61367-63-3Relevant academic research and scientific papers
Chain substituted cannabilactones with selectivity for the CB2 cannabinoid receptor
Alapafuja, Shakiru O.,Nikas, Spyros P.,Ho, Thanh C.,Tong, Fei,Benchama, Othman,Makriyannis, Alexandros
, (2019/10/11)
In earlier work, we reported a novel class of CB2 selective ligands namely cannabilactones. These compounds carry a dimethylheptyl substituent at C3, which is typical for synthetic cannabinoids. In the current study with the focus on the pharmacophoric side chain at C3 we explored the effect of replacing the C1′-gem-dimethyl group with the bulkier cyclopentyl ring, and, we also probed the chain's length and terminal carbon substitution with bromo or cyano groups. One of the analogs synthesized namely 6-[1-(1,9-dihydroxy-6-oxo-6H-benzo[c]chromen-3-yl) cyclopentyl] hexanenitrile (AM4346) has very high affinity (Ki = 4.9 nM) for the mouse CB2 receptor (mCB2) and 131-fold selectivity for that target over the rat CB1 (rCB1). The species difference in the affinities of AM4346 between the mouse (m) and the human (h) CB2 receptors is reduced when compared to our first-generation cannabilactones. In the cyclase assay, our lead compound was found to be a highly potent and efficacious hCB2 receptor agonist (EC50 = 3.7 ± 1.5 nM, E(max) = 89%). We have also extended our structure-activity relationship (SAR) studies to include biphenyl synthetic intermediates that mimic the structure of the phytocannabinoid cannabinodiol.
PYRAZOLOTHIAZOLE COMPOUND
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Page/Page column 29, (2011/04/25)
A compound represented by the formula (I) or pharmacologically acceptable salt thereof exhibits an excellent CRF receptor antagonism wherein X is a nitrogen atom or CH; R1 is -A11-A12; A11 is a single bond or a C1-6 alkylene group; A12 is a hydrogen atom, a C1-6 alkyl group or a C3-6 cycloalkyl group, etc.; R2 is -A21-A22; A21 is a single bond or a C1-6 alkylene group; A22 is a hydrogen atom, a C1-6 alkyl group, a C3-6 cycloalkyl group, a non-aromatic heterocyclic group, or a heteroaryl group, etc.; R3 is a C 1-6 alkyl group, a C3-6 cycloalkyl group, a C1-6 alkoxy group, a C3-6 cycloalkoxy C1-6 alkyl group, di-C1-6 alkyl amino group, a halogen atom, a cyano group, a formyl group, or a carboxyl group, etc; R4 is a hydrogen atom or a C1-6 alkoxy group; R5 is a halogen atom, a C1-6 alkyl group, or a C1-6 alkoxy group; R6 is a hydrogen atom, a C1-6 alkyl group, a C1-6 alkoxy group, a C1-6 alkylthio group, or a C1-6 alkyl sulfinyl group etc.; and R7 is a C1-6 alkyl group, a C1-6 alkoxy group, or a C1-6 alkylthio group
3-PHENYLPYRAZOLO[5,1-b]THIAZOLE COMPOUNDS
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Page/Page column 32, (2009/10/21)
A compound represented by the following formula (I), or salt thereof exhibits excellent CRF receptor antagonism, and sufficient pharmacological activity, safety and pharmacokinetic properties as a drug. wherein R1 represents the formula -A11-A12; R2 represents tetrahydrofurylmethyl, tetrahydropyranylmethyl or tetrahydropyranyl; A11 represents a single bond, methylene or 1,2-ethylene; A12 represents C1-6 alkyl, C3-6 cycloalkyl or C3-6 cycloalkyl having methyl; R3 represents methoxy, cyano, cyclobutyloxymethyl, methoxymethyl or ethoxymethyl; and R4 represents methoxy or chlorine.
Lipophilicity and serotonin agonist activity in a series of 4 substituted mescaline analogues
Nichols,Dyer
, p. 299 - 301 (2007/10/06)
Replacement of the 4 methoxy of mescaline with higher alkyl homologues or with bromine led to increased activity at serotonin receptors in a sheep umbilical artery preparation. This activity appears correlated with lipophilicity, as measured by 1 octanol water partition coefficients, but drops off when the 4 substituent is about five atoms in length. It is suggested that 3,4,5 trisubstitution may give compounds which are as active as those with the 2,4 5 substitution pattern.
