1,721,058 research outputs found
Preparation and pharmacological activities of homolupinanoyl anilides
No full textOn the pattern of well known dialkylaminoacyl anilides, a set of N-homolupinanoyl anilides was prepared and subjected to a broad pharmacological screening with in vivo and in vitro assays. As expected most compounds exhibited a strong antiarrhythmic activity, often comparable or superior to that of lidocaine and quinidine. Compound 1 exhibited an unusual profile as antiarrhythmic, being devoid of local anesthetic activity, calcium channel and beta adrenoceptor antagonism. Calcium channel blocking activity was seen in all aminobenzophenone derivatives, but not in the simpler anilides. Noteworthy are also the capacity of compound 7 to protect mice from a lethal dose of KCN, the moderate antihypertensive activity of 10 and, above all, the antagonism to guinea pig ileum contractile responses induced by several agents exhibited by compound 11, which deserves further investigation for a potential use in irritable bowel syndrome. Compound 11 showed also good relaxant activity on tracheal strips and inhibitory activity against arachidonate induced platelet aggregation. Finally, compound 11 displaced several radioligands from their respective binding sites. Most potent was displacement of [3H]pirenzepine (IC50 < or = 0.01 microM) from M1 binding sites of rat brain, while displacement of [3H] methylscopolamine from rat heart (M2) and submaxillary salivary glands (M3) preparations was much weaker (IC50 approximately equal to 2.4 and 1.3 microM, respectively)
2-{4-[ω-[4-(2-methoxyphenyl)-1-piperazinyl]alkoxy]phenyl}-2H-benzotriazole s and their N-oxides as ligands for some 5-hydroxytryptamine, dopamine and adrenergic receptor subtypes
No full textWe have prepared and studied some new 2-methoxyphenylpiperazine derivatives as combined ligands for 5-hydroxytryptamine 5-HT(1A) and dopamine D3 receptor subtypes. The compounds displayed affinity for 5-HT(1A) and D3 receptors, which improved with the lengthening of the intermediate aliphatic chain. Conversely, binding to 5-HT(2A), D2 and α1-receptor subtypes was affected in an irregular, and mainly negative, manner by the chain length. Benzotriazole derivatives with 4-5 methylenes exhibited good or excellent selectivity for 5-HT(1A) and D3 vs 5-HT(2A), D2 and α1-receptors
Preparation and pharmacological activities of 10-homolupinanoyl-2-R-phenothiazines
No full textPursuing our researches on quinolizidinyl derivatives of phenothiazine and on the ground of antidepressive, diuretic, antianginal and antiarrhythmic activities of several 10-(3-dialkylamino) propionylphenothiazines (as chloracizine, moricizine, etc.), six 10-homolupinanoyl-2-R-phenothiazines were prepared and subjected to a broad pharmacological screening with in vivo and in vitro assays. Most of these compounds exerted strong antiarrhythmic activity (compounds 1, 3 and 5 were comparable or superior to lidocaine and quinidine in three tests), calcium antagonism on guinea pig ileum and left atria, antagonism to smooth muscle contractile responses induced by several agents and inhibition of rabbit platelet aggregation induced by PAF and ADP. A few other activities were characteristic of single compounds, as antagonism to central and peripheral effects of oxotremorine 1, moderate antihypertensive activity 5, local anesthetic activity and antagonism to substance P 2, antiinflammatory activity with low or absent gastric irritation 2, 3, powerful saluretic action 6, inhibition of arachidonate induced platelet aggregation 1 and antagonism to PAF induced mortality 1, 4. The last activity is very unusual and deserves further investigation. The capacity of compound 1 to displace specific ligands from several receptors was also investigated. Significant binding for M1 (IC50 = 0.03 microM), M3 (IC50 = 10 microM), sigma receptors and Na+ channels (IC50 = 1 microM) were evidentiated
2-{4-[ω-[4-(2-methoxyphenyl)-1-piperazinyl] alkoxy] phenyl}phthalimides as ligands for some 5-HT, dopamine and adrenergic receptor subtypes
No full textWe have prepared and studied some new 2-methoxyphenylpiperazine derivatives as combined ligands for 5-HT1A and D3 receptor subtypes. The introduction of a phenyloxy moiety between the phthalimido group and the polymethylene chain of nanserone does not impair the typical high affinity for 5-HT1A receptors, but reduces in different measures the affinity for 5-HT2, D2 and α1-receptors. Good affinity for the D3-receptor subtype has also been observed. The polymethylene chain length remains a critical factor in determining optimal affinity and selectivity
Synthesis and biological investigations of 1-(tetrahydropyran-2'-yl)- and 1-(tetrahydrofuran-2'-yl)benzimidazoles and 1/2-(tetrahydropyran-2'-yl)- and 1/2-(tetrahydrofuran-2'-yl)benzotriazoles
No full textSets of benzimidazole and benzotriazole derivatives bearing on position 1 or 2 a tetrahydrofuranyl or tetrahydropyranyl moieties were prepared through the addition of the suitable benzazoles on 2,3-dihydrofuran and 3,4-dihydro-2H-pyran. The reactions were carried on either without solvent or in carbon tetrachloride solution. In the last case some peculiar chlorinated side products were isolated and characterized. Twenty compounds were screened for in vitro antitumoral and anti-HIV-1 activities and found poorly active or completely inactive. On the other hand several compounds exhibited good tracheal relaxant activity in vitro; compound 8, 11, 16, 24 and 26 resulted more active than theophylline in this test, while compound 11 was comparable to amrinone till the concentration of 3 micrograms/ml. Finally, compound 5 resulted endowed with a strong diuretic and saluretic activity at the dose of 3 mg/Kg, thus representing a new lead for discovering new diuretic agents
Quinolizidine derivatives as ligands for sigma receptors
No full textA set of 1α/1β-[(4-R-phenyl)ethyl]quinolizidines was synthetized and together with selected intermediates was tested for affinity to sigma-1 receptor. Some compounds displayed good affinity for the relevant receptor, with Ki in the nanomolar range, and good selectivity versus σ2, 5-HT2A and D2 receptor subtypes
N-homolupinanoyl and N-(omega-lupinylthio)alkanoyl derivatives of some tricyclic systems as ligands for muscarinic M1 and M2 receptor subtypes
No full textA set of N-homolupinanoyl- and N-(omega-lupinylthio)alkanoyl derivatives of tricyclic systems (as phenothiazine, iminodibenzyl and dihydropyridobenzodiazepinone) has been prepared and tested for affinity for rat muscarinic M(1) and M(2) receptor subtypes labeled with [3H]pirenzepine and [3H]AF-DX 384. Good affinity for both M(1) and M(2) subtypes was displayed by most compounds, often with nanomolar K(i) values, which for lupinylthiopropionyl- and lupinylthiobutyryl-phenothiazines (13-16) were comparable to those of pirenzepine and methoctramine, respectively. However, only moderate selectivity for one or the other subtype was seen
1-(arylalkyl)quinolizidine derivatives and thio-isosteric analogs as ligands for sigma receptors
No full textA set of 1-(arylalkyl)quinolizidines, isosteric thio analogs, and variously functionalized congeners were synthesized and tested for affinity to sigma1 and sigma2 receptor subtypes, by displacing [3H]-(+)-pentazocine and [3H]DTG from guinea pig brain and rat brain prepns., resp. All compds. exhibited a good affinity for the sigma1 subtype, with subnanomolar Ki values for the best of them, while only modest or poor affinity for the sigma2 subtype was obsd. Some structure-activity relationships were put forward
[Quinolizidine derivatives with antimicrobial activity]
No full textThirty quinolizidinyl derivatives, together with two dialkylaminoalkyl analogues, were tested at concentration up to 160 mg/l for antimicrobial activity against 17 microrganisms, including gram-positive and gram-negative strains, Mycobac, tuberculosis, Trichom, vaginalis, fungi and yeasts. The most common activity found is that against Mycobac, tuberculosis, followed by that against gram-positive strains; several compounds [(I a), (I b), (I c), (II a), (III a), (VIII e), (XIX e), (XXI e)] exhibit a good or a very high level of activity. Concerning the gram-negative bacteria, activity is found only against Escherichia coli and is random and usually slight, as is that against fungi, yeasts and protozoa. Compounds (I a), (III a) and (XXI e) are of interest for their high activity and for their broad spectrum of activity, while compound (X e) is peculiar for its selectivity against Mycobac. tuberculosis
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