Lead exposure at a covered outdoor firing range.
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Environmental Exposure↗
Biomedical subjects
M Modica
Publications and source records attributed to M Modica.
Design, synthesis and binding properties of novel and selective 5-HT3 and 5-HT4 receptor ligands.
This work reports the synthesis and the binding tests on the 5-HT3 and 5-HT4 receptors of new thienopyrimidopiperazine and piperazinylacylaminodimethylthiophene derivatives, in order to identify potent and selective ligands for each receptor. The 3-amino-2-(4-benzyl-1-piperazinyl)-5,6-dimethyl-thieno[2,3-d]pyrimidin-4(3H)-one derivative 28 showed the highest affinity and selectivity for the 5-HT3 over the 5-HT4 receptor (5-HT3 Ki=3.92 nM, 5-HT4 not active), whereas the 2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butanoylamino]-4,5-dimethyl-3-thiophenecarboxylic acid ethyl ester (41) showed the highest affinity and selectivity for the 5-HT4 over the 5-HT3 receptor (5-HT4 Ki=81.3 nM, 5-HT3 not active). Conformational analyses were carried out on the compounds of the piperazinylacylaminodimethylthiophene series (39-42) taking compound 41 as the template.
Animals↗
High potent and selective arylpiperazine derivatives as ligands for the 5-HT1A receptor.
This paper reports the synthesis and affinities on the 5-HT1A versus the alpha1A receptors of new arylpiperazinylalkylthiothienopyrimidine and thiadiazole derivatives 16-24. Arylpiperazines 16-23 show affinities values in the nanomolar range for the 5-HT1A receptor. The compound 16 is highly potent (Ki 0.26 nM, selectivity 28), the derivatives 20 and 21 are less potent, but highly selective (Ki 9.40 and 5.06 nM, selectivity 207 and 73, respectively).
Animals↗
Synthesis of new [1,3,4]thiadiazolo[3,2-a]thieno[2,3-d]pyrimidinone derivatives with antiinflammatory activity.
New thiadiazolothienopyrimidinones were synthesized in continuation of efforts to prepare thienopyrimidine derivatives with analgesic and antiinflammatory activities. In this study, the effect of various substituents in the thiophene ring on the pharmacological activity of the compounds was investigated.
Analgesics↗
Design, synthesis and binding properties of novel and selective 5-HT(3) and 5-HT(4) receptor ligands.
This work reports the synthesis and the binding tests on the 5-HT(3) and 5-HT(4) receptors of new thienopyrimidopiperazine and piperazinylacylaminodimethylthiophene derivatives, in order to identify potent and selective ligands for each receptor. The compound with higher affinity and selectivity for the 5-HT(3) over the 5-HT(4) receptor was the 3-amino-2-(4-benzyl-1-piperazinyl)-5,6-dimethyl-thieno[2,3-d]pyrimidin-4(3H)-one 28 (5-HT(3) K(i)=3.92 nM, 5-HT(4) not active), the compound with higher affinity and selectivity for the 5-HT(4) over the 5-HT(3) receptor was the 2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butanoylamino]-4,5-dimethyl-3-thiophenecarboxylic acid ethyl ester 41 (5-HT(4) K(i)=81.3 nM, 5-HT(3) not active). Conformational analyses were carried out on the compounds of the piperazinylacylaminodimethylthiophene series (39-42) taking compound 41 as the template.
Animals↗
Synthesis and pharmacological screening of 1,3,4-thiadiazino[2,3-b]quinazoline derivatives.
Derivatives of 1,3,4-thiadiazino[2,3-b]quinazoline 7, 9, 9a, 12, 12a, and 13 were prepared from the 3-amino-6-bromo-2,3-dihydro-2-thioxo-4-(1H)-quinazolinone (2) and its analogue without bromine. A series of the title derivatives with or without bromine was tested and the results of pharmacological screening are discussed.
Acetic Acid↗
[[(Arylpiperazinyl)alkyl]thio]thieno[2,3-d]pyrimidinone derivatives as high-affinity, selective 5-HT1A receptor ligands.
A series of 2-[[(4-aryl-1-piperazinyl)alkyl]thio]thieno[2,3-d]pyrimidin-4 (1H)-one and 3-substituted 2-[[(4-aryl-1-piperazinyl)alky]thio]thieno[2,3-d]pyrimidin-4 (3H)-one derivatives was prepared and evaluated for in vitro 5-HT1A receptor affinity by radioligand binding assays; the selectivity for 5-HT1A receptors rather than alpha 1-adrenoceptors was also examined (ratio of the IC50 alpha 1 to IC50 5-HT1A). The binding tests gave indications about the best features of the [(arylpiperazinyl)alkyl]thio moiety and of the substituents on the thiophene and pyrimidinone rings for efficacious and selective 5-HT1A ligands. The most effective derivative for displacing [3H]-8-OH-DPAT from rat hippocampal membranes was the 3-amino-2-[[3-[4-(2-methoxyphenyl)-1-piperazinyl] propyl]thio]-5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one (70) (IC50 = 0.3 nM) with selectivity of 24 for the 5-HT1A over the alpha 1-adrenoceptor. Compound 73, where the 2-methoxyphenyl on the N4 piperazine ring was replaced with a pyrimidine group, showed the best selectivity, with a ratio of 74, while its affinity IC50 for 5-HT1A was 6.8 nM. These results, compared to those for compounds 46 (IC50 24 nM; selectivity 2) and 49 (IC50 226 nM; selectivity 5), N3 unsubstituted analogues of derivatives 70 and 73, show the importance of an amino group in position 3 of the thienopyrimidine system for the interaction with 5-HT1A receptor binding sites, although this fragment can affect the affinity and selectivity only if linked to the (arylpiperazinyl)alkyl moiety. The better selectivity of piperidine 74 (IC50 0.8; selectivity 45) compared to the analogous piperazine 70 is also noteworthy. Twenty of the 30 molecules used for determining the binding affinity to 5-HT1A and alpha 1-adrenergic receptors were selected for QSAR analysis using a series of molecular descriptors and calculated with the TSAR software.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
[Usefulness of computerized dynamic capillaroscopy in the monitoring of treatment of progressive systemic sclerosis with synthetic prostacyclin].
The aim of this study was to evaluate the variations of blood flow velocity in the skin microcirculation before and after vasoactive drugs' administration. Eight patients affected by progressive systemic sclerosis have been treated with synthesis prostacyclin for six hours during a period of fifteen days at the standard dosage of 0.5-2 ng/kg/min. We used computerized dynamic capillaroscopy with Capiflow technique to evaluate cutaneous microcirculation before and after the treatment. The Capiflow technique is a new videophotometric technique to study and quantify the diameter, density and velocity blood flow in the nutritional skin capillary. The quantitative analysis of blood flow velocity detected an increase, statistically significant, at the end of the treatment. The statistic analysis was performed by "t Student" test.
Adult↗
Synthesis of aminothienopyrimidine and thienotriazolopyrimidine derivatives as potential anticonvulsant agents.
New aminothienopyrimidines and derivatives of the new thienotriazolopyrimidine ring system were synthesized to investigate their anticonvulsant activity. The tricyclic compounds 6a, c, e, f, m, o and p and two bicyclic derivatives 4f and 4o were tested. The pharmacological screening results are reported and discussed.
Animals↗
Synthesis and pharmacological properties of thieno[2',3':4,5]pyrimido [2,1-b][1,3,4]thiadiazine derivatives.
A new series of 2-substituted-7,8-dimethyl-3H,9H-thieno[2',3':4,5]pyrimido[2,1- b][1,3,4]thiadiazin-9-ones 5a-d and 6a,b was synthesized through the hydrazinium(1+) salt of 3-amino-2,3-dihydro-5,6-dimethyl-2-thioxo- thieno[2,3-d]pyrimidin-4(1H)-one, 2. These derivatives and two analogs 10a,b were tested for their analgesic and antiinflammatory properties. The pharmacological results are discussed in comparison with those of related compounds previously tested.
Analgesics↗
Synthesis and pharmacological properties of benzothiazole, 1,3-4-oxadiazole and 1,3,4-thiadiazole derivatives.
The reaction of the 2-amino-substituted 1,3,4-oxadiazoles 9, 10 and the benzothiazoles 11, 12 with ethyl cyanoacetate is described. The obtained cyanoacetamide derivatives 13-16 gave the benzylidene derivatives 18-21 by condensation with benzaldehyde. 2-Phenyl-5-amino-1,3,4-oxadiazolo[3,2-a]pyrimidin-7-one (17) was also obtained. Moreover, the preparation of 6,7,8,9-tetraydro-5H-1,3,4-thiadiazolo[2,3-b]quinazolin++ +-5-thio-derivatives 22-25 and N-(1,3,4-thiadiazol-2-yl-5-substituted)-3,4-5,6-tetrahydro-anthran ilic acids 26-29 is also described. All above compounds and compounds, related to them, 1-8 were tested for their analgesic and antiinflammatory activities and the pharmacological screening results are reported and discussed.
Animals↗
[Ventricular diastole in progressive systemic sclerosis].
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Adolescent↗
Synthesis of 2,3-dihydro-3-amino-6-phenyl-2-thioxothieno [2,3-d] pyrimidin-4 (1H)-one and of potential antiinflammatory agents 2-aryl-7-phenyl-3H, 9H-pyrimido [2,1-b]thieno-[2',3':4,5]]1,3,4] thiadiazin-9-ones.
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Acetates↗
High affinity and selectivity of [[(arylpiperazinyl)alkyl]thio]thieno[2,3-d]pyrimidinone derivatives for the 5-HT(1A) receptor. Synthesis and structure-affinity relationships.
In this work we report the affinity of new thienopyrimidinones for 5-HT(1A)Rs and the selectivity versus alpha(1)ARs. The 3-amino-2-[[3-[4-(2-methoxyphenyl)-1-piperazinyl]propyl]thio]-6-ethyl -thieno[2,3-d]pyrimidin-4(3H)-one 27 is the most potent and selective (Ki 0.19 nM, selectivity 115). Compound 31 with the N4 piperazine orthonitrophenyl nucleus instead of the orthomethoxyphenyl also shows a good affinity and selectivity (Ki 1. 46 nM, selectivity 84). The results of derivatives 28, 29 and 30 (Ki 3.28, 12.59 and 4.38 nM; selectivity 24, 4 and 5, respectively), which have, respectively, an ethyl, an allyl and an acetylamino group instead of an N3 amino group, indicate the importance of this last group for the interaction with 5-HT(1A)R. Comparison of the results for the superior homologue 53 (Ki 3.72 nM, selectivity 51) and the inferior homologue 52 (5-HT(1A) Ki 1499 nM, alpha(1)A Ki NA) of 2-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-6,7-dimethyl-8H-[1, 3,4]thiadiazolo[3,2-a]thieno[2,3-d]pyrimidin-8-one 57 (Ki 23 nM, selectivity 5) shows how important the length of the chain binding the two heterocyclic systems is in the interaction with 5-HT(1A)Rs and alpha(1)ARs.
Animals↗
Prevalence of valvular regurgitation in structurally normal hearts: a colour-Doppler study.
AIM: To evaluate, by colour-Doppler echocardiography, the effects of ageing on the continence of the heart valves in patients with normal hearts. METHODS: We reviewed all the consecutive echocardiographic examinations performed in our laboratory from 1988 to 1994. From a total of 4592 records, 1654 (977 from females and 677 from males) were selected as normal-that is, not having excluded any kind of valvular, chamber or wall pathology of the heart. These records alone were considered in the study. RESULTS: One or more valve regurgitations were evident on 286 of the records (17.3%; 202 from females and 84 from males); regurgitation was always mild and was more frequent in females (20.7% compared with 12.4% of males; P < 0.001). Mitral regurgitation was the most frequent (49.3% of all regurgitant valves), followed by tricuspid, aortic and pulmonary. In age groups 0-17 years and > or = 60 years there was no sex difference in regurgitation. With ageing, there was an increasing trend in prevalence of regurgitation of the mitral, aortic and tricuspid valves in females (P < 0.001, P < 0.001 and P < 0.05, respectively), and of aortic and mitral valves in males (P < 0.001 for both). Multiple regurgitation (two or three valves) was not sex-dependent, but showed an increasing trend with ageing (from 13% to 27.5% of records showing regurgitation; positive trend, P < 0.005). CONCLUSIONS: Prevalence of mild valvular regurgitation is age-dependent, but is more common in women than in men aged 18-59 years; there is no sex-related difference in patients aged 60 years or more.
Adolescent↗