- Simple Tetrahydroisoquinolines Are Potent and Selective Kappa Opioid Receptor Antagonists
-
Potent and selective κ opioid receptor antagonists have been derived from the N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine class of pure opioid receptor antagonists. In order to determine if the 3-hydroxyphenyl and/or the piperidine amino groups are required for obtaining the pure opioid antagonists, (3R)-7-hydroxy-N-[(1S)-2-methyl-1-(piperidine-1-ylmethyl)propyl]-1,2,3,4-tetrahydroiosquinoline-3-carboxamide (1), which does not have a 4-(3-hydroxyphenyl) group, and (3R)-N-(1R)-1-(cyclohexylmethyl)-2-methylpropyl]-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (2), which does not have a 4-hydroxylphenyl or a piperidine amino group, were synthesized and evaluated for their [35S]GTPγS binding properties at the μ, δ, and κ opioid receptors. Surprisingly compound 1 remained a pure opioid antagonist with a Ke = 6.80 nM at the κ opioid receptor and is 21- and 441-fold selective for the κ receptor relative to the μ and δ opioid receptors, respectively. Even more unexpected and novel is the finding that 2 has a Ke = 0.14 nM at κ and is 1730- and 4570-fold selective for κ relative to the μ and δ opioid receptors, respectively.
- Kormos, Chad M.,Ondachi, Pauline W.,Runyon, Scott P.,Thomas, James B.,Mascarella, S. Wayne,Decker, Ann M.,Navarro, Hernán A.,Carroll, F. Ivy
-
p. 742 - 745
(2017/07/22)
-
- Enantioselective Synthesis of Dialkylated α-Hydroxy Carboxylic Acids through Asymmetric Phase-Transfer Catalysis
-
In the presence of an L-tert-leucine-derived urea-ammonium salt as phase-transfer catalyst, a highly enantioselective alkylation of 5H-oxazol-4-ones with various benzyl bromides and allylic bromides has been developed to furnish catalytic asymmetric synthesis of biologically important dialkylated α-hydroxy carboxylic acids with a broad scope. This is the first example of an L-amino acid-derived urea-ammonium salt being used as a phase-transfer catalyst with excellent catalytic efficiency.
- Duan, Shaobo,Li, Sanliang,Ye, Xinyi,Du, Nuan-Nuan,Tan, Choon-Hong,Jiang, Zhiyong
-
p. 7770 - 7778
(2015/08/18)
-
- GLYCINE REUPTAKE INHIBITOR AND USE THEREOF
-
Disclosed are a glycine reuptake inhibitor and the use thereof. The glycine reuptake inhibitor is a compound of formula I, or isomers, pharmaceutically acceptable salts or solvates thereof, wherein R1 is one or more groups selected from hydrogen, halogen,
- -
-
-
- Highly active chiral phosphoramide-Zn(II) complexes as conjugate acid-base catalysts for enantioselective organozinc addition to ketones
-
(Chemical Equation Presented) A highly efficient enantioselective organozinc (R2Zn) addition to ketones catalyzed by chiral phosphoramide-Zn(II) complexes (1-10 mol %) has been developed. These complexes serve as conjugate Lewis acid-Lewis base
- Hatano, Manabu,Miyamoto, Takashi,Ishihara, Kazuaki
-
p. 4535 - 4538
(2008/03/12)
-
- Enantioselective conjugate addition to cyclic enones with scalemic lithium organo(amido)cuprates, part IV. Relationship between ligand structure and enantioselectivity
-
Scalemic lithium amides derived from primary and secondary amines react with organocopper compounds in ether or dimethyl sulfide to form lithium organo(amido)cuprates capable of enantioselective conjugate addition to 2-cycloalkenones. The most successful heterocuprate, in which the chiral ligand is (S)-N-methyl-1-phenyl-2-(1-piperidinyl)ethanamine, (S)-MAPP, 13, reacts with cyclic enones to form products with up to 97% ee. Nonlinear asymmetric induction was observed with the cuprate formed from ligand 13.
- Rossiter, Bryant E.,Eguchi, Masakatsu,Miao, Guobin,Swingle, Nicole M.,Hernandez, Amelia E.,Vickers, Denise,Fluckiger, Ezdan,Greg Patterson,Vasavi Reddy
-
p. 965 - 986
(2007/10/02)
-