5-乙酰基-4-甲基-1,3-噻唑-2(3H)-酮 | 32497-14-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 5-乙酰基-4-甲基-1,3-噻唑-2(3H)-酮
• 英文名称: 5-acetyl-4-methylthiazol-2(3H)-one
• 英文别名: 5-acetyl-4-methyl-3H-1,3-thiazol-2-one
• CAS: 32497-14-6
• 化学式: C₆H₇NO₂S
• 分子量: 157.193
• InChiKey: UHFCISPGLMHKSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  71.5
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 储存条件：
  | 室温 |

反应信息

• 作为反应物：
  描述：

  5-乙酰基-4-甲基-1,3-噻唑-2(3H)-酮 在 potassium carbonate 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 4.0h， 生成 5-(2-(4-chloro-2-methoxyphenylamino)pyrimidin-4-yl)-3,4-dimethylthiazol-2(3H)-one
  参考文献：
  名称：

  发现作为有效Mnk2抑制剂的5-（2-（苯氨基）嘧啶-4-基）噻唑-2（3H）-one衍生物：合成，SAR分析和生物学评估

  摘要：

  人类促分裂原激活蛋白激酶（MAPK）相互作用激酶（Mnks）对eIF4E的磷酸化对于人类肿瘤的发生和发展至关重要。靶向Mnks可能提供一种新颖的抗癌治疗策略。然而，迄今为止缺乏选择性的Mnk抑制剂已经阻碍了药理学靶标的验证和临床药物的开发。在此，我们首次报告了一系列5-（2-（苯基氨基）嘧啶-4-基）噻唑-2（3 H一种衍生物作为Mnk抑制剂。几种衍生物表现出非常强的Mnk2抑制活性。针对一组癌细胞系测试了最具活性和选择性的化合物，结果证实了这些Mnk抑制剂的细胞类型特异性作用。详细的细胞机制研究表明，Mnk抑制剂能够降低抗凋亡蛋白Mcl-1的表达水平，并能促进MV4-11急性髓性白血病细胞的凋亡。

  DOI：

  10.1002/cmdc.201300552
• 作为产物：
  描述：

  4-氨基-3-戊烯-2-酮 在 硫酸 、 双氧水 作用下， 以 水 为溶剂， 反应 3.0h， 生成 5-乙酰基-4-甲基-1,3-噻唑-2(3H)-酮
  参考文献：
  名称：

  过氧化氢介导的氨基吡唑，氨基尿嘧啶和烯胺的快速室温无金属C（sp 2）-H硫氰化

  摘要：

  已经开发了一种在水性介质中使用过氧化氢作为良性氧化剂和硫氰酸铵对氨基吡唑，氨基异恶唑，氨基异噻唑，氨基尿嘧啶和脂肪族烯胺进行C（sp 2）-H硫氰化的快速无金属室温室温方法作为硫氰化剂。另一方面，在氨基唑的情况下，过氧化氢和硫氰酸铵的反应，然后一锅加NaOH，提供了相应的二硫化物；在氨基尿嘧啶的情况下，观察到了嘧啶稠合的2-氨基噻唑。该方法的显着特征是使用了环保型氧化剂，反应可调性以获取不同的产品，广泛的底物范围以及良好的产率。

  DOI：

  10.1021/acs.joc.0c01738

文献信息

• Thiazole derivatives and pharmaceutical composition comprising the same
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US04649146A1

  公开（公告）日：1987-03-10

  The invention relates to novel pharmaceutical compounds for treatment for ulcer of the formula: ##STR1## wherein R.sup.1 is lower alkyl, carboxy, hydroxymethyl, halomethyl, lower alkylthiomethyl or hydroxyiminomethyl, R.sup.2 is hydrogen, hydroxy, lower alkyl, pyridyl, amino, lower alkylamino, pyridylamino or guanidino optionally substituted with dimethylaminomethylene, R.sup.3 is dihydroisoquinolyl which may be substituted with halogen, lower alkyl, lower alkoxy, carboxy, hydroxy, pyridyl, amino, lower alkylamino, pyridylamino or guanidino, Q is --CO--, and n is an integer of 0 or 1, and pharmaceutically acceptable salts thereof.

  该发明涉及一种用于治疗溃疡的新型药物化合物，其化学式为：##STR1## 其中R.sup.1为较低的烷基、羧基、羟甲基、卤代甲基、较低的烷基硫甲基或羟基亚甲基，R.sup.2为氢、羟基、较低的烷基、吡啶基、氨基、较低的烷基氨基、吡啶基氨基或胍基，可选择地取代二甲氨基亚甲基，R.sup.3为二氢异喹啉基，可取代卤素、较低的烷基、较低的烷氧基、羧基、羟基、吡啶基、氨基、较低的烷基氨基、吡啶基氨基或胍基，Q为--CO--，n为0或1，以及其药学上可接受的盐。
• Synthesis of Five- and Six-Membered<i>N</i>-Phenylacetamido Substituted Heterocycles as Formyl Peptide Receptor Agonists
  作者：Claudia Vergelli、Igor A. Schepetkin、Giovanna Ciciani、Agostino Cilibrizzi、Letizia Crocetti、Maria Paola Giovannoni、Gabriella Guerrini、Antonella Iacovone、Liliya N. Kirpotina、Richard D. Ye、Mark T. Quinn

  DOI：10.1002/ddr.21370

  日期：2017.2

  Preclinical Research

  临床前研究
• AROMATIC 5-MEMBERED HETEROCYCLIC DERIVATIVE HAVING TRPV4-INHIBITING ACTIVITY
  申请人：Shionogi & Co., Ltd.

  公开号：US20150038483A1

  公开（公告）日：2015-02-05

  The present invention is related to a compound represented by formula (I) wherein R 1 is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclyl, or the like; X is —N(R 3 )—, —O—, or —S—; Y is ═C(R 4 )—, or ═N—; Z is —N(R 7 )—, —O—, or —S—; R 2 is substituted or unsubstituted alkyloxy, or the like, or a group represented by the following formula: —(CR 2a R 2b ) n —R 2c , wherein R 2a is each independently a hydrogen atom, halogen, or the like; R 2b is each independently a hydrogen atom, halogen, or the like; R 2a and R 2b which are attached to the same carbon atom may be taken together to form oxo, a substituted or unsubstituted non-aromatic carbocycle, or the like; two of R 2a which are attached to the adjacent carbon atoms and/or two of R 2b which are attached to the adjacent carbon atoms may be taken together to form a bond; R 2c is substituted or unsubstituted aromatic carbocyclyl, or the like; n is an integer from 1 to 3; R 3 and R 7 are each independently a hydrogen atom, substituted or unsubstituted alkyl, or the like; R 4 and R 5 are each independently a hydrogen atom, halogen, substituted or unsubstituted alkyl, or the like; R 6 is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or the like, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising thereof.

  本发明涉及一种由式（I）表示的化合物，其中R1是氢原子，取代或未取代的烷基，取代或未取代的芳香环烷基等；X是—N(R3)—，—O—或—S—；Y是═C(R4)—或═N—；Z是—N(R7)—，—O—或—S—；R2是取代或未取代的烷氧基等，或以下式表示的基团：—(CR2aR2b)n—R2c，其中R2a分别是氢原子，卤素等；R2b分别是氢原子，卤素等；附在同一碳原子上的R2a和R2b可以共同形成氧化物，取代或未取代的非芳香环烷基等；附在相邻碳原子上的两个R2a和/或附在相邻碳原子上的两个R2b可以共同形成键；R2c是取代或未取代的芳香环烷基等；n是1到3的整数；R3和R7分别是氢原子，取代或未取代的烷基等；R4和R5分别是氢原子，卤素，取代或未取代的烷基等；R6是氢原子，卤素，取代或未取代的烷基等，或其药学上可接受的盐，或包含其的药物组合物。
• [EN] PYRIMIDIN-4-YL-3, 4-THIONE COMPOUNDS AND THEIR USE IN THERAPY<br/>[FR] COMPOSES DE PYRIMIDIN-4-YL-3, 4-THIONE ET LEUR UTILISATION A DES FINS THERAPEUTIQUES
  申请人：CYCLACEL LTD

  公开号：WO2005042525A1

  公开（公告）日：2005-05-12

  The present invention relates to compounds of formula: (I), or pharmaceutically acceptable salts thereof, wherein R1 and R5 are each independently H, C(ORj’) or a hydrocarbyl group optionally substituted by one or more R6 groups; R2, R3, and R4 are each independently H, alkyl or alkenyl, each of which may be optionally substituted with one or more R7 groups; R6 and R7 are each independently halogen, NO2, CN, (CH2)mORa, O(CH2)nORb, (CH2)pNRcRd, CF3, COORe, CONRfRg, CORh, SO3H, SO2Ri, SO2NRjRk, (CH2)qNRa’CORg’, Rf’, (CH2)rNRb’SO2Rh’, SO2NRd’Ri’, SO2NRe'(CH2)s,ORc', heterocycloalkyl or heteroaryl, wherein said heterocycloalkyl and heteroaryl may be optionally substituted by one or more substituents selected from aralkyl, sulfonyl, Rm and CORn; Rg', Rh', Ri' and Rj' are each independently selected from alkyl, aryl, aralkyl and heteroaryl, each of which may be optionally substituted with one or more substituents selected from halogen, OH, NO2, NH2 CF3 and COOH; m, p, q and r are each independently 0, 1, 2 or 3; n and s are each independently 1, 2, or 3; and Ra-n and Ra'-f' are each independently H or alkyl. Further aspects of the invention relate to pharmaceutical compositions comprising such compounds, and their use in the preparation of a medicament for treating one or more of the following: a proliferative disorder, a viral disorder, a CNS disorder, a stroke, alopecia and diabetes.

  本发明涉及以下结构的化合物：(I)，或其药学上可接受的盐，其中R1和R5分别独立地为H、C(ORj’)或一个或多个R6基团取代的烃基团；R2、R3和R4分别独立地为H、烷基或烯基，每个基团可能选择性地用一个或多个R7基团取代；R6和R7分别独立地为卤素、NO2、CN、(CH2)mORa、O(CH2)nORb、(CH2)pNRcRd、CF3、COORe、CONRfRg、CORh、SO3H、SO2Ri、SO2NRjRk、(CH2)qNRa’CORg’、Rf’、(CH2)rNRb’SO2Rh’、SO2NRd’Ri’、SO2NRe'(CH2)s、ORc'、杂环烷基或杂芳基，其中所述的杂环烷基和杂芳基可以选择性地用一个或多个从芳基烷基、磺酰基、Rm和CORn中选择的取代基团取代；Rg'、Rh'、Ri'和Rj'分别独立地选择自烷基、芳基、芳基烷基和杂芳基，每个基团可能选择性地用一个或多个从卤素、OH、NO2、NH2、CF3和COOH中选择的取代基团取代；m、p、q和r分别独立地为0、1、2或3；n和s分别独立地为1、2或3；以及Ra-n和Ra'-f'分别独立地为H或烷基。本发明的进一步方面涉及包含这种化合物的药物组合物，以及它们在制备治疗以下一种或多种疾病的药物中的用途：增生性疾病、病毒性疾病、中枢神经系统疾病、中风、脱发和糖尿病。
• Thiazole derivatives, processes for the preparation thereof and
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US04735957A1

  公开（公告）日：1988-04-05

  New thiazole derivatives of the formula: ##STR1## wherein R.sup.1 is lower alkyl, carboxy, a drivative of carboxy, hydroxymethyl, halomethyl, lower alkylthiomethyl, hydroxyiminomethyl or alkenyl which may be substituted with lower alkoxycarbonyl, pyridyl or cyano, R.sup.2 is hydrogen, hydroxy, lower alkyl, pyridyl, amino, lower alkylamino, pyridylamino, arylamino, acylamino, N-(lower)alkylN-acylamino, guanidino optionally substituted with dimethylaminomethylene, or ar(lower)alkylamino optionally substituted with lower alkoxy, R.sup.3 is lower alkyl, halo(lower)alkyl or N-containing unsaturated heterocyclic group which may be substituted with halogen, lower alkyl, lower alkoxy, carboxy, a derivative of carboxy, hydroxy, pyridyl, amino, lower alkylamino, pyridylamino, arylamino, acylamino, N-(lower)alkyl-N-acylamino, guanidino, N-oxide or ar(lower)alkylamino optionally substituted with lower alkoxy, Q is --CO--, and n is an integer of 0 or 1, provided that when both of R.sup.1 and R.sup.3 are lower alkyl then n is an integer of 1 and R.sup.2 is lower alkyl, pyridyl, amino, lower alkylamino, pyridylamino, arylamino, acylamino, N-(lower)alkyl-N-acylamino, guanidino optionally substituted with dimethylaminomethylene, or ar(lower)alkylamino optionally substituted with lower alkoxy, and when R.sup.1 is lower alkyl and R.sup.3 is halo(lower)alkyl then n is an integer of 1, and pharmaceutically acceptable salts thereof, and processes for preparation thereof and pharmaceutical composition comprising the same. These derivatives and pharmaceutically acceptable salts thereof are useful as cardiotonic agents and anti-ulcer agents.

  新的噻唑衍生物的化学式为：##STR1## 其中R.sup.1是较低的烷基，羧基，羧基衍生物，羟甲基，卤代甲基，较低的烷基硫甲基，羟基亚胺甲基或烯基，该烯基可以用较低的烷氧羰基，吡啶基或氰基取代，R.sup.2为氢，羟基，较低的烷基，吡啶基，氨基，较低的烷基氨基，吡啶基氨基，芳基氨基，酰基氨基，N-(较低)烷基N-酰基氨基，瓜二氨基可选地用二甲氨基甲基取代，或者是可选地用较低的烷氧基取代的ar(较低)烷基氨基，R.sup.3是较低的烷基，卤代(较低)烷基或含氮的不饱和杂环基，该基可以用卤代，较低的烷基，较低的烷氧基，羧基，羧基衍生物，羟基，吡啶基，氨基，较低的烷基氨基，吡啶基氨基，芳基氨基，酰基氨基，N-(较低)烷基-N-酰基氨基，瓜二氨基，N-氧化物或可选地用较低的烷氧基取代的ar(较低)烷基氨基取代，Q为--CO--，n为0或1的整数，但当R.sup.1和R.sup.3都是较低的烷基时，n为1的整数，而R.sup.2为较低的烷基，吡啶基，氨基，较低的烷基氨基，吡啶基氨基，芳基氨基，酰基氨基，N-(较低)烷基-N-酰基氨基，瓜二氨基可选地用二甲氨基甲基取代，或者是可选地用较低的烷氧基取代的ar(较低)烷基氨基，而当R.sup.1为较低的烷基且R.sup.3为卤代(较低)烷基时，n为1的整数，以及其药学上可接受的盐，以及其制备方法和包含其的制药组合物。这些衍生物及其药学上可接受的盐可用作心力衰竭药物和抗溃疡药物。