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At least 19 recordsLinked to original sources
PubMedDate not supplied

Synthesis of hexahydro-1,4-thiazepine derivatives with expected pharmacological activity. Part I. N-alkyl(hydroxyalkyl)-hexahydro-1,4-thiazepines and 2-(hexahydro-1,4-thiazepinyl)-ethyl esters of phenoxyacetic acids.

New N-alkyl or N-hydroxyalkyl derivatives of hexahydro-1,4-thiazepine(compounds 1--6, Table 2) were obtained by condensation of 2-chloroethyl-3-chloropropyl sulfide with appropriate primary amines. Estrification of 2-hydroxyethylhexahydro-1,4-thiazepine by chloride of appropriate phenoxyacetic acids yielded 2-(hexahydro-1,4-thiazepinyl)-ethyl esters of phenoxyacetic acids (compounds 7--12, Table 4).

Animals↗
PubMed1983

Synthesis of perhydro-1,4-thiazepines, of expected pharmacological activity. Part III. 4-(2-hydroxyethyl)-perhydro-1,4-thiazepine esters.

New esters, derivatives or the title aminoalcohol, were obtained by three classical methods in the reaction of 4-(2-hydroxyethyl)-perhydro-1,4-thiazepine (HEPT) with chlorides (method a), acid potassium salts (method b), and sodium HEPT salts with acid chlorides (method c). Compounds 3 and 5 have weak spasmolytic properties; 5 in a dose of approx. 50 mg/kg strongly depressed the central nervous system.

Animals↗
PubMed1992

Determination of cystathionine and perhydro-1,4-thiazepine-3,5-dicarboxylic acid in the urine of a patient with cystathioninuria using column liquid chromatography-mass spectrometry.

A method for the measurement of cystathionine and perhydro-1,4-thiazepine-3,5-dicarboxylic acid in the urine of a patient with cystathioninuria has been developed, using column liquid chromatography-mass spectrometry. Cystathionine and perhydro-1,4-thiazepine-3,5-dicarboxylic acid were determined by scanning the [M + H]+ ions of each compound. The recoveries were 80-92.4% for cystathionine and 80-100% for perhydro-1,4-thiazepine-3,5-dicarboxylic acid after ion-exchange treatment. The results agreed well with those obtained using an amino acid analyser. The concentrations found for cystathionine and perhydro-1,4-thiazepine-3,5-dicarboxylic acid were 1.289 +/- 0.099 mg/ml and 0.310 +/- 0.0067 mg/ml, respectively.

Cystathionine↗
PubMed1999

Design, synthesis, and biological evaluation of potent thiazine- and thiazepine-based matrix metalloproteinase inhibitors.

The synthesis and enzyme inhibition data for a series of thiazine- and thiazepine-based matrix metalloproteinase (MMP) inhibitors are described. The thiazine- and thiazepine-based inhibitors were discovered by optimization of hetererocyclic sulfonamide-based inhibitors. The most potent series of inhibitors was obtained by modification of the amino acid D-penicillamine. This amino acid provides a gem-dimethyl group on the thiazine or thiazepine ring which has a dramatic effect on the in vitro potency of this series. In particular, the sulfide 4a and the sulfone 5a were potent, broad-spectrum inhibitors of the MMPs with IC(50)'s against MMP-1 of 0.8 and 1.9 nM, respectively. The binding mode of this novel thiazepine-based series of MMP inhibitors was established based on X-ray crystallography of the complex of stromelysin and 4a.

Crystallography, X-Ray↗
PubMed1986

Angiotensin-converting enzyme inhibitors: new orally active 1,4-thiazepine-2,5-diones, 1,4-thiazine-2,5-diones, and 1,4-benzothiazepine-2,5-diones possessing antihypertensive activity.

The preparation of a series of 1,4-thiazepine-2,5-diones, 1,4-thiazine-2,5-diones, and 1,4-benzothiazepine-2,5-diones and their ability in inhibiting the activity of angiotensin-converting enzyme (ACE) in vitro and in vivo were examined. These compounds are assumed to act as prodrugs since they undergo rapid ring-opening reactions to give the corresponding biologically active free SH compounds when incubated with rat plasma or when treated with aqueous 0.1 N HCl or phosphate buffer (pH 7.4). The thiazepines 23-25 and 30 are potent inhibitors of ACE when administered po to rats and are comparable in potency to captopril (1). The most active thiazines in rats, po, were 42 and 45. Of the benzothiazepines studied, 22a was the most active in inhibiting ACE in the conscious normotensive rat, ID50 = 0.15 mg/kg, po. The acute antihypertensive effects of oral administration of a number of these compounds on mean arterial pressure and heart rate were studied in spontaneously hypertensive rats (SHR) maintained on a sodium-deficient diet.

Administration, Oral↗
PubMed1998

Metabolism of cystathionine, N-monoacetylcystathionine, perhydro-1,4-thiazepine-3,5-dicarboxylic acid, and cystathionine ketimine in the liver and kidney of D,L-propargylglycine-treated rats.

Experimental cystathioninuria was induced by injection of D,L-propargylglycine in rats. The novel cystathionine metabolites, N-monoacetylcystathionine (NAc-cysta), perhydro-1,4-thiazepine-3,5-dicarboxylic acid (PHTZDC), and cystathionine ketimine (CK), were identified previously in the urine of patients with cystathioninuria and D,L-propargylglycine-treated rats. In this study, we identified these compounds in the liver and kidney of D,L-propargylglycine-treated rats using liquid chromatography-mass spectrometry with an atmospheric pressure chemical ionization interface system (LC/APCI-MS) and an amino acid analyzer. The metabolism of these compounds in the liver and kidney of D,L-propargylglycine-treated rats was also studied. PHTZDC, NAc-cysta, and CK were accumulated in the rat tissues in proportion to the content of cystathionine after D,L-propargylglycine administration. The concentrations of these compounds in the liver were higher than those in the kidney, and these compounds reached maxima earlier in the liver than in the kidney.

Alkynes↗
PubMed1987

Angiotensin-converting enzyme inhibitors: perhydro-1,4-thiazepin-5-one derivatives.

alpha-[6-[[(S)-1-(Ethoxycarbonyl)-3-phenylpropyl]amino]-5-oxoperhydro -1,4-thiazepin-4-yl]acetic acids (monoester monoacids) and their dicarboxylic acids having the hydrophobic substituents at the 2- or 3-position of the thiazepinone ring were prepared and assayed for angiotensin-converting enzyme (ACE) inhibitory activity. The dicarboxylic acids having the pseudoequatorial amino groups at the 6-position and the pseudoequatorial hydrophobic substituents at the 2- or 3-position of the chair conformation of the thiazepinone ring had potent in vitro inhibitory activity. The monoester monoacids having the hydrophobic substituents at the 2-position suppressed pressor response to angiotensin I for a longer duration than those having the substituents at the 3-position when administered orally. The structure-activity relationship was studied by conformational energy calculations of the thiazepinone ring.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Accumulation of cystathionine, cystathionine ketimine, and perhydro-1,4-thiazepine-3,5-dicarboxylic acid in whole brain and various regions of the brain of D, L-propargylglycine-treated rats.

Experimental cystathioninuria was induced in rats by administration of the cystathionine gamma-lyase inhibitor, D,L-propargylglycine. The cystathionine metabolites, cystathionine ketimine (CK) and perhydro-1,4-thiazepine-3,5-dicarboxylic acid (PHTZDC), were identified in whole brain and various regions of the brain in D,L-propargylglycine-treated rats. The concentration of CK and PHTZDC in whole brain and various regions of the brain increased gradually after administration of D,L-propargylglycine, and reached the highest value at about 20 hours. CK and PHTZDC accumulated in whole brain and various regions of the brain in proportion to the amount of accumulated cystathionine after D,L-propargylglycine administration. The concentration of these compounds in the cerebellum was higher versus the other regions of the rat brain.

Alkynes↗
PubMed1987

Hexahydro-1,4-thiazepine-3,5-dicarboxylic acid and thiomorpholine-3,5-dicarboxylic acid are present in normal human urine.

Hexahydro-1,4-thiazepine-3,5-dicarboxylic acid and thiomorpholine-3,5-dicarboxylic acid, simply referred to as cyclothionine and TMDA, respectively, are two cyclic sulfur-containing imino acids detected in bovine brain. Human urine has been investigated to establish the occurrence of these imino acids as common constituents under normal conditions. The morning urine of healthy subjects has been analyzed for enrichment of these compounds by using an ion-exchange procedure. Gas/liquid chromatography of the final extracts revealed the presence of peaks coeluting with authentic cyclothionine and TMDA. The latter compound eluted very close to an unknown sulfur-containing compound. A resolved peak of TMDA has been obtained by high-performance liquid chromatography of the final extracts derivatized with phenylisothiocyanate. Selected ion monitoring with multiple-ion detection applied to the compounds separated by gas chromatography revealed the presence of the respective molecular ions and of the decarboxylated fragments, thus confirming the identification of cyclothionine and TMDA in human urine.

Adult↗
PubMed1992

[Studies on zwitter-ionization of drugs. I. Synthesis and pharmacological activities of N-alkylcarboxylic acid derivatives of 4-(2-chlorodibenz-[b,f][1,4]oxazepin-11-yl)piperazine, 4-(2-chlorodibenzo[b, f]-[1,4]thiazepin-11-yl)piperazine, and 4-(11H-dibenz-[b,e]azepin-6-yl)piperazine].

The piperazine N-alkylcarboxylic acids of 2-chlorodibenz[b,f][1,4] oxazepine (3a), 2-chlorodibenzo[b,f] [1,4] thiazepine (3b), and dipenz[b,e] azepine (3c) from the corresponding piperazines (1a-c, R1 = H) were synthesized via the piperazine N-alkylcarboxylates (2a-c). The pharmacological activities of the piperazine N-alkylcarboxylic acids (3a-c) were evaluated. Compared with the parent compounds (1a-c), 3a-c (n = 1-5) showed weak inhibitory activities on the uptake of noradrenaline and 5-hydroxytryptamine (5-HT) into hypothalamus vesicles and moderate antagonistic actions to 5-HT2 and H1 in several tissues.

Amoxapine↗
PubMedDate not supplied

Some pharmacological properties of perhydro-1,4-thiazepine and perhydro-1,2,5-dithiazepine derivatives.

Some newly synthesized perhydro-1,2,5-dithiazepine derivatives have antihistaminic, anticholinergic and spasmolytic properties. One perhydro-1,4-thiazepine derivative, compound 3, produces also a weak local anesthetic effect. The activity of the investigated compounds is lower than that of reference compounds; diphenhydramine, antazoline and papaverine.

Anesthetics, Local↗
PubMed1979

Possible psychopharmacological agents. Part 3: Synthesis and CNS activity of some new fluorine-containing pyrazolo[3,4-e][1,4]thiazepines.

A series of new fluorine-containing pyrazolo [3,4-e][1,4]thiazepines has been synthesized by the condensation of 5-amino-3/1, 3-substituted pyrazole with appropriate arylaldehydes or ketones and mercaptoacetic acid in dry toluene. All synthesized compounds have been characterized by their m.p.'s elemental analysis, IR, H-NMR and F-NMR. A representative number of compounds has also been screened for their CNS activity and found to act as mild stimulants.

Analgesics↗
PubMedDate not supplied

Studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines. XI. Synthesis and biological activity of several naphtho- and quinolino-1,4-thiazine and -1,4-thiazepine derivatives containing the imidazole ring.

Several derivatives of naphthol[1,2-b]imidazo[1',2'-d]-1,4-thiazine and -1,4-thiazepine and imidazo[1',2'-4,5]-1,4-thiazino[3,2-c]quinoline and -1,4-thiazepino[3,2-c] quinoline have been synthesized. These compounds and other imidazo[2,1-d][1,5]benzothiazepine derivatives, previously synthesized, have been tested for their possible pharmacological activities. One of these substances displayed inhibitory activity on CNS, others showed an appreciable antiinflammatory effect. None of the naphtho and quinolino derivatives showed affinity for the benzodiazepine receptor.

Animals↗
PubMed1996

Studies on annelated 1,4-benzothiazines and 1,5-benzothiazepines. X--Synthesis and inhibition of benzodiazepine receptor binding of new 1,4-thiazine and 1,5-thiazepine polycondensed heterocycles with steroidal structure.

Some naphtho[1,2,-b]-s-triazolo[4,3-d]-1,4-thiazine and 1,5-thiazepine and s-triazolo[4', 3'-4,5]-1,4-thiazino[3,2-c]quinoline derivatives have been synthesized and tested for their ability to displace [3H]RO 15-1788 binding from bovine brain membranes. Several compounds showed moderate binding affinity for the benzodiazepine receptor.

Animals↗