691001-87-3

Upstream product

• 182821-15-4 (R)-((R)-2-Hydroxy-1-phenyl-ethylamino)-[(1S,2S,3R)-2-(morpholine-4-carbonyl)-3-phenyl-cyclopropyl]-acetonitrile 
• 177187-97-2 (R)-((S)-2-Hydroxy-1-phenyl-ethylamino)-[(1R,2R,3S)-2-(morpholine-4-carbonyl)-3-phenyl-cyclopropyl]-acetonitrile 
• 177188-03-3 (S)-((R)-2-Hydroxy-1-phenyl-ethylamino)-[(1R,2S,3S)-2-(morpholine-4-carbonyl)-3-phenyl-cyclopropyl]-acetonitrile 
• 177188-00-0 (R)-((S)-2-Hydroxy-1-phenyl-ethylamino)-[(1R,2S,3S)-2-(morpholine-4-carbonyl)-3-phenyl-cyclopropyl]-acetonitrile 
• 177188-06-6 (S)-((R)-2-Hydroxy-1-phenyl-ethylamino)-[(1R,2R,3R)-2-(morpholine-4-carbonyl)-3-phenyl-cyclopropyl]-acetonitrile 
• 177188-05-5 (R)-((S)-2-Hydroxy-1-phenyl-ethylamino)-[(1R,2R,3R)-2-(morpholine-4-carbonyl)-3-phenyl-cyclopropyl]-acetonitrile 
• 177188-10-2 (S)-((R)-2-Hydroxy-1-phenyl-ethylamino)-[(1R,2S,3R)-2-(morpholine-4-carbonyl)-3-phenyl-cyclopropyl]-acetonitrile 
• 177188-09-9 (R)-((S)-2-Hydroxy-1-phenyl-ethylamino)-[(1R,2S,3R)-2-(morpholine-4-carbonyl)-3-phenyl-cyclopropyl]-acetonitrile 
• 177187-98-3 (S)-((R)-2-Hydroxy-1-phenyl-ethylamino)-[(1R,2R,3S)-2-(morpholine-4-carbonyl)-3-phenyl-cyclopropyl]-acetonitrile 
• 177035-69-7 (R)-((S)-2-Hydroxy-1-phenyl-ethylamino)-[(1S,2S,3R)-2-(morpholine-4-carbonyl)-3-phenyl-cyclopropyl]-acetonitrile 
• 177187-99-4 (S)-((R)-2-Hydroxy-1-phenyl-ethylamino)-[(1S,2S,3R)-2-(morpholine-4-carbonyl)-3-phenyl-cyclopropyl]-acetonitrile 
• 177188-01-1 (R)-((S)-2-Hydroxy-1-phenyl-ethylamino)-[(1S,2R,3R)-2-(morpholine-4-carbonyl)-3-phenyl-cyclopropyl]-acetonitrile 
• 177188-02-2 (S)-((R)-2-Hydroxy-1-phenyl-ethylamino)-[(1S,2R,3R)-2-(morpholine-4-carbonyl)-3-phenyl-cyclopropyl]-acetonitrile 
• 177188-04-4 (R)-((S)-2-Hydroxy-1-phenyl-ethylamino)-[(1S,2S,3S)-2-(morpholine-4-carbonyl)-3-phenyl-cyclopropyl]-acetonitrile 

Relevant academic research and scientific papers

A concise route to β-cyclopropyl amino acids utilizing 1,2-dioxines and stabilized phosphonate nucleophiles

(Chemical Equation Presented) 1,2-Dioxines react with glycine-derived phosphonate nucleophiles via a multistep cascade reaction to give β-cyclopropyl amino acid derivatives in good yield with excellent control of the cyclopropane stereocentres. The cyclopropyl ketones were oxidized to the corresponding carboxylic esters using Baeyer-Villiger conditions. Standard deprotection protocols produced a series of known β-cyclopropyl amino acids that are selective and potent agonists or antagonists of the metabotropic glutamate receptors in excellent yields.

(2R,1'S,2'R,3'S)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCG-13), the first potent and selective competitive antagonist of phospholipase D- coupled metabotropic glutamate receptors: Asymmetric synthesis and preliminary biological properties

The asymmetric synthesis of(2R,1'S,2'R,3'S)-2-(2'-carboxy-3'- phenylcyclopropyl)glycine (PCCG-13), a trisubstituted carboxycyclopropylglycine endowed with unusual stereochemical features, is described. Preliminary biological evaluation demonstrates PCCG-1

Synthesis and pharmacological characterization of all sixteen stereoisomers of 2-(2'-carboxy-3'-phenylcyclopropyl)glycine. Focus on (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine, a novel and selective group II metabotropic glutamate receptors antagonist

All 16 2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCGs) stereoisomers 32-47 have been prepared from the corresponding racemic aldehydes 12-15 following an enantiodivergent synthetic protocol. Compounds 32-47 were evaluated by a number of binding and functional experiments as potential ligands for several classes of excitatory amino acid receptors, including metabotropic glutamate receptors (mGluR1a, mGluR2, mGluR4) and ionotropic glutamate receptors (NMDA, KA, AMPA) as well as sodium-dependent and calcium/chloride-dependent glutamate transport systems. The stereolibrary of compounds 32-47 appears to be endowed with a peculiar pharmacological profile. PCCG-2 (33) and PCCG-3 (34) displaced labeled kainate at low micromolar concentration; PCCG-9 (40) and PCCG-11 (42) weakly interacted with the NMDA site; PCCG-5 (36), PCCG-10 (41), and PCCG-12 (43) showed to be potent inhibitors of Ca2+/Cl--dependent glutamate transport system. Most interestingly, PCCG-4(35) has been shown to be able to antagonize (IC50 = 8 μM) the effects of glutamate on forskolin-stimulated cAMP formation in BHK cells expressing mGluR2. Uneffective at mGluR1, 35 is a weak mGluR4 agonist (EC50 = 156 μM) and has no effect on either ionotropic receptors or glutamate transport systems, thus demonstrating to be a novel selective mGluR2 antagonist with a 6-fold increase in potency over previously reported antagonists.

Asymmetric synthesis of enantiomerically pure (2S,1'S,2'S,3'R)-phenylcarboxycyclopropylglycine (PCCG-4): A potent and selective ligand at group II metabotropic glutamate receptors

The enantioselective synthesis of (2S,1'S,2'S,3'R)-2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCG-4, 3), a potent and selective mGluR2 antagonist is described.