2-Amino- and 2-alkylthio-4H-3,1-benzothiazin-4-ones: synthesis, interconversion and enzyme inhibitory activities.
The synthetic access to 2-sec-amino-4H-3,1-benzothiazin-4-ones 2 was explored. Compounds 2 were available from methyl 2-thioureidobenzoates 1, 2-thioureidobenzoic acids 3, and novel 2-thioureidobenzamides 6, respectively, under different conditions. 2-Alkylthio-4H-3,1-benzothiazin-4-ones 5 have been prepared from anthranilic acid following a two step route. Both, benzothiazinones 2 and 5 underwent ring cleavage reactions to produce thioureas 1 and 6, respectively. Twelve benzothiazinones were evaluated as inhibitors against a panel of eight proteases and esterases to identify one selective inhibitor of human cathepsin L, 2b, and one selective inhibitor of human leukocyte elastase, 5i.
Häcker
Hans-Georg
HG
Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany. hhaecker@uni-bonn.de
Grundmann
Florian
F
Lohr
Friederike
F
Ottersbach
Philipp A
PA
Zhou
Jing
J
Schnakenburg
Gregor
G
Gütschow
Michael
M
D000818:Animals; D001565:Benzoates / Q000737:chemistry / Q000378:metabolism; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors; D002417:Cattle; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D003546:Cysteine Endopeptidases; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D002787:Sterol Esterase / Q000037:antagonists & inhibitors; D013890:Thiourea / Q000737:chemistry / Q000378:metabolism
D001565:Benzoates; D004791:Enzyme Inhibitors; D002787:Sterol Esterase; D002403:Cathepsins; D002918:Chymotrypsin; D019272:Leukocyte Elastase; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; D013890:Thiourea