WIN 64821, a novel neurokinin antagonist produced by an Aspergillus sp. I. Fermentation and isolation

WIN 64821, a nonpeptide neurokinin antagonist, was isolated from a strain of Aspergillus sp., SC319. The compound was produced in different fermentation media with greatest yields observed when the culture was grown in a synthetic medium supplemented with L-tryptophan and L-phenylalanine. After 6 days fermentation, yields greater than 600 mg/liter were obtained. Two analogs of WIN 64821 were also identified in the culture extracts and subsequently tested for biological activity. WIN 64821 was the most potent compound isolated from this culture and exhibited activity as a substance P-binding inhibitor with submicromolar potency against the human neurokinin 1 receptor.