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Following the above general procedure C, the reaction was purified by flash-column chromatography on silica gel to provide the desired ethyl 4-(adamantylamino)-3-(pyrimidin-5-ylmethylamino)benzoate (SRS16-41, Scheme 3) (80 mg, 0.197 mmol, 80%)

Recently, a human gene mutation of PAPP-A2, a circulating and tissue protease with IGFBP-5 (and to some extent IGFBP-3) as its primary substrate (Gaudamauskes et al), was demonstrated to have a marked growth phenotype involving fetal and post-natal growth retardation in children in a consanguineous family (43)

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Specifically, DIO1 has a bidirectional effect on thyroid hormones: it can promote the conversion of low bioactive T4 to highly bioactive T3 and facilitate the conversion of highly bioactive T3 to low bioactive DIT [110]