Synthesis Of PF0713 And The Research Of Quinazoline For The Sigma-1 Receptor

Pain is a very important medical research areas. Our group have done some reasrch for anesthesia and analgesia to against pain.PF0713 is a kind of alkylphenols and it is a new kind of intravenous anesthetic. It has some advantages over propofol, such as low-dose and low-administered pain. There is no systematic research on how to synthesis PF0713, now. This research summarized the research associated with the way of synthesis of propofol and 2,6-di-sec-butylphenol. And our group did some reaserch about the method to synthesis of 2,6-di-sec-butylphenol by Claisen rearrangement. This method products less unwanted production than the method to synthesis of 2,6-di-sec-butylphenol which by Fridel-Crafts reaction. And this reaction can occur at lower temperatures. At the same time, this research summarized the chiral separation methods of obtaining PF0713. Our group developed the method to obtain PF0713 by chiral chromatographic separation, which is easier.Sigma-1 receptor is one of the hot medical research areas. This research existed the computer models of the sigma-1 receptor antagonist to designed a series of quinazoline compounds. We studied the structure-activity relationship of these compounds by in vitro screening to selected candidate drug molecules. We did some reaserch about the mechanism and dose-response relationship of the candidate drug molecules.(1) This reasch designed and synthesized 39 new quinazoline compounds.(2) This reasch screened above quinazoline compounds by receptor binding test of sigma-1 receptor and sigma-2 receptor. There were 9 compounds have strong affinity with sigma-1 receptor and have no affinity with sigma-2 receptor. We summaried the structure-activity relationship by this studied.(3) This reasch did the functional tests of zjc04 and zjc14. The results showed these two compounds were sigma-1 receptor antagonist.(4) This reasch did some reasch about the zjc04 and zjc14 by experimental rat model of formalin. The test suggest zjc04 had obviously active labor pains. Zjc04 had strong affinity and specific selectivity for the sigma-1 receptor. And it was sigma-1 receptor antagonist and had analgesic activity, moreover, it had valuable for futher pharmacological.