Dataset Information

Synthesis and Antibacterial Activity of Benzo[4,5]isothiazolo[2,3-a]pyrazine-6,6-dioxide Derivatives.

ABSTRACT: Using a routine procedure, a number of derivatives of the benzo[4,5]isothiazolo[2,3-a]pyrazine-6,6-dioxide ring system have been synthesized from readily available starting materials. A series of chalcones were synthesized, which were subsequently reacted with chlorosulfonic acid to generate chalcone sulfonyl chlorides. The chalcone sulfonyl chlorides were then treated with bromine to generate dibromo chalcone sulfonyl chlorides. These were subsequently reacted with 1,2-diaminopropane and 2-methyl-1,2-diaminopropane in boiling ethanol resulting in compounds 2-10 and 11-19 respectively, in 12-80% yields. The products were characterized by spectral analysis and the definitive structure of compound 11 was determined by X-ray crystallography. The synthesized compounds were screened for potential antibacterial properties against Bacillus subtilis, Escherichia coli, Proteus vulgaris and Staphylococcus aureus.

SUBMITTER: Bassin JP

PROVIDER: S-EPMC6150388 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Synthesis and Antibacterial Activity of Benzo[4,5]isothiazolo[2,3-a]pyrazine-6,6-dioxide Derivatives.

Bassin Jatinder P JP Botha Michelle J MJ Garikipati Rajesh R Goyal Madhu M Martin Lee L Shah Amit A

Molecules (Basel, Switzerland) 20171104 11

Using a routine procedure, a number of derivatives of the benzo[4,5]isothiazolo[2,3-<i>a</i>]pyrazine-6,6-dioxide ring system have been synthesized from readily available starting materials. A series of chalcones were synthesized, which were subsequently reacted with chlorosulfonic acid to generate chalcone sulfonyl chlorides. The chalcone sulfonyl chlorides were then treated with bromine to generate dibromo chalcone sulfonyl chlorides. These were subsequently reacted with 1,2-diaminopropane and ...[more]

PMID: 29113049

Similar Datasets

Project description:In previous work, we applied the rotation-limiting strategy and introduced a substituent at the 3-position of the pyrazolo [3,4-d]pyrimidin-4-amine as the affinity element to interact with the deeper hydrophobic pocket, discovered a series of novel quinazolinones as potent PI3K? inhibitors. Among them, the indole derivative 3 is one of the most selective PI3K? inhibitors and the 3,4-dimethoxyphenyl derivative 4 is a potent and selective dual PI3K?/? inhibitor. In this study, we replaced the carbonyl group in the quinazolinone core with a sulfonyl group, designed a series of novel 2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide derivatives as PI3K? inhibitors. After the reduction of nitro group in N-(2,6-dimethylphenyl)-2-nitrobenzenesulfonamide 5 and N-(2,6-dimethylphenyl)-2-nitro-5-fluorobenzenesulfonamide 6, the resulting 2-aminobenzenesulfonamides were reacted with trimethyl orthoacetate to give the 3-methyl-2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide derivatives. After bromination of the 3-methyl group, the nucleophilic substitution with the 3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine provided the respective iodide derivatives, which were further reacted with a series of arylboronic acids via Suzuki coupling to furnish the 2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide derivatives 15a-J and 16a-d. In agreement with the quinazolinone derivatives, the introduction of a 5-indolyl or 3,4-dimethoxyphenyl at the affinity pocket generated the most potent analogues 15a and 15b with the IC50 values of 217 to 266 nM, respectively. In comparison with the quinazolinone lead compounds 3 and 4, these 2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide derivatives exhibited much decreased PI3K? inhibitory potency, but maintained the high selectivity over other PI3K isoforms. Unlike the quinazolinone lead compound 4 that was a dual PI3K?/? inhibitor, the benzthiadiazine 1,1-dioxide 15b with the same 3,4-dimethoxyphenyl moiety was more than 21-fold selective over PI3K?. Moreover, the introducing of a fluorine atom at the 7-position of the 2H-benzo[e][1,2,4]thiadiazine 1,1-dioxide core, in general, was not favored for the PI3K? inhibitory activity. In agreement with their high PI3K? selectivity, 15a and 15b significantly inhibited the SU-DHL-6 cell proliferation.

Dataset Information

Synthesis and Antibacterial Activity of Benzo[4,5]isothiazolo[2,3-a]pyrazine-6,6-dioxide Derivatives.

Publications

Synthesis and Antibacterial Activity of Benzo[4,5]isothiazolo[2,3-a]pyrazine-6,6-dioxide Derivatives.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets