4-甲基-6-硫氧代-3,6-二氢-2H-1,3-噻嗪-2-酮 | 97309-82-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 碳二硫内酯
• 中文名称: 4-甲基-6-硫氧代-3,6-二氢-2H-1,3-噻嗪-2-酮
• 英文名称: 4-methyl-6-thioxo-3,6-dihydro-2H-1,3-thiazin-2-one
• 英文别名: 4-methyl-6-sulfanylidene-3H-1,3-thiazin-2-one
• CAS: 97309-82-5
• 化学式: C₅H₅NOS₂
• 分子量: 159.233
• InChiKey: YUGIHNAYVCMXIZ-UHFFFAOYSA-N

物化性质

• 熔点：
  199-200 °C(Solv: benzene (71-43-2); ethanol (64-17-5))
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  86.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-甲基-6-硫氧代-3,6-二氢-2H-1,3-噻嗪-2-酮 、 N-Boc-哌嗪 以 异丙醇 为溶剂， 反应 10.0h， 以288 mg的产率得到tert-butyl 4-[(2Z)-3-amino-2-butenethioyl]-1-piperazinecarboxylate
  参考文献：
  名称：

  Design and synthesis of DPP-IV inhibitors lacking the electrophilic nitrile group

  摘要：

  A series of (4 beta-substituted)-L-prolylpyrrolidine analogs lacking the electrophilic nitrile function were synthesized and their dipeptidyl peptidase IV (DPP-IV) inhibitory activity and duration of ex vivo activity were evaluated. Structural optimization of a N-(3-phenyl-1,2,4-thiadiazol-5-yl) piperazine analog 8, which was found by high-speed analog synthesis, was carried out to improve the potency and duration of action. A representative compound 26 was evaluated to assess its effect on the plasma glucose level after the oGTT (oral glucose tolerance test) in normal rats. Structure-activity relationships (SAR) are also presented. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.11.031
• 作为产物：
  描述：

  2-Amino-4-methyl-6H-1,3-thiazinthion-(6) 以 乙醇 为溶剂， 反应 8.0h， 以60%的产率得到4-甲基-6-硫氧代-3,6-二氢-2H-1,3-噻嗪-2-酮
  参考文献：
  名称：

  Schroth, Werner; Hildebrandt, Albrecht; Becker, Ulrich, Zeitschrift fur Chemie, 1985, vol. 25, # 1, p. 20 - 21

  摘要：

  DOI：

文献信息

• [EN] PHENOXYTRIAZOLES<br/>[FR] PHÉNOXYTRIAZOLES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2018087018A1

  公开（公告）日：2018-05-17

  The present invention relates to a compound of formula I, HetAr is a five or six membered heteroaryl group, selected from wherein R1 is hydrogen, halogen, lower alkyl, lower alkoxy or lower alkyl substituted by halogen, and may be the same or different, if two R1 occur; R2 is lower alkyl or a mono- or polydeutered derivative thereof, lower alkyl substituted by halogen or lower alkoxy, lower alkenyl unsubstituted or substituted by halogen, cycloalkyl or CH2-cycloalkyl unsubstituted or substituted by halogen, heterocycloalkyl or CH2-heterocycloalkyl unsubstituted or substituted by lower alkyl; R3 is halogen, lower alkyl, lower alkyl substituted by halogen, lower alkoxy substituted by halogen or S(0)2-lower alkyl; n is 1, 2 or 3; if n is >1, then R3 may be the same or different; or to a pharmaceutically active acid addition salt thereof, to a racemic mixture or to its corresponding enantiomer and/or an optical isomer and/or stereoisomer thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.

  本发明涉及一种具有式I的化合物，其中HetAr是选择自的五元或六元杂环芳基，其中R1是氢、卤素、较低烷基、较低烷氧基或被卤素取代的较低烷基，且可以相同或不同，如果存在两个R1；R2是较低烷基或其单重或多重氘代衍生物，被卤素取代的较低烷基或较低烷氧基，未取代或被卤素取代的较低烯基，未取代或被卤素取代的环烷基或CH2-环烷基，未取代或被卤素取代的杂环烷基或 -杂环烷基，被较低烷基取代的卤素、较低烷基、被卤素取代的较低烷基、被卤素取代的较低烷氧基或S(0)2-较低烷基；n为1、2或3；如果n>1，则R3可以相同或不同；或其药学活性酸盐，或其外消旋混合物，或其对映体和/或光学异构体和/或立体异构体。这些化合物可用于治疗阿尔茨海默病、脑淀粉样血管病、遗传性脑出血伴淀粉样变性、荷兰型（HCHWA-D）、多梗死性痴呆、拳击性痴呆或唐氏综合征。
• [EN] BRIDGED PIPERIDINE DERIVATIVES<br/>[FR] DÉRIVÉS DE PIPÉRIDINE PONTÉS
  申请人：HOFFMANN LA ROCHE

  公开号：WO2017042114A1

  公开（公告）日：2017-03-16

  The present invention relates to compounds of formula (I); hetaryl is a five membered heteroaryl group, containing 1 to 3 heteroatoms, selected from O, S or N; R1 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, S-lower alkyl substituted by halogen or lower alkoxy substituted by halogen, or two neighboring carbon atoms may form on phenyl an additional ring containing -O-CH2-O-; n is 1 to 5; R2 is hydrogen or lower alkyl substituted by halogen; R3 is hydrogen or lower alkyl substituted by halogen; or to pharmaceutically active acid addition salts thereof, to racemic mixtures or to its corresponding enantiomers or optical isomers or stereoisomers thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.

  本发明涉及式(I)的化合物；hetaryl是一个含有1至3个杂原子（O、S或N）的五元杂芳基团；R1是氢、卤素、低碳链烷基、低碳链烷氧基、被卤素取代的低碳链烷基、被卤素取代的S-低碳链烷基或被卤素取代的低碳链烷氧基，或者邻近的两个碳原子可在苯基上形成一个含有-O-CH2-O-的额外环；n为1至5；R2是氢或被卤素取代的低碳链烷基；R3是氢或被卤素取代的低碳链烷基；或其药用酸加合物、消旋混合物、对映体或光学异构体或立体异构体。这些化合物可用于治疗阿尔茨海默病、脑淀粉样血管病、遗传性脑出血伴淀粉样病变的荷兰型（HCHWA-D）、多梗塞性痴呆、拳击性痴呆或唐氏综合征。
• Stepwise Design of γ-Secretase Modulators with an Advanced Profile by Judicious Coordinated Structural Replacements and an Unconventional Phenyl Ring Bioisostere
  作者：Rosa María Rodríguez Sarmiento、Caterina Bissantz、Johan Bylund、Anja Limberg、Werner Neidhart、Roland Jakob-Roetne、Lisha Wang、Karlheinz Baumann

  DOI：10.1021/acs.jmedchem.0c00909

  日期：2020.8.13

  modulator (GSM) lead compound, we utilized sequential structural replacements to improve the potency (IC50), pharmacokinetic properties including the free fraction (fraction unbound (fu)) in plasma, and in vivo efficacy. Importantly, we used novel CF3-alkoxy groups as bioisosteric replacements of a fluorinated phenyl ring and properties such as lipophilicity, solubility, metabolic stability, and free

  从我们以前的γ-分泌酶调节剂（GSM）铅化合物RO6800020（1）开始，我们利用顺序结构置换来提高效能（IC 50），药代动力学特性，包括血浆中的游离级分（未结合分数（fu））和体内功效。重要的是，我们使用了新型CF 3-烷氧基可作为氟化苯环的生物等位替代物，并具有诸如亲脂性，溶解性，代谢稳定性和游离级分之类的特性，可以保持CNS渗透所需的低Pgp外排。另外，通过降低芳香性，我们防止了光毒性。三唑并吡啶核中的其他取代干扰了与磷脂酰肌醇4-激酶催化β（PIK4CB）的结合。我们还介绍了较少的不具有共价结合（CVB）责任的亲脂性头部杂环。在这些改变之后，对三氟乙氧基生物等位取代的进一步修饰使得性质如亲脂性以及效力重新平衡。我们的优化策略以体内活性RO7101556（18B）具有优异的性能，并被选为高级候选人。
• SCHROTH, W.;HILDEBRANDT, A.;SPITZNER, R.;BECKER, U.;FREITAY, S.;AKRAM, M., Z. CHEM., 1985, 25, N 1, 20-21
  作者：SCHROTH, W.、HILDEBRANDT, A.、SPITZNER, R.、BECKER, U.、FREITAY, S.、AKRAM, M.

  DOI：——

  日期：——