{"title":"Synthesis and PASS-assisted evaluation of new heterocyclic compounds containing hydroquinoline scaffolds","authors":"Gizachew Mulugeta Manahelohe, Khidmet Safarovich Shikhaliev","doi":"10.1186/s13065-024-01267-3","DOIUrl":null,"url":null,"abstract":"<div><p>Currently, there is a growing interest in the synthesis of heterocyclic compounds containing hydroquinoline fragments. This surge can be attributed to the broad range of pharmaceutical and industrial applications that these compounds possess. In this study, the synthesis of both linear and fused heterocyclic systems that incorporate hydroquinoline fragments was described. Furthermore, the pharmacological activity spectra of the synthesized compounds were predicted using the in silico method, employing the Prediction of Activity Spectra of Substances (PASS) program. Hydroquinolines containing the nitrile functionality <b>7</b> and <b>8</b> were synthesized through the reaction of the corresponding hydroquinolinecarbaldehyde <b>5a</b>,<b> 6b</b> with hydroxylamine hydrochloride and iodine in aqueous ammonia under ambient conditions, respectively. 2-Phenyl-1,3-oxazol-5(4 H)-ones <b>9a</b>,<b> b</b> and <b>10a</b>,<b> b</b> were synthesized via the condensation of compounds <b>5a</b>,<b> b</b> and <b>6a</b>,<b> b</b> with hippuric acid in acetic acid in 30–60% yield. When the methyl activated 7-methylazolopyrimidines <b>11a</b>,<b> b</b> were reacted with N-alkyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline-6-carbaldehydes <b>6a</b>,<b> b</b>, 60–70% yield of triazolo/pyrazolo[1,5-a]pyrimidin-6-yl carboxylic acids <b>12a</b>,<b> b</b> were obtained. The condensation of 7-hydroxy-1,2,3,4-tetramethyl-1,2-dihydroquinoline <b>3 h</b> with dimethylacetylenedicarboxylate (DMAD) and ethyl acetoacetate afforded cyclic products <b>16</b> and <b>17</b>, respectively. The condensation reaction of 6-formyl-7-hydroxy-1,2,2,4-tetramethyl-1,2-dihydroquinoline <b>5e</b> with methylene-active compounds such as ethyl cyanoacetate/dimethyl-3-oxopentanedioate/ethyl acetoacetate/diethylmalonate/Meldrum’s acid afforded 3-substituted coumarins <b>19</b> and <b>21</b> containing dihydroquinoline moiety. The pentacyclic coumarin <b>22</b> was obtained via the tandom condensation reaction of malononitrile with <b>5e</b> in the presence of a catalytic amount of piperidine in ethanol. The biological activities of the synthesized compounds were predicted using the PASS program. Based on the prognosis, compounds <b>13a</b>, <b>b</b>, and <b>14</b> exhibited a high likelihood of being active as inhibitors of gluconate 2-dehydrogenase, as well as possessing antiallergic, antiasthmatic, and antiarthritic properties, with a probability value (Pa) ranging from 0.849 to 0.870. Furthermore, it was discovered that compounds <b>7</b> and <b>8</b> tended to act as effective progesterone antagonists and displayed antiallergic, antiasthmatic, and antiarthritic effects (Pa = 0.276–0.827). Among the hydroquinolines containing coumarin moieties, compounds <b>17</b>, <b>19a</b>, and <b>19c</b> were predicted to be potent progesterone antagonists, with Pa values of 0.710, 0.630, and 0.615, respectively.</p><h3>Graphical Abstract</h3><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":496,"journal":{"name":"BMC Chemistry","volume":"18 1","pages":""},"PeriodicalIF":4.3000,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://bmcchem.biomedcentral.com/counter/pdf/10.1186/s13065-024-01267-3","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"BMC Chemistry","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1186/s13065-024-01267-3","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Currently, there is a growing interest in the synthesis of heterocyclic compounds containing hydroquinoline fragments. This surge can be attributed to the broad range of pharmaceutical and industrial applications that these compounds possess. In this study, the synthesis of both linear and fused heterocyclic systems that incorporate hydroquinoline fragments was described. Furthermore, the pharmacological activity spectra of the synthesized compounds were predicted using the in silico method, employing the Prediction of Activity Spectra of Substances (PASS) program. Hydroquinolines containing the nitrile functionality 7 and 8 were synthesized through the reaction of the corresponding hydroquinolinecarbaldehyde 5a, 6b with hydroxylamine hydrochloride and iodine in aqueous ammonia under ambient conditions, respectively. 2-Phenyl-1,3-oxazol-5(4 H)-ones 9a, b and 10a, b were synthesized via the condensation of compounds 5a, b and 6a, b with hippuric acid in acetic acid in 30–60% yield. When the methyl activated 7-methylazolopyrimidines 11a, b were reacted with N-alkyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline-6-carbaldehydes 6a, b, 60–70% yield of triazolo/pyrazolo[1,5-a]pyrimidin-6-yl carboxylic acids 12a, b were obtained. The condensation of 7-hydroxy-1,2,3,4-tetramethyl-1,2-dihydroquinoline 3 h with dimethylacetylenedicarboxylate (DMAD) and ethyl acetoacetate afforded cyclic products 16 and 17, respectively. The condensation reaction of 6-formyl-7-hydroxy-1,2,2,4-tetramethyl-1,2-dihydroquinoline 5e with methylene-active compounds such as ethyl cyanoacetate/dimethyl-3-oxopentanedioate/ethyl acetoacetate/diethylmalonate/Meldrum’s acid afforded 3-substituted coumarins 19 and 21 containing dihydroquinoline moiety. The pentacyclic coumarin 22 was obtained via the tandom condensation reaction of malononitrile with 5e in the presence of a catalytic amount of piperidine in ethanol. The biological activities of the synthesized compounds were predicted using the PASS program. Based on the prognosis, compounds 13a, b, and 14 exhibited a high likelihood of being active as inhibitors of gluconate 2-dehydrogenase, as well as possessing antiallergic, antiasthmatic, and antiarthritic properties, with a probability value (Pa) ranging from 0.849 to 0.870. Furthermore, it was discovered that compounds 7 and 8 tended to act as effective progesterone antagonists and displayed antiallergic, antiasthmatic, and antiarthritic effects (Pa = 0.276–0.827). Among the hydroquinolines containing coumarin moieties, compounds 17, 19a, and 19c were predicted to be potent progesterone antagonists, with Pa values of 0.710, 0.630, and 0.615, respectively.
期刊介绍:
BMC Chemistry, formerly known as Chemistry Central Journal, is now part of the BMC series journals family.
Chemistry Central Journal has served the chemistry community as a trusted open access resource for more than 10 years – and we are delighted to announce the next step on its journey. In January 2019 the journal has been renamed BMC Chemistry and now strengthens the BMC series footprint in the physical sciences by publishing quality articles and by pushing the boundaries of open chemistry.