On November 13, 2003, Venkatesan, Aranapakam Mudumbai; Mansour, Tarek Suhayl; Abe, Takao; Yamamura, Itsuki; Takasaki, Tsuyoshi; Agarwal, Atul; Dos Santos, Osvaldo; Sum, Fuk-Wah; Lin, Yang-I. published a patent.Name: Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate The title of the patent was Preparation of bicyclic 6-alkylidene-penems as β-lactamase inhibitors for use against bacterial infections or diseases. And the patent contained the following:
The present invention provides bicyclic 6-alkylidene-penems (shown as I; variables defined below; e.g. II), pharmaceutical compositions and the use thereof for the treatment of bacterial infection or disease in a patient in need thereof. IC50 values for inhibition of β-lactamase from 4 sources are tabulated for >30 examples of I; in vitro minimal inhibitory concentrations against 9 types of bacteria are tabulated for >30 examples of I; ED50 values for protective effects of >30 examples of I (sometimes combined with piperacillin) in mice are tabulated. For I: one of A and B is H and the other is an (un)substituted fused bicyclic heteroaryl group; X is O or S; R5 is H, C1-C6 alkyl, C5-C6 cycloalkyl, or CHR3OCOC1-C6alkyl; and R3 is H, C1-C6 alkyl, C5-C6 cycloalkyl, (un)substituted aryl, or (un)substituted heteroaryl. The compounds I when combined with β-lactam antibiotics will provide an effective treatment against life threatening bacterial infections. Forty example preparations of I are included. For example, II was prepared in 5 steps (25, 91, 76, 40, 18 % yields, resp.) starting from 1-benzoyl-4-piperidone and Et mercaptoacetate and involving intermediates Et 5-benzoyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-2-carboxylate, (5-benzyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)methanol, 2-formyl-5-benzyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridine and 4-nitrobenzyl 6-[(acetyloxy)(5-benzyl-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl)methyl]-6-bromo-7-oxo-4-thia-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate. The experimental process involved the reaction of Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate(cas: 153597-59-2).Name: Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate
The Article related to bicyclic alkylidene penem beta lactamase inhibitor antibacterial, beta lactam antibiotic codrug bicyclic alkylidene penem preparation, Heterocyclic Compounds (More Than One Hetero Atom): Thiazoles, Isothiazoles and other aspects.Name: Ethyl 6,7-dihydro-5H-pyrazolo[5,1-b][1,3]oxazine-2-carboxylate
Referemce:
Pyrazole – Wikipedia,
Pyrazoles – an overview | ScienceDirect Topics