38002-89-0Relevant academic research and scientific papers
New diarylmethylpiperazines as potent and selective nonpeptidic δ opioid receptor agonists with increased in vitro metabolic stability
Plobeck,Delorme,Wei,Yang,Zhou,Schwarz,Gawell,Gagnon,Pelcman,Schmidt,Yue,Walpole,Brown,Zhou,Labare,Payza,St-Ogne,Kamassah,Morin,Projean,Ducharme,Roberts
, p. 3878 - 3894 (2007/10/03)
Nonpeptide δ opioid agonists are analgesics with a potentially improved side-effect and abuse liability profile, compared to classical opioids. Andrews analysis of the NIH nonpeptide lead SNC-80 suggested the removal of substituents not predicted to contribute to binding. This approach led to a simplified lead, N,N-diethyl-4-[phenyl(1-piperazinyl)methyl]benzamide (1), which retained potent binding affinity and selectivity to the human δ receptor (IC50 = 11 nM, μ/δ = 740, κ/δ > 900) and potency as a full agonist (EC50 = 36 nM) but had a markedly reduced molecular weight, only one chiral center, and increased in vitro metabolic stability. From this lead, the key pharmacophore groups for δ receptor affinity and activation were more clearly defined by SAR and mutagenesis studies. Further structural modifications on the basis of 1 confirmed the importance of the N,N-diethylbenzamide group and the piperazine lower basic nitrogen for δ binding, in agreement with mutagenesis data. A number of piperazine N-alkyl substituents were tolerated. In contrast, modifications of the phenyl group led to the discovery of a series of diarylmethylpiperazines exemplified by N,N-diethyl-4-[1-piperazinyl(8-quinolinyl)-methyl]benzamide (56) which had an improved in vitro binding profile (IC50 = 0.5 nM, μ/δ = 1239, EC50 = 3.6 nM) and increased in vitro metabolic stability compared to SNC-80.
S-trifluorobutenyl derivatives and pesticidal uses thereof
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, (2008/06/13)
S-trifluorobutenyl thiocarbonic acid esters of the formula STR1 and salts thereof, wherein X is R1 N or S and Y is RS or R3 R2 N; wherein R is a metal or a radical selected from alkyl, cycloalkylalkyl, halocycloalkylalkyl, alkenyl, haloalkyl, haloalkenyl, alkynyl, alkoxyalkyl, alkylthioalkyl, alkoxycarbonylalkyl, halophenoxyalkyl, trialkylsilylalkyl, (vinyl)dialkylsilylalkyl, (allyl)dialkylsilylalkyl, 2-chlorothiophene-5-ylmethyl, phenylalkyl, halophenylalkyl, nitrophenylalkyl, haloalkylphenylalkyl, dialkyl-2,3-dihydrobenzofuran-7-yl, [2-methyl-(1,1'-biphenyl)-3-yl]methyl, 3-phenoxybenzyl, phenylthioalkyl, halophenylthioalkyl, dialkylphosphoryl, dialkylthiophosphoryl, dialkylisoxazolylalkyl and thienylisoxazolylalkyl; wherein R1 is alkyl, cycloalkyl, cyano, dialkyl-2,3-dihydrobenzofuran-7-yl, halophenyl, halophenylalkyl, haloalkoxyphenyl, pyridinyl, halopyridinyl, alkyl-1,3,4-thiadiazolyl, haloalkyl-1,3,4-thiadiazolyl, benzothiazolyl, dialkyloxazolyl or thiazolinyl; wherein R2 is hydrogen or alkyl; and wherein R3 is alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, dialkylaminoalkyl, dialkyl-2-oxazolyl, 2-thiazolinyl, 2-benzothiazolyl, 4-phenyl-2-thiazolyl, alkyl-1,3,4-thiadiazolyl, haloalkyl-1,3,4-thiadiazolyl, pyridinyl, halopyridinyl, phenyl, halophenyl, halophenylalkyl, haloalkoxyphenyl, or dialkyl-2,3-dihydrobenzofuran-7-yl; provided that: when X is S, Y is R3 R2 N, when X is R1 N, Y is RS, R1 is other than alkyl and R is other than haloalkenyl; and when X is R1 N where R1 is CN and Y is RS, R is other than alkali metal. The compounds exhibit nematicidal and anthelmintic activity and are useful in agriculture and veterinary practice.
