4-异丙基-1,3-噻唑-5-甲醛 | 261710-80-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-异丙基-1,3-噻唑-5-甲醛
• 英文名称: 4-isopropyl-thiazole-5-carbaldehyde
• 英文别名: 4-(1-methylethyl)thiazole-5-carboxaldehyde；4-propan-2-yl-1,3-thiazole-5-carbaldehyde
• CAS: 261710-80-9
• 化学式: C₇H₉NOS
• 分子量: 155.221
• InChiKey: CUMFTMHDINTVBT-UHFFFAOYSA-N

物化性质

• 沸点：
  255.3±28.0 °C(Predicted)
• 密度：
  1.159±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  58.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-异丙基-1,3-噻唑-5-甲醛 在 5percent Pd/BaSO₄ sodium hydroxide 、 氢气 、 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 20.0 ℃ 、220.64 kPa 条件下， 反应 47.33h， 生成 4-Hydroxy-6-isopropyl-6-[2-(4-isopropyl-thiazol-5-yl)-ethyl]-5,6-dihydro-pyran-2-one
  参考文献：
  名称：

  4-Hydroxy-5,6-dihydropyrones as Inhibitors of HIV Protease:  The Effect of Heterocyclic Substituents at C-6 on Antiviral Potency and Pharmacokinetic Parameters

  摘要：

  Due largely to the emergence of multi-drug-resistant HIV strains, the development of new HIV protease inhibitors remains a high priority for the pharmaceutical industry. Toward this end, we previously identified a 4-hydroxy-5,6-dihydropyrone lead compound (CI-1029, 1) which possesses excellent activity against the protease enzyme, good antiviral efficacy in cellular assays, and promising bioavailability in several animal species. The search for a suitable backup candidate centered on the replacement of the aniline moiety at C-6 with an appropriately substituted heterocyle. In general, this series of heterocyclic inhibitors displayed good activity (in both enzymatic and cellular tests) and-low cellular toxicity; furthermore, several analogues exhibited improved pharmacokinetic parameters in animal models. The compound with the best combination of high potency, low toxicity, and favorable bioavailabilty was (S)-3-(2-tertbutyl-4-hydroxymethy1- 5-methyl-phenylsulfanyl)-4-hydroxy-6-isopropyl-6-(2-thiophen-3-yl-ethyl)-5,6-dihydro-pyran-2-one (13-(S)). This thiophene derivative also exhibited excellent antiviral efficacy against mutant HIV protease and resistant HIV strains. For these reasons, compound 13-(S) was chosen for further preclinical evaluation.

  DOI：

  10.1021/jm0003844
• 作为产物：
  描述：

  (4-异丙基-1,3-噻唑-5-基)甲醇 在 manganese dioxide 作用下， 以 乙腈 为溶剂， 反应 4.0h， 以to give 4-(1-methylethyl)thiazole-5-carboxaldehyde (360 mg, 110% of the theoretical amount)的产率得到4-异丙基-1,3-噻唑-5-甲醛
  参考文献：
  名称：

  Dehydroamino acids

  摘要：

  化合物的公式为1和1-1，其中R1是氢，羟基，氨基或卤素，R2是氢，羟基或卤素，R3是氢（公式1）或R1是氢，R2和R3与它们连接的乙烯基共同形成苯，吡咯，吡咯烷，氧代吡咯烷，吡唑，三唑或咪唑（公式1-1），A是2R4R5是氢，甲基，乙基或卤素，但R4R5不能都是氢; 1）B是氢或低烷基; 或2）B是3，其中R6R7R8和R9独立地是氢，羟基，氨基磺酰基，卤素，低烷氧基，氰基，氨基，低烷基，低烷基氨基或硝基; 或3）B是4，其中R10是氢，羟基，卤素或低烷基，C是具有0到3个异原子的五元或六元环，所述异原子从氮，氧和硫中选择，所述环可以是未取代的或单取代的或二取代的，所述取代基为低烷基，环烷基，氨基或取代氨基; 4）B是5，其中X和Y独立地是亚甲基或氮; 或5）B是6，其中至少有一个T，U，V或W是氮，任何为碳的T，U，V或W可以用低烷基，低烷基氨基，低烷氧基，羟基，氨基磺酰基，卤素，氰基，氨基或硝基取代; 或6）B是7，其中Y是碳或氮; 或7）B是具有1到3个异原子的五元芳香环，所述异原子从氮，氧和硫中选择，所述环可以是未取代的或单取代的或二取代的，所述取代基为低烷基，环烷基，三氟低烷基，氨基，卤素，取代氨基，或者所述环可以与包含0到3个异原子的五元或六元芳香环融合; 以及其药学上可接受的盐，相关的前药，制药组合物和治疗方法，这些化合物对于治疗银屑病是有用的。

  公开号：

  US20020161237A1

文献信息

• Dehydroamino acids
  申请人：——

  公开号：US20020161237A1

  公开（公告）日：2002-10-31

  Compounds of formula 1 and 1-1, 1 wherein R 1 is hydrogen, hydroxy, amino or halogen, R 2 is hydrogen, hydroxy, or halogen and R 3 is hydrogen (Formula 1) or R 1 is hydrogen and R 2 and R 3 taken together with the ethenylene group connecting them form phenyl, pyrrole, pyrroline, oxopyrroline, pyrazole, triazole, or imidazole (Formula 1-1), A is 2 R 4 R 5 are hydrogen, methyl, ethyl or halogen except that R 4 r 5 cannot both be hydrogen; and 1) B is hydrogen, or lower alkyl; or 2) B is 3 where R 6 R 7 R 8 and R 9 are independently hydrogen, hydroxy, aminosulfonyl, halogen, lower alkoxy, cyano, amino, lower alkyl, lower alkyl amino, or nitro; or 3) B is 4 where R 10 is hydrogen, hydroxy, halogen, or lower alkyl and C is a five- or six- membered ring with 0 to 3 heteroatoms which heteroatoms are selected from nitrogen, oxygen, and sulfur, which ring may be unsubstituted or mono- or di- substituted with lower alkyl, cycloalkyl, amino, or substituted amino; 4) B is 5 where X and Y are independently methylene or nitrogen; or 5) B is 6 where at leat one of T, U, V, or W is nitrogen, and any of T, U, V or W which is carbon may be substituted with lower alkyl, lower alkyl amino, lower alkoxy, hydroxy, aminosulfonyl, halogen, cyano, amino, or nitro; or 6) B is 7 where Y is carbon or nitrogen; or 7) B is a five-membered aromatic ring with 1 to 3 heteratoms selected from nitrogen, oxygen, and sulfur which ring may be unsubstituted or mono- or di-substituted with lower alkyl, cycloalky, trifluoroloweralkyl, amino, halogen, substituted amino, or which ring may be fused with a 5 or 6 membered aromatic ring containing 0 to 3 heteroatoms which heteroatoms are selected from nitrogen, oxygen, and sulfur; and pharmaceutically acceptable salts thereof, and related prodrugs, pharmaceutical compositions and methods of treatment, which compounds are useful for treating psoriasis.

  式1和1-1的化合物， 其中R1是氢，羟基，氨基或卤素，R2是氢，羟基或卤素，R3是氢（式1）或R1是氢，R2和R3连同连接它们的乙烯基团形成苯基，吡咯，吡咯烯，氧代吡咯烯，吡唑，三唑或咪唑（式1-1），A是 R4R5是氢，甲基，乙基或卤素，但R4R5不能同时为氢；和 1）B是氢或低碳烷基；或 2）B是 R6R7R8和R9独立地是氢，羟基，氨基磺酰基，卤素，低烷氧基，氰基，氨基，低烷基，低烷基氨基或硝基； 或3）B是 R10是氢，羟基，卤素或低碳烷基，C是具有0到3个异原子的五元或六元环，这些异原子选自氮，氧和硫，该环可以未取代或单取代或双取代为低烷基，环烷基，氨基或取代氨基； 4）B是 X和Y独立地是亚甲基或氮；或 5）B是 至少T，U，V或W中的一个是氮，任何是碳的T，U，V或W可以被低烷基，低烷基氨基，低烷氧基，羟基，氨基磺酰基，卤素，氰基，氨基或硝基取代；或 6）B是 Y是碳或氮； 或 7）B是具有1到3个异原子的氮，氧和硫中选择的五元芳香环，该环可以未取代或单取代或双取代为低烷基，环烷基，三氟低烷基，氨基，卤素，取代氨基，或该环可以与含有0到3个异原子的五元或六元芳香环融合，这些异原子选自氮，氧和硫；及其药学上可接受的盐，相关的前药，药物组合物和治疗方法，这些化合物对治疗牛皮癣有用。
• HIV protease inhibitors
  申请人：Warner-Lambert Company

  公开号：US06528510B1

  公开（公告）日：2003-03-04

  The present invention relates to novel dihydropyrones with tethered heterocycles having improved pharmacologic properties which potently inhibit the HIV aspartyl protease blocking HIV infectivity. The dihydropyrones are useful in the development of therapies for the treatment of viral infections and diseases, including AIDS. The present invention is also directed to methods of synthesis of the dihydropyrones and intermediates useful in the preparation of the final compounds.

  本发明涉及具有改进药理特性的新型带有连环杂环的二氢吡喃，能有效抑制HIV天冬氨酸蛋白酶，阻断HIV的感染性。这些二氢吡喃在开发治疗病毒感染和疾病，包括艾滋病的疗法方面是有用的。本发明还涉及合成这些二氢吡喃的方法，以及在制备最终化合物中有用的中间体。
• HIV PROTEASE INHIBITORS
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP1112269A2

  公开（公告）日：2001-07-04
• DEHYDROAMINO ACIDS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1261579A1

  公开（公告）日：2002-12-04
• US4053618A
  申请人：——

  公开号：US4053618A

  公开（公告）日：1977-10-11