Lack of oxygen from the 2 position from substance 59 further reduced the aerobic as well as anaerobic activity emphasizing the importance of oxygen at this position for both anaerobic as well as aerobic activity. And in addition, removing the side chain from 60 leading to 61 also triggered an inactive compound with this specific compound being distinctive because it is the 4 nitro isomer of metronidazole underscoring the importance of the place of the nitro group for the anaerobic activity of metronidazole. The electron donating potential at the 2 position of the oxazine Chk inhibitor ring was found to be essential for activity since the replacement of the oxygen with carbon in 62 considerably affected both aerobic as well as anaerobic activity with some recovery of anaerobic activity seen with the unsaturated species indicating that SAR for aerobic and anaerobic activity are different and are dependant on the technology at this position. This concept was further supported by the observation that replacement of the 2 position oxygen with electron donating groups, for example nitrogen or sulfur, had no effect on the aerobic activity but decreased anaerobic capability, whereas replacement with electron withdrawing groups dramatically paid down or abrogated aerobic Meristem activity without much effect on anaerobic activity. The fact that the substituent on the oxazine ring provides a compound more active than PA 824 suggested the existence of a larger hydrophobic pocket near the active site of the enzyme that interacts with the drug. SAR of the end of PA 824 was examined, to explore the level of the hydrophobic pocket. The issue of solubility of those compounds with the additional hydrophobe was eradicated by substituting the ether analog with the corresponding amine analog where in fact the aminoderivatives of 49 and PA 824 produced compounds 70 and 71 with slightly increased activity. On increasing the linker dimension connecting the 6 position amine with the trifuoromethoxybenzene fragrant moiety from two to four carbons, the aerobic activity was found to sequentially enhance with aerobic activity reaching a maximum with the aminobutyl 824, whereas the 5 carbon linker in aminopentyl 824 had decreased activity. There is no significant development of the anaerobic natural product library activity on changing the linker size, indicating a different SAR for anaerobic and aerobic activity with respect to the hydrophobic tail area of the drug. Further exploration of the hydrophobic binding pocket was undertaken with o, m and plinked biphenyl analogs attached to the nitroimidazooxazine via ether linkage. The e linked biphenyls showed action, accompanied by the m linked analogs, while the p linked biphenyl analogs were one of the most active. The game development didn’t change significantly with alternatives in the second aryl ring. This suggested that the hydrophobic pocket is pretty much linear with moderate tolerability across the terminus of the next aryl ring.