119907-02-7Relevant articles and documents
Mild, calcium catalysed Beckmann rearrangements
Kiely-Collins,Sechi,Brennan,McLaughlin
, p. 654 - 657 (2018)
A mild calcium catalysed Beckmann rearrangement has been realised, which forgoes the more traditional harsh reactions conditions associated with the transformation. The catalyst system is shown to be tolerant towards a wide variety of functional groups relevant to natural product synthesis and medicinal chemistry and the synthetic utility of the reaction has also been investigated. A preliminary mechanistic investigation was performed to understand the nature of the incoming nucleophile and a possible reaction pathway is described.
Synthesis, Crystal Structure, and Insecticidal Activity of Steroidal N-Piperidone
Ma, Shichuang,Jiang, Weiqi,Hu, Yuxiao,Wang, Qiangping,Wu, Wenjun,Shi, Baojun
, p. 1467 - 1476 (2022/02/10)
A series of steroidal piperidone derivatives were synthesized, and their agricultural activities were evaluated against Myzus persicae, Aphis citricola, Brevicoryne brassicae Linn., and Bemisia tabaci (Gennadius). Most of the tested compounds exhibited potent insecticidal activity against these four pests. Compound I-9 displayed the highest activity against M. persicae, A. citricola, and Brevicoryne brassicae, with LC50 values of 11.3, 10.4, and 8.68 μg/mL, respectively. The mode of action test indicated that these derivatives had superior contact and systemic insecticidal activity against M. persicae. In addition, we initially explored whether the foregut and midgut might be the action sites of the target derivatives against M. persicae. Furthermore, a field trial showed that the control of compound I-9 was similar to that of acetamiprid against M. persicae, at a dose of 50 μg/mL; the control rates were 97.8 and 99.2% after 14 and 21 days, respectively. The structure-activity relationship of these analogues provided some important insights for the discovery and development of new insecticides to solve the current pesticide resistance crisis.
Design, synthesis, brine shrimp lethality and cytotoxicity of some novel 17a-aza-D-homo-androster-17-one derivatives
Hong, Dongfeng,Ma, Yiming,Song, Siyao,Li, Na,Wang, Junru
supporting information, p. 3985 - 3991 (2020/04/27)
In this work, twenty-eight novel 17a-aza-D-homo-androster-17-one derivatives, which divided into two categories, were synthesized with commercial available starting material (dehydroepiandrosterone) via oximation reaction, Beckmann rearrangement, hydroxyl protection, N-alkylation and deprotection. All compounds were characterized by 1H NMR, 13C NMR and HRMS. The structure of 14 g was also identified by X-ray single crystal diffraction. The bioactivities, brine shrimp toxicity and cytotoxicity, of all derivatives were tested. The results indicated that compounds 11 h, 11i, 11 m, 11 s, 14 b and 14 g exhibited excellent toxicity against brine shrimp with LC50 values ranging from 5.34 to 16.89 μg/mL, and compounds 11 s and 14 g displayed significant cytotoxicity against HT29 cells and A549 cells with IC50 values of 9.70 μM and 8.85 μM, respectively. Structure-activity relationships are discussed based on the results obtained from our research, and some important determinants for further modification of steroids towards the development of novel drug candidates are identified.
Copper-Catalyzed Aza-Sonogashira Cross-Coupling To Form Ynimines: Development and Application to the Synthesis of Heterocycles
Lavernhe, Rémi,Torres-Ochoa, Rubén O.,Wang, Qian,Zhu, Jieping
supporting information, p. 24028 - 24033 (2021/10/07)
Nitrogen-substituted alkynes, such as ynamines and ynamides, are versatile synthetic building blocks. Ynimines bearing additional nucleophilic and electrophilic centers relative to ynamines and ynamides are expected to have high synthetic potential. However, their chemical reactivity remains unexplored owing mainly to the lack of synthetic accessibility. We report herein a versatile copper-catalyzed synthesis of ynimines from readily available O-acetyl ketoximes and terminal alkynes. A wide range of O-acetyl ketoximes derived from diaryl ketones, aryl alkyl ketones and dialkyl ketones underwent cross-coupling with a diverse set of terminal alkynes to afford the ynimines in good to excellent yields. An unprecedented [5+1] heteroannulation reaction exploiting the reactivity of the ynimine generated in situ was subsequently developed for the synthesis of medicinally important heterocycles, including isoquinolines, azaindoles, azabenzofurans, azabenzothiophenes and carbolines.
Steroid piperidone derivatives and synthesis methods and applications thereof
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Paragraph 0045; 0055-0056, (2022/01/06)
The present invention discloses a steroidal piperidone derivative and its synthesis method and application, steroid piperidone derivative having a chemical structure expressed by formula (1) or formula (2), wherein R is an alkyl, phenyl or substituted phenyl and any one of the heterocyclic; Is the best method for the preparation of steroid piperidone derivatives of the present invention; the steroid piperidone derivatives provided by the present invention have been bioassayed to confirm that aphids, leaf mites, rice planthoppers and whiteflies and other sucking insects exhibit good toxicity and activity, can be applied to plant pest control.
Sensitized Aliphatic Fluorination Directed by Terpenoidal Enones: A "visible Light" Approach
Bume, Desta Doro,Harry, Stefan Andrew,Pitts, Cody Ross,Lectka, Thomas
, p. 1565 - 1575 (2018/02/09)
In our continued effort to address the challenges of selective sp3 C-H fluorination on complex molecules, we report a sensitized aliphatic fluorination directed by terpenoidal enones using catalytic benzil and visible light (white LEDs). This sensitized approach is mild, simple to set up, and an economical alternative to our previous protocol based on direct excitation using UV light in a specialized apparatus. Additionally, the amenability of this protocol to photochemical flow conditions and preliminary evidence for electron-transfer processes are highlighted.
Synthesis and antiproliferative activity of 3-aza steroids as 5α-reductase inhibitors
Kaur, Milanpreet,Dhingra, Richa,Bhardwaj,Dhingra, Neelima
, p. 1335 - 1346 (2017/11/14)
Background: Dihyrdotestosterone (DHT), the most potent circulating androgen hormone, is produced by stereoselective reduction of testosterone (T) under catalysis of NADPH dependent enzyme steroid 5α-reductase (5AR). The DHT production is related to many pathological conditions and endocrine diseases such as Benign Prostatic Hyperplasia (BPH). Many years ago, the use of 5AR inhibitors for the possible control or suppression of DHT formation has become years ago a therapeutic target for the treatment of BPH. During last two decades, several non steroidal and steroidal compounds have been synthesized as reversible and irreversible 5AR inhibitors. Methods: Present study describes the synthesis of 17β-substituted amides of 3-aza-A-homo-4a-androsten-4-one starting from 16-Dehydropregnelone acetate (16-DPA). The structure of newly synthesized compounds was established on the basis of TLC and various spectroscopic studies and compounds were subjected for their in vitro cytotoxicity studies using prostate cancer cell lines PC-3. Results and Conclusion: Synthesized compounds (13a to 13h) showed better cytotoxicity as compared to reference drug and 3-Aza-A-homo-17β-(4-nitrobenzamido)-4a-androsten-4-one (13b) showed an excellent antiproliferative activity as compared to Dutasteride.
Model steroidal androgen receptor inhibitor, its preparation method and medical use thereof (by machine translation)
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Paragraph 0023; 0058; 0059; 0060, (2017/05/19)
The invention relates to the field of pharmaceutical chemistry, and in particular relates to a series of steroidal androgen receptor inhibitor, a process for their preparation and their medical use, especially as the prevention or treatment of androgen-receptor related diseases, such as prostatic cancer of the use of the medicament. (by machine translation)
Synthesis and biological evaluation of 3-tetrazolo steroidal analogs: Novel class of 5α-reductase inhibitors
Aggarwal, Saurabh,Mahapatra, Manoj Kumar,Kumar, Rajnish,Bhardwaj, Tilak R.,Hartmann, Rolf W.,Haupenthal, J?rg,Kumar, Manoj
, p. 779 - 788 (2016/02/09)
In the present study, a series of steroidal tetrazole derivatives of androstane and pregnane have been prepared in which the tetrazole moiety was appended at C-3 and 17a-aza locations. 3-Tetrazolo-3,5-androstadien-17-one (6), 3-tetrazolo-19-nor-3,5-androstadien-17-one (10), 3-tetrazolo-3,5-pregnadien-20-one (14), 17a-substituted 3-tetrazolo-17a-aza-d-homo-3,5-androstadien-17-one (26-31) and 3-(2-acetyltetrazolo)-17a-aza-d-homo-3,5-androstadien-17-one (32) were synthesized from dehydroepiandrosterone acetate (1) through multiple synthetic steps. Some of the synthesized compounds were evaluated for their in vitro 5α-reductase (5AR) inhibitory activity by measuring the conversion of [3H] androstenedione in human embryonic kidney (HEK) cells. In vivo 5α-reductase inhibitory activity also showed a significant reduction (p 50 being 15.6 nM as compared to clinically used drug finasteride (40 nM). There was also a significant inhibition of 5AR-1 with IC50 547 nM compared to finasteride (453 nM).
Protein-binding properties of a designed steroidal lactam compound
Zhang, Hua-Xin,Liu
, p. 30 - 36 (2014/01/17)
Introducing amide bonds into a steroid nucleus or its side chain may reduce the acute toxicity and enhance the pharmaceutical activity. In this work, a designed steroidal amide compound, named 3β-hydroxy-17-aza-d-homo-5- androsten-17-one (HAAO), was synthesized and identified. The interactions between HAAO and human serum albumin (HSA) were studied by multiple spectroscopic methods and molecular modeling procedures. It was found that HAAO locates in Sudlow's site I in subdomain IIA of HSA molecules, relying on hydrogen bonds and van der Waals power to form HAAO-HSA complexes at ground state. The number of binding sites, binding constants, enthalpy change (ΔHθ), Gibbs free energy change (ΔG θ) and entropy change (ΔSθ) were calculated at different temperatures based on fluorescence quenching theory and classical thermodynamic equation. The percentages content of the HSA's secondary structures in presence of HAAO were detected by circular dichroism (CD) spectra and compared with those in no presence of HAAO. In addition, the experimental results of both binding site and conformational change were further confirmed by molecular modeling investigation, in which more details of the binding were visually unfolded. The information provided by the study may be useful for designing novel chemotherapeutic drugs and be helpful both in the early stages of drug discovery and in clinical practice.
