Structure-activity relationships conformational restriction

Kanne, D.B., and Abood, L.G. 1988. Synthesis and biological characterization of pyridohomotropanes. structure-activity relationships of conformationally restricted nicotinoids. JMed Chem 31, 506-509. 

Renaud J, Bischoff SF, Buhl T, Floersheim P, Fournier B, Geiser M, Halleux C, Kallen J, Keller H, Ramage P. Selective estrogen receptor modulators with conformationally restricted side chains Synthesis and structure-activity relationship of ERalpha-selective tetrahydroisoquinoline ligands. J Med Chem 2005 48 364-79. 

The rigid phenylene analogue is more potent in the dog than the flexible molecules cimetidine and tiotidine given i.v., but is similar to cimetidine p.o. Structure-activity relationships are described. 2 Blolsosterlc design and restricted conformation provided the rationale for the synthesis of the trlazole j that was somewhat more potent than cimetidine. 

Leutienizing Hormone Releasing Hormone (LHRH) - Structure-activity relationships of LHRH (pGlu-Hls-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) have been examined by determining the effects of systematic modification of each residue on biological activity.The possible conformational effects of these modifications have been examined,but only a few attempts have been made at specific conformational restriction. 

To investigate this dendritic effect, a dimeric model compound was synthesized which mimics the tethered relationship of two catalytic units within one branch of the PAMAM dendrimer. All dendritic catalysts were more active in the HKR than the parent complex. Furthermore, the dendritic catalysts also displayed significantly higher activity than the dimeric model compound. The authors proposed that this positive dendritic effect arises from restricted conformation imposed by the dendrimer structure, thereby creating a bigger effective molarity of [Co(salen)] units. Alternatively, the multimeric nature of the dendrimer, may lead to higher order in productive cooperative interactions between the catalytic units. 

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