Antagonist narrative

Main character and goal Antagonist Catalytic event Resolution Dramatic arc Narrative style Narrative shape Tone... 

Santa Claus character all represent urban cynicism. They fulfill the role of antagonist, not in the sense that the main character hates them, but rather in terms of the social and psychological attitude they represent. They have given up hope. The plot, the effort to save the world by throwing money from the top of the Empire State Building, is not a success. So Fupper s conversion of Amanda, the effort to rescue her, to offer her his love, becomes his offer of hope. To save one person without hope is to save the world. This is the moral of the Granofsky/Swanhaus screenplay. It is unusual in that we care about the fate of those who represent hopelessness, the antagonists in the narrative. 

The above narrative exemplifies a successful lead identification story, ensued by a successful lead optimization that led to the discovery of the FDA-approved drug vorapaxar. The original hit (2) was a racemic synthetic analog of himbacine, a natural product that has no thrombin receptor activity. Had we made this analog in the absolute chirality of himbacine, we would have missed the hit, since the thrombin receptor antagonist activity is exclusive to the unnatural e t-him-bacine series. The lead optimization efforts encountered several obstacles, as highlighted by the discontinuation of two recommended candidates. Within the project, we had to return several times to secondary lead generation and optimization in order to address the liabilities such as liver enzyme induction and sub-optimal mass balance that we encountered in the development candidates. 

Wienen W, Hauel N, Van Meel JCA, Narr B, Ries U, Entzeroth M (1993) Pharmacological characterization of the novel nonpeptide angiotensin II receptor antagonist BIBR 277. Brit J Pharmacol 110(l) 245-252... 

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