Synthesis and Biological Activity of Several Modified 5α-Androstanolone Derivatives
Identifieur interne : 000237 ( Pmc/Corpus ); précédent : 000236; suivant : 000238Synthesis and Biological Activity of Several Modified 5α-Androstanolone Derivatives
Auteurs : N. Sh. Nadaraia ; N. N. Barbakadze ; M. L. Kakhabrishvili ; B. Sylla ; A. Pichette ; U. S. MakhmudovSource :
- Chemistry of Natural Compounds [ 0009-3130 ] ; 2018.
Abstract
Several new N-containing epiandrosterone derivatives modified by phenylacetic acid chloride were synthesized for biological activity studies. Compounds with antiviral activity were discovered among them and 3β-hydroxy-1′-aryl-3′-methyl-5′-androstano[17,16-d]pyrazolines prepared by us earlier.
Url:
DOI: 10.1007/s10600-018-2330-2
PubMed: NONE
PubMed Central: 7087839
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Synthesis and Biological Activity of Several Modified 5<italic>α</italic>-Androstanolone Derivatives</title><author><name sortKey="Nadaraia, N Sh" sort="Nadaraia, N Sh" uniqKey="Nadaraia N" first="N. Sh." last="Nadaraia">N. Sh. Nadaraia</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0428 8304</institution-id><institution-id institution-id-type="GRID">grid.412274.6</institution-id><institution>I. Kutateladze Institute of Pharmacochemistry,</institution><institution>Tbilisi State Medical University,</institution></institution-wrap>0159 Tbilisi, Georgia</nlm:aff></affiliation></author><author><name sortKey="Barbakadze, N N" sort="Barbakadze, N N" uniqKey="Barbakadze N" first="N. N." last="Barbakadze">N. N. Barbakadze</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0428 8304</institution-id><institution-id institution-id-type="GRID">grid.412274.6</institution-id><institution>I. Kutateladze Institute of Pharmacochemistry,</institution><institution>Tbilisi State Medical University,</institution></institution-wrap>0159 Tbilisi, Georgia</nlm:aff></affiliation></author><author><name sortKey="Kakhabrishvili, M L" sort="Kakhabrishvili, M L" uniqKey="Kakhabrishvili M" first="M. L." last="Kakhabrishvili">M. L. Kakhabrishvili</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0428 8304</institution-id><institution-id institution-id-type="GRID">grid.412274.6</institution-id><institution>I. Kutateladze Institute of Pharmacochemistry,</institution><institution>Tbilisi State Medical University,</institution></institution-wrap>0159 Tbilisi, Georgia</nlm:aff></affiliation></author><author><name sortKey="Sylla, B" sort="Sylla, B" uniqKey="Sylla B" first="B." last="Sylla">B. Sylla</name><affiliation><nlm:aff id="Aff2">LASEVE, Universite Quebec a Chicoutimi, Chicoutimi, QC G7H 2B1 Canada</nlm:aff></affiliation></author><author><name sortKey="Pichette, A" sort="Pichette, A" uniqKey="Pichette A" first="A." last="Pichette">A. Pichette</name><affiliation><nlm:aff id="Aff2">LASEVE, Universite Quebec a Chicoutimi, Chicoutimi, QC G7H 2B1 Canada</nlm:aff></affiliation></author><author><name sortKey="Makhmudov, U S" sort="Makhmudov, U S" uniqKey="Makhmudov U" first="U. S." last="Makhmudov">U. S. Makhmudov</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2110 259X</institution-id><institution-id institution-id-type="GRID">grid.419209.7</institution-id><institution>S. Yu. Yunusov Institute of the Chemistry of Plant Substances,</institution><institution>Academy of Sciences of the Republic of Uzbekistan,</institution></institution-wrap>Tashkent, Uzbekistan</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmc">7087839</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7087839</idno><idno type="RBID">PMC:7087839</idno><idno type="doi">10.1007/s10600-018-2330-2</idno><idno type="pmid">NONE</idno><date when="2018">2018</date><idno type="wicri:Area/Pmc/Corpus">000237</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000237</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Synthesis and Biological Activity of Several Modified 5<italic>α</italic>-Androstanolone Derivatives</title><author><name sortKey="Nadaraia, N Sh" sort="Nadaraia, N Sh" uniqKey="Nadaraia N" first="N. Sh." last="Nadaraia">N. Sh. Nadaraia</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0428 8304</institution-id><institution-id institution-id-type="GRID">grid.412274.6</institution-id><institution>I. Kutateladze Institute of Pharmacochemistry,</institution><institution>Tbilisi State Medical University,</institution></institution-wrap>0159 Tbilisi, Georgia</nlm:aff></affiliation></author><author><name sortKey="Barbakadze, N N" sort="Barbakadze, N N" uniqKey="Barbakadze N" first="N. N." last="Barbakadze">N. N. Barbakadze</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0428 8304</institution-id><institution-id institution-id-type="GRID">grid.412274.6</institution-id><institution>I. Kutateladze Institute of Pharmacochemistry,</institution><institution>Tbilisi State Medical University,</institution></institution-wrap>0159 Tbilisi, Georgia</nlm:aff></affiliation></author><author><name sortKey="Kakhabrishvili, M L" sort="Kakhabrishvili, M L" uniqKey="Kakhabrishvili M" first="M. L." last="Kakhabrishvili">M. L. Kakhabrishvili</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0428 8304</institution-id><institution-id institution-id-type="GRID">grid.412274.6</institution-id><institution>I. Kutateladze Institute of Pharmacochemistry,</institution><institution>Tbilisi State Medical University,</institution></institution-wrap>0159 Tbilisi, Georgia</nlm:aff></affiliation></author><author><name sortKey="Sylla, B" sort="Sylla, B" uniqKey="Sylla B" first="B." last="Sylla">B. Sylla</name><affiliation><nlm:aff id="Aff2">LASEVE, Universite Quebec a Chicoutimi, Chicoutimi, QC G7H 2B1 Canada</nlm:aff></affiliation></author><author><name sortKey="Pichette, A" sort="Pichette, A" uniqKey="Pichette A" first="A." last="Pichette">A. Pichette</name><affiliation><nlm:aff id="Aff2">LASEVE, Universite Quebec a Chicoutimi, Chicoutimi, QC G7H 2B1 Canada</nlm:aff></affiliation></author><author><name sortKey="Makhmudov, U S" sort="Makhmudov, U S" uniqKey="Makhmudov U" first="U. S." last="Makhmudov">U. S. Makhmudov</name><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2110 259X</institution-id><institution-id institution-id-type="GRID">grid.419209.7</institution-id><institution>S. Yu. Yunusov Institute of the Chemistry of Plant Substances,</institution><institution>Academy of Sciences of the Republic of Uzbekistan,</institution></institution-wrap>Tashkent, Uzbekistan</nlm:aff></affiliation></author></analytic><series><title level="j">Chemistry of Natural Compounds</title><idno type="ISSN">0009-3130</idno><idno type="eISSN">1573-8388</idno><imprint><date when="2018">2018</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">Several new N-containing epiandrosterone derivatives modified by phenylacetic acid chloride were synthesized for biological activity studies. Compounds with antiviral activity were discovered among them and 3β-hydroxy-1′-aryl-3′-methyl-5′-androstano[17,16-d]pyrazolines prepared by us earlier.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Gan, C" uniqKey="Gan C">C Gan</name></author><author><name sortKey="Cui, J" uniqKey="Cui J">J Cui</name></author><author><name sortKey="Su, S" uniqKey="Su S">S Su</name></author><author><name sortKey="Lin, Q" uniqKey="Lin Q">Q Lin</name></author><author><name sortKey="Jia, L" uniqKey="Jia L">L Jia</name></author><author><name sortKey="Fan, L" uniqKey="Fan L">L Fan</name></author><author><name sortKey="Huang, Y" uniqKey="Huang Y">Y Huang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ke, S" uniqKey="Ke S">S Ke</name></author><author><name sortKey="Shi, L" uniqKey="Shi L">L Shi</name></author><author><name sortKey="Yang, Z" uniqKey="Yang Z">Z 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K">KG Mulkidzhanyan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wightman, F" uniqKey="Wightman F">F Wightman</name></author><author><name sortKey="Lighty, Dl" uniqKey="Lighty D">DL Lighty</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leuba, V" uniqKey="Leuba V">V Leuba</name></author><author><name sortKey="Le Tourneau, D" uniqKey="Le Tourneau D">D Le Tourneau</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rzheznikov, Vm" uniqKey="Rzheznikov V">VM Rzheznikov</name></author><author><name sortKey="Golubovskaya, Le" uniqKey="Golubovskaya L">LE Golubovskaya</name></author><author><name sortKey="Minailova, On" uniqKey="Minailova O">ON Minailova</name></author><author><name sortKey="Keda, Bi" uniqKey="Keda B">BI Keda</name></author><author><name sortKey="Ivanenko, Ti" uniqKey="Ivanenko T">TI Ivanenko</name></author><author><name sortKey="Fedotov, Vp" uniqKey="Fedotov V">VP Fedotov</name></author><author><name sortKey="Sushinina, Lp" uniqKey="Sushinina L">LP Sushinina</name></author><author><name sortKey="Titova, Ta" uniqKey="Titova T">TA Titova</name></author><author><name sortKey="Tolkachev, Vn" uniqKey="Tolkachev V">VN Tolkachev</name></author><author><name sortKey="Osetrova, Ip" uniqKey="Osetrova I">IP Osetrova</name></author><author><name sortKey="Smirnova, Zs" uniqKey="Smirnova Z">ZS Smirnova</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nadaraia, Ns" uniqKey="Nadaraia N">NS Nadaraia</name></author><author><name sortKey="Kakhabrishvili, Ml" uniqKey="Kakhabrishvili M">ML Kakhabrishvili</name></author><author><name sortKey="Onashvili, Eo" uniqKey="Onashvili E">EO Onashvili</name></author><author><name sortKey="Barbakadze, Nn" uniqKey="Barbakadze N">NN Barbakadze</name></author><author><name sortKey="Getia, Mz" uniqKey="Getia M">MZ Getia</name></author><author><name sortKey="Pichette, A" uniqKey="Pichette A">A Pichette</name></author><author><name sortKey="Sikharulidze, Mi" uniqKey="Sikharulidze M">MI Sikharulidze</name></author><author><name sortKey="Makhmudov, Us" uniqKey="Makhmudov U">US Makhmudov</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Diffraction, O" uniqKey="Diffraction O">O Diffraction</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sheldrick, Gm" uniqKey="Sheldrick G">GM Sheldrick</name></author></analytic></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Chem Nat Compd</journal-id><journal-id journal-id-type="iso-abbrev">Chem Nat Compd</journal-id><journal-title-group><journal-title>Chemistry of Natural Compounds</journal-title></journal-title-group><issn pub-type="ppub">0009-3130</issn><issn pub-type="epub">1573-8388</issn><publisher><publisher-name>Springer US</publisher-name><publisher-loc>New York</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmc">7087839</article-id><article-id pub-id-type="publisher-id">2330</article-id><article-id pub-id-type="doi">10.1007/s10600-018-2330-2</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Synthesis and Biological Activity of Several Modified 5<italic>α</italic>-Androstanolone Derivatives</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Nadaraia</surname><given-names>N. Sh.</given-names></name><address><fax> (99352) 52 00 23</fax><email>nnadaraia@ymail.com</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Barbakadze</surname><given-names>N. N.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Kakhabrishvili</surname><given-names>M. L.</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Sylla</surname><given-names>B.</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Pichette</surname><given-names>A.</given-names></name><address><fax>(1) 418 545 50 12</fax><email>andre_pichette@uqac.ca</email></address><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Makhmudov</surname><given-names>U. S.</given-names></name><address><email>earl-sharp@rambler.ru</email></address><xref ref-type="aff" rid="Aff3">3</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0428 8304</institution-id><institution-id institution-id-type="GRID">grid.412274.6</institution-id><institution>I. Kutateladze Institute of Pharmacochemistry,</institution><institution>Tbilisi State Medical University,</institution></institution-wrap>0159 Tbilisi, Georgia</aff><aff id="Aff2"><label>2</label>LASEVE, Universite Quebec a Chicoutimi, Chicoutimi, QC G7H 2B1 Canada</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2110 259X</institution-id><institution-id institution-id-type="GRID">grid.419209.7</institution-id><institution>S. Yu. Yunusov Institute of the Chemistry of Plant Substances,</institution><institution>Academy of Sciences of the Republic of Uzbekistan,</institution></institution-wrap>Tashkent, Uzbekistan</aff></contrib-group><pub-date pub-type="epub"><day>14</day><month>4</month><year>2018</year></pub-date><pub-date pub-type="ppub"><year>2018</year></pub-date><volume>54</volume><issue>2</issue><fpage>310</fpage><lpage>314</lpage><history><date date-type="received"><day>25</day><month>7</month><year>2017</year></date></history><permissions><copyright-statement>© Springer Science+Business Media, LLC, part of Springer Nature 2018</copyright-statement><license><license-p>This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.</license-p></license></permissions><abstract id="Abs1"><p id="Par1">Several new N-containing epiandrosterone derivatives modified by phenylacetic acid chloride were synthesized for biological activity studies. Compounds with antiviral activity were discovered among them and 3β-hydroxy-1′-aryl-3′-methyl-5′-androstano[17,16-d]pyrazolines prepared by us earlier.</p></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>antiviral activity</kwd><kwd>epiandrosterone</kwd><kwd>modification</kwd><kwd>phenylacetic acid</kwd><kwd>hydrazones</kwd><kwd>pyrazolines</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© Springer Science+Business Media, LLC, part of Springer Nature 2018</meta-value></custom-meta></custom-meta-group></article-meta></front><body><p id="Par2">Syntheses of biologically active oximes, hydrazones, or carbazones of steroidal ketones have been the subject of much research [<xref ref-type="bibr" rid="CR1">1</xref>–<xref ref-type="bibr" rid="CR4">4</xref>]. Several hydrazones and oximes of 5α-steroids that were previously synthesized by us also exhibited high antituberculosis, antiviral, and anti-inflammatory activity [<xref ref-type="bibr" rid="CR5">5</xref>–<xref ref-type="bibr" rid="CR7">7</xref>].</p><p id="Par3">Addition of fragments of natural compounds to organic molecules is known to produce new and previously unknown biological properties.</p><p id="Par4">Phenylacetic acid synthesized by plants can exhibit auxin-like activity according to some reports [<xref ref-type="bibr" rid="CR8">8</xref>, <xref ref-type="bibr" rid="CR9">9</xref>]. Steroidal esters of phenylacetic-acid derivatives exhibited characteristic antitumor activity [<xref ref-type="bibr" rid="CR10">10</xref>]. The drug perandren is a phenylacetate ester of testosterone that is used for osteoporosis, breast cancer, etc.</p><p id="Par5">The structure–activity relationship was studied using esterification of epiandrosterone (<bold>1</bold>) by phenylacetic acid chloride to produce modified ketone <bold>2</bold>. Reactions of <bold>2</bold> with hydroxylamine, <italic>m</italic>-nitrobenzoic or nicotinic acid hydrazides, and semi- or thiosemicarbazides synthesized derivatives <bold>3</bold>–<bold>7</bold>.</p><graphic position="anchor" xlink:href="10600_2018_2330_Figa_HTML" id="MO1"></graphic><p id="Par6">Herein, the antiviral activities of new <bold>3</bold>–<bold>7</bold> and steroids <bold>9</bold>–<bold>12</bold> that were prepared by us earlier from pregnenolone <bold>8</bold> [<xref ref-type="bibr" rid="CR11">11</xref>] are reported. The structures were 3′-hydroxy-1′-<italic>p</italic>-chlorophenyl- (<bold>9</bold>), 3 <italic>β</italic> -hydroxy-1′-<italic>p</italic>-bromophenyl- (<bold>10</bold>), 3<italic>β</italic>-hydroxy-1′-<italic>p</italic>-methylphenyl-3<italic>β</italic>-methyl-5′-androstano[17,16-<italic>d</italic>]pyrazoline (<bold>11</bold>), and 5′-preg-16-en-3<italic>β</italic>-ol-20-one <italic>p</italic>-nitrophenylhydrazone (<bold>12</bold>).</p><p id="Par7">The structures of <bold>2</bold>–<bold>7</bold> were confirmed using IR, NMR, and mass spectra. The IR spectrum of ketone <bold>2</bold> showed C=O absorption bands at 1700 and 1750 cm<sup>–1</sup>. Singlets for angular 18- and 19-CH<sub>3</sub> protons in the PMR spectrum (in CDCl<sub>3</sub>) appeared at δ 0.86 and 1.27 ppm; a multiplet for the 3α-proton, 4.72; aromatic protons, 7.28–7.33; and phenylacetoxy methylene proton, 3.60. The <sup>13</sup>C NMR spectrum of <bold>2</bold> had resonances for phenyl-ring C atoms in the range 126.9–134.3 ppm; for O–C=O and C=O, 171.1 and 221.3, respectively.</p><p id="Par8">IR spectra of <bold>3</bold>–<bold>5</bold> contained absorption bands for ester C=O at 1735, 1729, and 1728 cm<sup>–1</sup>, respectively; NHCO groups (hydrazones <bold>4</bold> and <bold>5</bold>), 1665 and 1651; C=N– and aromatic C=C stretching vibrations, 1680, 1640, and 1610 and 1524, 1531, and 1589, respectively; and NH (hydrazones <bold>4</bold> and <bold>5</bold>) and OH groups (oxime <bold>3</bold>), 3450, 3370, and 3260. The IR spectrum of <bold>4</bold> also had characteristic bands for Ar–NO2 stretching vibrations at 1500 and 1348 cm<sup>–1</sup>.</p><p id="Par9">PMR spectra of <bold>3</bold>–<bold>7</bold> showed singlets for angular 18- and 19-CH3 groups at 0.83, 0.77, 0.85, 0.82, 0.84, and 0.89, 0.82, 0.87, 0.88, 0.90 ppm, respectively; multiplets for 3α-protons of 3<italic>β</italic>-esters, 4.69, 4.61, 4.61, 4.59; phenyl aromatic protons, in the range 7.17–7.34. Singlets for the phenylacetoxy methylene protons appeared at δ 3.58–3.50 ppm; aromatic protons of steroid hydrazones <bold>4</bold> and <bold>5</bold>, 7.32–8.93. The NH protons gave two singlets for the <italic>cis</italic>-conformers at 8.93 and 10.32 ppm, respectively; <italic>trans</italic>-conformer, 8.48 and 10.25. The oxime hydroxyl proton of <bold>3</bold> appeared as a broad singlet at 7.93 ppm. The NH protons of <bold>6</bold> and <bold>7</bold> were found at 8.54 and 9.55 ppm, respectively. The NH2 protons of semicarbazone <bold>6</bold> appeared as a broad singlet at 5.81 ppm; thiosemicarbazone <bold>7</bold>, two broad singlets at 7.03 and 7.79. The <sup>13</sup>C NMR spectrum of <bold>3</bold> contained peaks for phenyl-ring C atoms in the range 126.9–134.3 ppm; C=N and C=O, 171.1 and 171.3, respectively. The <sup>13</sup>C NMR spectrum of hydrazone <bold>4</bold> had resonances for all aromatic C atoms in the range 125.8–147.4 ppm; amide C atom, 166.7; C=N and O–C=O, 168.3 and 171.2, respectively. The 13C NMR spectrum of <bold>7</bold> had resonances for phenyl-ring C atoms in the range 126.9–134.3 ppm; C=N, C=O, and C=S, 167.4, 171.2, and 178.9, respectively. The molecular ions <italic>m</italic>/<italic>z</italic> [M + H]<sup>+</sup> for steroids <bold>2</bold>–<bold>7</bold> agreed with the empirical formulas.</p><p id="Par10">The structure of <bold>2</bold> was also confirmed by an X-ray crystal structure analysis (XSA) (Fig. <xref rid="Fig1" ref-type="fig">1</xref> and Table <xref rid="Tab1" ref-type="table">1</xref>).<fig id="Fig1"><label>Fig. 1.</label><caption><p>Molecular structure of <bold>2</bold>.</p></caption><graphic xlink:href="10600_2018_2330_Fig1_HTML" id="MO2"></graphic></fig><table-wrap id="Tab1"><label>Table 1.</label><caption><p>Main Crystallographic and X-ray Structure Analysis Parameters for <bold>2</bold></p></caption><table frame="hsides" rules="groups"><thead><tr><th>Parameter</th><th><bold>2</bold></th><th>Parameter</th><th><bold>2</bold></th></tr></thead><tbody><tr><td>Molecular formula</td><td>C<sub>27</sub>H<sub>36</sub>O<sub>3</sub></td><td>ρ, g/cm<sup>3</sup></td><td>1.184</td></tr><tr><td>MM, g/mol</td><td>408.6</td><td>Crystal size, mm</td><td>0.3 × 0.4 × 00.4</td></tr><tr><td>System</td><td>Orthorhombic</td><td>Scan range</td><td>3.31≤ θ ≤75.78</td></tr><tr><td>Space group</td><td>P 2<sub>1</sub>2<sub>1</sub>2<sub>1</sub></td><td>μ<sub>exp</sub>, cm<sup>–1</sup></td><td>0.587</td></tr><tr><td>Z</td><td>4</td><td>Number of reflections</td><td>3907</td></tr><tr><td><italic>a</italic>, Å</td><td>6.1398 (2)</td><td>Number of reflections with I > 2σ(I)</td><td>2884</td></tr><tr><td><italic>b,</italic> Å</td><td>16.5469 (5)</td><td>R1 (I > 2σ (I) and total)</td><td>0.0485 (0.0668)</td></tr><tr><td><italic>c</italic>, Å</td><td>22.5683 (8)</td><td>WR<sub>2</sub></td><td>0.1250 (0.1388)</td></tr><tr><td>α</td><td>90.00</td><td>GOOF</td><td>0.868</td></tr><tr><td>β</td><td>90.00</td><td>Electron-density difference peaks (e Å<sup>–3</sup>)</td><td>0.13 and –0.16</td></tr><tr><td>γ</td><td>90.00</td><td>CCDC</td><td>1570849</td></tr><tr><td><italic>V</italic>, Å<sup>3</sup></td><td>2292.8 (2)</td><td></td><td></td></tr></tbody></table></table-wrap></p><p id="Par11">The orientation of the oxy substituent was 3<italic>β</italic>-equatorial; of the C10 and C13 methyls, <italic>β</italic>-axial. This was confirmed by the Flack parameter of –0.5(4) that became 0.8(3) for the inverted calculation. The molecule of <bold>2</bold> had a ketone [C17=O, 1.207(3) Å] according to the bond length. As expected, the ring fusions were A/B-, B/C-, and C/D-<italic>trans</italic>. Rings A, B, and C had canonical chair conformations; five-membered ring D, C14-envelope.</p><p id="Par12">Antiviral activity of <bold>3</bold>–<bold>7</bold> and <bold>9</bold>–<bold>12</bold> was studied and showed that hydrazone <bold>4</bold> had high; <bold>5</bold>, <bold>10</bold>, and <bold>12</bold>, moderate; and pyrazoline <bold>9</bold>, weak antiviral activity against <italic>Polio virus</italic> (Vero 76 cell culture, strain Type 3, WM-3) (Table <xref rid="Tab2" ref-type="table">2</xref>). The other steroids were inactive. Hydrazones <bold>4</bold> and <bold>5</bold> were weakly active against <italic>Sars corona virus</italic> (Vero 76 cell culture, strain Urbani). The other compounds were inactive. Compounds <bold>5</bold>, <bold>9</bold>, and <bold>12</bold> were weakly active whereas the other steroids were inactive against <italic>Rift valley fevervirus</italic> (Vero 76 cell culture, strain MP-12). Only hydrazone <bold>5</bold> exhibited weak activity against <italic>Takaribe virus</italic> (Vero cell culture, strain TRVL-11573). All steroids <bold>3</bold>–<bold>7</bold> and <bold>9</bold>–<bold>12</bold> were inactive against <italic>Venezuelan equine encephalitis virus</italic>, <italic>Respiratory syncytial virus</italic>, <italic>Influenza A virus</italic> H<sub>1</sub>N<sub>1</sub>, and <italic>Dengue virus</italic> (Vero cell culture, MA-104, MDCK; Vero 76; strains TC-83; A-2; California 07.2009; Type 2, New Guinea C, respectively).<table-wrap id="Tab2"><label>Table 2.</label><caption><p>Data for <italic>in vitro</italic> Screening of Antiviral Activity of <bold>3</bold>–<bold>7</bold> and <bold>9</bold>–<bold>12</bold></p></caption><table frame="hsides" rules="groups"><thead><tr><th rowspan="2">Compound</th><th colspan="3"><italic>Polio virus</italic> (Pirodavir)</th><th colspan="3"><italic>SARS corona virus</italic> (M128533)</th><th colspan="3"><italic>Rift Valley fever virus</italic> (Ribavirin)</th><th colspan="3"><italic>Tacaribe virus</italic> (Ribavirin)</th></tr><tr><th>c</th><th>CC<sub>50</sub></th><th>Sl<sub>50</sub></th><th>EC<sub>50</sub></th><th>CC<sub>50</sub></th><th>Sl<sub>50</sub></th><th>EC<sub>50</sub></th><th>CC<sub>50</sub></th><th>Sl<sub>50</sub></th><th>EC<sub>50</sub></th><th>CC<sub>50</sub></th><th>Sl<sub>50</sub></th></tr></thead><tbody><tr><td colspan="13">Visual (cytopathic effect/toxicity)</td></tr><tr><td><bold>3</bold></td><td>2.8</td><td>3.2</td><td>1.1</td><td>>3.2</td><td>3.2</td><td>0</td><td>3.2</td><td>8.6</td><td>2.7</td><td>3.2</td><td>3.2</td><td>1</td></tr><tr><td><bold>4</bold></td><td>0.32</td><td>100</td><td>310</td><td>3.2</td><td>15</td><td>4.7</td><td>31</td><td>68</td><td>2.2</td><td>31</td><td>46</td><td>1.5</td></tr><tr><td><bold>5</bold></td><td>1</td><td>10</td><td>10</td><td>6.8</td><td>32</td><td>4.7</td><td>3.2</td><td>13</td><td>4.1</td><td>3.2</td><td>15</td><td>4.7</td></tr><tr><td><bold>6</bold></td><td>22</td><td>100</td><td>4.5</td><td>>32</td><td>32</td><td>0</td><td>>100</td><td>>100</td><td>0</td><td>32</td><td>42</td><td>1.3</td></tr><tr><td><bold>7</bold></td><td>3.4</td><td>12</td><td>3.5</td><td>3.7</td><td>28</td><td>7.6</td><td>3.2</td><td>5.6</td><td>1.8</td><td>>13</td><td>13</td><td>0</td></tr><tr><td><bold>9</bold></td><td>3.2</td><td>22</td><td>6.9</td><td>>5.2</td><td>5.2</td><td>0</td><td>1.8</td><td>12</td><td>6.7</td><td>12</td><td>24</td><td>2</td></tr><tr><td><bold>10</bold></td><td>2.4</td><td>>100</td><td>>42</td><td>>28</td><td>28</td><td>0</td><td>1.9</td><td>14</td><td>7.4</td><td>>30</td><td>30</td><td>0</td></tr><tr><td><bold>11</bold></td><td>32</td><td>>100</td><td>>3.1</td><td>>32</td><td>32</td><td>0</td><td>>100</td><td>>100</td><td>0</td><td>>100</td><td>>100</td><td>0</td></tr><tr><td><bold>12</bold></td><td>0.32</td><td>10</td><td>31</td><td>>19</td><td>19</td><td>0</td><td>3.2</td><td>10</td><td>3.1</td><td>5</td><td>18</td><td>3.6</td></tr><tr><td>Control</td><td>0.32</td><td>>10</td><td>>31</td><td>0.68</td><td>>100</td><td>>150</td><td>6.8</td><td>>1000</td><td>>150</td><td>6.5</td><td>>1000</td><td>>150</td></tr><tr><td colspan="13">Neutral red (cytopathic effect/toxicity)</td></tr><tr><td><bold>3</bold></td><td>2.8</td><td>3.6</td><td>1.3</td><td>>4.3</td><td>4.3</td><td>0</td><td>6.6</td><td>7.5</td><td>1.1</td><td>>4.8</td><td>4.8</td><td>0</td></tr><tr><td><bold>4</bold></td><td>0.35</td><td>>100</td><td>>290</td><td>4.6</td><td>24</td><td>5.2</td><td>>56</td><td>56</td><td>0</td><td>>32</td><td>32</td><td>0</td></tr><tr><td><bold>5</bold></td><td>0.52</td><td>20</td><td>38</td><td>2.2</td><td>21</td><td>9.5</td><td>1.2</td><td>5.2</td><td>4.3</td><td>4.1</td><td>18</td><td>4.4</td></tr><tr><td><bold>6</bold></td><td>92</td><td>>100</td><td>>1.1</td><td>>100</td><td>>100</td><td>0</td><td>>100</td><td>>100</td><td>0</td><td>>100</td><td>>100</td><td>0</td></tr><tr><td><bold>7</bold></td><td>7</td><td>26</td><td>3.7</td><td>>17</td><td>17</td><td>0</td><td>3.2</td><td>3.9</td><td>1.2</td><td>>24</td><td>24</td><td>0</td></tr><tr><td><bold>9</bold></td><td>2.2</td><td>100</td><td>45</td><td>>28</td><td>28</td><td>0</td><td>1.7</td><td>14</td><td>8.2</td><td>25</td><td>28</td><td>1.1</td></tr><tr><td><bold>10</bold></td><td>3.1</td><td>15</td><td>4.8</td><td>3.2</td><td>4.5</td><td>1.4</td><td>2.3</td><td>14</td><td>6.1</td><td>12</td><td>27</td><td>2.3</td></tr><tr><td><bold>11</bold></td><td>30</td><td>>100</td><td>>3.3</td><td>36</td><td>63</td><td>1.8</td><td>>100</td><td>>100</td><td>0</td><td>>100</td><td>>100</td><td>0</td></tr><tr><td><bold>12</bold></td><td>0.28</td><td>19</td><td>68</td><td>>5.5</td><td>5.5</td><td>0</td><td>2.8</td><td>5</td><td>1.8</td><td>7</td><td>20</td><td>2.9</td></tr><tr><td>Control</td><td>0.3</td><td>>10</td><td>>33</td><td>1.8</td><td>>100</td><td>>56</td><td>8.6</td><td>>1000</td><td>>120</td><td>7.1</td><td>>1000</td><td>>140</td></tr></tbody></table><table-wrap-foot><p>EC<sub>50</sub> is the compound concentration inhibiting virus replication by 50%; CC<sub>50</sub>, compound concentration reducing cell survival by 50%; SI<sub>50</sub> = CC<sub>50</sub>/EC<sub>50</sub>.</p></table-wrap-foot></table-wrap></p><sec id="Sec1"><title>Experimental</title><p id="Par13">PMR and <sup>13</sup>C NMR spectra were recorded from CDCl<sub>3</sub> and DMSO-d<sub>6</sub> solutions with TMS internal standard on a Bruker Avance 400 instrument (400.13 MHz for <sup>1</sup>H and 100.61 MHz for <sup>13</sup>C). IR spectra were taken from KBr pellets on a Varian 660 FTIR spectrometer. Mass spectra were obtained on an HPLC-APCIMS (positive mode)-Agilent 1100 Series with an Inertsil PREP-ODS column (6.0 × 250 mm) and elution of steroids by H<sub>2</sub>O–MeCN (20:80). Melting points were determined on a NAGEMA apparatus. The course of reactions and purity of synthesized compounds were monitored by TLC on Silufol UV-254 plates using C<sub>6</sub>H<sub>6</sub>–Me<sub>2</sub>CO (10:1, 6:1). Chromatograms were detected using phosphomolybdic acid solution (10%) in EtOH followed by heating.</p><p id="Par14"><bold>3</bold><italic>β</italic><bold>-Phenylacetoxy-5</bold>α<bold>-androstan-17-one (2).</bold> A solution of epiandrosterone <bold>1</bold> (0.3 g, 1 mmol) in anhydrous C6H6 (20 mL) and anhydrous Py (0.3 mL) was treated with phenylacetic acid chloride (0.19 g, 1.2 mmol), refluxed for 6 h, cooled to room temperature, diluted with H<sub>2</sub>O, and extracted with Et2O (3 × 20 mL). The Et<sub>2</sub>O extracts were washed with H<sub>2</sub>O, Na<sub>2</sub>CO<sub>3</sub> solution, and H<sub>2</sub>O; dried over Na<sub>2</sub>SO<sub>4</sub>; and evaporated to isolate <bold>2</bold> (0.31 g, 74%), mp 160–162C. IR spectrum (KBr, <italic>v</italic>, cm<sup>–1</sup>): 1750, 1700 (C=O), 1535 (arom. ring). <sup>1</sup>H NMR spectrum (CDCl<sub>3</sub>, δ, ppm): 0.86 (3H, s, 18-CH<sub>3</sub>), 1.27 (3H, s, 19-CH<sub>3</sub>), 2.20–2.45 (2H, m, H-16), 3.60 (2H, s, <underline>CH</underline><sub><underline>2</underline></sub>C<sub>6</sub>H<sub>5</sub>), 4.72 (1H, m, H-3), 7.28–7.33 (5H, m, C<sub>6</sub>H<sub>5</sub>). <sup>13</sup>C NMR spectrum (CDCl<sub>3</sub>, δ, ppm): 12.2, 13.8, 20.4, 21.7, 27.3, 28.2, 29.6, 30.8, 31.5, 33.8, 35.0, 35.4, 36.7, 41.7 (CH<sub>2</sub>C<sub>6</sub>H<sub>5</sub>), 44.6, 47.7, 51.3, 54.3, 74.0 (C-3), 126.9 (C-4′), 128.5 (C-3′, 5′), 129.2 (C-2′, 6′), 134.3 (C-1′), 171.1 (O–C=O), 221.3 (C=O). LC-MS <italic>m/z</italic> 409.6 [M + H]<sup>+</sup>. C<sub>27</sub>H<sub>36</sub>O<sub>3</sub>. MM 408.6.</p><p id="Par15"><bold>17-Hydroxyimino-3</bold><italic>β</italic><bold>-phenylacetoxy-5</bold>α<bold>-androstane (3).</bold> A mixture of ketone <bold>2</bold> (0.5 g, 1.44 mmol) and hydroxylamine hydrochloride (0.1 g, 1.47 mmol) in Py (5 mL) was heated for 3 h at 65°C, cooled, and poured into ice water (30 mL). The precipitate was filtered off, rinsed with H<sub>2</sub>O, and dried. Crystallization from MeOH produced oxime <bold>3</bold> (0.45 g, 86%), mp 154–156C. IR spectrum (KBr, <italic>v</italic>, cm<sup>–1</sup>): 3260 (OH), 1735 (C=O), 1680 (C=N), 1524 (arom. ring). <sup>1</sup>H NMR spectrum (CDCl<sub>3</sub>, δ, ppm): 0.83 (3H, s, 18-CH<sub>3</sub>), 0.89 (3H, s, 19-CH<sub>3</sub>), 2.40–2.56 (2H, m, H-16), 3.58 (2H, s, <underline>CH</underline><sub>2</sub>C<sub>6</sub>H<sub>5</sub>), 4.69 (1H, m, H-3), 7.26–7.34 (5H, m, C<sub>6</sub>H<sub>5</sub>), 7.93 (1H, br.s, C=N–OH). <sup>13</sup>C NMR spectrum (CDCl<sub>3</sub>, δ, ppm): 12.2, 17.2, 20.7, 23.1, 25.0, 27.3, 28.3, 31.4, 33.9, 34.0, 34.8, 35.6, 36.6, 41.7 (<underline>C</underline>H<sub>2</sub>C<sub>6</sub>H<sub>5</sub>), 44.0, 44.6, 53.8, 54.3, 74.1 (C-3), 126.9 (C-4′), 128.4 (C-3′, 5′), 129.1 (C-2′, 6′), 134.3 (C-1′), 171.1 (C=N), 171.3 (O–C=O). LC-MS <italic>m/z</italic> 424.6 [M + H]<sup>+</sup>. C<sub>27</sub>H<sub>37</sub>NO<sub>3</sub>. MM 423.6.</p><p id="Par16"><bold>3</bold><italic>β</italic><bold>-Phenylacetoxy-5</bold>α<bold>-androstan-17-one</bold><bold><italic>m</italic></bold><bold>-nitrobenzoylhydrazone (4)</bold> was prepared by the literature method [<xref ref-type="bibr" rid="CR5">5</xref>]. Yield 72%, mp 184–186C. IR spectrum (KBr, <italic>v</italic>, cm<sup>–1</sup>): 3450 (NH), 1729 (C=O), 1665 (NH–CO), 1640 (C=N), 1531 (arom. ring), 1500 and 1348 (Ar-NO<sub>2</sub>). <sup>1</sup>H NMR spectrum (CDCl<sub>3</sub>, δ, ppm, J/Hz): 0.77 (3H, s, 18-CH<sub>3</sub>), 0.82 (3H, s, 19-CH<sub>3</sub>), 2.23–2.37 (2H, m, H-16), 3.51 (2H, s, <underline>CH</underline><sub>2</sub>C<sub>6</sub>H<sub>5</sub>), 4.61 (1H, m, H-3), 7.17–7.25 (5H, m, C<sub>6</sub>H<sub>5</sub>), 7.54 (1H, t, J = 8.1, H-5″), 8.10 (1H, d, J = 7.1, H-6″), 8.26 (1H, d, J = 7.3, H-4″), 8.40 (1H, s, H-2″), 8.48 (1H, br.s, <italic>trans-</italic>NH), 8.93 (1H, br.s, <italic>cis</italic>-NH). <sup>13</sup>C NMR spectrum (CDCl<sub>3</sub>, δ, ppm): 12.3, 16.9, 20.7, 23.4, 25.2, 27.4, 28.4, 30.8, 31.4, 33.9, 34.9, 35.7, 36.8, 41.8 (<underline>C</underline>H<sub>2</sub>C<sub>6</sub>H<sub>5</sub>), 44.7, 51.5, 53.5, 54.4, 74.3 (C-3), 125.8 (C-2″), 126.2 (C-4″), 127.0 (C-4′), 128.5 (C-3′, 5′), 130.1 (C-5″), 129.2 (C-2′, 6′), 133.6 (C-6″), 134.4 (C-1′), 136.5 (C-1″), 147.4 (C-3″), 166.7 (NHCO), 168.3 (C=N), 171.2 (O–C=O). LC-MS <italic>m/z</italic> 572.8 [M + H]<sup>+</sup>. C<sub>34</sub>H<sub>41</sub>N<sub>3</sub>O<sub>5</sub>. MM 571.8.</p><p id="Par17">Steroids <bold>5</bold>–<bold>7</bold> were prepared analogously.</p><p id="Par18"><bold>3</bold><italic>β</italic><bold>-Phenylacetoxy-5</bold>𝛂<bold>-androstan-17-one Nicotinoylhydrazone (5).</bold> Yield 81%, mp 108–110C. IR spectrum (KBr, <italic>v</italic>, cm<sup>–1</sup>): 3370 (NH), 1728 (CO), 1651 (NHCO), 1610 (C=N), 1589 (arom. ring), 1535 (Py ring). <sup>1</sup>H NMR spectrum (DMSO-d<sub>6</sub>, δ, ppm): 0.85 (3H, s, 18-CH<sub>3</sub>), 0.87 (3H, s, 19-CH<sub>3</sub>), 2.34–2.56 (2H, m, H-16), 3.51 (2H, s, CH<sub>2</sub>C<sub>6</sub>H<sub>5</sub>), 4.61 (1H, m, H-3), 7.17–7.30 (5H, m, C<sub>6</sub>H<sub>5</sub>), 7.32–8.93 (4H, m, C<sub>5</sub>H<sub>4</sub>), 10.25 (1H, br.s, <italic>trans</italic>-NH), 10.32 (1H, br.s, <italic>cis</italic>-NH). LC-MS <italic>m/z</italic> 528.3 [M + H]<sup>+</sup>. C<sub>33</sub>H<sub>41</sub>N<sub>3</sub>O<sub>3</sub>. MM527.3.</p><p id="Par19"><bold>3</bold><italic>β</italic><bold>-Phenylacetoxy-5</bold>α<bold>-androstan-17-one Semicarbazone (6).</bold> Yield 79%, mp 250–252C. IR spectrum (KBr, <italic>v</italic>, cm<sup>–1</sup>): 3479, 3194 (NH<sub>2</sub>, NH), 1726, 1697 (CO), 1630 (C=N), 1581 (arom. ring). <sup>1</sup>H NMR spectrum (DMSO-d<sub>6</sub>, δ, ppm): 0.82 (3H, s, 18-CH<sub>3</sub>), 0.88 (3H, s, 19-CH<sub>3</sub>), 2.18–2.37 (2H, m, H-16), 3.50 (2H, s, CH<sub>2</sub>C<sub>6</sub>H<sub>5</sub>), 4.59 (1H, m, H-3), 5.81 (2H, br.s, NH<sub>2</sub>), 7.17–7.30 (5H, m, C<sub>6</sub>H<sub>5</sub>), 8.54 (1H, s, NH). LC-MS <italic>m/z</italic> 466.3 [M + H]<sup>+</sup>. C<sub>28</sub>H<sub>39</sub>N<sub>3</sub>O<sub>3</sub>. MM.465.3.</p><p id="Par20"><bold>3</bold><italic>β</italic><bold>-Phenylacetoxy-5</bold>α<bold>-androstan-17-one Thiosemicarbazone (7).</bold> Yield 84%, mp 215–217C. 1H NMR spectrum (DMSO-d<sub>6</sub>, δ, ppm): 0.84 (3H, s, 18-CH<sub>3</sub>), 0.90 (3H, s, 19-CH<sub>3</sub>), 2.32–2.55 (2H, m, H-16), 3.50 (2H, s, CH<sub>2</sub>C<sub>6</sub>H<sub>5</sub>), 4.59 (1H, m, H-3), 7.18–7.32 (5H, m, C<sub>6</sub>H<sub>5</sub>), 7.03 (1H, br.s, NH<sub>2</sub>) and 7.79 (1H, br.s, NH<sub>2</sub>), 9.55 (1H, s, NH). <sup>13</sup>C NMR spectrum (CDCl<sub>3</sub>, δ, ppm): 12.2, 17.0, 20.6, 23.3, 26.0, 27.3, 28.2, 31.3, 33.8, 33.9, 34.9, 35.6, 36.7, 41.7 (<underline>C</underline>H<sub>2</sub>C<sub>6</sub>H<sub>5</sub>), 44.6, 44.9, 53.3, 54.3, 74.0 (C-3), 126.9 (C-4′), 128.5 (C-3′, 5′), 129.1 (C-2′, 6′), 134.3 (C-1′), 167.4 (C=N), 171.2 (O–C=O), 178.9 (C=S). LC-MS <italic>m/z</italic> 482.7 [M + H]<sup>+</sup>. C<sub>28</sub>H<sub>39</sub>N<sub>3</sub>O<sub>2</sub>S. MM 481.7.</p><p id="Par21"><bold>Antiviral activity</bold> of the synthesized compounds was studied in the framework of the international program “AACF Antiviral Testing in Animals” at the Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases, University of Utah, USA. In particular, all newly tested compounds were evaluated initially a) for inhibition of virus cytopathic effects (CPE assay) and b) for uptake of neutral red dye (NR Dye Uptake Assay) that stained undamaged virus cells. The color intensity was determined spectrophotometrically. The experimental results from a) were used to calculate the 50% inhibitory (cytotoxic) concentration CC<sub>50</sub>; from b), the 50% effective concentration EC<sub>50</sub>. Antiviral activity of each tested compounds was characterized by the selectivity index (SI<sub>50</sub>), which was the ratio of CC<sub>50</sub> to EC<sub>50</sub>. As a rule, SI50 values of 10 or more indicated the presence of antiviral activity for the compound. The method was described in detail before [<xref ref-type="bibr" rid="CR12">12</xref>].</p><p id="Par22"><bold>XSA.</bold> A single crystal of <bold>2</bold> for the XSA was obtained by slow evaporation of an appropriate solvent at room temperature. Unit-cell constants of the crystal of <bold>2</bold> were determined and refined on a CCDXcalibur Ruby diffractometer (Oxford Diffraction) using Cu Kα-radiation (300 K, graphite monochromator) [<xref ref-type="bibr" rid="CR13">13</xref>]. A three-dimensional dataset of reflections was obtained on the same diffractometer. Absorption corrections for the crystals were made semi-empirically using the SADABS program [<xref ref-type="bibr" rid="CR14">14</xref>].</p><p id="Par23">Table <xref rid="Tab1" ref-type="table">1</xref> presents the main XSA and refinement parameters for the structure of <bold>2</bold>.</p><p id="Par24">The structure was solved by direct methods using the SHELXS-97 program suite and refined using the SHELXL-97 program [<xref ref-type="bibr" rid="CR15">15</xref>]. All nonhydrogen atoms were refined by full-matrix anisotropic least-squares methods (over <italic>F</italic><sup>2</sup>). Positions of H atoms were found geometrically and refined with fixed isotropic thermal factors <italic>U</italic><sub><italic>iso</italic></sub> = n<italic>U</italic><sub><italic>eq</italic></sub>, where n = 1.5 for methyls and 1.2 for others and <italic>U</italic><sub><italic>eq</italic></sub> is the equivalent isotropic thermal factor of the corresponding C atom.</p><p id="Par25">Results from the XSA were deposited as a CIF-file in the Cambridge Crystallographic Data Centre (CCDC).</p></sec></body><back><fn-group><fn><p>Translated from <italic>Khimiya Prirodnykh Soedinenii</italic>, No. 2, March–April, 2018, pp. 260–264.</p></fn></fn-group><ack><title>Acknowledgment</title><p>The work was financially supported by the Shota Rustaveli National Science Foundation of Georgia (Grant No. YS-2016-51, Potential Bioactive Steroidal Nitrogen-containing Compounds).</p></ack><ref-list id="Bib1"><title>References</title><ref id="CR1"><label>1.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gan</surname><given-names>C</given-names></name><name><surname>Cui</surname><given-names>J</given-names></name><name><surname>Su</surname><given-names>S</given-names></name><name><surname>Lin</surname><given-names>Q</given-names></name><name><surname>Jia</surname><given-names>L</given-names></name><name><surname>Fan</surname><given-names>L</given-names></name><name><surname>Huang</surname><given-names>Y</given-names></name></person-group><source>Steroids</source><year>2014</year><volume>87</volume><fpage>99</fpage><pub-id pub-id-type="doi">10.1016/j.steroids.2014.05.026</pub-id><pub-id pub-id-type="pmid">24928726</pub-id></element-citation></ref><ref id="CR2"><label>2.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ke</surname><given-names>S</given-names></name><name><surname>Shi</surname><given-names>L</given-names></name><name><surname>Yang</surname><given-names>Z</given-names></name></person-group><source>Bioorg. 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