First asymmetric synthesis of (−)-(2S, 3R)-methanoproline

Hercouet, A.; Bessieres, Bernard; Corre, M. Le

doi:10.1016/0957-4166(96)00139-5

Cited by 26 publications

(12 citation statements)

References 9 publications

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“…Synthesis of compounds 42 commenced with Boc protection of key intermediate 38 , which afforded compound 39 . The ester group reduction in compound 39 with LiAlH 4 yielded alcohol 40 .…”

Section: Chemistrysupporting

confidence: 90%

“…The general synthetic strategy used for the synthesis of the new compounds reported here is summarized in Schemes 1−7. The starting materials L-pyroglutaminol (1) and L-pyroglutamic acid and substituted hydroxy pyridines were sourced from commercial vendors, whereas starting materials 38 33 and 43 34 were synthesized as reported in the literature. The synthesis of compounds 9 commenced with the reaction of (S)-5-(hydroxymethyl)-2-pyrrolidinone 1 (Scheme 1) with TBDPS-Cl, which afforded compound 2.…”

Section: ■ Chemistrymentioning

confidence: 99%

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Discovery and Development of 3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane Hydrochloride (SUVN-911): A Novel, Potent, Selective, and Orally Active Neuronal Nicotinic Acetylcholine α4β2 Receptor Antagonist for the Treatment of Depression

et al. 2020

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A series of chemical optimizations guided by in vitro affinity at the α4β2 receptor in combination with selectivity against the α3β4 receptor, pharmacokinetic evaluation, and in vivo efficacy in a forced swim test resulted in identification of 3-(6chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane hydrochloride (9h, SUVN-911) as a clinical candidate. Compound 9h is a potent α4β2 receptor ligand with a K i value of 1.5 nM. It showed >10 μM binding affinity toward the ganglionic α3β4 receptor apart from showing selectivity over 70 other targets. It is orally bioavailable and showed good brain penetration in rats. Marked antidepressant activity and dose-dependent receptor occupancy in rats support its potential therapeutic utility in the treatment of depression. It does not affect the locomotor activity at doses several folds higher than its efficacy dose. It is devoid of cardiovascular and gastrointestinal side effects. Successful long-term safety studies in animals and phase-1 evaluation in healthy humans for safety, tolerability, and pharmacokinetics paved the way for its further development.

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“…Synthesis of compounds 42 commenced with Boc protection of key intermediate 38 , which afforded compound 39 . The ester group reduction in compound 39 with LiAlH 4 yielded alcohol 40 .…”

Section: Chemistrysupporting

confidence: 90%

Section: ■ Chemistrymentioning

confidence: 99%

Discovery and Development of 3-(6-Chloropyridine-3-yloxymethyl)-2-azabicyclo[3.1.0]hexane Hydrochloride (SUVN-911): A Novel, Potent, Selective, and Orally Active Neuronal Nicotinic Acetylcholine α4β2 Receptor Antagonist for the Treatment of Depression

et al. 2020

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“…The preparation of the l-and D-Phecontaining dipeptides 6 and 7 was carried out as reported earlier. 25 The 1 H-and 13 C NMR data for 1-7 are listed in Tables 2-4.…”

Section: Methodsmentioning

confidence: 99%

β-Turn Preferences Induced by 2,3-Methanophenylalanine Chirality

et al. 1998

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The model dipeptides RCO-L-Pro-c 3 Phe-NHMe, where c 3 Phe stands for each of the four cyclopropane analogues of phenylalanine (2,3-methanophenylalanine), have been studied in solution by using 1 H NMR and FT-IR spectroscopy and in the solid state by using X-ray diffraction. The conformational behavior of these compounds has been compared to that of the analogous Ac 3 c and L-or D-Phe-containing dipeptides. When associated to proline, the cyclopropane residues in the so-called i + 2 position exhibit a marked tendency to β-folding in solution, even in DMSO. The type II β-turn is generally favored, but the βI/βII-turn ratio depends both on the experimental conditions (solvent, solution, or solid state) and on the chirality of the c 3 Phe moiety, which rigidly fixes the orientation of the phenyl ring with respect to the peptide backbone. The (2S,3S)c 3 Phe residue, analogous to L-Phe with the χ 1 angle constrained to about 0°, is the most propitious to βI-folding in the i + 2 position of a putative β-turn.

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“…The key step in these syntheses was the condensation of the corresponding cyclic sulfates with methyl benzylideneglycinate. 97,98 Several methanologues of natural amino acids have been prepared by functionalisation of a dihydroxy-derivative 57 synthesised starting from D-glyceraldehyde. 99 Transition metal complexes are often used in the stereoselective syntheses of ACC derivatives both as catalysts and reagents.…”

Section: -Aminocyclopropanecarboxylic Acid and Its Derivativesmentioning

confidence: 99%