| Title : Structure-activity studies related to ABT-594, a potent nonopioid analgesic agent: effect of pyridine and azetidine ring substitutions on nicotinic acetylcholine receptor binding affinity and analgesic activity in mice - Holladay_1998_Bioorg.Med.Chem.Lett_8_2797 |
| Author(s) : Holladay MW , Bai H , Li Y , Lin NH , Daanen JF , Ryther KB , Wasicak JT , Kincaid JF , He Y , Hettinger AM , Huang P , Anderson DJ , Bannon AW , Buckley MJ , Campbell JE , Donnelly-Roberts D , Gunther KL , Kim DJ , Kuntzweiler TA , Sullivan JP , Decker MW , Arneric SP |
| Ref : Bioorganic & Medicinal Chemistry Lett , 8 :2797 , 1998 |
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Abstract :
Analogs of A-98593 (1) and its enantiomer ABT-594 (2) with diverse substituents on the pyridine ring were prepared and tested for affinity to nicotinic acetylcholine receptor binding sites in rat brain and for analgesic activity in the mouse hot plate assay. Numerous types of modifications were consistent with high affinity for [3H]cytisine binding sites. By contrast, only selected modifications resulted in retention of analgesic potency in the same range as 1 and 2. Analogs of 2 with one or two methyl substituents at the 3-position of the azetidine ring also were prepared and found to be substantially less active in both assays. |
| PubMedSearch : Holladay_1998_Bioorg.Med.Chem.Lett_8_2797 |
| PubMedID: 9873625 |
Holladay MW, Bai H, Li Y, Lin NH, Daanen JF, Ryther KB, Wasicak JT, Kincaid JF, He Y, Hettinger AM, Huang P, Anderson DJ, Bannon AW, Buckley MJ, Campbell JE, Donnelly-Roberts D, Gunther KL, Kim DJ, Kuntzweiler TA, Sullivan JP, Decker MW, Arneric SP (1998)
Structure-activity studies related to ABT-594, a potent nonopioid analgesic agent: effect of pyridine and azetidine ring substitutions on nicotinic acetylcholine receptor binding affinity and analgesic activity in mice
Bioorganic & Medicinal Chemistry Lett
8 :2797
Holladay MW, Bai H, Li Y, Lin NH, Daanen JF, Ryther KB, Wasicak JT, Kincaid JF, He Y, Hettinger AM, Huang P, Anderson DJ, Bannon AW, Buckley MJ, Campbell JE, Donnelly-Roberts D, Gunther KL, Kim DJ, Kuntzweiler TA, Sullivan JP, Decker MW, Arneric SP (1998)
Bioorganic & Medicinal Chemistry Lett
8 :2797