Ring-substituted anilines Subject

In this chapter we will primarily be concerned with the reactivity, selectivity and mechanistic aspects of anilines as nucleophiles in addition and substitution reactions. We will deal with A-substituted as well as ring-substituted anilines. We do not intend to present an exhaustive review of this subject but to survey the more important recent works in this field. 

The same lead structure, sulfisoxazole (11), was also identified by Bristol Meyers Squibb, via the screening hit sulfathiazole (14). In this instance modification of the aniline led, via a naphthalene ring, to the substituted biphenyl 15 " however, preclinical PK studies indicated that the attached isobutyl group was subject to extensive hydroxy-lation. Replacement of this group with an isoxazole ring imparted metabolic stability, and expansion of the SAR at the tolerant 2 -position provided the clinical candidate edo-nentan (16). ... 

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