(+/-)-4-hydroxy-3,5-dimethyl-5-octyl-5H-thiophen-2-one | 348113-81-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氢噻吩类
• 英文名称: (+/-)-4-hydroxy-3,5-dimethyl-5-octyl-5H-thiophen-2-one
• 英文别名: 2(5H)-Thiophenone, 4-hydroxy-3,5-dimethyl-5-octyl-；4-hydroxy-3,5-dimethyl-5-octylthiophen-2-one
• CAS: 348113-81-5
• 化学式: C₁₄H₂₄O₂S
• 分子量: 256.409
• InChiKey: LOVFARKOSKKFGH-UHFFFAOYSA-N

物化性质

• 熔点：
  81-83 °C
• 沸点：
  364.6±42.0 °C(Predicted)
• 密度：
  1.042±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  62.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-4-hydroxy-3,5-dimethyl-5-octyl-5H-thiophen-2-one 、 硫酸二甲酯 以was obtained 37 (30 mg, 71%)的产率得到(+/-)-4-methoxy-3,5-dimethyl-5-octyl-5H-thiophen-2-one
  参考文献：
  名称：

  Compounds, pharmaceutical compositions containing same, and methods of use for same

  摘要：

  一种药物组合物，包括药物稀释剂和IV式化合物，其中R21 = H，C1-C20烷基，环烷基，烯基，芳基，芳基烷基或烷基芳基，-CH2OR25，-C（O）R25，-CO（O）R25，-C（O）NR25R26，-CH2C（O）R25或-CH2C（O）NHR25，其中R25和R26各自独立地为H，C1-C10烷基，环烷基，烯基，芳基，芳基烷基或烷基芳基，可选地含有一个或多个卤素原子。R22 = -OH，-OR27，-OCH2C（O）R27，-OCH2C（O）NHR27，-OC（O）R27，-OC（O）OR27，-OC（O）NHNH-R5或-OC（O）NR27R28，其中R27和R28各自独立地为H，C1-C20烷基，环烷基，烯基，芳基，芳基烷基或烷基芳基，并且R27和R28可以各自选项地含有卤素原子; R23和R24，相同或不同，为C1-C20烷基，环烷基，烯基，芳基，芳基烷基或烷基芳基。使用这种配方的方法包括治疗癌症，减轻体重，治疗微生物感染，抑制神经肽Y和/或脂肪酸合酶，以及刺激CPT-1。

  公开号：

  US07649012B2
• 作为产物：
  描述：

  n-octyl triflate 在 sodium hexamethyldisilazane 、 三乙胺 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 2.67h， 生成 (+/-)-4-hydroxy-3,5-dimethyl-5-octyl-5H-thiophen-2-one
  参考文献：
  名称：

  灵活合成（5R）-硫菌霉素的应用，以开发新型I型脂肪酸合酶抑制剂。

  摘要：

  脂肪酸合酶（FAS）催化乙酰基引物与丙二酰辅酶A加成的两个碳单元的顺序缩合，从而合成棕榈酸酯。哺乳动物FAS的β-酮酰基合酶结构域的抑制导致在体外和体内对多种癌细胞的选择性细胞毒性。同样，FAS抑制剂可导致小鼠食物摄入减少和体重下降。天然存在的硫菌素（TLM）被用作开发新型I型FAS抑制剂的模板。使用灵活的合成方法，获得了具有选择性FAS活性并显示出抗癌和减肥效果的TLM结构类似物家族。化合物13a和13d抑制纯FAS（ZR-75-1乳腺癌，IC（50）=50微克/毫升），并在BalbC小鼠中显示出有效的体重减轻（> 5％）。TLM衍生物的另一个子类（23b-d，31a）具有FAS活性（IC（50）=5％），并且对癌细胞具有细胞毒性（IC（50）<38 microg / mL）。最后，第三个子类（16b，29，30）对FAS也有效（IC（50）=

  DOI：

  10.1021/jm049389h

文献信息

• Novel compounds, pharmaceutical compositions containing same, and methods of use for same
  申请人：Kuhajda P. Francis

  公开号：US20060247302A1

  公开（公告）日：2006-11-02

  A pharmaceutical composition comprising a phamaceurtical diluent and a compound of formula IV wherein R 21 ═H, C 1 -C 20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, —CH 2 OR 25 , —C(O)R 25 , —CO(O)R 25 , —C(O)NR 25 R 26 , —CH 2 C(O)R 25 , or —CH 2 C(O)NHR 25 , where R 25 and R 26 are each independently H, C 1 -C 10 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing one or more halogen atoms. R 22 ═—OH, —OR 27 , —OCH 2 C(O)R 27 , —OCH 2 C(O)NHR 27 , —OC(O)R 27 , —OC(O)OR 27 , —OC(O)NHNH—R 5 , or —OC(O)NR 27 R 28 , where R 27 and R 28 are each independently H, C 1 -C 20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, and where R 27 and R 28 can each optionally contain halogen atoms; R 23 and R 24 , the same or different from each other, are C 1 -C 20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl. Methods of using such formulations for the treatment of cancer, to effect weight loss, to treat microbially-based infections, to inhibit neuropeptide-Y and/or fatty acid synthase, and to stimulate CPT-1.

  一种制药组合物，包括一种制药稀释剂和一种公式IV的化合物，其中R21═H、C1-C20烷基、环烷基、烯基、芳基、芳基烷基或烷基芳基、—CH2OR25、—C（O）R25、—CO（O）R25、—C（O）NR25R26、—CH2C（O）R25或—CH2C（O）NHR25，其中R25和R26各自独立地为H、C1-C10烷基、环烷基、烯基、芳基、芳基烷基或烷基芳基，可选含有一个或多个卤素原子；R22═—OH、—OR27、—OCH2C（O）R27、—OCH2C（O）NHR27、—OC（O）R27、—OC（O）OR27、—OC（O）NHNH—R5或—OC（O）NR27R28，其中R27和R28各自独立地为H、C1-C20烷基、环烷基、烯基、芳基、芳基烷基或烷基芳基，且R27和R28均可选含有卤素原子；R23和R24相同或不同，为C1-C20烷基、环烷基、烯基、芳基、芳基烷基或烷基芳基。使用这种配方的方法包括用于治疗癌症、减轻体重、治疗微生物感染、抑制神经肽Y和/或脂肪酸合成酶以及刺激CPT-1。
• NOVEL COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME, AND METHODS OF USE FOR SAME
  申请人：Kuhajda Francis P.

  公开号：US20100120901A1

  公开（公告）日：2010-05-13

  A pharmaceutical composition comprising a pharmaceutical diluent and a compound of formula IV wherein R 21 =H, C 1 -C 20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, —CH 2 OR 25 , —C(O)R 25 , —CO(O)R 25 , —C(O)NR 25 R 26 , —CH 2 C(O)R 25 , or —CH 2 C(O)NHR 25 , where R 25 and R 26 are each independently H, C 1 -C 10 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, optionally containing one or more halogen atoms. R 22 =—OH, —OR 27 , —OCH 2 C(O)R 27 , —OCH 2 C(O)NHR 27 , —OC(O)R 27 , —OC(O)OR 27 , —OC(O)NHNH—R 5 , or —OC(O)NR 27 R 28 , where R 27 and R 28 are each independently H, C 1 -C 20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl, and where R 27 and R 28 can each optionally contain halogen atoms; R 23 and R 24 , the same or different from each other, are C 1 -C 20 alkyl, cycloalkyl, alkenyl, aryl, arylalkyl, or alkylaryl. Methods of using such formulations for the treatment of cancer, to effect weight loss, to treat microbially-based infections, to inhibit neuropeptide-Y and/or fatty acid synthase, and to stimulate CPT-1.

  一种药物组合物，包括药物稀释剂和式 IV 化合物，其中 R21 = H、C1-C20 烷基、环烷基、烯基、芳基、芳基烷基或烷基芳基、-CH2OR25、-C（O）R25、-CO（O）R25、-C（O）NR25R26、-CH2C（O）R25或-CH2C（O）NHR25，其中 R25 和 R26 分别独立地是 H、C1-C10 烷基、环烷基、烯基、芳基、芳基烷基或烷基芳基，可选含有一个或多个卤素原子。R22 = -OH、-OR27、-OCH2C（O）R27、-OCH2C（O）NHR27、-OC（O）R27、-OC（O）OR27、-OC（O）NHNH-R5 或-OC（O）NR27R28，其中 R27 和 R28 各自独立地是 H、C1-C20 烷基、环烷基、烯基、芳基、芳基烷基或烷基芳基，且 R27 和 R28 每个都可以选择性地含有卤素原子；R23 和 R24，相同或不同，是 C1-C20 烷基、环烷基、烯基、芳基、芳基烷基或烷基芳基。使用这种组合物的方法包括治疗癌症，减轻体重，治疗微生物感染，抑制神经肽 Y 和/或脂肪酸合酶，以及刺激 CPT-1。
• Analogues of thiolactomycin as potential anti-malarial and anti-trypanosomal agents
  作者：S Jones

  DOI：10.1016/j.bmc.2003.11.023

  日期：2004.2.15

  A series of analogues of the naturally occurring antibiotic thiolactomycin (TLM) have been synthesised and evaluated for their ability to inhibit the growth of the malaria parasite, Plasmodium falciparum. Thiolactomycin is an inhibitor of Type II fatty acid synthase which is found in plants and most prokaryotes, but not an inhibitor of Type I fatty acid synthase in mammals. A number of the analogues showed inhibition equal to or greater than TLM. The introduction of hydrophobic alkyl groups at the C3 and C5 positions of the thiolactone ring lead to increased inhibition, the best showing a fourteenfold increase in activity over TLM. In addition, some of the analogues showed activity when assayed against the parasitic protozoa, Trypanosoma cruzi and Trypanosoma brucei. (C) 2003 Elsevier Ltd. All rights reserved.
• Structure−Activity Relationships at the 5-Position of Thiolactomycin:  An Intact (5<i>R</i>)-Isoprene Unit Is Required for Activity against the Condensing Enzymes from <i>Mycobacterium </i><i>t</i><i>uberculosis</i> and <i>Escherichia </i><i>c</i><i>oli</i>
  作者：Pilho Kim、Yong-Mei Zhang、Gautham Shenoy、Quynh-Anh Nguyen、Helena I. Boshoff、Ujjini H. Manjunatha、Michael B. Goodwin、John Lonsdale、Allen C. Price、Darcie J. Miller、Ken Duncan、Stephen W. White、Charles O. Rock、Clifton E. Barry、Cynthia S. Dowd

  DOI：10.1021/jm050825p

  日期：2006.1.1

  Thiolactomycin inhibits bacterial cell growth through inhibition of the beta-ketoacyl-ACP synthase activity of type II fatty acid synthases. The effect of modifications of the 5-position isoprenoid side chain on both IC(50) and MIC were determined. Synthesis and screening of a structurally diverse set of 5-position analogues revealed very little tolerance for substitution in purified enzyme assays, but a few analogues retained MIC, presumably through another target. Even subtle modifications such as reducing one or both double bonds of the diene were not tolerated. The only permissible structural modifications were removal of the isoprene methyl group or addition of a methyl group to the terminus. Cocrystallization of these two inhibitors with the condensing enzyme from Escherichia coli revealed that they retained the TLM binding mode at the active site with reduced affinity. These results suggest a strict requirement for a conjugated, planar side chain inserting within the condensing enzyme active site.
• [EN] NOVEL COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME, AND METHODS OF USE FOR SAME<br/>[FR] NOUVEAUX COMPOSES, NOUVELLES COMPOSITIONS PHARMACEUTIQUES CONTENANT CES COMPOSES ET PROCEDES D'UTILISATION CORRESPONDANTS
  申请人：FASGEN LLC

  公开号：WO2005117590A3

  公开（公告）日：2006-07-27