Tag: M.W=150-200

Mohamed, Abdalla R. published the artcileDesign, synthesis and in silico insights of new 7,8-disubstituted-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione derivatives with potent anticancer and multi-kinase inhibitory activities, Application of 3-Aminobenzo[d]isothiazole 1,1-dioxide, the publication is Bioorganic Chemistry (2021), 104569, database is CAplus and MEDLINE.

7,8-Disubstituted-1,3-dimethyl-1H-purine-2,6(3H,7H)-dione I [R¹= Ph, phenylcarbamoyl, p-tolylcarbamoyl, etc.; R² = bromo, (2,4-dioxo-1H-pyrimidin-6-yl)amino] were selected based on the characteristic pharmacophoric features required for PI3K and B-Raf oncogenes inhibition was synthesized. All the synthesized compounds were evaluated for their in-vitro anticancer activity. I [R¹= phenyl; R² = (2,4-dioxo-1H-pyrimidin-6-yl)amino] and I [R¹=p-tolylcarbamoyl; R² = bromo] displayed an acceptable potent activity according to the DTP-NCI and were further evaluated in the NCI five doses assay. To validate the design, compounds with the highest mean growth inhibition percent were screened against the target PI3Kα and B-RafV600E confirmed their multi-kinase activity. The tested compounds showed promising multi-kinase activity. I [R¹= phenyl; R² = (2,4-dioxo-1H-pyrimidin-6-yl)amino] and I [R¹=p-tolylcarbamoyl; R² = bromo] anticancer effectiveness and multi-kinase activity against PI3Kα and B-Raf_V600E were consolidated by the inhibition of B-Raf_WT, EGFR and VEGFR-2 with IC₅₀ in the sub-micromolar range. Further investigations on the most potent I [R¹= phenyl; R² = (2,4-dioxo-1H-pyrimidin-6-yl)amino] and I [R¹=p-tolylcarbamoyl; R² = bromo] were carried out and studied their safety on normal cell line, in-silico profiling and predicted ADME characteristics.

Bioorganic Chemistry published new progress about 7668-28-2. 7668-28-2 belongs to isothiazole, auxiliary class Sulfamide,Amine,Benzothiazole, name is 3-Aminobenzo[d]isothiazole 1,1-dioxide, and the molecular formula is C7H6N2O2S, Application of 3-Aminobenzo[d]isothiazole 1,1-dioxide.

Referemce:
https://en.wikipedia.org/wiki/Isothiazole,
Isothiazole – ScienceDirect.com

Mameli, Efisio published the artcilePyrolysis of ammonium saccharin and of ammonium thiosaccharin. Saccharinimine and pseudosaccharinamine, Product Details of C7H6N2O2S, the publication is Gazzetta Chimica Italiana (1940), 855-74, database is CAplus.

The work is a continuation of that on the comparative behavior of saccharin (I) and thiosaccharin (II) (cf. M.-M., C. A. 29, 3998.8). Various modifications of the Defournel method of preparing NH₄ saccharin (III) were tried, including temperature, concentration, and proportion of reagents. At 170°, III loses its crystallinity; at 210° it softens and evolves NH₃; at 222° it melts; at 233-5° the evolution of NH₃ increases and a brown liquid is formed; at 240-60° NH₃ is no longer evolved, and a yellow-brown, vitreous mass remains. The latter, extracted with Et₂O (to remove I), then with water, the aqueous extract evaporated, the residue extracted with Et₂O, and purified from boiling water, yields 33% of 0-C₆H₄(CONH₂)SO₂ONH₄ (IV), m. 257-60° (cf. various m. ps., e. g., Ber. 22, 759 (1889); Am. Chem. J. 18, 825(1896); 30, 370(1903)). After the Et₂O and water extractions, a solid substance remains, which, purified by boiling water, yields 50% of C₆H₄.SO₂.NH.C:NH (V), m. 315°. NH₄ thiosaccharin (VI) was prepared by a method already described (cf. M.-M., C. A. 10, 1174) and by new methods (II and (NH₄)₂CO₃, II and urea, II and thiourea, etc.), which will be published later. At 170°, VI evolves NH₃, H₂S and unidentified vapors; at 225°, evolution of gases is more intense; at 224-50° the mass reddens; at 285° the residue softens and contracts; at 295-300° it melts to a dark liquid, and evolves H₂S. Elimination of H₂S is usually complete at 270°. The residue, extracted with Et₂O and then with water, as before, does not yield IV. The final residue is V. To compare V with the supposedly identical compound already known, it was prepared by 8 methods: (1) pyrolysis of III; (2) pyrolysis of VI; (3) heating I and (NH₄)₂CO₃ at 250°; (4) heating II and (NH₄)₂CO₃ at 300°; (5) heating I and urea at 250°; (6) heating II and urea at 150°; (7) action of NH₃ on chloropseudosaccharin, and (8) pyrolysis of saccharin oxime. Methods (3), (4) and (5) are new, and the details will be published later. The yield by method (1) was 50%; that by method (2) was 80-85%. The products by all methods m. 315°. An extensive study of V was carried out. Its crystalline form depends on the conditions of crystallization; but all forms m. 315° and have the same solubility and chem. properties, so the different forms are polymorphic rather than tautomeric. Aqueous solutions of V are slightly acid to litmus. It is insoluble in dilute or concentrated HCl, dilute or 60% H₂SO₄, aqueous alkali carbonates, and dilute NH₄OH. It is soluble in 10% NaOH and KOH, slightly soluble in concentrated NH₄OH and 6% aqueous alkalies. V is precipitated from its alk. solutions by acids and by CO₂, whereas I and II are precipitated from their alk. solutions by acids but not by CO₂. In 30% aqueous alkalies, V dissolves in part, and in part forms alkali salts, which dissolve only by dilution with water. The earlier discovery that cold aqueous alkalies hydrolyze V to I and NH₃ (cf. M.-M., C. A. 29, 3998.8) was confirmed, and it was further found that when V and 5% NaOH are allowed to stand several days or are heated 2 h., o-C₆H₄(SO₂NH₂)CO₂H is formed. Because of the behavior of V with aqueous alkalies, it was impossible to prepare alkali salts. When aqueous or alc. NaOH or KOH solutions of V were allowed to evaporate, I was obtained, and when alc. NH₃ solutions were evaporated, V was recovered. Hot aqueous V does not reduce NH₃-AgNO₃, but precipitates the Ag salt, C₇H₅O₂N₂SAg, of V. The best method is to dissolve V in a min. of 10% NaOH or preferably NH₄OH, and precipitate by excess AgNO₃ solution The fact that V is less acidic than I is shown also by their behavior toward 5KBr-KBrO₃ mixtures and 5KI-KIO₃ mixtures I liberates Br and I; V liberates neither (II gives a precipitate which was not studied). V is slightly soluble in cold AcOH, PhNH₂ and C₅H₅N, and readily soluble in hot PhNH₂, hot C₅H₅N, cold concentrated H₂SO₄ and 80% H₂SO₄, from all of which solutions it is precipitated unaltered by addition of water, whereas II and C₅H₅N react. When KNO₂ is added to a solution of V in concentrated or 80% H₂SO₄, there is no reaction. V does not react with H₂S, (NH₄)₂S, BzH, piperonal or PhCH:CHCHO at room temperature, or with AlCl₃ or Na₂SO₄ at 200°. Hot aqueous V does not reduce NH₃-AgNO₃, but precipitates the Ag salt, C₇H₅O₂N₂SAg, of V, which is not altered by prolonged boiling of the liquid It can be prepared also by dissolving V in a min. of 10% NaOH, or preferably NH₄OH, and adding excess AgNO₃. The instability of alk. solutions of V made it impossible to prepare its Na and NH₄ salts. V in dilute EtOH, NH₂OH.HCl (4 mols.) and NaOAc (4 mols.), heated 90 min., yields saccharin oxime, m. 208-10° (cf. M.-M., C. A. 27, 2682). The results in general point to the constitution of V as C₆H₄.SO₂.NH.C:NH, rather than C₆H₄.SO₂.N:CNH₂, i. e., pseudosaccharinamine, which was supposed to have the constitution of the probably identical compound, m. 315°, prepared otherwise by Jesurum (Ber. 26, 2294, 2298(1893)) and by others. In the same way, the iminoamide of saccharincarboxylic acid, prepared by Zincke and Greune (C. A. 16, 2322) should have the constitution: H₂NCOC₆H₃.SO₂.NH.C:NH, rather than H₂NCOC₆H₃.SO₂.N:CNH₂. The transformation of III and of VI as described has few precedents, either with respect to the formation of IV or of V; in fact the formation of V from III and from VI is a new type of transposition, in which III and VI lose H₂O and H₂S, resp., following which a group containing N migrates from a N atom to an adjacent C atom, thus: The transformation of O:C:NNH₄ to O:C(NH₂)₂, involves only migration of a group containing N from a N atom to a C atom, without dehydration. If this were true of III, the product would be NCNH₂ or HN:C:NH. Nor is the transformation of the -CONHCO- group to the -C(:NH)OCO-group, which takes place in the pyrolysis of imides, analogous to the pyrolysis of III.

Gazzetta Chimica Italiana published new progress about 7668-28-2. 7668-28-2 belongs to isothiazole, auxiliary class Sulfamide,Amine,Benzothiazole, name is 3-Aminobenzo[d]isothiazole 1,1-dioxide, and the molecular formula is C7H6N2O2S, Product Details of C7H6N2O2S.

Referemce:
https://en.wikipedia.org/wiki/Isothiazole,
Isothiazole – ScienceDirect.com

Riggin, R. M. published the artcileCharacterization of impurities in commercial lots of sodium saccharin produced by the Sherwin-Williams process. II. Mutagenicity, Category: isothiazole, the publication is Food and Chemical Toxicology (1983), 21(1), 11-17, database is CAplus and MEDLINE.

All individual components identified in solvent extracts of specific manufacturing lots of saccharin  [81-07-2] produced by the Sherwin-Williams process were nonmutagenic. The mutagenic activity of saccharin lot S-1469 was traced to a moderately polar chromatog. fraction representing impurities present in the saccharin at a level of <1.5 ppm, but was not attributable to a single component. In view of the low level of mutagenic activity observed and the low concentration of total impurities in Sherwin-Williams saccharin, the mutagenic material(s) are probably of no significance in animal feeding studies.

Food and Chemical Toxicology published new progress about 7668-28-2. 7668-28-2 belongs to isothiazole, auxiliary class Sulfamide,Amine,Benzothiazole, name is 3-Aminobenzo[d]isothiazole 1,1-dioxide, and the molecular formula is C7H6N2O2S, Category: isothiazole.

Referemce:
https://en.wikipedia.org/wiki/Isothiazole,
Isothiazole – ScienceDirect.com

Tkachuk, Volodymyr published the artcileCyclic acyl amidines as unexpected C4-donors for fully substituted pyridine ring formation in the base mediated reaction with malononitrile, Recommanded Product: 3-Aminobenzo[d]isothiazole 1,1-dioxide, the publication is Tetrahedron Letters (2019), 60(30), 1959-1963, database is CAplus.

A new one-step, pseudo four-component approach for the synthesis of fully substituted pyridines via ring-opening of the cyclic acyl amidine of 3-amino-1H-isoindol-1-one and its aza-analogs during the reaction with malononitrile in the presence of sodium methoxide, followed by pyridine ring closure is reported. This method allows the one-step preparation of previously unknown 2-(pyridin-4-yl)(hetero)aryl carboxamides in good yields under mild reaction conditions.

Tetrahedron Letters published new progress about 7668-28-2. 7668-28-2 belongs to isothiazole, auxiliary class Sulfamide,Amine,Benzothiazole, name is 3-Aminobenzo[d]isothiazole 1,1-dioxide, and the molecular formula is C10H6INO3, Recommanded Product: 3-Aminobenzo[d]isothiazole 1,1-dioxide.

Referemce:
https://en.wikipedia.org/wiki/Isothiazole,
Isothiazole – ScienceDirect.com

Jensen, Klaus G. published the artcilePhosphoramides. XIX. Phosphorus pentoxide amine hydrochloride reagents in the synthesis of 3-amino-1,2-benzisothiazole 1,1-dioxides and 3-aminothieno[3,4-d]isothiazole 1,1-dioxides, Name: 3-Aminobenzo[d]isothiazole 1,1-dioxide, the publication is Zeitschrift fuer Naturforschung, Teil B: Anorganische Chemie, Organische Chemie (1981), 36B(12), 1640-3, database is CAplus.

Aminobenzisothiazole dioxides I (R = H, R¹ = alkyl, cycloalkyl; RR¹N = morpholino, piperidino) were prepared by heating saccharin and the hydrochlorides of primary and secondary aliphatic amines with P₂O₅ and N,N-dimethylcyclohexylamine at 240°. 3-Aminothienoisothiazole dioxides II (R² = Pr, Me₂CHCH₂, EtCHMe) were similarly prepared from thieno[3,4-d]isothiazol-3(2H)-one 1,1-dioxide. In biol. screening against lymphocytic leukemia I were inactive.

Zeitschrift fuer Naturforschung, Teil B: Anorganische Chemie, Organische Chemie published new progress about 7668-28-2. 7668-28-2 belongs to isothiazole, auxiliary class Sulfamide,Amine,Benzothiazole, name is 3-Aminobenzo[d]isothiazole 1,1-dioxide, and the molecular formula is C7H6N2O2S, Name: 3-Aminobenzo[d]isothiazole 1,1-dioxide.

Referemce:
https://en.wikipedia.org/wiki/Isothiazole,
Isothiazole – ScienceDirect.com

Schapira, Celia B. published the artcile3-Oxo-1,2-benzoisothiazoline-2-acetic acid 1,1-dioxide derivatives. I. Reaction of esters with alkoxides, Application In Synthesis of 7668-28-2, the publication is Journal of Heterocyclic Chemistry (1980), 17(6), 1281-8, database is CAplus.

Reaction of the benzisothiazolineacetic acids I (R = Me, Et, Me₂CH, Me₂CHCH₂CH₂, Ph) with alk. alkoxides was carried out under various conditions. Under mild conditions, o-(RO₂C)C₆H₄SO₂NHCH₂COR (II) were obtained with good yields. Reaction of I or II with Na alkoxides under drastic conditions gave the esters III. Transesterification was observed when esters I were treated with NaOMe. Esters III were hydrolyzed in concentrated aqueous NaOH giving the acid III (R = H). Attempts to recrystallize III (R = H) from water resulted in its decarboxylation to give 2H-1,2-benzothiazin-4(3H)one 1,1-dioxide. III(R = H) could not be obtained by acid hydrolysis of esters III or by rearrangement of 3-oxo-1,2-benzoisothiazoline-2-acetic acid 1,1-dioxide. The rearrangement apparently took place by ethanolysis of the carboxamide linkage to the open sulfonamides (fast step) followed by a Dieckmann cyclization (slow step). Transesterification took place in the open sulfonamides.

Journal of Heterocyclic Chemistry published new progress about 7668-28-2. 7668-28-2 belongs to isothiazole, auxiliary class Sulfamide,Amine,Benzothiazole, name is 3-Aminobenzo[d]isothiazole 1,1-dioxide, and the molecular formula is C7H6N2O2S, Application In Synthesis of 7668-28-2.

Referemce:
https://en.wikipedia.org/wiki/Isothiazole,
Isothiazole – ScienceDirect.com

Barr, C. R. published the artcileThe reaction of 3-(chlorosulfonyl)benzoyl chloride with amines, Related Products of isothiazole, the publication is Journal of the American Chemical Society (1951), 4131-3, database is CAplus.

cf. U.S. patent 2,484,477, C.A. 44, 7695f. m-ClCOC₆H₄SO₂Cl (I) can react with 2 different amines in 2 stages. The carboxamide is formed in the 1st reaction, the sulfonamide in the 2nd. This property is used to prepare, (1) mixed amides of the type RR’NCOC₆H₄SO₂NR”R”’, and (2) pure compounds containing SO₃H groups. PhNH₂ (1.80 g.) in 20 cc. dry PhMe added during 10 min. to 5.28 g. I in 50 cc. boiling PhMe, and the mixture refluxed 30 min. and kept 2 hrs. at 10° yielded 5.3 g. m-(chlorosulfonyl)-benzanilide (II), fine, white needles from PhMe, m. 155-6°. PhNH₂ (3.8 g.) in 30 cc. PhMe added dropwise to 4.8 g. I in 50 cc. PhMe, the mixture stirred overnight, filtered, and the solid stirred into 500 cc. water yielded 4.5 g. II, m. 155-6°. PhNH₂ (3.8 g.) in 30 cc. PhMe added dropwise to 4.8 g. I in 50 cc. PhMe, and the mixture refluxed 1.5 hrs., and let stand overnight yielded 6 g. m-sulfobenzoic acid dianilide (III), m. 176-7°. II and PhNH₂.HCl (1 mole of each) yielded III. PhNH₂ (0.63 g.) added to I g. II in 10 cc. PhMe at room temperature, the mixture heated to 90°, cooled to room temperature, and diluted with 20 cc. water yielded III, m. 176-7° (from PhMe and alc.). II (1 g.) refluxed 1 hr. water and the solution concentrated on the steam bath yielded quantitatively m-(phenylcarbamyl)benzenesulfonic acid (IV). PhNH₂ (2 cc.) and 1 g. IV in 10 cc. 90% EtOH with 2 cc. Et₂O yielded 1 g. PhNH₂ salt of IV, white needles, m. 249-51°. I (23.9 g.) added to 21.8 g. o-H₂NC₆H₄OH in 350 cc. dioxane, the mixture filtered after 15 min., the solid washed with 50 cc. dioxane, and the filtrate diluted with 400 cc. hexane yielded 24 g. 3-(chlorosulfonyl)-2′-hydroxybenzanilide (V), small, tan crystals from (CHCl₂)₂, m. 183° (decomposition). V (1 g.) stirred into 5 cc. PhNH₂ and the excess PhNH₂ removed with 100 cc. 10% HCl yielded 0.8 g. 3-(phenylsulfamyl)-2′-hydroxybenzanilide (VI), fine, white needles from PhMe, m. 170°. The procedure used for VI with 5 g. V and 10 g. MeHNPh yielded 5 g. of the 3-(methylphenylsulfamyl) compound, m. 158° (from PhMe). p-H₂NC₆H₄OH (2.9 g.) and 0.04 mole NaOAc in 50 cc. AcOH heated 5 min. on the steam bath, the solution treated with 4.78 g. I in 50 cc. AcOH, and the mixture heated 1.75 hrs. on the steam bath, chilled 15 min. at 0°, and diluted with 500 cc. water yielded 5.24 g. 3-(chlorosulfonyl)-4′-hydroxybenzanilide, m. 170°. 1-Phenyl-3-amino-5-pyrazolone (C.A. 36, 6536.8) (10 g.) stirred 20 min. on the steam bath with 10.6 g. m-O₂NC₆H₄– COCl and 7 cc. (CO₂Et)₂, and the mixture refluxed and stirred with 5O cc. EtOH and cooled yielded 14.5 g. 1-phenyl-3-(m- nitrobenzamido)-5-pyrazolone (VII), m. 215-20°. VII (16 g.) refluxed in 145 cc. AcOH, 15 cc. water, and 80 cc. EtOH, 16.0 g. powd. Fe added at once, the mixture boiled 10 min., filtered hot, and the filtrate diluted with 100 cc. water and cooled without stirring yielded 11.0 g. 1-phenyl-3-(m-amino- benzamido)-5-pyrazolone (VIII), lustrous, brown crystals, m. 220-2°. VIII (2.94 g.) and 1.64 g. NaOAc in 55 cc. AcOH (at 50°) added to 2.39 g. I in 25 cc. AcOH, the mixture stirred 3 hrs. at room temperature, filtered, washed with 100 cc. water, and stirred into 300 cc. water yielded 5.2 g. 1-phenyl-3-{m-[m-(m-chlorosulfonyl)benzamido] benzamido}-5-pyrazolone, white crystals m. 188-90° (containing 1 mole AcOH). I (6.6 g.) added all at once to 4.4 g. 1-aminoanthraquinone in 130 cc. hot PhMe, and the mixture refluxed 1.25 hrs. and cooled to room temperature yielded 6.9 g. 1-[m-(chlorosulfonyl)-benzamidolanthraquinone, long amber neeldes from PhMe, m. 219-22° (decomposition).

Journal of the American Chemical Society published new progress about 7668-28-2. 7668-28-2 belongs to isothiazole, auxiliary class Sulfamide,Amine,Benzothiazole, name is 3-Aminobenzo[d]isothiazole 1,1-dioxide, and the molecular formula is C7H6N2O2S, Related Products of isothiazole.

Referemce:
https://en.wikipedia.org/wiki/Isothiazole,
Isothiazole – ScienceDirect.com

Stoss, Peter published the artcileCyclic sulfoximides. IV. 3-Imino-3H-1λ4,2-benzisothiazole 1-oxides, Safety of 3-Aminobenzo[d]isothiazole 1,1-dioxide, the publication is Chemische Berichte (1975), 108(12), 3855-63, database is CAplus.

2-Sulfinylbenzamides I (R = Me, Ph) cyclized with hydrazoic acid to yield benzisothiazole oxides II, which are cyclic sulfoximides. II reacted with BrCN or H2NCN, R2COCl [R2 = C6H4R3 (R3 = o-OH, m-OMe, o-OAc), OMe, OCHMeEt, OCH2CH2OMe, cyclohexyloxy, PPh, alkyl, CH2Ph, CH2OC6H4Cl-p, OEt], R4NCX (R4 = Ph, CH2CH2Cl, Bu, X = O; R4 = allyl, X = S), and N,N’-carbonyldiimidazole to give imino-N-substituted derivatives III, IV, V, and VI, resp.

Chemische Berichte published new progress about 7668-28-2. 7668-28-2 belongs to isothiazole, auxiliary class Sulfamide,Amine,Benzothiazole, name is 3-Aminobenzo[d]isothiazole 1,1-dioxide, and the molecular formula is C13H9FO2, Safety of 3-Aminobenzo[d]isothiazole 1,1-dioxide.

Referemce:
https://en.wikipedia.org/wiki/Isothiazole,
Isothiazole – ScienceDirect.com

Hettler, Hans published the artcileMass-spectroscopic fragmentation behavior of benzisothiazole S,S-dioxide derivatives, Name: 3-Aminobenzo[d]isothiazole 1,1-dioxide, the publication is Organic Mass Spectrometry (1969), 2(11), 1117-33, database is CAplus.

The fragmentation behavior of derivatives of benzisothiazole S,S-dioxide is discussed. A series of degradation processes typical for this class of compounds is observed, whose relative importance, however, largely depends on the substituents present. Provided it is energetically favorable, fragmentation of the substituents (frequently followed by expulsion of SO2) prevails; otherwise, degradation of the heteroaromatic ring is observed (sometimes with rearrangements involving the SO2 group). No parallels between thermal and electron-impact-induced rearrangements have been observed

Organic Mass Spectrometry published new progress about 7668-28-2. 7668-28-2 belongs to isothiazole, auxiliary class Sulfamide,Amine,Benzothiazole, name is 3-Aminobenzo[d]isothiazole 1,1-dioxide, and the molecular formula is C7H6N2O2S, Name: 3-Aminobenzo[d]isothiazole 1,1-dioxide.

Referemce:
https://en.wikipedia.org/wiki/Isothiazole,
Isothiazole – ScienceDirect.com