Synthesis and pharmacological evaluation of new (E)- and (Z)-3-aryl-4-styryl-1H-pyrazoles as potential cannabinoid ligands

Abstract

New (Z)-and (E)-1-alkyl-3-(2-hydroxyphenyl)-4-styryl-1H-pyrazoles and (Z)-and (E)-3(5)-(2-alkyloxyphenyl)-4-styryl-1H-pyrazoles were prepared by alkylation of (Z)-and (E)-3(5)-(2-hydroxyphenyl)-4-styryl-1H-pyrazoles with a long chain alkyl bromide in basic medium. The affinity of these alkylated pyrazoles to both human CB 1 and CB 2 type cannabinoid receptors was evaluated. The results showed that some of them exhibit affinity towards CB 1 cannabinoid receptors in the nanomolar range.

Pyrazoles as Key Scaffolds for the Development of Fluorine-18-Labeled Radiotracers for Positron Emission Tomography (PET)

“…Abdel-Maksoud et al have demonstrated antitumoral activity of several compounds with a pyrazole and sulfonamide moieties [19]; antibacterial and antifungal activity of pyrazole was demonstrated by Chowdary et al [20]. Pyrazoles also showed good activity as monoamine oxidase inhibitors, antidepressant and anticonvulsant agents [21], as BRAF inhibitors [22] and DNA gyrase inhibitors [23] and present antileishmanial, anti-inflammatory, analgesic, antidiabetic and cannabinoid activity; cyclin-dependent kinase and tissue-nonspecific alkaline phosphatase inhibitory activity and moderate antihepatotoxic activity, among others [9,11,[24][25][26][27][28][29]. In 2013, Prabhu et.…”

“…Since the discovery of the first nonbenzodiazepine ligand for TSPO, the isoquinoline carboxamide PK11195 (36) [70][71][72], several families of compounds were evaluated as TSPO ligands-among them, [ 11 (41), which are pyrazolo[1,5-a]pyrimidine acetamides ( Figure 15) [72,73].…”

“…PET is based on the detection of tiny amounts (picomolar) of a biological substance labeled with a short-lived positron-emitting radionuclide (PET tracer) without disturbing the biological system and has the advantage of being a noninvasive, functional and highly sensitive technique which provides a great wealth of information [1]. The PET tracers are drugs or biomolecules labeled with radionuclides such as 11 C, 13 N, 15 O, 18 F, 64 Cu, 68 Ga, 89 Zr and 124 I. Since radionuclides can replace the stable analogues, the PET probes have the same chemical structure as the drugs and biomolecules without altering their biological activity.…”

“…Following our interest in the synthesis and biological evaluation of pyrazole-type compounds envisaging their use in medicine [9][10][11][12][13][14] and considering their huge potential for application in PET field, herein we present an overview of pyrazole-derived PET radiotracers developed in the last 20 years. Pyrazoles labeled with 18 F radionuclide will be the focus of this review article, given the aforementioned advantages of this radionuclide for routine PET imaging.…”

Styrylpyrazoles: Properties, Synthesis and Transformations

“…Three partially reduced forms may also exist: 1-pyrazolines 2, 2-pyrazolines 3 and 3-pyrazolines 4, and a fully reduced form known as pyrazolidine 5 (Figure 1) [1,2]. Pyrazole and its derivatives occupy a prime place in medicinal chemistry because they are present in several drugs with real medicinal applications, such as celecoxib (Celebrex ® ), sildenafil (Viagra ® ), rimonabant, lonazolac, fomepizole, penthiopyrad, doramapimod, sulfaphenazole and in several remarkable compounds with a wide range of pharmacological activities, namely anticancer [3], analgesic, anti-inflammatory and antioxidant [4][5][6][7], antibacterial and antifungal [8,9] antipyretic, antidepressant and anticonvulsant [10,11], antidiabetic [12] and cannabinoid activities [13,14], among Pyrazole and its derivatives occupy a prime place in medicinal chemistry because they are present in several drugs with real medicinal applications, such as celecoxib (Celebrex ® ), sildenafil (Viagra ® ), rimonabant, lonazolac, fomepizole, penthiopyrad, doramapimod, sulfaphenazole and in several remarkable compounds with a wide range of pharmacological activities, namely anticancer [3], analgesic, anti-inflammatory and antioxidant [4][5][6][7], antibacterial and antifungal [8,9] antipyretic, antidepressant and anticonvulsant [10,11], antidiabetic [12] and cannabinoid activities [13,14], among others [15][16][17][18][19][20][21]. Along with the medicinal applications, pyrazoles are also useful as agrochemicals, such as herbicides, others [15]…”