4//-l,2,4-Thiadiazine

Thieno[3,4-( ]-l,2,4-thiadiazine dioxide 33 and thieno[2,3-i ]-l,2,4-thiadiazine dioxide 34 (prepared as shown in Scheme 8 and Equation (10), Section 10.09.9.1.1) undergo electrophilic substitution on the thiophene ring regio-selectively as shown in Scheme 6 <1997H(45)1767>. 

The parent thieno[3,4- ]-l,2,4-thiadiazine dioxide 35 undergoes regioselective alkylation at N-2 to give, for example, compound 36. This can then be followed by alkylation at N-4 (Scheme 7) <1999BMC2811, 2000EJM751>. 

H-1,2,4-thiadiazine, 4//-l,2,4-thiadiazine, and 2//-1,2,6-thiadiazine, respectively. If the sulfur atom exhibits a valency other than 2, then the valency is indicated by including the small Greek letter X after the numeral that specifies the ring sulfur atom, followed by a superscript numeral to indicate the valency of the sulfur atom. For instance, structure VIII is named 3//-1 A4,2,6-thiadiazine. The four thiadiazine systems can give rise to benzo-derivatives, i.e. structures IX-XII examples of all four types are known. 

The reaction of 4,5-dihydro-4//-l,2,4-thiadiazine 1,1-dioxides 142, which have a leavable group in the 3-position (Y = OR1, SR1, NH2), with two molecules of an alkyl isocyanate (RNCO) produces the condensed system 143, while the alkyl isothiocyanate yields the different condensed system 145. The former reaction apparently proceeds through intermediate 144, i.e., by reaction at the 4-position. On the other hand, the first molecule of the isothiocyanate may, by analogy, react at the 2-position via a corresponding intermediate (74BSF1917). 

Chloromethylbenzo-l,2,4-thiadiazine 1,1-dioxide forms quaternary salts, e.g. 8 (n = 1), with pyridine, 2- and 3-picolines, and iso-quinoljne, but the 3-(2 -chloroethyl) compound gives a lower yield of the salt, e.g. 8 (% = 2), because some of the halogen derivative is converted into the 3-vinyl compound. ... 

Phenothiazines, benzo-l,2,4-thiadiazine 1,1-oxides, fluoroquinolones, nicotinic acid, and nitrofuran derivative as potentially dangerous photosensitizers 98MI11. 

Vega and co-workers synthesized a variety of oxazolo[3,2- hetero[l,2,4]thiadiazine-.9,.9-dioxides such as the thieno... 

The first synthesis of pyrazolo[5,l-c]-l,2,4-thiadiazines 116 and pyrazolo[3,4-c]-l,2-thiazines 118 was reported by Aiello and co-workers <76JHC615>. Compound 115 was heated five degrees above its melting point to afford the novel ring system 116. However, compound 117 gave compound 118 when treated with triethylamine. 

Benzamides e.g. MS-275 8 are one of the more common hydroxamic acid alternatives but are often less potent. Recent exceptions to this pattern include substituted pyridyl [29] and thiazolyl [30] benzamides, such as 9 and 10 with HDAC1 enzyme IC50s of 19nM and 29 nM, respectively and series of benzamides substituted with other heterocycles, such as indazoles [31] and benzo [l,2,4]thiadiazines [32], many with HDAC2 IC50s of <50 nM. The addition of... 

For ring closure to //-fused [l,2,4]thiadiazines, two approaches were published during recent years. Chern et al. <1998JME3128> reported that derivatives 186 containing allylamino or allylsulfanyl group in position 3 of the... 

Two different c-fused [l,2,4]thiadiazines were synthesized nearly at the same time, and the syntheses are shown in Scheme 30. Boverie et al. <2001JPL973> reported a procedure for the imidazole ring closure, which is fairly... 

Synthesis and structural studies of new 3-alkylamino-pyrido[43-e][l,2,4]thiadiazine 1,1-dioxides have been reported <99T5419>. 

Oxidation of pyrido[23-c][l,2,4]thiadiazines 94 with sodium hypochlorite and, separately, iR-chloroperbenzoic add affords the 1,1-dioxide derivatives 95 and the 5-oxide derivatives 97, respectively. Oxidation of 1,1-dioxide derivatives yields the novel 1,13-trioxides 96 <98T13645>. 

The reduction of 3-(4-bromobenzamidoaminomethyl)-477-pyrido[4,3-< ]-l,2,4-thiadiazine 1,1-dioxide 34 with sodium borohydride in aqueous sodium hydroxide gave the 2,3-dihydro derivative 35 (Equation 3) <1997BSB781>. 

The pyrido[2,3- ]-l,2,4-thiadiazine 1,1-oxides 267 are readily prepared by the reaction of 2-aminopyridine-3-sulfonamides 266 with sources of C-1 units such as orthoesters (Equation 28 Table 20), <1998T13645, 2003S1603> and anhydrides (Equation 29 Table 21) <1995T3221, 2000JME1456>. 

This group also prepared a number of substituted pyrido[4,3-r ]-l,2,4-thiadiazines 197, 269, 270, and 271 by the reaction of suitably substituted aminopyridinesulfonamides 224 with a range of C-1 units, such as anhydrides (Equation 32), <1996JME937> aldehydes (Equation 33, Table 23) <1998JME2946>, and l,l -thiocarbonyldiimi-dazole (Scheme 46) <1998T4935>. 

Intramolecular conjugate addition of /3-sulfonylstyrenes 39 (74JMC549) and 40 (R2 = Ar) (72BCJ1893) affords the 4H- and 5,6-dihydro-l,2,4-thiadiazines 41 and 42, respectively. Compound 39 is produced by sulfonyl-... 

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