The work detailed in this thesis involves the synthesis, computational analysis and biological evaluation of a series of macrocycles against Kv1 channels that could lead to a novel therapeutic for the neurological disorder multiple sclerosis (MS). The initial SAR study focuses on porphyrin derivatives possessing various alkyl ammonium substituents. The results obtained from the initial SAR study with the porphyrins was used to design a new non-conjugated scaffold based on the calix[4]pyrroles. However, the synthesis of the target calix[4]pyrroles was not achieved. Alternatively, a comparative model of rat Kv1.1 was constructed and the results of the porphyrin SAR study were modelled. This computational work led to the identification of a new dipyrromethane small molecule inhibitor which was successfully prepared. The new lead dipyrromethane DDAAKN01 proved to be selective and potent for the target potassium channel Kv1.1 which is believed to be associated with MS. The obtained IC50 value for DDAAKN01 was 14 µM, which is 40 times more potent than the current therapeutic 4-aminopyridine that is currently used for the treatment of MS. DDAAKN01 also showed high selectivity toward the Kv(1.1)4 channel whilst not interacting with normalised Kv(1.1)x(1.2)y channels. Further investigation into the mechanism of binding of DDAAKN01 using a comparative model of Kv1.1 led to the preparation of a new tetrapyrrole derivative DDAAKN02. DDAAKN02 was synthesised and biologically evaluated. The results for DDAAKN02 were superior to DDAAKN01 in both selectivity and potency. DDAAKN02 has a preliminary IC50 value of 8 µM. Both DDAAKN01 and DDAAKN02 have excellent potential as new candidates to alleviate the symptoms of MS and are presently being evaluated with MS in vivo models.