01952nas a2200217   4500008004100000022001400041245018200055210006900237260000900306520106300315653002101378653004201399653001901441653002201460653002301482100002701505700002801532700002601560700002501586856012301611       2021                        eng d  a0039-788100aNickel-catalyzed difunctionalization of alkynyl bromides with thiosulfonates and N-arylthio succinimides: a convenient synthesis of 1,2-thiosulfonylethenes and 1,1-dithioethenes0 aNickelcatalyzed difunctionalization of alkynyl bromides with thi  cAPR 3 a<p>An efficient nickel-catalyzed vicinal thiosulfonylation of 1bromoalkynes with thiosulfonates in the presence of cesium carbonate is described. An operationally simple and highly regioselective atom transfer radical addition (ATRA) of alkynyl bromides provides a wide range of (E)-1,2-thiosulfonylethenes (alpha-aryl-beta-thioarylvinyl sulfones) in moderate to high yields. The extensive substrate scope of both alkynyl bromides and thiosulfonates is explored with a broad range of functional groups. Indole-derived 1,1- bromoalkenes were also successfully explored in this 1,2-thiosulfonylation process. Moreover, the nickel-catalyzed geminal- dithiolation of alkynyl bromides with N-arylthio succinimides provides 1,1-dithioalkenes in high yields. The present protocol is reliable on gram scale, and a sequential one-pot bromination and thiosulfonylation of phenylacetylene is achieved in a scale-up synthesis. Following control experiments, a plausible mechanism is proposed to rationalize the experimental outcome and the vicinal thiosulfonylation.</p>10aalkynyl bromides10aatom transfer radical addition (ATRA)10athiosulfonates10athiosulfonylation10avinyl thiosulfones1 aKumari, Arram, Haritha1 aKumar, Jangam, Jagadesh1 aKrishna, Gamidi, Rama1 aReddy, Raju, Jannapu  uhttps://library.ncl.res.in/content/nickel-catalyzed-difunctionalization-alkynyl-bromides-thiosulfonates-and-n-arylthio02137nas a2200217   4500008004100000245016400041210006900205260000800274300001400282490000700296520127000303100003101573700002301604700002601627700002601653700002101679700002501700700003301725700003001758856013101788       2022                        eng d00aNovel pharmaceutical cocrystal of apalutamide, a nonsteroidal antiandrogen drug: synthesis, crystal structure, dissolution, stress, and excipient compatibility0 aNovel pharmaceutical cocrystal of apalutamide a nonsteroidal ant  cJAN  a1130-11420 v223 aApalutamide (APA), a second-generation nonsteroidal antiandrogen BCS Class II drug with poor solubility and high permeability. A novel 1:1 cocrystal of Apalutamide (APA) with methylparaben (MP) was identified by cooling crystallization during the cocrystal screening and characterized by various solid-state techniques, such as PXRD, DSC, TGA, FT-IR, and 13C solid-state CP-MAS NMR spectroscopy. The crystal structures of APA and its cocrystal (APA-MP) were determined by the SC-XRD technique. The crystal structure analysis of the APA-MP cocrystal revealed that the APA and MP molecules are connected through strong O–H···O hydrogen bonds. The novel cocrystal improves the solubility and dissolution rate in different physiological conditions compared to poorly soluble APA due to strong hydrogen bond between the drug and the coformer. The cocrystal is stable (physically and chemically) under stress conditions, such as exposure to the relative humidity, mechanical grinding, open exposure to atmosphere at cRT (critical room temperature) and compression pressure of 10 tons. In addition, the compatibility of the cocrystal with excipients used in the drug product of APA (ERLEADA) was also investigated, and no disproportionation of cocrystal was observed.1 aSaladi, Venkata, Narasayya1 aKammari, Bal, Raju1 aMandad, Pratap, Reddy1 aKrishna, Gamidi, Rama1 aSajja, Eswaraiah1 aThirumali, Rajan, S.1 aMarutapilli, Arthanareeswari1 aMathad, Vijayavitthal, T.  uhttps://library.ncl.res.in/content/novel-pharmaceutical-cocrystal-apalutamide-nonsteroidal-antiandrogen-drug-synthesis-crystal02754nas a2200229   4500008004100000245008700041210006900128260000900197300001200206490000700218520202400225653001702249653001202266653001502278653000902293653001902302100002502321700002002346700002602366700002102392856011102413       2024                        eng d00aNovel molecular adducts of an anti-cancer drug vandetanib with enhanced solubility0 aNovel molecular adducts of an anticancer drug vandetanib with en  cJAN   a248-2600 v263 a<p>The solubility, permeability, and dissolution rate of an active pharmaceutical ingredient (API) are critical factors in determining its pharmacokinetic performance in oral dosage forms. Modifying these properties can potentially enhance the drug's pharmacokinetics. Vandetanib (VDTB), classified as a class II anti-cancer drug in the biopharmaceutical classification system (BCS), suffers from low solubility (0.008 mg mL-1) and an extended pharmacokinetic half-life (19 days), necessitating the administration of high doses, which leads to undesirable side effects. To address this issue, we have employed a crystal engineering approach to enhance the solubility of VDTB. We employed the liquid-assisted grinding (LAG) method followed by the slow evaporation technique to prepare novel solid forms of VDTB by incorporating various aliphatic dicarboxylic acids, including succinic acid (SUA), adipic acid (ADA), pimelic acid (PIA), azelaic acid (AZA), and sebacic acid (SBA). These newly obtained solid forms were characterized by SC-XRD, PXRD, TGA, and DSC experiments. The crystal structure analyses revealed a proton transfer between the carboxylic acid group of aliphatic acids and the N-methyl piperidine moiety of VDTB, confirming salt/adduct formation. Additionally, all of the molecular salts were stabilized by charge-assisted N+-HMIDLINE HORIZONTAL ELLIPSISO- hydrogen bonds, while the parent VDTB crystal structure is stabilised by N-HMIDLINE HORIZONTAL ELLIPSISN interactions. Moreover, the solubility and dissolution rate of these new solid forms were assessed in a pH 7.4 phosphate buffer medium, with the results indicating that all of the solid forms, except for VDTB:SBA, exhibited higher solubility compared to pure VDTB. These findings offer promising prospects for the development of an improved VDTB formulation with enhanced pharmacokinetic properties. Successful attempt to improve the solubility and dissolution rate of Vandetanib - an anti-cancer drug, by crystal engineering approach.</p>
10aAmorfization10ahydrate10aParameters10aSalt10aThyroid-Cancer1 aBandaru, Ravi, Kumar1 aGiri, Lopamudra1 aKrishna, Gamidi, Rama1 aDandela, Rambabu  uhttps://library.ncl.res.in/content/novel-molecular-adducts-anti-cancer-drug-vandetanib-enhanced-solubility