2-Substituted thienotetrahydropyridine derivatives: Allosteric ectonucleotidase inhibitors was written by Schakel, Laura;Mirza, Salahuddin;Pietsch, Markus;Lee, Sang-Yong;Keuler, Tim;Sylvester, Katharina;Pelletier, Julie;Sevigny, Jean;Pillaiyar, Thanigaimalai;Namasivayam, Vigneshwaran;Guetschow, Michael;Mueller, Christa E.. And the article was included in Archiv der Pharmazie (Weinheim, Germany) in 2021.Computed Properties of C4H7NS The following contents are mentioned in the article:
The antithrombotic prodrugs ticlopidine and clopidogrel are thienotetrahydro-pyridine derivatives that are metabolized in the liver to produce thiols that irreversibly block ADP (ADP)-activated P2Y12 receptors on thrombocytes. In their native, nonmetabolized form, both drugs were reported to act as inhibitors of ectonucleoside triphosphate diphosphohydrolase-1 (NTPDase1, CD39). CD39 catalyzes the extracellular hydrolysis of nucleoside tri- and diphosphates, mainly ATP (ATP) and ADP, yielding adenosine monophosphate, which is further hydrolyzed by ecto-5′-nucleotidase (CD73) to produce adenosine. While ATP has proinflammatory effects, adenosine is a potent anti-inflammatory, immunosuppressive agent. Inhibitors of CD39 and CD73 have potential as novel checkpoint inhibitors for the immunotherapy of cancer and infection. In the present study, we investigated 2-substituted thienotetrahydropyridine derivatives, structurally related to ticlopidine, as CD39 inhibitors. Due to their substituent on the 2-position, they will not be metabolically transformed into reactive thiols and can, therefore, be expected to be devoid of P2Y12 receptor-antagonistic activity in vivo. Several of the investigated 2-substituted thienotetrahydropyridine derivatives showed concentration-dependent inhibition of CD39. The most potent derivative, 32, showed similar CD39-inhibitory potency to ticlopidine, both acting as allosteric inhibitors. Compound 32 showed an improved selectivity profile: While ticlopidine blocked several NTPDase isoenzymes, 32 was characterized as a novel dual inhibitor of CD39 and CD73. This study involved multiple reactions and reactants, such as Isopropylisothiocyanate (cas: 2253-73-8Computed Properties of C4H7NS).
Isopropylisothiocyanate (cas: 2253-73-8) belongs to esters. Volatile esters with characteristic odours are used in synthetic flavours, perfumes, and cosmetics. Certain volatile esters are used as solvents for lacquers, paints, and varnishes. Esters are more polar than ethers but less polar than alcohols. They participate in hydrogen bonds as hydrogen-bond acceptors, but cannot act as hydrogen-bond donors, unlike their parent alcohols. This ability to participate in hydrogen bonding confers some water-solubility.Computed Properties of C4H7NS
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics