I don't have any conclusions to report because I have recruited f...

I don't have any conclusions to report because I have recruited friends to help me. I got over my head as far as my understanding of this type of chemistry. I am particularly interested in what happens to the quinoline nitrogen during the metabolic break down of montelukast. Nitric oxide is an important molecule to the human body. BUT, however, in excess it is very toxic. The year of this study 1998, some medical researchers got the Nobel prize for their work on nitric oxide. http://nobelprize.org/nobel_prizes/medicine/laureates/1998/press.html So I am now working with friends to try to further understand the Merck report on the metabolism of montelukast. I found a Japanese researchers opinion of the connections of montelukast and the cysLT1 receptor showing the nitrogen as a key factor. I was also able to find some work done on mold spores that might give some clues because DPA - 2,6 pyridine dicarboxylic acid in the spore case might yield something about the receptor and/or quinolinic acid 2,3 pyridinedicarboxylic acid. I haven't concluded anything about Fenton reactions as of yet but that is always something to think about. If anyone has any chemist friends, we could use some real experts in this field not just someone like me, CC, who can read and collect research. J Med Chem. 1998 Apr 23;41(9):1439-45. Links Development of a three-dimensional CysLT1 (LTD4) antagonist model with an incorporated amino acid residue from the receptor.Zwaagstra ME, Schoenmakers SH, Nederkoorn PH, Gelens E, Timmerman H, Zhang MQ. Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, Vrije Universiteit, De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands. This paper describes the molecular modeling of leukotriene CysLT1 (or LTD4) receptor antagonists. Several different structural classes of CysLT1 antagonists were superimposed onto the new and highly rigid CysLT1 antagonist 8-carboxy-3'-[2-(2-quinolinyl)ethenyl]flavone (1, VUF 5017) to generate a common pharmacophoric arrangement. On the basis of known structure-activity relationships of CysLT1 antagonists, the quinoline nitrogen (or a bioisosteric equivalent thereof) and an acidic function were taken as the matching points. In order to optimize the fitting of acidic moieties of all antagonists, an arginine residue from the receptor was proposed as the interaction site for the acidic moieties. Incorporation of this amino acid residue into the model revealed additional interactions between the guanidine group and the nitrogen atoms of quinoline-containing CysLT1 antagonists. In some cases, the arginine may even interact with pi-clouds of phenyl residues of CysLT1 antagonists. The alignment of Montelukast (MK-476) suggests the presence of an additional pocket in the binding site for CysLT1 antagonists. The derived model should be useful for a better understanding of the molecular recognition of the leukotriene CysLT1 receptor. PMID: 9554877 [PubMed - indexed for MEDLINE]