2-methoxy-1(R,S)-methylethyl chloroformate | 75032-86-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机碳酸及其衍生物
• 英文名称: 2-methoxy-1(R,S)-methylethyl chloroformate
• 英文别名: 1-methyl-2-methoxyethyl chloroformate；2-methoxy-1-methylethyl chloroformate；2-methoxyisopropyl chloroformate；1-methoxypropan-2-yl carbonochloridate
• CAS: 75032-86-9
• 化学式: C₅H₉ClO₃
• 分子量: 152.578
• InChiKey: ZMNJVBZJWSGGMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  9
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  对乙酰氨基酚 、 2-methoxy-1(R,S)-methylethyl chloroformate 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以29%的产率得到4-(1'-methyl-2'-methoxyethyloxycarbonyloxy)acetanilide
  参考文献：
  名称：

  Topical Delivery of a Model Phenolic Drug: Alkyloxycarbonyl Prodrugs of Acetaminophen

  摘要：

  Purpose. To determine whether the delivery of a phenolic parent drug by its alkyloxycarbonyl (AOC) prodrugs through hairless mouse skin would show similar dependencies on water and lipid solubilities that similar prodrugs of more polar heterocyclic amide and imide parent drugs have shown.Methods. Flux through hairless mouse skin from suspensions in isopropyl myristate (J(MIPM)), solubilities in IPM (S-IPM) and water (S-AQ), and partition coefficients between isopropyl myristate (IPM) and pH 4.0 buffer (K-IPM:4.0) were measured for two series of AOC derivatives of acetaminophen ( APAP); their solubilities in pH 4.0 buffer (S-4.0) were estimated from S-IPM/K-IPM:4.0. Log J(MIPM) values were calculated from the n = 43 coefficients for the parameters in the transformed Potts-Guy (Roberts-Sloan) equation, and the average error of prediction (Delta log J'(IPM)) was calculated. The J(MIPM), S-IPM, S-4.0, and molecular weight ( MW) data for this series and two other series were combined with the n = 43 database to give a n = 61 database, and new best fit coefficients were determined for the Roberts-Sloan equation: log J(MIPM) = x + y log S-IPM + (1 - y) log S-4.0 - z MW.Results. All of the 4-AOC-APAP derivatives underperformed based on their predicted log J(MIPM) (Delta log J'(MIPM) = 0.275 +/- 0.147 log units) and, although the two more water soluble members of this more lipid soluble series were more effective than APAP, they were only marginally so: <2 times. Addition of three new series to the n = 43 database for the Roberts-Sloan equation did not substantially change the coefficients to the parameters: x, y, z, and r(2) = -0.322, 0.530, 0.00337 and 0.92, respectively.Conclusions. The topical delivery of a model phenolic drug by its AOC prodrugs through hairless mouse skin from IPM shows the same dependence on S-IPM, S-4.0, and MW as the delivery of polar heterocycles by their similar prodrugs.

  DOI：

  10.1023/b:pham.0000029281.12753.25
• 作为产物：
  描述：

  丙二醇甲醚 、 三光气 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 生成 2-methoxy-1(R,S)-methylethyl chloroformate
  参考文献：
  名称：

  Topical Delivery of a Model Phenolic Drug: Alkyloxycarbonyl Prodrugs of Acetaminophen

  摘要：

  Purpose. To determine whether the delivery of a phenolic parent drug by its alkyloxycarbonyl (AOC) prodrugs through hairless mouse skin would show similar dependencies on water and lipid solubilities that similar prodrugs of more polar heterocyclic amide and imide parent drugs have shown.Methods. Flux through hairless mouse skin from suspensions in isopropyl myristate (J(MIPM)), solubilities in IPM (S-IPM) and water (S-AQ), and partition coefficients between isopropyl myristate (IPM) and pH 4.0 buffer (K-IPM:4.0) were measured for two series of AOC derivatives of acetaminophen ( APAP); their solubilities in pH 4.0 buffer (S-4.0) were estimated from S-IPM/K-IPM:4.0. Log J(MIPM) values were calculated from the n = 43 coefficients for the parameters in the transformed Potts-Guy (Roberts-Sloan) equation, and the average error of prediction (Delta log J'(IPM)) was calculated. The J(MIPM), S-IPM, S-4.0, and molecular weight ( MW) data for this series and two other series were combined with the n = 43 database to give a n = 61 database, and new best fit coefficients were determined for the Roberts-Sloan equation: log J(MIPM) = x + y log S-IPM + (1 - y) log S-4.0 - z MW.Results. All of the 4-AOC-APAP derivatives underperformed based on their predicted log J(MIPM) (Delta log J'(MIPM) = 0.275 +/- 0.147 log units) and, although the two more water soluble members of this more lipid soluble series were more effective than APAP, they were only marginally so: <2 times. Addition of three new series to the n = 43 database for the Roberts-Sloan equation did not substantially change the coefficients to the parameters: x, y, z, and r(2) = -0.322, 0.530, 0.00337 and 0.92, respectively.Conclusions. The topical delivery of a model phenolic drug by its AOC prodrugs through hairless mouse skin from IPM shows the same dependence on S-IPM, S-4.0, and MW as the delivery of polar heterocycles by their similar prodrugs.

  DOI：

  10.1023/b:pham.0000029281.12753.25

文献信息

• [EN] COT MODULATORS AND METHODS OF USE THEREOF<br/>[FR] MODULATEURS DE COT ET LEURS PROCÉDÉS D'UTILISATION
  申请人：GILEAD SCIENCES INC

  公开号：WO2020252151A1

  公开（公告）日：2020-12-17

  The present disclosure relates generally to modulators of Cot (cancer Osaka thyroid) of generic Formula (I) and methods of use and manufacture thereof.

  本公开涉及一般性地与Cot（癌症大阪甲状腺）的通用化学式（I）的调节剂，以及其使用和制造方法。
• Amino-acid amide derivatives, agricultural or horticultural fungicides,
  申请人：Kumiai Chemical Industry Co., Ltd.

  公开号：US05574064A1

  公开（公告）日：1996-11-12

  The present invention provides an agricultural or horticultural fungicide including an effective amount of an amino-acid derivative represented by the formula: ##STR1## wherein R.sup.1 represents a lower alkyl group (optionally having at least one same or different substituent of a halogen atom, an alkoxy group, and a cyano group), R.sup.2 represents an ethyl group, or an n-propyl group, R.sup.3 represents a hydrogen atom or a lower alkyl group, R.sup.4 represents a hydrogen atom, R.sup.5, R.sup.6, and R.sup.7 independently represent a hydrogen atom or a lower alkyl group, R.sup.8 represents a hydrogen atom, or a lower alkyl group, Z.sup.1 and Z.sup.2 independently represent an oxygen atom or a sulfur atom, Z.sup.3 represents an oxygen atom, or a sulfur atom, Q represents a phenyl group, m represents an integer from 0 to 2, and n represents 0 or 1. The amino-acid amide derivatives according to the present invention exhibit superior control of cucumber downy mildew (Pseudoperonospora cubensis), tomato late blight (Phytophthora infestans), and grape downy mildew (Plasmopara viticola), and are effective for potato late blight (Phytophthora infestans). In addition, the agricultural or horticultural fungicides of the present invention are also characterized in that they are not harmful chemicals and exhibit excellent characteristics such as systemic action, residual activity, and persistence after rain-fall.

  本发明提供了一种农业或园艺杀菌剂，包括一种由以下式表示的氨基酸衍生物的有效量：##STR1##其中R.sup.1代表较低的烷基基团（可选地至少具有一个相同或不同的卤原子、烷氧基和氰基取代基），R.sup.2代表乙基基团或正丙基基团，R.sup.3代表氢原子或较低的烷基基团，R.sup.4代表氢原子，R.sup.5、R.sup.6和R.sup.7独立地代表氢原子或较低的烷基基团，R.sup.8代表氢原子或较低的烷基基团，Z.sup.1和Z.sup.2独立地代表氧原子或硫原子，Z.sup.3代表氧原子或硫原子，Q代表苯基，m代表从0到2的整数，n代表0或1。根据本发明的氨基酸酰胺衍生物表现出对黄瓜霜霉病（Pseudoperonospora cubensis）、番茄晚疫病（Phytophthora infestans）和葡萄霜霉病（Plasmopara viticola）的优越控制，并且对马铃薯晚疫病（Phytophthora infestans）有效。此外，本发明的农业或园艺杀菌剂还具有不含有害化学物质的特点，并表现出系统作用、残留活性和雨后持久性等优异特性。
• Amino-acid amide derivatives, method for producing the same, and
  申请人：Kumiai Chemical Industry Co., Ltd.

  公开号：US05811424A1

  公开（公告）日：1998-09-22

  The present invention provides an amino-acid amide derivative represented by the formula: ##STR1## (wherein R.sup.1 represents a lower alkyl group (optionally having at least one same or different substituent of a halogen atom), R.sup.2 represents an ethyl group, R.sup.3 represents a hydrogen atom, R.sup.4 represents a hydrogen atom, R.sup.5, R.sup.6, and R.sup.7 independently represent a hydrogen atom or a lower alkyl group, R.sup.8 represents a hydrogen atom, Z.sup.1 and Z.sup.2 independently represent an oxygen atom or a sulfur atom, Z.sup.3 represents an oxygen atom or a sulfur atom, Q represents a phenyl group, m represents an integer from 0 to 2, and n represents 0 or 1), and an agricultural or horticultural fungicide including an effective amount of the same. The amino-acid amide derivatives exhibit a superior control of plant diseases, particularly downy mildew and late blight, and are not harmful to plants.

  本发明提供了一种氨基酸酰胺衍生物，其表示为以下公式：##STR1##（其中R.sup.1代表较低的烷基（可选地具有至少一个相同或不同的卤素原子取代基），R.sup.2代表乙基基团，R.sup.3代表氢原子，R.sup.4代表氢原子，R.sup.5，R.sup.6和R.sup.7分别独立地代表氢原子或较低的烷基，R.sup.8代表氢原子，Z.sup.1和Z.sup.2独立地代表氧原子或硫原子，Z.sup.3代表氧原子或硫原子，Q代表苯基，m表示0到2的整数，n表示0或1），以及包括有效量的农业或园艺杀菌剂。氨基酸酰胺衍生物表现出优良的植物病害控制能力，特别是对霜霉病和晚疫病，且不对植物有害。
• Antiviral ethers of aspartate protease substrate isosteres
  申请人：Ciba-Geigy Corporation

  公开号：US05663200A1

  公开（公告）日：1997-09-02

  Antiretroviral compounds (which are effective, for example, against HIV) of the formula I ##STR1## in which R.sub.1 is an acyl radical lower-alkoxyl-lower-alkanoyl whose lower alkoxy radical is unsubstituted or is substituted by halogen, phenyl, lower alkoxy or a heterocyclic radical selected from piperidinyl, pyrrolidinyl, tetrahydropyranyl, tetrahydrofuranyl, thiazolidinyl, thiazolyl, indolyl or 4H-1-benzopyranyl which is unsubstituted or substituted by oxo, hydroxyl, amine, lower alkyl, lower-alkoxycarbonyl and/or phenyl-lower-alkoxycarbonyl; lower alkanoyl which is unsubstituted or is substituted by one of the said unsubstituted or substituted heterocyclic radicals; arylcarbonyl or heterocyclylcarbonyl which are substituted by heterocyclyl or heterocyclyl-lower-alkyl; phenyl-lower-alkanoyl which is substituted by hydroxyl and lower alkyl; or arylsulfonyl; or the residue of an amino acid which is defined in accordance with the description (and which may be acylated on the amino nitrogen by one of the abovementioned acyl radicals); R.sub.2 and R.sub.3 are in each case cyclohexyl, cyclohexenyl, phenyl, naphthyl or tetrahydronaphthyl which are unsubstituted or substituted by lower alkyl, phenyl, cyanophenyl, phenyl-lower-alkyl, halogen, halo-lower-alkyl, cyano, hydroxyl, lower alkoxy, phenyl-lower-alkoxyl, pyridyl-lower-alkoxy, lower-alkoxy-lower-alkoxy, lower-alkoxycarbonyl-lower-alkoxy, carboxyl-lower-alkoxy, hydroxyl-lower-alkoxy, carbamoyl-lower-alkoxy, cyano-lower-alkoxy, and phenyl-lower-alkanesulfonyl which is unsubstituted or substituted by halogen; R.sub.4 is lower alkyl, cyclohexyl or phenyl; and R.sub.5 is lower alkyl; and n is 1 or 2, or salts thereof, are novel.

  式I中的抗逆转录病毒化合物（例如针对HIV有效）## STR1 ##其中R.sub.1是酰基较低的烷氧基较低的酰基，其较低的烷氧基未取代或被卤素，苯基，较低的烷氧基或从哌啶基，吡咯烷基，四氢吡喃基，四氢呋喃基，噻唑烷基，噻唑基，吲哚基或未取代或取代为氧代，羟基，氨基，较低的烷基，较低的烷氧羰基和/或苯基-较低的烷氧羰基选择的杂环基团取代；未取代或取代为上述未取代或取代的杂环基团之一的未取代或取代的较低烷酰基；被杂环基或杂环基较低烷基取代的苯基羰基或杂环基羰基；被羟基和较低烷基取代的苯基较低烷酰基；或苯基磺酰基；或根据描述定义的氨基酸残基（并且可以通过上述酰基之一在氨基氮上酰化）；R.sub.2和R.sub.3分别是未取代或取代的环己基，环己烯基，苯基，萘基或四氢萘基，其未取代或被较低烷基，苯基，氰基苯基-较低烷基，卤素，卤代较低烷基，氰基，羟基，较低烷氧基，苯基-较低烷氧基，吡啶基-较低烷氧基，较低烷氧基-较低烷氧基，较低烷氧基羰基-较低烷氧基，羧基-较低烷氧基，羟基-较低烷氧基，氨基甲酰-较低烷氧基，氰基-较低烷氧基和未取代或取代为卤素的苯基-较低烷基磺酰基；R.sub.4是较低的烷基，环己基或苯基；而R.sub.5是较低的烷基；n为1或2，或其盐，是新颖的。
• Cot modulators and methods of use thereof
  申请人：Gilead Sciences, Inc.

  公开号：US10947259B2

  公开（公告）日：2021-03-16

  The present disclosure relates generally to modulators of Cot (cancer Osaka thyroid) and methods of use and manufacture thereof.

  本公开一般涉及Cot（癌症大阪甲状腺）的调节剂及其使用和制造方法。