15173-68-9Relevant academic research and scientific papers
Discovery of novel 3-hydroxyandrosta-5,7-Diene-17-Carboxylic acid derivatives as anti-inflammatory bowel diseases (IBD) agents
Chen, Jingxuan,Li, Ling,Liu, Jin,Yuan, Sijie,Liao, Wenzhen,Slominski, Andrzej T.,Li, Wei,?mijewski, Micha? A.,Chen, Jianjun
, (2021/05/04)
A series of steroidal compounds based on 3-hydroxyandrosta-5,7-diene-17-carboxylic acid core structure were designed, synthesized and bio-evaluated for their anti-inflammatory potency. Among them, compound 5c, 6f, and 6q effectively inhibited the producti
Steroid derivative and application thereof
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Paragraph 0018-0024, (2021/09/21)
The chemical structure of the derivative is shown by the following formula (I), the steroid derivative has anti-inflammatory biological activity, and LPS induced NO is obviously inhibited in the RAW264.7 cell.
Microwave-assisted synthesis of biologically relevant steroidal 17-exo-pyrazol-5'-ones from a norpregnene precursor by a side-chain elongation/heterocyclization sequence
Mótyán, Gerg?,Mérai, László,Kiss, Márton Attila,Schelz, Zsuzsanna,Sinka, Izabella,Zupkó, István,Frank, éva
, p. 2589 - 2596 (2018/10/21)
Multistep syntheses of novel 17β-pyrazol-5'-ones in the Δ5-androstane series were efficiently carried out from pregnenolone acetate. A steroidal 17-carboxylic acid was first synthesized as a norpregnene precursor by the bromoform reaction and subsequent acetylation. Its CDI-activated acylimidazole derivative was then converted to a β-ketoester containing a two carbon atom-elongated side chain than that of the starting material. A Knorr cyclization of the bifunctional 1,3-dicarbonyl compound with hydrazine and its monosubstituted derivatives in AcOH under microwave heating conditions led to the regioselective formation of 17-exo-hetero-cycles in good to excellent yields. The suppression of an acid-catalyzed thermal decarboxylation of the β-ketoester and thus a significant improvement in the yield of the desired heterocyclic products could be achieved by the preliminary liberation of the aryl-hydrazines from their hydrochloride salts in EtOH in the presence of NaOAc. The reaction rates were found to depend on the electronic character of the substituent present in the phenylhydrazine applied. The antiproliferative activities of the structurally related steroidal pyrazol-5'-ones and their deacetylated analogs were screened on three human adherent breast cancer cell lines (MCF7, T47D and MDA-MB-231): the microculture tetrazolium assay revealed that some of the presented derivatives exerted cell growth inhibitory effects on some of these cell lines comparable to those of the reference compound, cisplatin.
Synthesis of 17β-N-arylcarbamoylandrost-4-en-3-one derivatives and their anti-proliferative effect on human androgen-sensitive LNCaP cell line
Cortés-Benítez, Francisco,Cabeza, Marisa,Ramírez-Apan, María Teresa,Alvarez-Manrique, Berenice,Bratoeff, Eugene
, p. 737 - 746 (2016/07/19)
In this study, we report the synthesis and anti-proliferative effect of a set of eight androst-4-ene-3-one derivatives with different arylcarbamoyl groups at C-17. The novel compounds were prepared from commercially available 3β-hydroxy-5-pregnen-20-one a
Accessible Method for the Development of Novel Sterol Analogues with Dipeptide-like Side Chains That Act as Neuroinflammation Inhibitors
Chen, Hongli,Han, Chaojun,Wu, Jing,Liu, Xiaoyu,Zhan, Yuexiong,Chen, Jiakang,Chen, Yanke,Gu, Ruinan,Zhang, Li,Chen, Shuangshuang,Jia, Jia,Zhen, Xuechu,Zheng, Long Tai,Jiang, Biao
, p. 305 - 315 (2016/04/05)
A number of novel sterol derivatives with dipeptide-like side chains were synthesized using an Ugi four-component condensation method and assayed to test their anti-inflammatory effects in activated microglial cells. Compound 18b ((3S,10R,13S)-N-((R)-1-(tert-butylamino)-1-oxo-3-phenylpropan-2-yl)-3-hydroxy-N,10,13-trimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthrene-17-carboxamide) was identified as the most potent anti-inflammatory agent in the series of compounds analyzed. Compound 18b markedly inhibited the expression of proinflammatory factors, including inducible nitric oxide synthase, interleukin (IL)-6, IL-1β, tumor necrosis factor-α, and cyclooxygenase-2 in lipopolysaccharide-stimulated microglial cells. Further studies showed that compound 18b significantly suppressed the transcriptional activity of AP-1 and NF-κB in activated microglial cells, which was likely mediated by the inhibition of the p38 MAPK and JNK signal transduction pathways. In addition, compound 18b displayed neuroprotective effects in a microglial-conditioned medium/neuron coculture and an experimental focal ischemic mouse model.
Inhibition of neuroinflammation by synthetic androstene derivatives incorporating amino acid methyl esters on activated BV-2 microglia
Wu, Jing,Du, Juanjuan,Gu, Ruinan,Zhang, Li,Zhen, Xuechu,Li, Yuanchao,Chen, Hongli,Jiang, Biao,Zheng, Longtai
, p. 610 - 616 (2015/04/14)
Androstene derivatives incorporating amino acid methyl esters were prepared, and their anti-inflammatory effects were evaluated in lipopolysaccharide (LPS)-activated BV-2 microglial cells. Several compounds exhibited dose-dependent inhibition. The most active compound, methyl ((3S,10R,13S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthrene-17-carbonyl)-L-phenylalaninate (10) significantly suppressed LPS-induced expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Mechanistic studies revealed that compound 10 markedly inhibits phosphorylation of p38 mitogen-activated protein kinases (MAPKs) and subsequent transcription factor (NF-κB) and activator protein-1 (AP-1) activation. Furthermore, compound 10 decreased LPS-activated microglial neurotoxicity in a condition medium/HT-22 neuroblastoma co-culture model. Taken together, these results suggest 10 is a potential lead compound for the development of a novel therapeutic agent for neurodegenerative diseases.
An efficient approach to novel 17-5′-(1′,2′,4′)- oxadiazolyl androstenes via the cyclodehydration of cytotoxic O-steroidacylamidoximes, and an evaluation of their inhibitory action on 17α-hydroxylase/C17,20-lyase
Kovács, Dóra,W?lfling, János,Szabó, Nikoletta,Szécsi, Mihály,Kovács, Ida,Zupkó, István,Frank, éva
, p. 649 - 660 (2013/12/04)
Novel 17-exo-oxadiazoles in the androst-5-ene series were efficiently synthesized in a two-step sequence via the corresponding O-acylamidoxime intermediates (obtained from steroidal 17-carboxylic acids and amidoximes in the presence of coupling reagent), which then underwent tetrabutylammonium fluoride-induced cyclocondensation under mild reaction conditions. The synthesized compounds were subjected to in vitro pharmacological studies to investigate their inhibitory effect on rat testicular C17,20-lyase and their antiproliferative action on four malignant human adherent cell lines (HeLa, MCF7, A2780 and A431). One of the oxadiazolyl derivatives proved to exert significant enzyme-inhibitory action (IC50 = 0.60 μM), while some of the isolated O-acylated amidoxime intermediates displayed high cytotoxic activities on all examined cell lines, with IC50 values in the range 0.22-3.94 μM.
Design, synthesis, and biological action of 20 R -hydroxyvitamin D3
Lu, Yan,Chen, Jianjun,Janjetovic, Zorica,Michaels, Phillip,Tang, Edith K. Y.,Wang, Jin,Tuckey, Robert C.,Slominski, Andrzej T.,Li, Wei,Miller, Duane D.
supporting information; experimental part, p. 3573 - 3577 (2012/06/17)
The non-naturally occurring 20R epimer of 20-hydroxyvitamin D3 is synthesized based on chemical design and hypothesis. The 20R isomer is separated by semipreparative HPLC, and its structure is characterized. A comparison of 20R isomer to its 20S counterpa
The first synthesis of Krempene B
Shen, Li-Qun,Huang, Su-Yu,Tang, Yong,Lei, Fu-Hou
, p. 1398 - 1402 (2013/01/15)
The synthesis of Krempene B, which can be isolated from the marine soft coral Cladiella krempfi, is achieved in 23.9% overall yield from commercially available 3β-acetoxy-5-pregnen-20-one by 11 steps. Key transformations include the dienone-phenol rearrangement of steroids and Wittig reaction.
Novel oxysterols activate the Hedgehog pathway and induce osteogenesis
Stappenbeck, Frank,Xiao, Wei,Epperson, Matt,Riley, Mariko,Priest, Aaron,Huang, Danwen,Scott Thies, R.,Farouz, Francine,Nguyen, Khanhlinh,Jung, Michael E.
, p. 5893 - 5897,5 (2020/07/31)
Localized induction of bone formation is essential during orthopedic procedures that involve skeletal repair, such as surgical treatment of non-union bone fractures and degenerative disk disease. Herein we disclose the synthesis and biological evaluation of novel oxysterol derivatives designed as anabolic bone growth agents. Structure-activity relationship studies of oxysterol 4 have identified analogues such as 18, 21 and 30. These new analogues are characterized by higher potency in an osteoblast differentiation assay and/or by increased metabolic stability in human liver microsomes. Oxysterols 4, 18 and 21 were evaluated in vivo in a rat spinal fusion model.
