03693nas a2200313   4500008004100000022001400041245011200055210006900167260000800236300001300244490000700257520263800264653001802902653002502920653002202945653002602967653001902993653002903012100002403041700002203065700002303087700001903110700002403129700003303153700002003186700002103206700002303227856012903250       2020                        eng d  a1573-406400aAntidiabetic activity of dihydropyrimidine scaffolds and structural insight by single crystal x-ray studies0 aAntidiabetic activity of dihydropyrimidine scaffolds and structu  cJAN  a996-10030 v163 a<p>Background: This research project is designed to identify the anti-diabetic effects of the newly synthesized compounds to conclude the perspective of consuming one or more of these new synthetic compounds for diabetes management. Introduction: A series of dihydropyrimidine (DHPM) derivative bearing electron releasing and electron-withdrawing substituent's on phenyl ring (a-j) were synthesized and screened for antihyperglycemic(anti-diabetic) activity on streptozotocin (STZ) induced diabetic rat model. The newly synthesized compounds were characterized by using FT-IR, melting point, H-1 and C-13 NMR analysis. The crystal structure and supramolecular features were analyzed through single-crystal X-ray study. Anti-diabetic activity testing of newly prepared DHPM scaffolds was mainly based on their relative substituent on the phenyl ring along with urea and thiourea. Among the synthesized DHPM scaffold, the test compound c having chlorine group on phenyl ring at the ortho position to the hydropyrimidine ring with urea and methyl acetoacetate derivative shows moderate lowering of glucose level. However, the title compounds methyl 4-(4-hydroxy-3-methoxyphenyl)-6-methyl-2-thioxo-1,2,3,4-tetrahydropyrimi dine-5-carboxylate(g) and ethyl 4-(3-ethoxy-4-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydroprimidine- 5-carboxylate(h) having methoxy and ethoxy substituents on phenyl ring show significant hypoglycemic activity compared to the remaining compounds from the Scheme 1. Methods: The experimental rat models for the study were divided into 13 groups (n = 10); group 1 animals were treated with 0.5% CMC (0.5mL) (vehicle); group 2 were considered the streptozotocin (STZ)/nicotinamide diabetic control group (DC) and untreated, group 3 diabetic animals were administered with gliclazide 50 mg/kg and act as a reference drug group. The remaining groups of the diabetic animals were administered with the newly synthesized dihydropyrimidine compounds in a single dose of 50 mg/kg orally using the oral gavage, daily for 7 days continuously. The blood glucose level was measured before and 72 hrs after nicotinamide-STZ injection, for confirmation of hyperglycemia and type 2 diabetes development. Results: Blood glucose levels were significantly (p&lt;0.05) reduced after treatment with these derivatives. The mean percentage reduction for gliclazide was 50%, while that of synthesized compounds were approximately 36%. Conclusion: Our result suggests that the synthesized new DEEM derivative containing alkoxy group on the phenyl ring shows a significant lowering of glucose level compared to other derivatives.</p>
10aanti-Diabetic10ablood glucose levels10adihydropyrimidine10ahypoglycemic activity10aStreptozotocin10atype 2 diabetes mellitus1 aBairagi, Keshab, M.1 aYounis, Nancy, S.1 aEmeka, Promise, M.1 aSangtani, Ekta1 aGonnade, Rajesh, G.1 aVenugopala, Katharigatta, N.1 aAlwassil, Osama1 aKhalil, Hany, E.1 aNayak, Susanta, K.  uhttps://library.ncl.res.in/content/antidiabetic-activity-dihydropyrimidine-scaffolds-and-structural-insight-single-crystal-x10568nas a2200205   4500008004100000245015900041210006900200260000800269490000700277520974600284100002110030700002410051700002410075700002310099700003310122700003210155700002410187700002310211856012810234       2020                        eng d00aSynthesis, crystal structure and Hirshfeld surface analysis of the hydrated form of N’, N-(1,4-phenylenebis(methanylylidene) di(iso-nicotinic hydrazide)0 aSynthesis crystal structure and Hirshfeld surface analysis of th  cAUG0 v283 a<p><span style="color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-size: 18px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">The title compound, C</span><span style="font-size: 13.5px; line-height: 0; position: relative; bottom: -0.25em; color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">20</span><span style="color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-size: 18px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">H</span><span style="font-size: 13.5px; line-height: 0; position: relative; bottom: -0.25em; color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">16</span><span style="color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-size: 18px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">N</span><span style="font-size: 13.5px; line-height: 0; position: relative; bottom: -0.25em; color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">6</span><span style="color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-size: 18px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">O</span><span style="font-size: 13.5px; line-height: 0; position: relative; bottom: -0.25em; color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">2</span><span style="color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-size: 18px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">&nbsp;was synthesized by reflux with isonicotinic hydrazide and terephthaldehyde in ethanol solvent with the acidic condition. The single-crystal X-ray structure determination of the title compound,&nbsp;</span><em style="color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-size: 18px; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">N, N</em><span style="color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-size: 18px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">-(1,4-phenylene bis (methanylylidene) di(iso-nicotinic hydrazide), reveals that the molecule crystallizes in center of symmetry with water molecules (Dihydrated form, C</span><span style="font-size: 13.5px; line-height: 0; position: relative; bottom: -0.25em; color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">20</span><span style="color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-size: 18px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">H</span><span style="font-size: 13.5px; line-height: 0; position: relative; bottom: -0.25em; color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">16</span><span style="color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-size: 18px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">N</span><span style="font-size: 13.5px; line-height: 0; position: relative; bottom: -0.25em; color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">6</span><span style="color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-size: 18px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">O</span><span style="font-size: 13.5px; line-height: 0; position: relative; bottom: -0.25em; color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">2</span><span style="color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-size: 18px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">.2H</span><span style="font-size: 13.5px; line-height: 0; position: relative; bottom: -0.25em; color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">2</span><span style="color: rgb(46, 46, 46); font-family: NexusSerif, Georgia, &quot;Times New Roman&quot;, Times, STIXGeneral, &quot;Cambria Math&quot;, &quot;Lucida Sans Unicode&quot;, &quot;Microsoft Sans Serif&quot;, &quot;Segoe UI Symbol&quot;, &quot;Arial Unicode MS&quot;, serif; font-size: 18px; font-style: normal; font-variant-ligatures: normal; font-variant-caps: normal; font-weight: 400;">O) through N-H∙∙∙O and C-H∙∙∙O hydrogen bondings. Further, the crystal structure is stabilized by O-H∙∙∙O and weak C-H∙∙∙N hydrogen bondings with the formation of infinite chain and dimer. Further, surface analysis and fingerprint plot reveal that the significant hydrogen bonding such as H•••O (15.9%) and N•••H (11.4%) interactions play the most crucial role for its molecular packing.</span></p>1 aIngle, Kapil, S.1 aMohurle, Smital, A.1 aBairagi, Keshab, M.1 aShaikh, Tabrez, R.1 aVenugopala, Katharigatta, N.1 aChandrashekharappa, Sandeep1 aGonnade, Rajesh, G.1 aNayak, Susanta, K.  uhttps://library.ncl.res.in/content/synthesis-crystal-structure-and-hirshfeld-surface-analysis-hydrated-form-n%E2%80%99-n-1402241nas a2200301   4500008004100000022001400041245010500055210006900160260000900229300001100238490000900249520122300258653002901481653001701510653002501527653003601552100002401588700002601612700002501638700003301663700000501696700002401701700001901725700002401744700002201768700002301790856012601813       2021                        eng d  a0022-286000aChemistry, anti-diabetic activity and structural analysis of substituted dihydropyrimidine analogues0 aChemistry antidiabetic activity and structural analysis of subst  cMAR   a1294120 v12273 a<p>In an effort to identify an anti-diabetic agent, a series of methyl/ethyl 4-(hydroxyphenyl)-6-methyl-2-oxo/thioxo-1,2,3,4 tetrahydropyrimidine-5-carboxylate analogues (4a-h) have been synthesized, purified, and characterized by using Fourier-Transform Infrared Spectroscopy (FT-IR) and NMR (H-1 and C-13). The synthesized compounds were screened for anti-hyperglycemic activity using Streptozotocin (STZ) induced diabetic rat model. The anti-hyperglycemic activity of dihydropyrimidine (DHPM) compound is mainly analyzed with the variation of substituents present on the phenyl ring and urea/thiourea group on pharmacophoric features. Further, the crystal structure and supramolecular characteristics of two compounds 4c and 4f were analyzed through a single-crystal X-ray method and the Hirshfeld Surface Analysis, which shows hydrogen bonding through N-H center dot center dot center dot O and N-H center dot center dot center dot S interactions with the formation of ring motif in the crystal structure. It is interesting to note that among the title compounds, the 4a, 4e, 4f, and 4g significantly displayed a better hypoglycemic effect in vivo rat model study. (C) 2020 Elsevier B.V. All rights reserved.</p>
10aDihydropyrimidine (DHPM)10aHypoglycemia10aStreptozotocin (STZ)10aType-2 diabetes mellitus (T2DM)1 aBairagi, Keshab, M.1 aYounis, Nancy, Safwat1 aEmeka, Promise, Madu1 aVenugopala, Katharigatta, N.1 a1 aKhalil, Hany, Ezzat1 aSangtani, Ekta1 aGonnade, Rajesh, G.1 aMohanlall, Viresh1 aNayak, Susanta, K.  uhttps://library.ncl.res.in/content/chemistry-anti-diabetic-activity-and-structural-analysis-substituted-dihydropyrimidine