The 14-dehydration- and 14-H derivatives of the orexin 1 receptor (OX₁R) antagonist YNT-707 (2) were synthesized. The obtained derivatives showed higher affinities for OX₁R than the corresponding 14-hydroxy derivatives. The conformational analysis suggested that the 17-sulfonamide groups in the derivatives without the 14-hydroxy group have a greater tendency to be oriented toward the upper side of the D-ring compared with the 14-hydroxy derivatives. Additionally, the 14-dehydration-derivative with 6α-amide side chain showed significantly higher affinity than the 14-hydroxy derivative, while the corresponding 14-H derivative showed only slightly higher affinity. Thus, the 14-hydroxy group strongly affects the affinity of the antagonist for the OX₁R.

合成了orexin 1受体（OX ₁ R）拮抗剂YNT-707（2）的14-脱水和14-H衍生物。所获得的衍生物对OX ₁ R的亲和力高于相应的14-羟基衍生物。构象分析表明，与14-羟基衍生物相比，不具有14-羟基的衍生物中的17-磺酰胺基团具有更大的朝向D-环上侧取向的趋势。另外，具有6α-酰胺侧链的14-脱水衍生物显示出比14-羟基衍生物显着更高的亲和力，而相应的14-H衍生物仅显示出稍高的亲和力。因此，14-羟基强烈影响拮抗剂对OX ₁的亲和力R.