(2E)-1-((10R,13S)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3(β)-hydroxy-10,13-dimethyl-1H-cyclopenta[α]phenanthren-17(β)-yl)-3-phenylprop-2-en-1-one | 120793-61-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (2E)-1-((10R,13S)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3(β)-hydroxy-10,13-dimethyl-1H-cyclopenta[α]phenanthren-17(β)-yl)-3-phenylprop-2-en-1-one
• 英文别名: (2E)-1-((10R,13S)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3(β)-hydroxy-10,13-dimethyl-1H-cyclopenta[a]phenanthren-17(β)-yl)-3-phenylprop-2-en-1-one；(E)-21-benzyliden-3β-hydroxypregn-5-en-20-one；(21E)-3β-hydroxy-21-benzylidenepregn-5-en-20-one；3β-hydroxy-23t-phenyl-21.24-dinor-choladien-(5.22)-one-(20)；3β-Hydroxy-23t-phenyl-21.24-dinor-choladien-(5.22)-on-(20)；(E)-1-[(3S,8S,9S,10R,13S,14S,17S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl]-3-phenylprop-2-en-1-one
• CAS: 120793-61-5
• 化学式: C₂₈H₃₆O₂
• 分子量: 404.593
• InChiKey: KMYNFJUNXFDOIP-HCJDVJDWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2E)-1-((10R,13S)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3(β)-hydroxy-10,13-dimethyl-1H-cyclopenta[α]phenanthren-17(β)-yl)-3-phenylprop-2-en-1-one 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以88%的产率得到(E)-1-[(1S,2R,5S,7R,9S,11S,12S,15S,16S)-5-hydroxy-2,16-dimethyl-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadecan-15-yl]-3-phenylprop-2-en-1-one
  参考文献：
  名称：

  Synthesis and biological evaluation of 21-arylidenepregnenolone derivatives as neuroprotective agents

  摘要：

  A series of 21-arylidenepregnenolone derivatives and their corresponding epoxides were synthesized. The neuroprotective effects of these steroidal compounds against amyloid-beta(5-35)(A beta(25-35))- and hydrogen peroxide (H2O2)-induced neurotoxicity in PC12 cells, and oxygen-glucose deprivation (OGD)-induced neurotoxicity in SH-SY5Y cells were evaluated. The bioassay results indicated that several 3b-pregn-21-benzylidene-20-one derivatives displayed potent in vitro neuroprotective effects in different screening models, for example, compounds 2b, 3a, 3b, and 3s showing significant activities against A beta(25-35)-induced neurotoxicity in PC12 cells, 2b showing significant activities against H2O2-induced neurotoxicity in PC12 cells, and 2g, 3b, and 3e showing potent protection against OGD insult. The results suggested that introduction of an arylidene group into steroidal nucleus played an important role in neuroprotective activity, while the formation of epoxy group at C-5,6 could be also important for the neuroprotective activity in some degree. The pharmacological data reported here are helpful for the design of novel steroidal neuroprotective candidates. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.103
• 作为产物：
  描述：

  反式肉桂醛 、 孕烯醇酮 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 12.0h， 以87%的产率得到(2E)-1-((10R,13S)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-3(β)-hydroxy-10,13-dimethyl-1H-cyclopenta[α]phenanthren-17(β)-yl)-3-phenylprop-2-en-1-one
  参考文献：
  名称：

  Synthesis of D-ring-substituted (5′R)- and (5′S)-17β-pyrazolinylandrostene epimers and comparison of their potential anticancer activities

  摘要：

  Various steroidal benzylidenes were synthetized from pregnenolone with benzaldehyde and p-substituted benzaldehydes. The resulting 17 beta-chalconyl derivatives of pregnenolone were reacted with hydrazine hydrate in acetic acid solution. Regardless of the starting material, the ring-closure reaction afforded (in contrast with the literature data) a mixture of two steroidal pyrazoline epimers. The epimers were critical isomer pairs, which could be separated only in their acetylated form; their structures were investigated by NMR techniques. The in vitro inhibition of rat testicular C-17,C-20-lyase activity and the antiproliferative effects on four human cancer cell lines were measured, and the results obtained from the two epimer series were compared. (C) 2012 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2012.02.001

文献信息

• Neighboring Heteroatom Effect Unique to Aqueous Aldol Reactions of Water-Insoluble Substrates
  作者：Bo Li、Chunbao Li

  DOI：10.1021/jo500213b

  日期：2014.3.7

  In the aqueous aldol condensations, Li2CO3 was an efficient catalyst, and therefore base-liable groups such as epoxides, esters, and silyl groups could survive. For heteroaromatic ethanones, the aqueous aldol reactions were accomplished without PTC to give β-hydroxyketones in good yields. The water-mediated condensations of aldosyl hemiacetals with aromatic ketones led to a new carbohydrate-derived

  在Li +存在下和在水存在或不存在PTC的情况下，进行酮和醛的反应以生成醛醇产物。已经证明了水性反应相对于有机溶剂介导的反应的几个优点，包括更高的产率，更短的反应时间，更简单的纯化以及更好的官能团耐受性。在水中已经实现了一些在有机溶剂中不发生的反应。成功归因于相邻的杂原子效应。在水性羟醛缩合中，Li 2 CO 3硫醇是一种有效的催化剂，因此可与碱结合的基团（例如环氧化物，酯和甲硅烷基）可以幸免。对于杂芳族乙酮，在没有PTC的情况下完成了水性醛醇缩合反应，以良好的收率得到了β-羟基酮。水介导的醛基半缩醛与芳香族酮的缩合导致定量产率的新的碳水化合物衍生骨架。在某种程度上，这项研究扩大了醛醇缩合和反应的适用性。
• Synthesis of monomeric and dimeric steroids containing [1,2,4]triazolo[1,5-a]pyrimidines
  作者：Ailed Arenas-González、Luis Antonio Mendez-Delgado、Penélope Merino-Montiel、José M. Padrón、Sara Montiel-Smith、José Luis Vega-Báez、Socorro Meza- Reyes

  DOI：10.1016/j.steroids.2016.09.014

  日期：2016.12

  The synthesis of several monomeric and dimeric steroidal [1,2,4]triazolo[1,5-a]pyrimidines (TPs) derived from steroids are described. These derivatives were prepared from α,β-unsaturated carbonyl compounds through a Claisen Schmidt condensation and rearrangement of the spiro moiety followed by a cycloaddition with 3-amino-1,2,4-triazole. The antiproliferative activity of compounds 7, 13-15 was tested

  描述了几种单体和二聚体甾体 [1,2,4] 三唑并 [1,5-a] 嘧啶 (TP) 的合成。这些衍生物是由 α,β-不饱和羰基化合物通过 Claisen Schmidt 缩合和螺部分重排，然后与 3-氨基-1,2,4-三唑环加成制备的。测试了化合物 7、13-15 对人类癌细胞的抗增殖活性；几个 IG50 值低于 10μM。
• A Nature-Inspired Design Yields a New Class of Steroids Against Trypanosomatids
  作者：Elena Aguilera、Cintya Perdomo、Alejandra Espindola、Ileana Corvo、Paula Faral-Tello、Carlos Robello、Elva Serna、Fátima Benítez、Rocío Riveros、Susana Torres、Ninfa I. Vera de Bilbao、Gloria Yaluff、Guzmán Alvarez

  DOI：10.3390/molecules24203800

  日期：——

  biological activity against Leishmania infantum, Leishmania amazonensis, and Trypanosoma cruzi in vitro and in vivo. We also assayed their genotoxicity and acute toxicity in vitro and in mice. The best compound, a steroidal thiosemicarbazone compound 8 (ID_1260) was active in vitro (IC50 200 nM) and in vivo (60% infection reduction at 50 mg/kg) in Leishmania and T. cruzi. It also has low toxicity in vitro and

  恰加斯病和利什曼病是被世界卫生组织认定为公共卫生问题的地方性原生动物疾病。这些疾病影响着世界各地的数百万人，但目前还没有有效和低成本的治疗方法。从不同的生物体（蜱、植物、真菌）中分离出具有抗微生物和抗寄生虫活性的不同类固醇分子。这些分子具有复杂的结构，使得从头合成极其困难。在这项工作中，我们受天然类固醇的启发，设计了具有抗寄生虫潜力的新的更简单的化合物，并合成了一系列 19 种甾体亚芳基酮和噻唑烷肼。我们在体外和体内探索了它们对婴儿利什曼原虫、亚马逊利什曼原虫和克氏锥虫的生物活性。我们还在体外和小鼠中测定了它们的遗传毒性和急性毒性。最好的化合物，甾体缩氨基硫脲化合物 8 (ID_1260) 在体外 (IC50 200 nM) 和体内 (50 mg/kg 时感染减少 60%) 在利什曼原虫和克氏锥虫中均有活性。它还具有体外和体内低毒性（LD50 > 2000 mg/kg）和无遗传毒性作用，是一种有前景的抗锥虫药物开发化合物。
• Synthesis and Evaluation of Pyrimidine Steroids as Antiproliferative Agents
  作者：Alejandra Cortés-Percino、José Luis Vega-Báez、Anabel Romero-López、Adrián Puerta、Penélope Merino-Montiel、Socorro Meza-Reyes、José M. Padrón、Sara Montiel-Smith

  DOI：10.3390/molecules24203676

  日期：——

  A small and focused library of steroidal non-fused and fused pyrimidines was prepared from pregnenolone acetate and diosgenin, respectively. The key step was the cycloaddition reaction of nitrogen-containing 1,3-binucleophiles with the steroidal α,β-unsaturated ketone. Urea, thiourea and guanidine reacted in a similar manner and afforded the steroidal pyrimidines in good yields. The antiproliferative

  分别从醋酸孕烯醇酮和薯蓣皂苷元制备了一个小而集中的甾体非稠合嘧啶和稠合嘧啶文库。关键步骤是含氮 1,3-双亲核试剂与甾体 α,β-不饱和酮的环加成反应。尿素、硫脲和胍以类似的方式反应并以良好的产率提供甾体嘧啶。针对人类肿瘤细胞系的抗增殖试验给出了微摩尔范围内的 GI50 值，并且对健康的成纤维细胞没有影响。额外的实验表明，这些化合物不作为 P-糖蛋白底物，从而避免了耐药性的增加。由于其在低微摩尔范围内的强抗增殖活性，稠合甾体嘧啶硫酮被选为用于进一步测试的药物先导物。
• [EN] POLYNUCLEOTIDES FOR DISRUPTING IMMUNE CELL ACTIVITY AND METHODS OF USE THEREOF<br/>[FR] POLYNUCLÉOTIDES SERVANT À PERTURBER L'ACTIVITÉ DE CELLULE IMMUNITAIRE ET PROCÉDÉS POUR LES UTILISER
  申请人：MODERNATX INC

  公开号：WO2020227510A1

  公开（公告）日：2020-11-12

  The disclosure features isolated polynucleotides, such as mRNAs, encoding a polypeptide that disrupts immune cell activity, such as T cell or B cell activity, including mRNAs comprising one or more modified nucleobase. The immune cell disruptor polynucleotides encode a polypeptide that comprises a first domain that mediates association of the polypeptide with an immune cell component and a second domain that mediates inhibition of immune cell activity when the polypeptide is expressed in the immune cell. The disclosure also features methods of using the same, for example, for inhibiting immune responses when administered to a subject, such as to inhibit autoimmune reactions.

  该披露涉及孤立的多聚核苷酸，如编码破坏免疫细胞活性的多聚核苷酸，例如T细胞或B细胞活性的mRNA，包括包含一个或多个修饰的核碱基的mRNA。这些免疫细胞破坏多聚核苷酸编码一个包括第一个结构域的多肽，该结构域介导多肽与免疫细胞组分的结合，以及一个介导当多肽在免疫细胞中表达时抑制免疫细胞活性的第二结构域。该披露还涉及使用相同的方法，例如，将其用于向受试者施用时抑制免疫反应，例如用于抑制自身免疫反应。