，或可选择地取代的烷基，烯基或炔基，R2为H，烷基，羟基烷基，卤代烷基，烯基或炔基；取代烷基；烷基羰基；R3和R4为H，卤素，烷基，烯基，炔基，烷氧基，烷硫基，羟基烷基，卤代烷基，卤代烯基，或卤代炔基；或R3和R4形成一个，可选择的芳香或杂环，可选择地取代的环，R5为H，卤素，三氟甲基，-CN，或-NO2；R3，R4和R5中不全为H，R6和R9为H，卤素，羟基；烷基，羟基烷基，烷氧基，硫代烷基，卤代烷基，烯基，或炔基；R7和R8为H，卤素，羟基，硫氢基；烷氧基或烷硫基，可选择地由羟基和/或卤素取代；R7和R8中的一个不为H或卤素；或R7和R8中的一个为药用可接受的酯或硫酯基团，或R6为C1-3-烷基或，与R1或R2中的任一者一起，代表C1-3烷基或烯基链连接基，可选择地由甲基，三氟甲基，羟基，或卤素取代，以及其药用可接受的盐和酯，可用作选择性雄激素调节剂。
• IMIDAZOLIDINE DERIVATIVES, USES THEREFOR, PREPARATION THEREOF AND COMPOSITIONS COMPRISING SUCH
  申请人：NIQUE Francois

  公开号：US20100210699A1

  公开（公告）日：2010-08-19

  Compounds of formula (I): wherein X is O or S, R 1 is acyl, aldehyde, cycloalkyl, an optionally substituted alkyl, alkenyl or alkynyl, R 2 is H, alkyl, hydroxyalkyl, haloalkyl, alkenyl, or alkynyl; substituted alkyl; alkylcarbonyl; R 3 and R 4 are H, halogen, alkyl, alkenyl, alkynyl, alkoxyl, alkylthio, hydroxyalkyl, haloalkyl, haloalkenyl, or haloalkynyl; or R 3 and R 4 form an, optionally aromatic or heterocyclic, optionally substituted ring, R 5 is H, halogen, trifluoromethyl, —CN, or —NO 2 ; not all of R 3 , R 4 , and R 5 being H, R 6 and R 9 are H, halogen, OH; alkyl, hydroxyalkyl, alkoxyl, thioalkyl, haloalkyl, alkenyl, or alkynyl; R 7 and R 8 are H, halogen, OH, SH; alkoxyl or alkylthio optionally substituted by OH and/or halogen; one of R 7 and R 8 not being H or halogen; or one of R 7 and R 8 is a pharmaceutically acceptable ester or thioester grouping, or R 6 is C 1-3 -alkyl or, together with either R 1 or R 2 , represents C 1-3 alkylene or alkenylene linking group, optionally substituted by methyl, trifluoromethyl, OH, or halogen, and pharmaceutically acceptable salts and esters thereof, are useful as selective androgen modulators.

  化合物式（I）：其中X为O或S，R1为酰基，醛基，环烷基，可选取代的烷基，烯基或炔基，R2为H，烷基，羟基烷基，卤代烷基，烯基或炔基；取代烷基；烷基羰基；R3和R4为H，卤素，烷基，烯基，炔基，烷氧基，烷硫基，羟基烷基，卤代烷基，卤代烯基或卤代炔基；或R3和R4形成一个可选的芳香或杂环，可选取代的环，R5为H，卤素，三氟甲基，—CN或—NO2；R3，R4和R5不全为H，R6和R9为H，卤素，OH；烷基，羟基烷基，烷氧基，硫代烷基，卤代烷基，烯基或炔基；R7和R8为H，卤素，OH，SH；烷氧基或烷硫基，可选取代为OH和/或卤素；R7和R8中的一个不为H或卤素；或R7和R8中的一个是药物可接受的酯或硫酯基团，或R6为C1-3烷基或与R1或R2中的一个共同表示C1-3烷基或烯基链连接基团，可选取代为甲基，三氟甲基，OH或卤素，以及其药物可接受的盐和酯，用作选择性雄激素调节剂。
• US8168667B2
  申请人：——

  公开号：US8168667B2

  公开（公告）日：2012-05-01
• [EN] INIDAZOLIDINE DERIVATIVES, USES THEREFOR, PREPARATION THEREOF AND COMPOSITIONS COMPRISING SUCH<br/>[FR] DÉRIVÉS DE L'INIDAZOLIDINE, UTILISATIONS, PRÉPARATION DE CES DERNIERS ET COMPOSITIONS LES RENFERMANT
  申请人：PROSKELIA SAS

  公开号：WO2007137874A2

  公开（公告）日：2007-12-06

  (EN) Compounds of formula (I): wherein X is O or S, R1 is acyl, aldehyde, cycloalkyl, an optionally substituted alkyl, alkenyl or alkynyl, R2 is H. alkyl, hydroxyalkyl, haloalkyl, alkenyl, or alkynyl; substituted alkyl; alkylcarbonyl; R3 and R4 are H, halogen, alkyl, alkenyl, alkynyl, alkoxyl, alkylthio, hydroxyalkyl, haloalkyl, haloalkenyl, or haloalkynyl; or R3 and R4 form an, optionally aromatic or heterocyclic, optionally substituted ring, R5 is H, halogen, trifluoromethyl, -CN, or -NO2; not all of R3, R4, and R5 being H, R6 and R9 are H, halogen, OH; alkyl. hydroxyalkyl, alkoxyl, thioalkyl, haloalkyl, alkenyl, or alkynyl; R7 and R8 are H, halogen, OH, SH; alkoxyl or alkylthio optionally substituted by OH and/or halogen; one of R7 and R8 not being H or halogen; or one of R7 and R8 is a pharmaceutically acceptable ester or thioester grouping, or R6 is C1-3-alkyl or, together with either R1 or R2, represents C1-3 alkylene or alkenylene linking group, optionally substituted by methyl, trifluoromethyl, OH, or halogen, and pharmaceutically acceptable salts and esters thereof, are useful as selective androgen modulators.(FR) L'invention porte sur des composés de la formule (I), dans laquelle X est O ou S; R1 est un acyle, aldéhyde, cycloalkyle, un alkyle, alcényle ou alkynyle facultativement substitué; R2 est H, alkyle, hydroxyalkyle, haloalkyle, alcényle, ou alkynyle; alkyle substitué; alkylcarbonyle; R3 et R4 sont H, halogène, alkyle, alcényle, alkynyle, alcoxyle, alkylthio, hydroxyalkyle, haloalkyle, haloalcényle ou haloalkynyle; ou R3 et R4 forment un noyau facultativement aromatique ou hétérocyclique, facultativement substitué; R5 est H, halogène, trifluorométhyle, -CN, ou -NO2; R3, R4, et R5 n'étant pas tous H; R6 et R9 sont H, halogène, OH; alkyle, hydroxyalkyle, alcoxyle, thioalkyle, haloalkyle, alcényle ou alkynyle; R7 et R8 sont H, halogène, OH, SH; alcoxyle ou alkylthio facultativement substitués par OH et/ou par un halogène; R7 ou R8 n'étant pas H ou un halogène; ou R7 ou R8 est un regroupement ester ou thioester pharmaceutiquement acceptable, ou R6 est C1-3-alkyle ou, avec R1 ou R2, représente un groupe de liaison C1-3 alkylène ou alcénylène, facultativement substitué par un méthyle, trifluorométhyle, OH, ou un halogène, et des sels et esters pharmaceutiquement acceptables de ces derniers, lesquels composés sont utilisés comme modulateurs sélectifs du récepteur des androgènes.
• Tandem optimization of target activity and elimination of mutagenic potential in a potent series of N-aryl bicyclic hydantoin-based selective androgen receptor modulators
  作者：Lawrence G. Hamann、Mark C. Manfredi、Chongqing Sun、Stanley R. Krystek、Yanting Huang、Yingzhi Bi、David J. Augeri、Tammy Wang、Yan Zou、David. A. Betebenner、Aberra Fura、Ramakrishna Seethala、Rajasree Golla、Joyce E. Kuhns、John A. Lupisella、Celia J. Darienzo、Laura L. Custer、Jennifer L. Price、James M. Johnson、Scott A. Biller、Robert Zahler、Jacek Ostrowski

  DOI：10.1016/j.bmcl.2007.01.076

  日期：2007.4

  Pharmacokinctic studies in cynomolgus monkeys with a novel prototype selective androgen receptor modulator revealed trace amounts of an aniline fragment released through hydrolytic metabolism. This aniline fragment was determined to be mutagenic in an Ames assay. subsequent concurrent optimization for target activity and avoidance of mutagenicity led to the identification of a pharmacologically superior clinical candidate without mutagenic potential. (c) 2007 Elsevier Ltd. All rights reserved.