Biomolecules 2019 Mollica.Pdf
biomolecules Article Discovery of Orexant and Anorexant Agents with Indazole Scaffold Endowed with Peripheral Antiedema Activity Marilisa P. Dimmito 1, Azzurra Stefanucci 1,*, Stefano Pieretti 2 , Paola Minosi 2, Szabolcs Dvorácskó 3, Csaba Tömböly 3, Gokhan Zengin 4 and Adriano Mollica 1 1 Department of Pharmacy, University of Chieti-Pescara “G. d’Annunzio”, Via dei Vestini 31, 66100 Chieti, Italy; marilisa.dimmito@unich.it (M.P.D.); a.mollica@unich.it (A.M.) 2 Istituto Superiore di Sanità, Centro Nazionale Ricerca e Valutazione Preclinica e Clinica dei Farmaci, Viale Regina Elena 299, 00161 Rome, Italy; stefano.pieretti@iss.it (S.P.); Paola.minosi@iss.it (P.M.) 3 Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Temesvári krt. 62, 6726 Szeged, Hungary; dszabolcsbiol@gmail.com (S.D.); tomboly.csaba@brc.mta.hu (C.T.) 4 Department of Biology, Science Faculty, Selcuk University, 42005 Konya, Turkey; gokhanzengin@selcuk.edu.tr * Correspondence: a.stefanucci@unich.it; Tel.: +39-0871-3554-482 Received: 7 August 2019; Accepted: 11 September 2019; Published: 16 September 2019 Abstract: The endocannabinoid system represents an integrated neuronal network involved in the control of several organisms’ functions, such as feeding behavior. A series of hybrids of 5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide (mimonabant), a well-known inverse agonist of the type-1 cannabinoid receptor (CB1), once used as an antiobesity drug, and the N-(2S)-substitutes of 1-[(4-fluorophenyl)methyl]indazole-3-carboxamide with 1-amino-3-methyl-1-oxobutane (AB-Fubinaca), 1-amino-3,3-dimethyl-1-oxobutane (ADB-Fubinaca), and 3-methylbutanoate (AMB-Fubinaca), endowed with potent agonistic activity towards cannabinoid receptors CB1 and CB2 were in solution as C-terminal amides, acids, methyl esters and N-methyl amides.
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