On June 19, 2014, Ahmed, Mahbub; Ashall-Kelly, Alexander; Bloomfield, Graham Charles; Gueritz, Louisa; McKenna, Jeffrey; McKenna, Joseph; Mutton, Simon; Parmar, Rakesh; Sheperd, Jon; Wright, Paul published a patent.Application In Synthesis of 2-(Oxiran-2-ylmethyl)isoindoline-1,3-dione The title of the patent was Preparation of tricyclic compounds as CFTR channel inhibitors for treating polycystic kidney disease and diarrhea. And the patent contained the following:
The invention provides tricyclic compounds of general formula I or a pharmaceutical salt thereof, their use for inhibiting the CFTR channel, and methods of treating disease using same, particularly polycystic kidney disease and diarrhea. For I, R1 is Ph, (C4-C7)cycloalkenyl or a 5-6-membered heteroaryl ring, all optionally substituted; R2 is (C1-C6)alkyl, (C3-C7)cycloalkyl, (C4-C7)cycloalkenyl, etc., all optionally substituted; each R3 independently is Me or ethyl; R4 is hydrogen, (C1-C4)alkyl, halo(C1-C4)alkyl, etc.; R4′ is H or methyl; R4a is hydrogen, (C1-C4)alkyl, halo(C1-C4)alkyl, etc.; and X is O, NH, NMe, or -CH2-O- wherein the O atom is attached to the -C(R4)(R4′) atom of the ring. Pharmaceutical compositions containing I, alone or in combination with other active agents, are also disclosed. Synthetic procedures for preparing I are exemplified. Example compound (R)-II was prepared by reacting intermediate III with 5-methylfuran-2-carboxaldehyde and subjecting the racemate formed to chiral separation Using the Ion Works Quatro assay (R)-II had a CFTR IC50 of 1.58 μM. The experimental process involved the reaction of 2-(Oxiran-2-ylmethyl)isoindoline-1,3-dione(cas: 5455-98-1).Application In Synthesis of 2-(Oxiran-2-ylmethyl)isoindoline-1,3-dione
The Article related to tricyclic compound preparation cftr channel inhibitor polycystic kidney disease, diarrhea treatment tricyclic compound cftr channel inhibitor, Heterocyclic Compounds (More Than One Hetero Atom): Pyrimidines and Quinazolines and other aspects.Application In Synthesis of 2-(Oxiran-2-ylmethyl)isoindoline-1,3-dione
Referemce:
Amide – Wikipedia,
Amide – an overview | ScienceDirect Topics