ChemInform Abstract: CHOLINERGIC COMPOUNDS PART 5, NEW SYNTHESIS AND FURTHER PHARMACOLOGICAL EVALUATION OF DESETHERMUSCARINE

Abstract

Der Ester (I) reagiert mit Dimethylamin zum Amid (II), welches bei der Hydroxylierung (Diboran/Wasserstoffperoxid) neben den Isomeren (III) und (IV) überwiegend das Hydroxy‐amid (V) liefert.

Molecular Requirements of the Active Site of Cholinergic Receptors XV: Synthesis and Biological Activity of 2,3-Dehydrodeoxamuscarone and 2,3-Dehydrodeoxamuscarines

“…Introduction of the carbonyl group in 111 to give I1 improved both muscarinic and nicotinic activities. The specificity of 11, as far as muscarinic activity is concerned as revealed by the EPMRN/EPMRM ratio, remained low; its activity was 10 times lower than that of the corresponding muscarones but nearly equivalent to that of deoxamuscarone (11). The influence of the double bond, which imposed a planar configuration to the methyl group at position 2, did not seem to be relevant in this case.…”

“…The reduction of the carbonyl group was eventually achieved with 9-borabicyclo[3.3.1]nonane (9) since other common reducing agents gave saturation of the double bond through a 1,4-addition to the enone system (7,lO). The reaction of either VIIa or VIIb, separated by column chromatography, with dimethylamine in a sealed tube a t 80' invariably gave the cis-isomer (VIIIa) through isomerization, possibly at C-1 (11,12). The reduction of VIIIa with aluminum lithium hydride followed by the reaction of IXa with methyl iodide gave Ia.…”

“…To gain more information on the dualism of the active site of the cholinergic receptors, cis-and trans-3methyl -4hydroxy -1 -(NJV-dimethylaminomethy1)cyclopent-2-ene methiodides (cis-and trans-2,3-dehydrodeoxamuscarines, Ia and Ib) and 3-methyl-4-oxo-l-(NJVdimethylaminomethyl)cyclo-pent-2-ene methiodide (2,3-dehydrodeoxamuscarone, 11) were synthesized and tested. Their pharmacological results were compared with those of 3-methyl-l-(N,N-dimethylaminomethyl)cyclopent-2-ene methiodide (III), because it incorporates a …”

Muscarine and water: Ab initio potentials

“…The five-atom chain always terminates with a methyl group and the latter is considered necessary for correct binding at the muscarinic receptors. This rule has been experimentally confirmed in more recent years on both muscarine and related compounds [12].…”

Affinity and efficacy correlate with chemical structure more than potency does in a series of pentatomic cyclic muscarinic agonists

“…where RAmUs and RAx are the percentages of the receptor to be occupied by muscarine and by the compound under study respectively to elicit 50% of the maximal response. Compounds 3, 4, 5, 7, 8, 9, were prepared as already described (Melchiorre et al, 1975;Elferink & Salemink, 1975;Pigini et al, 1981;. (±)Muscarine (1) and dibenamine were purchased from Sigma Chemical Company.…”