On April 27, 2006, Burgey, Christopher S.; Paone, Daniel V.; Shaw, Anthony W.; Nguyen, Diem N.; Deng, Zhengwu J.; Williams, Theresa M.; Vacca, Joseph P.; Selnick, Harold G.; Potteiger, Craig M. published a patent.Quality Control of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate The title of the patent was Imidazolo[1,2-a]azepane and triazolo[4,3-a]azepane derivatives as CGRP receptor antagonists and their preparation, pharmaceutical compositions, and use for treatment of diseases in which CGRP is involved such as headache, migraine and cluster headache. And the patent contained the following:
Compounds of formula I and formula II are useful as antagonists of CGRP receptors and useful in the treatment or prevention of diseases in which the CGRP is involved, such as headache, migraine and cluster headache. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which CGRP is involved. Compounds of formula I and II wherein Z is (un)substituted piperidine or (un)substituted spiropiperidine; A is C(R2)2, O, SOm, or NR2; B is [C(R2)2]n; D is N or CR1; R1 is H, (un)substituted C1-6 alkyl, (un)substituted C2-6 alkenyl, (un)substituted C2-6 alkynyl, (un)substituted C3-6 cycloalkyl, (un)substituted heterocyclyl, or (un)substituted (hetero)aryl; each R2 is independently H, (un)substituted C0-6 alkyl, (un)substituted C2-6 alkenyl, (un)substituted C2-6 alkynyl, (un)substituted C3-6 cycloalkyl, (un)substituted heterocyclyl, (un)substituted (hetero)aryl; any two R2 on the same or adjacent atoms optionally join to form cycloalkyl, (hetero)aryl, or heterocycloalkyl ring; W is O, NR4 or C(R4)2; R4 is H, (un)substituted (fluoro)C1-6 alkyl, (un)substituted C3-6 cycloalkyl, and (un)substituted (hetero)aryl, or benzyl; X is C or S; Y is O, (R4)2, NCN, NSO2Me or NCONH2; or Y is O2 when X is S; m is O, 1, or 2; n is 1 or 2; and pharmaceutically acceptable salts and diastereoisomers thereof are claimed in this invention. Example compound III was prepared by condensation of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-thioxoazepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide with 1-amino-3-methylbutan-2-ol to give N-[(3R,6S)-6-(2,3-difluorophenyl)-2-[(2-hydroxy-3-methylbutyl)imino]azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide TFA salt, which underwent oxidation to give example compound III. All the invention compounds were evaluated for their activity as antagonists of the CGRP receptor. From the assay, the example compounds, in general, exhibited Ki or IC50 values of less than about 50 μM. The experimental process involved the reaction of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate(cas: 883984-95-0).Quality Control of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate
The Article related to imidazoloazepane triazoloazepane preparation pharmaceutical composition cgrp receptor antagonist, triazoloazepane imidazoloazepane preparation treatment headache migraine cgrp receptor antagonist and other aspects.Quality Control of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate
Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem