As a promising new target for chemotherapy G-quadruplexes (G4) have drawn great interest from the scientific community. Current chemotherapeutic agents exhibit broad toxicity to patients; G4 has the potential to be selectively targeted by novel chemotherapeutic agents that exhibit toxicity specific towards cancer cells. Anthracenyl isoxazolyl amides (AIMs) have shown potent anti-tumor activity and have evidence to support them as G4 binding molecules. Studies of the AIMs unique mechanism of action require an efficient synthesis of target molecules. For our system, methods traditionally used to synthesize isoxazoles were inefficient and gave poor yields. A critical comparison of methods to prepare sterically hindered 3-aryl isoxazoles containing fused aromatic rings using the nitrile oxide cycloaddition (NOC) revealed that modification of the method of Bode, Hachisu, Matsuura and Suzuki (BHMS), was far superior to that of the enamine method. Utilization of either triethyl amine as a base or sodium enolates of diketone, ketoester and ketoamide dipolarophiles gave much higher yields as well as fewer by-products from the NOC. Here-in is reported the improved synthesis of 3-aryl-isoxazoles via an adaption of the BHMS method. Included in this report is the crystallographic data for Ethyl 3-(10'-bromo-9'-anthracenyl)-5-methyl-4-isoxazolcarboxylate. As seen in the crystal structure of the chapter 2 title compound the isoxazole plane is nearly orthogonal to the plane of the anthracene; which is thought to be a necessity for the AIMs to interact with G4. This conformation is ideal for both pi-stacking with the guanine decks and polar interactions with the phosphate backbone of quadruplex DNA.

BACKGROUND: Concern has increased worldwide with regard to the over-prescribing of antibiotics, as well as the fact that more bacteria strains are developing resistance to antibiotics. According to research, a great deal of this use is for what has been called “non-pharmacological” reasons. The reduction of unnecessary antibiotic use and exploration of the reasons for ”irrational prescribing” has become a public health priority. OBJECTIVE: To study the reasons cited by Icelandic general practitioners for their “non-pharmacological” prescribing of antibiotics. DESIGN: A qualitative interview-study with research dialogues guided by the Vancouver School of doing phenomenology. SETTING: General practice. PARTICIPANTS: 16 general practitioners: 11 in the maximum variety sample and 5 in the theoretical sample. RESULTS: The most important reasons for prescribing antibiotics in situations with low pharmacological indications (non-pharmacological prescribing) were an unstable doctor-patient relationship due to lack of continuity of care, patient pressure in a stress-loaded society, the doctor’s personal characteristics, particularly zeal and readiness to serve, and finally, the insecurity and uncertainty of the doctor who falls back upon the prescription as a coping strategy in a difficult situation. CONCLUSION:The causes of non-pharmacological prescribing of antibiotics are highly varied, and relational factors in the interplay between the doctor and the patient are often a key factor. Therefore, it is of great importance for the general practitioner to know the patient and to become better equipped to resist patient pressure, in order to avoid the need to use the prescription as a coping strategy. Continuity of medical care and a stable doctor-patient relationship may be seen as the core concepts in this study and the most important task for the GPs is to promote the patients’ trust. / <p>ISBN 91-7997-091-5</p>