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This observation permitted us to investigate an alternative Diels¨CAlder/aza¨CWittig reaction sequence that afforded the tricyclic skeleton 9, which contained an unmasked basic nitrogen amenable to alkylation or amidation as desired (Scheme 3). ÕâÒ»¹Û²ìʹµÃÎÒÃÇ¿ÉÒÔÑо¿ÌṩÈý»·¹Ç¼Ü9µÄ¿ÉÑ¡Diels¨CAlder/aza¨CWittig ·´Ó¦ÐòÁУ¬Èý»·¹Ç¼Ü9Öк¬ÓÐδ¼ÓÐÞÊΡ¢Ò×ÓÚ°´Ðè½øÐÐÍé»ù»¯»òõ£°·»¯µÄ¼îÐÔµª¡£The scaffold readily participated in reductive amination with a diverse range of aldehydes to provide a collection of tertiary amines in this series. Ö§¼ÜʹµÃ¶àÖÖ¶àÑùµÄÈ©ÀàÒ×ÓÚ·¢Éú»¹Ô°±»¯·´Ó¦¶øµÃµ½Ò»ÏµÁеÄÊå°·¡£Given the precedent of diverse GPCR binding observed for the basic nitrogen-containing compounds previously profiled (see Figs. 3 and 4), we reasoned that this collection of compounds would afford interesting screening results. »ùÓÚÏÈǰÑо¿µÄ¼îÐÔº¬µª»¯ºÏÎï¸÷ÒìµÄGPCRÇ׺ÍÐÔÏÈÀý£¬ÎÒÃÇÍÆÀí´ËϵÁл¯ºÏÎïÓ¦¸Ã¾ßÓв»´íµÄɸѡ½á¹û¡£We were inclined toward screening against the opioid receptors and Sig-Rs based on the association of these receptors with antitussive activity (40, 41), and we began our profiling investigations with these. ÎÒÃÇÇãÏòÓÚÕë¶Ô°¢Æ¬ÊÜÌåºÍÓëÕò¿È»îÐÔÏà¹ØµÄSig-R½øÐÐɸѡ£¬ÎÒÃÇÒѾ¿ªÊ¼Óйصĺá¶ÏÃæÑо¿¡£ |
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