4-(1,2,5,6-Tetrahydro-1-alkyl-3-pyridinyl)-2-thiazolamines: a novel class of compounds with central dopamine agonist properties

Abstract

The design, synthesis, and pharmacological properties of a novel type of 4-(1,2,5,6-tetrahydro-1-alkyl-3-pyridinyl)-2-thiazolamine with dopaminergic properties are described. In particular, 4-(1,2,5,6-tetrahydro-1-propyl-3-pyridinyl)-2-thiazolamine (4c, PD 118440) and its allyl analogue (4i, PD 120697) have been identified as orally active dopamine (DA) agonists with pronounced central nervous system effects in tests that include [3H]-haloperidol and [3H]-N-propylnorapomorphine binding, inhibition of striatal DA synthesis, inhibition of DA neuronal firing, inhibition of spontaneous locomotor activity, and reversal of reserpine-induced depression in rats. The DA autoreceptor selectivity of these heterocyclic analogues of 3-(1-propyl-3-piperidinyl)phenol (3-PPP) was also evaluated. In this series, DA agonist activity was found to be highly dependent on the size of the N-alkyl substituent, the saturation level of the six-membered ring, and the mode of attachment of the 2-aminothiazole ring.

Reaction of N,N-disubstituted hydrazinecarbothioamides with 2-bromo-2-substituted acetophenones

“…Free radicals and reactive sulfur species such as thiol radicals are frequently synthesized through many biological processes and may be considered as indicators of biological inadequacy. In recent times, the applications of thiazoles have found in drug development for the treatment of allergies 6 , hypertension, 7 inflammation, 8 schizophrenia, 9 bacterial, 10 HIV infections, 11 and hypnotics 12 . Moreover, thiazoles have been used for the treatment of pain, 13 as fibrinogen receptor antagonists with antithrombotic activity 14 and as new inhibitors of bacterial DNA gyrase B.…”

Synthesis, Anticancer and Antioxidant Activity of Novel 2,4-Disubstituted Thiazoles

“…Thiazole derivatives have been extensively studied and so far, a variety of biological activities have been reported, for a large number of their derivatives, such as antihypertensive, anti-inflammatory, antischizophrenia, antibacterial, anti-HIV, hypnotics, antiallergic, analgesic, fibrinogen receptor antagonist, bacterial DNA gyrase B inhibitor and antitumor activities. [10][11][12][13][14][15][16][17][18][19][20][21][22] Also they have wide range of applications in organic functional materials such as fluorescent dyes 23 and liquid crystals.…”

Synthesis of New 3-Heteroarylindoles as Potential Anticancer Agents

“…Monoindole and bisindole have been intensively studied and the results revealed that most of them have biological activities; for example, indole-3-carbinol, found in Brassica plants, is a potential cancer protective agent [5,6]. Thiazoles can be found in drug development for the treatment of allergies [7], hypertension [8], inflammation [9], schizophrenia [10], bacterial infections [11], HIV [12], sleep disorders [13], and for the treatment of pain [14], as fibrinogen receptor antagonists with antithrombotic activity [15] and as new inhibitors of bacterial DNA gyrase B [16]. The 1,2,4-triazolopyrimidines have also attracted growing interest due to their important pharmacological activities, such as antitumor, antimalarial, antimicrobial, anti-inflammatory, and antifungal activity, as well as macrophage activation [17][18][19][20][21][22].…”