Thiazine Derivatives Research Articles

Studies on chalcogen-containing heterocycles. Part 38: Regio- and stereoselective tandem addition–iodocyclization of 2-ethynylphenyl isothiocyanates with N- and O-nucleophiles affording 4-(iodoalkylidene)benzo[d][1,3]thiazines

The treatment of the o-ethynylphenyl isothiocyanates with primary and secondary amines in 1,2-DCE, followed by the addition of I2 and then heating resulted in the regio- and stereoselective tandem addition–iodocyclization to give the (4E)-2-amino-4-(1-iodomethylidene)benzo[d][1,3]thiazine derivatives as the sole product in high yields via the 6-exo-dig mode cyclization. The 2-alkoxy-1,3-benzothiazines were similarly produced from the o-ethynylphenyl isothiocyanates and the corresponding sodium alkoxides.

Effect of the thiazine and thiourea derivatives as NO-synthase effectors on the survival of leukemic cells

The effector activity of thiazine and thiourea derivatives towards various forms of NO-synthase (NOS) in vitro and ex vivo was compared with their cytotoxic effect on human lymphocytes and leukemic cells. A thiazine derivative was revealed that exhibits a selective effect only on malignant cells and is an inhibitor of inducible and neuronal NOS.

ChemInform Abstract: Access to a Wide Range of Sultams by Cyclodialkylation of α‐Substituted Methanesulfonanilides.

AbstractThe present new method constitutes a simple and efficient route to thiazine and thiazole derivatives.

ChemInform Abstract: A Facile One‐Pot Synthesis of Functionalized Thiazines in Water.

AbstractA simple procedure allows the synthesis of thiazine derivatives by a three‐component reaction.

Synthesis and Antibacterial Evaluation of Novel Heterocyclic Compounds Containing a Sulfonamido Moiety

Aiming for the synthesis of new heterocyclic compounds containing a sulfonamido moiety suitable for use as antibacterial agents, the precursor ethyl {[4-N-(4,6-dimethylpyrimidin-2-yl)sulfamoyl]phenylazo}cyanoacetate was reacted with a variety of active methylene compounds producing pyran, pyridine and pyridazine derivatives. Also, the reactivity of the precursor hydrazone towards hydrazine derivatives to give pyrazole and oxazole derivatives was studied. On the other hand, treatment of the same precursor with urea, thiourea and/or guanidine hydrochloride furnished pyrimidine and thiazine derivatives, respectively. The newly synthesized compounds were tested for antibacterial activity, whereby eight compounds were found to have high activities.

Synthesis of 3,4-dihydro-2H-1,4-benzo[b]thiazine derivatives via DABCO-catalyzed one-pot three-component condensation reactions

A series of 3,4-dihydro-2H-1,4-benzo[b]thiazines (34 examples) were efficiently synthesized in good to excellent yields through a 1,4-diazabibicyclo[2.2.2]octane (DABCO) catalyzed one-pot, three-component reaction of 2-aminobenzenethiol, aromatic aldehydes and α-halogenated ketones in the presence of K2CO3. The mechanism for this process was briefly discussed with a tentative catalytic cycle proposed.

Synthesis of Polycyclic Imidazo[1,4]thiazine Derivatives by an ANRORC Domino Reaction

Abstract10bH‐6‐Oxa‐1‐thia‐3a,5‐diazaacephenanthrylenes can be easily obtained by a sodium hydrogen carbonate catalyzed anionic domino reaction of thiazolium salts with salicylic aldehydes. It is presumed that the domino sequence includes Kröhnke condensation, nucleophilic cyclization, and ANRORC (addition of nucleophile/ring opening/ring closure) steps. To the best of our knowledge, this is a first example of a multistep anionic domino reaction incorporating an ANRORC transformation. The initial generality of the method is demonstrated by using 3‐hydroxypyridine‐2‐carbaldehyde as a carbonyl component.

ChemInform Abstract: Synthesis of Thiazine and Thiazepine Derivatives from (Z)‐2‐Cyano‐3‐mercapto‐3‐(phenylamino)acrylamide.

AbstractDepending on the substrate used the reaction with the title amide (II) leads to thiazine or thiazepine derivatives.

Structure–activity relationship study of pyrimido[1,2-c][1,3]benzothiazin-6-imine derivatives for potent anti-HIV agents

3,4-Dihydro-2H,6H-pyrimido[1,2-c][1,3]benzothiazin-6-imine (PD 404182) is an antiretroviral agent with submicromolar inhibitory activity against human immunodeficiency virus-1 (HIV-1) and HIV-2 infection. In the current study, the structure–activity relationships of accessory groups at the 3- and 9-positions of pyrimido[1,2-c][1,3]benzothiazin-6-imine were investigated for the development of more potent anti-HIV agents. Several different derivatives containing a 9-aryl group were designed and synthesized using Suzuki–Miyaura cross-coupling and Ullmann coupling reactions. Modification of the m-methoxyphenyl or benzo[d][1,3]dioxol-5-yl group resulted in improved anti-HIV activity. In addition, the 2,4-diazaspiro[5.5]undec-2-ene-fused benzo[e][1,3]thiazine derivatives were designed and tested for their anti-HIV activities. The most potent 9-(benzo[d][1,3]dioxol-5-yl) derivative was two–threefold more effective against several strains of HIV-1 and HIV-2 than the parent compound, PD 404182.

ChemInform Abstract: Copper‐Catalyzed Domino Intramolecular Cyclization: A Facile and Efficient Approach to Polycyclic Indole Derivatives.

AbstractUnder optimized conditions using Cu2O/DMEDA as catalyst system, dibromovinyl salicylanilides and the corresponding N‐ and S‐analogues (VII) and (X), and anilide (XIII) undergo the title cyclization to give indolo‐fused oxazine, pyrimidine, thiazine and imidazole derivatives.

Synthesis of Thiazine and Thiazepine Derivatives from (Z)-2-Cyano-3-Mercapto-3-(Phenylamino)Acrylamide

The reaction of ( Z)-2-cyano-3-mercapto-3-(phenylamino)acrylamide with teteracyanoethylene and 2-dicyanomethyleneindan-1,3-dione gave thiazine derivatives. While its reaction with 1,4-naphthoquinone, 2,3-dicyano-1,4-naphthoquinone and/or 2,3-dichloro-1,4-naphthoquinone led to the formation of the corresponding napthothiazepine derivatives.

ChemInform Abstract: An Efficient and Simple Route to Prospective Biologically Active Isoindoloquinazoline, Pyrimidine and Thiazine Derivatives Using 2‐Amino‐N′‐arylbenzamidine and Related Compounds as Starting Materials.

The reaction of (Z)-2-amino-N′-arylbenzamidines 1, 2-amino-4,5,6,7-tetrahydrobenzo[b]-thiophene-3-carboxamide (4) and 4-amino-5-substituted-2-(phenylamino)thiophene-3-carboxamides 12 with o-phthalaldehyde (2), terephthalaldehyde (9), and 4-formyl[2.2]paracyclophane (16) in ethanol under reflux conditions afforded isoindoloquinazoline, thienopyrimidine, pyrimidine and thiazine derivatives, respectively. The products were characterized based on their spectroscopic data and elemental analysis.

In(OTf)3-catalyzed tandem aza-Piancatelli rearrangement/Michael reaction for the synthesis of 3,4-dihydro-2H-benzo[b][1,4]thiazine and oxazine derivatives

Furan-2-yl(phenyl)methanol derivatives undergo smooth aza-Piancatelli rearrangement with 2-aminothiophenol and 2-aminophenol in the presence of 10 mol% In(OTf)3 in acetonitrile at room temperature to afford the corresponding 3,4-dihydro-2H-benzo[b][1,4]thiazine or oxazine derivatives respectively in good yields with high selectivity in short reaction times. The salient features of this methodology are good yields, high selectivity, low catalyst loading and faster reaction times. The structure of the products was established by nOe studies and X-ray crystallography.

Inactivation of Glucosamine‐6‐Phosphate Synthase by N3‐Oxoacyl Derivatives of L‐2,3‐Diaminopropanoic Acid

N(3)-Oxoacyl derivatives of L-2,3-diaminopropanoic acid 1-4, containing either an epoxide group or a conjugated double bond system, inactivate Saccharomyces cerevisiae glucosamine-6-phosphate (GlcN-6-P) synthase in a time- and concentration dependent manner. The results of kinetics studies on inactivation suggested a biphasic course, with formation of the enzyme-ligand complex preceding irreversible modification of the enzyme. The examined compounds differed markedly in their affinity to the enzyme active site. Inhibitors containing a phenyl ketone moiety bound much more strongly than their methyl ketone counterparts. The molecular mechanism of enzyme inactivation by phenyl ketone compounds 1 and 3 was elucidated by using a stepwise approach with 2D NMR, MS and UV-visible spectroscopy. A substituted thiazine derivative was identified as the final product of a model reaction between an epoxide compound, 1, and L-cysteine ethyl ester (CEE); and the respective cyclic product, found as a result of reaction between 1 and CGIF tetrapeptide, was identical to the N-terminal fragment of GlcN-6-P synthase. On the other hand, the reaction of a double-bond-containing compound, 3, with CEE, CGIF and GlcN-6-P synthase led to the formation of a C-S bond, without any further conversion or rearrangement. Molecular mechanisms of the reactions studied are proposed.

An efficient one-pot synthesis of pyrimido[2,1- b][1,3]thiazine derivatives by reaction of activated acetylenes, thiouracils, and isocyanides

The reactive 1:1 zwitterionic intermediate, formed by the addition of isocyanides to dialkyl acetylenedicarboxylates, was trapped by thiouracils to yield a ketenimine intermediate, which cyclized and then rearranged to afford pyrimido[2,1- b][1,3]thiazines in good yields.

An Efficient and Simple Route to Prospective Biologically Active Isoindoloquinazoline, Pyrimidine and Thiazine Derivatives Using 2-Amino-N-Arylbenzamidine and Related Compounds as Starting Materials

The reaction of (Z)-2-amino-N`-arylbenzamidines 1, 2-amino-4,5,6,7-tetrahydrobenzo[b]-thiophene-3-carboxamide (4) and 4-amino-5-substituted-2-(phenylamino)thiophene-3-carboxamides 12 with o-phthalaldehyde (2), terephthalaldehyde (9), and 4-formyl[2.2]paracyclophane (16) in ethanol under reflux conditions afforded isoindoloquinazoline, thienopyrimidine, pyrimidine and thiazine derivatives, respectively. The products were characterized based on their spectroscopic data and elemental analysis.

ChemInform Abstract: Synthesis of 4‐Aryl‐azetidinones via Intramolecular Alkylation of Nucleophilic Arenes Using Acyliminium Cations.

AbstractVinyloxy‐ or formyloxyazetidinones bearing N‐(arylthiomethyl) or N‐(aryloxymethyl) substituents (I) and (IX) undergo Lewis acid‐mediated intramolecular arylation of the azetidinone ring to give azetidine‐fused thiazine (II) or oxazine derivatives (X).

Practical and Efficient Synthesis of 3-Aryl-2H-benzo[1,4]thiazine Derivatives Catalyzed by KHSO4

KHSO4 efficiently catalyzes the condensation of o-aminothiophenols and 2-bromo-1-aryl-ethanones to yield 3-aryl-2H-benzo[1,4]thiazines in good yields.

An Efficient and Simple Route to Prospective Biologically Active Isoindoloquinazoline, Pyrimidine and Thiazine Derivatives Using 2-Amino-N'-Arylbenzamidine and Related Compounds as Starting Materials

An Efficient and Simple Route to Prospective Biologically Active Isoindoloquinazoline, Pyrimidine and Thiazine Derivatives Using 2-Amino-N'-Arylbenzamidine and Related Compounds as Starting Materials

Adsorption of NO synthase inhibitor on dehydroxylated silica

A series of thiazine derivatives with the NO inhibiting effect was synthesized. These derivatives can be used in the treatment of gastrointestinal diseases, as well as antihypotensive (antishock) drugs. The potentially prolonged effect of these substances was studied by the adsorption of 2-N-benzoyl-2-amino-5,6-dihydro-4H-1,3-thiazine hydrobromide (I) on silica (nonporous Polysorb MP with specific surface area S = 330 m2/g and narrow-porous KSS-3 silica gel with S = 600 m2/g). The dehydroxylation of a silica surface significantly increased the adsorption of I. The adsorption kinetic curves of I showed a peak due to the rehydroxylation and deactivation of the silica surface in aqueous solutions. The adsorption rate in physiological solution of I was shown to decrease at a lower concentration of I on the surface of dehydroxylated silica and larger silica particles.