Derivatives of 3-cyano-6-phenyl-4-(3`-pyridyl)-pyridine-2(1H)-thione and their neurotropic activity (original) (raw)
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Monatshefte für Chemie - Chemical Monthly, 2008
A series of substituted pyridine derivatives were prepared from 2-chloro-6-ethoxy-4-acetylpyridine, which was prepared from the corresponding citrazinic acid as starting material. Reaction of acetylpyridine with thiophene-2-carboxaldehyde afforded the 2-chloro-6-ethoxy-4--(2-thienyl)acryloylpyridine, which was reacted with malononitrile in refluxing ethanol in the presence of piperidine as a catalyst to afford the cyanoaminopyrane derivative. Acryloylpyridine was treated with urea or guanidine hydrochloride in refluxing ethanolic potassium hydroxide to give the corresponding pyrimidinone and aminopyrimidine derivatives. The latter was condensed with hydrazine hydrate or phenyl hydrazine to give pyrazoline and N-phenylpyrazoline derivatives. Finally, cycloaddition reaction of acryloylpyridine with thiourea yielded thioxopyrimidine, which was treated with 2-bromopropionic acid, 3-bromopropionic acid, or bromoacetic acid to yield methylthiazolo-, thiazino-, and thiazolopyrimidine derivatives. The arylmethylene derivative was prepared by reacting thiazolopyrimidine with benzaldehyde or by reacting thioxopyrimidine with benzaldehyde and bromoacetic acid in one step. The pharmacological screening showed that many of these compounds have good analgesic and antiparkinsonian activities comparable to Valdecoxib + and Benzatropine + as reference drugs.
Studies on the Synthesis of Some New Cyanopyridine-Thione and Thieno[2,3-b]pyridine Derivatives
Phosphorus, Sulfur, and Silicon and the Related Elements, 2007
The work included in this article involves the synthesis of new cyanopyridinethiones as good synthons for new thieno[2,3-b]pyridines with anticipated biological activities. Thus, the reaction of β-aryl-α-thiocarbamoylacrylonitrile (1a-c) with (2-thenoyl)-ω,ω,ω-trifluoroacetone led to an unexpected formation of 4-aryl-3-cyano-6-(2-thienyl)pyridine-2(1H)-thiones (4a-c). In contrast, the reaction of 1a,b with ethyl acetoacetate produced 4-aryl-3-cyano-5-ethoxycarbonyl-6methylpyridine-2(1H)-thiones (12a,b). The reaction of compound 4a with methyl iodide gave 2-methylthio derivative 6, which upon treatment with hydrazine hydrate furnished pyrazolopyridine 7. Treatment of 4a-c with chloroacetaimde, in the presence of sodium ethoxide, led to the formation of 3-amino-4-aryl-6-(2-thienyl)thieno[2,3-b]pyridine-2-carboxamides (8a-c). The reactions of 8a with some aromatic aldehydes and/or cycloalkanones were carried out and their products were identified. Compounds 12a,b were reacted with chloro-N-arylacetamides to give ethyl 4-aryl-2-(N-aryl)carbamoylmethylthio-3-cyano-6-methylpyridine-5carboxylates (13a-j). Upon treatment of compounds 13a-j with sodium alkoxide in alcohol, they underwent an intramolecular Thorpe-Ziegler cyclization to furnish ethyl 3-amino-4-aryl-2-(N-aryl)carbamoyl-6-methylthieno[2,3-b]pyridine-5-carboxylates (14a-j). Compounds 14a-j, in turn, were reacted with triethyl orthoformate and/or carbon disulfide to give corresponding pyridothienopyrimidinone derivatives 15a-j and 18. Pyridothienotriazinone analogs 17a-j were synthesized via diazotisation of compounds 14a-j.
Pharmacological Evaluation of Some New 6Amino/Methyl Pyridine Derivatives
Chemical & Pharmaceutical Bulletin, 2003
Pyridines were reported to possess anticonvulsant, 1,2) cardiotonic, 3) antihypertensive, 4) b-adrenergic blocking activity. 5) Aryloxypropanolamines were reported to be associated with b-adrenergic blocking, 6,7) CNS depressant 8) and hypotensive 9) activities. In view of this potential nature of these moieties, it was thought worthwhile to study the effects of two pharmacophoric moieties like pyridine and propanolamine/ethanediamine in a single molecule. We have reported the potential anticonvulsant activity of arylaminopropanolamine 10) of pyridine and arylaminopropanolamine/ aryloxyaminopropane, to continue our work with the same intention, it was envisaged that, chemical entities with both pyridine and arylaminopropanolamine/ethanediamine moieties would result in compounds of interesting biological activities.
Synthesis, in vitro Antibacterial and in vivo Anti-Inflammatory Activity of Some New Pyridines
Pharmaceutical Chemistry Journal, 2017
Reaction of 4,6-diamino-3-cyano-2-methylthiopyridine (I) with chloroacetyl chloride or acetic acid afforded the corresponding 6-acetamide derivatives IIa and IIb, respectively. Chloroacetamide derivative IIa reacted with various thiols, secondary amines, potassium thiocyanate, compounds containing active methylene group, 1-anilino-2,2-dicyanoethenethiolate, and o-mercatocyanopyridines to give S-alkyl, N-alkyl, thiazole, pyrrole, thiophene, and thienopyridine derivatives, respectively. Antibacterial and anti-inflammatory activities of some new pyridine derivatives were studied.
Chemistry of Heterocyclic Compounds, 2009
The reaction of 2-chloro-4,6-dimethylpyridine-3-carbonitrile with hydrazine hydrate, hydroxylamine, and anthranilic acid afforded the corresponding pyrazolo, isoxazolo, and pyridoquinazoline derivatives. Alkylation of 2-mercapto-4,6-dimethylpyridine-3-carbonitrile with ethyl chloroacetate or phenacyl bromide followed by cyclization in NaOH gave thienopyridine derivatives. Diazotization of ethyl 3-amino-4,6-dimethylthiеno[2,3-b]pyridine-2-carboxylate followed by the reaction with thiourea, guanidine carbonate, and hydroxylamine hydrochloride gave the corresponding thienopyridine derivatives. The biological activity of some new compounds has been discussed.
Synthesis and antiallergic activity of pyridothienopyrimidines
Bioorganic & Medicinal Chemistry, 1998
AbstractÐThe synthesis of a series of pyridothienopyrimidines and their evaluation as inhibitors or inducers of the release of histamine from rat mast cells is reported. The activity was measured after immunological stimulation with ovoalbumin and chemical stimulation with polymer 48/80 and the drugs adryamicin and vinorelbine. The experiments were carried out with and without preincubation of the stimulus with the cells before addition of the drug. Several pyridothienopyrimidines show inhibitory IC 50 values in the range 2±25 mM, indicating they are up to 100 times more potent than cromoglycate (DSCG) and 10 times greater than Ketotifen. Compound 9l is a potent inhibitor in all the conditions tested and shows IC 50 =9±25 mM. Pyridothienopyrimidines 4l and 9e are very strong inducers of histamine release in the immunological (4l, 170±230%) and chemical (9e, 100±150%) assays, respectively. Compounds 4l and 9i are cytotoxic in vitro (IC 50 =0.1±0.2 mg/mL) against P-388, A-549, HT-29, and MEL-28 tumor cell lines. #
Bioorganic & Medicinal Chemistry, 2011
Benzopyranoxazine (+)-7 (PD 128907) is the most dopamine (DA) D3 receptor-selective agonist presently known. The only structural feature which distinguishes 7 from the analogous nonselective naphthoxazines is an oxygen atom in the 6-position. To extend this series of tricyclic DA agonists we used a classic bioisoster approach and synthesized thiopyran analogues of 7, which have a sulfur atom in the 6-position. We prepared trans-4-n-propyl-3,4,4a,10b-tetrahydro-2H,5H-[1]benzothiopyrano[4, 3-b]-1,4-oxazin-9-ol (9, trans-9-OH-PTBTO), its enantiomers ((+)-9 and (-)-9), the racemic cis-analogue (10), and the racemic trans-sulfoxide (11) and studied the potency and selectivity for DA receptors of these compounds. As with other rigid DA agonists, the highest affinity for DA receptors resided in one of the enantiomers, in this case the (-)-enantiomer of 9. On the basis of a single-crystal X-ray analysis of a key intermediate, the absolute configuration of (-)-9 was found to be 4aS,10bR, which is homochiral with (+)-(4aR,10bR)-7. In contrast to (+)-7 however, (-)-9 displayed no selectivity for any of the DA receptors. In addition, it has affinity for 5HT1A receptors. (+/-)-cis-4-n-Propyl-3,4,4a,10b-tetrahydro-2H,5H-[1]benzothiopyrano++ +[4,3-b]-1,4-oxazin-9-ol (10), which was expected to be inactive, displayed affinity and selectivity for the DA D3 receptor, whereas the sulfoxide 11 displayed some DA D3 selectivity, but with a lower affinity. Further pharmacological evaluation revealed that (-)-9 is a very potent full agonist at DA D2 receptors and a partial agonist at DA D3 receptors. The cis-analogue (+/-)-10 displayed the same profile, but with lower potency. These findings were confirmed in vivo: in reserpinized rats (-)-9 displayed short-acting activation of locomotor activity (DA D2 agonism) and also lower lip retraction and flat body posture, (5HT1A agonism). Compound (+/-)-10 had no effect on locomotor activity. In unilaterally 6-OH-DA lesioned rats, (-)-9 gave short-acting locomotor activation. Furthermore, in microdialysis studies in rat striatum, (-)-9 potently decreased DA release, confirming its activation of presynaptic DA D2 receptors.
Synthesis and Biological Evaluation of Some New Thienopyridine and Thienopyrimidine Derivatives
1983
Reactions of 3-amino-2-(4-bromobenzoyl)-4-cyano-5-phenyl-aminothiophene (3a) or 2- acetyl-3-amino-4-cyano-5-phenylamino-thiophene (3b) with a variety of active methylene compounds, such as ethyl cyanoacetate, ethyl acetoacetate, ethyl benzoylacetate and diethyl malonate, yielded the corresponding thieno(3,2-b)pyridine-2-one derivatives (4a,b-7a,b). Also the reaction of (3a) or (3b) with formamide and formic acid, afforded the corresponding thieno(3,2-d)pyrimidine derivatives (8a,b). While the reaction of compound (3a) with phenyl isothiocyanate, yielded thieno(3,2-b)pyrimidin-2-thione derivative (9).
Brazilian Journal of Pharmaceutical Sciences, 2019
Pyrimidine derivative 3 was afforded through the reaction of compound (1) with 5-ureidohydantion (2). Product 3 underwent a cyclization to produce fused pyrimidine derivative 7, although the latter product 7 was synthesized through one step via the reaction of compound (1) with 5-ureidohydantion (2) using another catalyst. Compound 3 was oriented to react with cyclic ketones 8a,b in the presence of elemental sulfur, salicylaldehyde (10), aryldiazonium chlorides 12a,b and ω-bromo-4-methoxy-acetophenone (14), which afforded, fused thiophene derivatives 9a,b, coumarin derivative 11, arylhdrazono derivatives 13a,b and 4-methoxyphenyl butenyl derivative 15, respectively. The latter product 15 was reacted with either potassium cyanide (16a) or potassium thiocyanide (16b) to form cyano and thiocyano derivatives 17a,b, respectively. Compound 17a underwent further cyclization to afford pyridopyrimidine derivative 19. Compound 15 was reacted with either hydrazine (20a) or phenylhydrazine (20b) to produce hydrazo derivatives 21a,b and these products were cyclize to produce pyrrole derivatives 23a,b. Finally, 5-ureidohydantion (2) was reacted with compounds 24a,b,c to afford pyrimidine derivatives 25a,b,c. The structures of the synthesized compounds were confirmed using IR, 1 H NMR, 13 C NMR and mass spectrometry techniques. Compounds 11 and 19 have promising as analgesic and antipyretic activities.
Synthesis and CNS activities of pyridopyrazinone and pyridodiazepinone derivatives
PubMed, 1994
New tricyclic derivatives with cyclocondensed pyrido-pyrazine 7,10 and pyrido-diazepine 20a,20b skeletons were synthetized and biologically investigated. The compounds, preliminarily tested on explorative, muscle relaxing, antinociceptive, spontaneous motor activities and influence on the narcotic effect of Evipan, revealed interesting CNS depressant and analgesic activities. The pyrido[2,3-e]pyrrolo[1,2-a]pyrazine structure of 7 appeared the most promising for analgesic and neuroleptic activities. The above compounds were assayed also for their capacity to inhibit DNA synthesis in Ehrlich ascites tumor cells; 20a appeared to be able of inducing a significant inhibition.