Novel 1-alkynyl substituted 1,2-dihydroquinoline derivatives from nimesulide (and their 2-oxo analogues): A new strategy to identify inhibitors of PDE4B

4-Hydroxyquinolin-2-ones and their Close Structural Analogues as a New Source of Highly Effective Pain-Killers

“…Besides, isolation of biologically active substances from the plant or animal raw material, their subsequent purification and standardization is, as a rule, difficult and time-consuming. That is why it is quite natural that the search of new analgesics of the quinoline Internet resources reveals a lot of publications concerning the given topics [17][18][19][20][21][22][23]. Thus, promising substances are created based on various derivatives both quinoline (3) itself and its hydrogenized analogs (4).…”

N-{2-[3-(3-Formyl-2-oxoquinolin-1(2H)-yl)prop-1-ynyl]phenyl}acetamide

“…In continuation of our efforts to identify novel small molecules of potential pharmacological interest, we have recently reported the synthesis and PDE4 inhibitory properties of 2-quinolone derivatives [8]. In further continuation of our earlier work, we now report the synthesis of a novel analogue i.e., N-{2-[3-(3-formyl-2-oxoquinolin-1(2H)yl)prop-1-ynyl]phenyl}acetamide.…”

“…In further continuation of our earlier work, we now report the synthesis of a novel analogue i.e., N-{2-[3-(3-formyl-2-oxoquinolin-1(2H)yl)prop-1-ynyl]phenyl}acetamide. The alkynylation of iodoarenes via C-C bond forming reaction under Pd-Cu catalysis (the Sonogashira coupling) [9] was used in our earlier synthesis [8]. The methodology offered a very convenient, mild and one-step process for the direct coupling of terminal alkynes with iodoarene to provide the desired internal alkynes of medicinal value [10].…”

Selective Phosphodiesterase 4B Inhibitors: A Review

“…Further investigation established a basis for the development of potent PDE4-selective and dual PDE3/4-selective inhibitors [ 44 ]. In a separate communication [ 45 ] authors disclosed (−)-6-[7-methoxy-2-(trifluoromethyl)pyrazolo[1,5-a]pyridin-4-yl]-5-methyl-4,5-dihydro-3(2 H )-pyridazinone ( 18 ) ( Figure 8 ) as a dual PDE3/4 inhibitor (PDE4B IC 50 0.47) with potent bronchodilatory and anti-inflammatory activities and an improved therapeutic window over roflumilast in a number of in vitro and in vivo models used for pharmacological profiling.…”