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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). The scaffold readily participated in reductive amination with a diverse
range of aldehydes to provide a collection of tertiary amines in this series. 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. 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.
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ÑÌÔÆÌýÓê(½ð±Ò+10, ·­ÒëEPI+1): ·Ç³£¸Ðл 2011-07-21 09:00:56
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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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