- Proton-in-flight mechanism for the spontaneous hydrolysis of N-methyl O-phenyl sulfamate: Implications for the design of steroid sulfatase inhibitors
-
The hydrolysis of N-methyl O-phenyl sulfamate (1) has been studied as a model for steroid sulfatase inhibitors such as Coumate, 667 Coumate, and EMATE. At neutral pH, simulating physiological conditions, hydrolysis of 1 involves an intramolecular proton transfer from nitrogen to the bridging oxygen atom of the leaving group. Remarkably, this proton transfer is estimated to accelerate the decomposition of 1 by a factor of 1011. Examination of existing kinetic data reveals that the sulfatase PaAstA catalyzes the hydrolysis of sulfamate esters with catalytic rate accelerations of ～104, whereas the catalytic rate acceleration generated by the enzyme for its cognate substrate is on the order of ～1015. Rate constants for hydrolysis of a wide range of sulfuryl esters, ArOSO2X-, are shown to be correlated by a two-parameter equation based on pKa ArOH and pKaArOSO2XH.
- Edwards, David R.,Wolfenden, Richard
-
experimental part
p. 4450 - 4453
(2012/06/30)
-
- Indole, azaindole and related heterocyclic sulfonylureido piperazine derivatives
-
This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with sulfonylureido piperazine derivatives of Formula I. These compounds possess unique antiviral activity, whether used alone or in combination with other antivirals, antiinfectives, immunomodulators or HIV entry inhibitors. More particularly, the present invention relates to the treatment of HIV and AIDS. 1wherein: Z is 2Q is selected from the group consisting of: 3—W— is 4—represents a carbon-carbon bond or does not exist; and A is NR13R14.
- -
-
Page/Page column 33
(2010/02/05)
-
- SYNTHESIS OF METHYLSULFAMIDIC ACID.
-
Methylsulfamidic acid (MSA) and its homologs are key substances in production of synthetic sweeteners, dyes, and means of control of agricultural pests. A method has been devised for production of MSA by sulfonation of dimethylurea with 20-30% oleum in absence of a solvent by 75-80 degree , followed by isolation of MSA by crystallization in 70-75% sulfuric acid. The dependence of the MSA yield on different reaction conditions was studied. Three reaction routes studied were: sulfonation with sulfur trioxide, sulfonation with oleum in a solvent, and sulfonation with oleum without a solvent.
- Gareev,Bol'shedvorskaya,Cherkashina,Flippova,Gaer,Vereshchagin,Sakovich
-
p. 1013 - 1016
(2007/10/02)
-
