Cerebrovasodilatation through selective inhibition of the enzyme carbonic anhydrase. 1. Substituted benzenedisulfonamides

Abstract

A series of substituted benzenedisulfonamide carbonic anhydrase inhibitors is described and their anticonvulsant activities are listed. One compound, 4-(4-methoxypiperidinosulfonyl)-2-chlorobenzenesulfonamide (19, UK-12130), was found to have anticonvulsant activity in animals at a dose level that gave only a minimal diuretic effect. 19 selectively increased cerebral blood flow in animals and man without producing an unacceptable level of metabolic acidosis.

.beta.-Adrenergic blocking agents. 19. 1-Phenyl-2-[[(substituted-amido)alkyl]amino]ethanols

“…NMR spectra for all the compounds described were recorded either on a Varían HA100D or a Varían A60 using tetramethylsilane as the internal standard and were consistent with the assigned structures. 2-[(2-Acetamidoethyl)amino]-1-phenylethanol (5). Method A.…”

Three new aromatic sulfonamide inhibitors of carbonic anhydrases I, II, IV and XII

“…The crude solid was filtered and purified by crystallization from 2-propanol. 4-Sulfamoylbenzenesulfamoylchloride (V) was prepared by multistep synthesis from 4-aminobenzenesulfonamide as starting compound, treated with sodium Three 17 . The crude product was crystallized from 1,2-dichloroethane as colorless compound, yield 58%, m.p.…”

“…The measured physicochemical characteristic of this product corresponds to the similar data found in ref. 17.…”

Traceless solid-phase synthesis of multiple sulfonamide-containing cyclic sulfides exploiting microwave irradiation

“…1) are known to show a number of intriguing biological activities, such as antimalarial effect, 1 VLA-4 antagonistic effect, 2 RyR receptors modulatory effect, 3 antiobesity effect, 4 and inhibitory effect on matrix metalloproteinase, 5 TACE, 6 phenylethanolamine N-methyltransferase, 7 FKBP12, 8 carbonic anhydrase, 9 IKK2, 10 and type II 17b-hydroxysteroid dehydrogenase. 11 Therefore, it is believed that these skeletons and their analogs are very attractive templates for chemical libraries to generate novel bioactive compounds in high-throughput screenings (HTS).…”

“…Compounds A-C have previously been synthesized using conventional solutionphase methods [1][2][3][4][5][6][7][8][9][10][11] , although these methods are somewhat problematic for development of chemical libraries. Solution-phase methods are inappropriate for multi-step syntheses involved in chemical library development due to the purification required in each step.…”