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Biomedical subjects

C Martini

Publications and source records attributed to C Martini.

At least 163 records · Page 9Linked to original sources
PubMed1993

Benzodiazepine receptor affinity and interaction of new indole derivatives.

Recently, several derivatives, in which tryptamine, tyramine, and dopamine moieties are linked to the indole nucleus by an oxalyl bridge, were tested for their affinity and efficacy at the benzodiazepine receptor (BzR). To better define the structure-activity relationships (SAR) several phenylethylamine derivatives were also synthesized and tested for their affinity at the BzR. Compounds bearing a protic group on the aromatic system of the side chain show a pharmacological profile of inverse agonist, while the products lacking this group behave as partial agonist. We now report the affinity data at the BzR of new compounds in which the distance between the phenyl ring and the amide group of the side chain has been changed. The benzylamine derivatives showed a good affinity at the BzR, generally higher than that of the phenylethylamine derivatives. In this series the pharmacological profile showed to be opposite to that of the corresponding phenylethylamine derivatives, since the compounds substituted with protic groups on the phenyl ring behaved as partial agonists. Moreover, a probable interaction with the receptor site is hypothesized.

Animals↗
PubMed1993

Synthesis of 7-(2-dimethylaminovinyl) derivatives of pyrazolo[1,5-a] pyrimidines, as precursors of new tricyclic series. Binding studies of BDZ receptor.

A series of 7-dimethylaminovinylpyrazolo[1,5-a]pyrimidines bearing an acetyl or an ethoxycarbonyl group at the 6-position turned out to be useful intermediates for the synthesis of pyrazolo[1,5-a]pyrido[3,4-e]pyrimidines and 8H-pyrazolo[5',1':2,3]pyrimido[5,4-d][1,2]diazepines. These tricyclic derivatives were studied for their affinity for the central benzodiazepine receptor, and meaningful suggestions about the structure-affinity relationship were obtained. Some of the above intermediates were also reacted with S-methylthiourea, to give a mixture of pyrazolo[5',1':1,2]pyrimido[5,6-e][1,3]diazocines and pyrazolo[1,5-a]quinazolines.

Binding, Competitive↗
PubMed1993

Studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines. VII. Synthesis and inhibition of benzodiazepine receptor binding of some 4,5-dihydro-tetrazolo[5,1-d]-1,5-benzothiazepines and 5-phenyl-s-triazolo[3,4-d]-1,5-benzothiazepines.

The 4,5-dihydro-tetrazolo[5,1-d]-1,5-benzothiazepines 3a-k and the 5-phenyl-s-triazolo[3,4-d]-1,5-benzothiazepines 6a-f and 11a-c have been prepared and tested for their ability to displace [3H] flunitrazepam binding from bovine brain membranes. Some of the triazoloderivatives showed moderate binding affinity for the benzodiazepine receptor.

Animals↗
PubMed1993

Reaction of 1-aminophthalazines with alpha-halocarbonyl compounds: imidazo[2,1-a]phthalazines and their benzodiazepine receptor activities.

The one-pot synthesis and the benzodiazepine receptor binding activity of some imidazo[2,1-a]phthalazines bearing different substituents at position-2 and/or 3 and/or 6 is reported. The dissimilar binding results of the reported compounds are discussed in relation to the nature and/or position of the substituents on the tricyclic ring system.

Animals↗
PubMed1992

Benzodiazepine receptor affinity and interaction of some N-(indol-3-ylglyoxylyl)amine derivatives.

Several derivatives, in which tryptamine, tyramine, and dopamine moieties are linked to the indole nucleus by an oxalyl bridge, were tested for their ability to displace the specific binding of [3H]flunitrazepam from bovine brain membranes. GABA ratio and in vivo tests for the most potent compounds showed they behave as inverse agonists at the benzodiazepine receptor (BzR). To better define the structure-activity relationship (SAR) of this kind of ligand, several phenylethylamine derivatives were synthesized to evaluate their affinity to BzR. Some of these derivatives (17, 21, 24, 26, and 30) were found to exhibit high affinity (Ki = 0.51-0.085 microM) for BzR and possessed a partial agonist activity, although their chemical structure is closely related to tryptamine 2-6, tyramine 7-11, and dopamine 12-16 derivatives. A different interaction of these ligands to the receptor site is hypothesized. Moreover, all the prepared 1-methyl derivatives exhibited very low binding affinity to BzR.

Animals↗
PubMed1992

Conformational effects on the activity of drugs. 13. A revision of previously proposed models for the activation of alpha- and beta-adrenergic receptors.

The alpha 1-, alpha 2-, beta 1-, and beta 2-adrenergic properties of the 2-(3,4-dihydroxyphenyl)morpholines 3 and 4 (2-DPMs), of the 3-(3,4-dihydroxyphenyl)-3-piperidinols 5 and 6 (3-DPPs), and of the trans-2-amino-5,6-dihydroxytetrahydronaphthalen-1-ols 7 and 8 and the trans-2-amino-6,7-dihydroxytetrahydronaphthalen-1-ols 9 and 10 (2-ADTNs) were evaluated in vitro both by radioligand binding assays and by functional tests on isolated preparations and compared with those of norepinephrine (NE, 1) and isoprenaline (ISO, 2). Through a comparison of the stereostructures of the compounds examined with their biopharmacological properties, it was possible to revise previously proposed molecular models for the direct activation of alpha- and beta-adrenergic receptors. The revised models (A-C) provided information about the conformational requirements of adrenergic drugs, which substantially fit in with the results of several published studies involving conformationally-restricted adrenoceptor agonists. The different position of the catecholic hydroxyl groups in model B, which refers to the alpha 2 receptors, and in model C, which refers to the beta receptors, confirms the importance of the rotameric position of the aromatic ring of catecholamines in the interaction with the alpha- and beta-adrenergic receptor.

Animals↗
PubMed1992

Specific inhibition of binding to benzodiazepine receptors by 1,2,3-triazole derivatives.

Certain 1,2,3-triazole derivatives were prepared and tested for their ability to displace [3H]diazepam that was bound to bovine brain membrane protein. All the tested compounds are essentially lacking in this ability, except for B.1, which inhibited binding of [3H]diazepam in 50% of the trials at 2.5 microM. The structure of B.1, with a 1,2,3-triazole ring with acidic properties, supports the hypothesis proposed for binding to the benzodiazepine receptor site. Comparison of B.1 with 1,2,3-triazole derivatives bearing a bicyclic substituent in position 1 of the heterocyclic ring suggests that a high steric hindrance increases the affinity of a compound for the benzodiazepine receptor.

Animals↗
PubMed1992

Binding of the benzodiazepine ligand [3H]-RO 15-1788 to membrane preparations of the rabbit and turtle retina.

1. We have studied the binding of [3H]-RO 15-1788 to membrane preparations of the retina of rabbit (Lepus cunicula) and turtle (Pseudemys scripta elegans). 2. In both species, [3H]-RO 15-1788 binding was maximal at 0 degrees C and decreased with increasing temperature. It was saturable, protein concentration-dependent and specific. Flunitrazepam, unlabelled RO 15-1788 and ethyl-beta-carboline were the most effective displacers, whereas RO 5,4864 was ineffective. 3. In both turtle and rabbit retina, Scatchard analysis indicated the presence of a single binding site for [3H]-RO 15-1788. The KD was 0.75 nM in both turtle and rabbit, while the Bmax were 520 and 250 fmol/mg protein in turtle and rabbit respectively. A study of the association rate of [3H]-RO 15-1788 binding revealed faster kinetics in turtle, as compared to rabbit.

Animals↗
PubMed1992

Tricyclic heteroaromatic systems. Synthesis and benzodiazepine binding activity of 1-substituted-3-methyl- and 3-phenylpyrazolo[4,5-c]quinolin-4-ones.

The synthesis and the benzodiazepine binding activity of some 3-methyl- and 3-phenylpyrazolo[4,5-c]quinolin-4-ones bearing a heterocyclic or a substituent which is different from an aryl moiety at position-1 are reported. Molecular modelling is used to correlate the binding affinity to the chemical features and to justify the reduced receptor affinities of the reported compounds with respect to that of CGS 8216 which is taken as the lead compound.

Animals↗
PubMed1991

Tricyclic heteroaromatic systems: [1]benzopyrano-pyrazol-4-ones as benzodiazepine receptor ligands.

The synthesis of a series of 8-substituted 1,4-dihydro-1-aryl-3-methyl-[1]benzopyrano[3,4-d]pyrazol-4-ones (series 7) 2,4-dihydro-2-aryl-3-methyl[1]benzopyrano[4,3-c]pyrazol-4-ones (series 8) is reported. Compounds of series 7 and 8 were tested for their ability to displace [3H]flunitrazepam from bovine brain membranes and for their in vitro biological activity. The results allowed some conclusions to be drawn about the structural requirements of the benzodiazepine recognition site within this class of unusual ligands.

Animals↗
PubMed1991

On the significance of Lhermitte's sign in oncology.

We present three cases of Lhermitte's sign out of twenty consecutive cases of epidural spinal cord compression due to metastatic cancer. The three patients were diagnosed with epidural thoracic compressions. The literature on Lhermitte's sign is reviewed with emphasis on the differential diagnosis of this symptom in oncological patients.

Adult↗