Analogs of 3-quinuclidinyl benzilate

Abstract

A number of analogues of 3-quinuclidinyl benzilate (QNB) have been synthesized and their affinities to muscarinic receptor from rat or dog ventricular muscle measured. We have determined that the muscarinic receptor can to a different degree accommodate either a halogen in the ortho, meta, or para position of one phenyl ring or the replacement of one phenyl ring with an alkyl group. Our in vitro competition studies show that the affinities lie within a 270-fold range, from the highest affinity compound, 3-quinuclidinyl alpha-hydroxy-alpha-cyclopentylphenylacetate (2), to the lowest affinity compound, 3-quinuclidinyl alpha-hydroxy-alpha-2-propargylphenylacetate (11).

Dual Use Research of Concern: Derivatives of 3-Quinuclidinyl Benzilate (Bz)

“…In general, the higher the dose, the quicker the subject reached incapacitation and the longer the subject remained incapacitated. Doubling the ID 50 dose significantly increased the D 50 . The researchers concluded that BZ and other glycolate esters showed a multiple compartment distribution with differing elimination rates.…”

“…All of the compounds examined in this study were considered potent anticholinergic agents. The LD 50 and ED 50 for these compounds are shown below (Table 5). Compound 344 (2-thienyl derivative) was the most potent anticholinergic compound based on the ED 50 for inhibiting spasms induced by acetylcholine (Table 5).…”

“…The paper measured mydriatic effects of a compound by comparing the dilation of the pupil compared to the dilation seen with 10 mg/kg atropine -the maximal dilation effect observed. The effective dose (ED 50 ) was a calculated concentration that caused 50% of the maximum dilation. Anti-tremorine effects were measured by injections of 10 mg/kg tremorine and noting the number of times the mouse crossed a beam in 30 minutes.…”

“…Data were analyzed using a Probit analysis where the fraction of subjects that reached a specific endpoint was plotted against the logarithm of the dose. To alleviate stress they attempted to administer doses no higher than the ID 50 (dose that caused incapacitation of 50% of the subjects); this did not always happen.…”

“…The D 50 was a measurement of duration; the length of time between the time for the first Number Facility score that falls below 25% and the time during recovery that the Number Facility Test score reaches 75%. The researchers also estimated an LD 50 (lethal dose that results in 50% fatalities in humans) based on historical atropine data.…”