Synthesis of novel triplet drugs with 1,3,5-trioxazatriquinane skeletons and their pharmacologies. 3: Synthesis of novel triplet drugs with the bis(epoxymethano) or bis(dimethylepoxymethano) structure (double-capped triplet)
详细信息 查看全文
- 作者：Naohisa Wada ; Hideaki Fujii ; Koji Koyano ; Shigeto Hirayama ; Takashi Iwai ; Toru Nemoto ; Hiroshi Nagase ; nagaseh@pharm.kitasato-u.ac.jp
- 关键词：Cap structure ; DiMe-cap structure ; Double-capped triplet ; Opioid ; Oxazoline
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：15 December, 2012
- 年：2012
- 卷：22
- 期：24
- 页码：7551-7554
- 全文大小：692 K
文摘
Novel double-capped triplet drugs, which have one pharmacophore unit and two epoxymethano or dimethylepoxymethano structures (termed cap or diMe-cap structures, respectively) were synthesized. Key intermediate oxazoline 16 derived from acetone enabled the effective synthesis of double-capped triplets. SYK-134 (7a) and SYK-135 (8a) with N-cyclopropylmethyl substituent and cap structures showed selectivities for the ¦Ê opioid receptor. On the other hand, the N-Me series exhibited selectivities for the ¦Ì opioid receptor. The double-capped triplet drugs with diMe-cap structures preferred the ¦Ì receptor independently of their N-substituents. SYK-385 (19b), one of the ¦Ì-selective double-capped triplet drugs, showed the highest selectivity for the ¦Ì receptor among the reported ¦Ì-selective nonpeptide ligands.