22613-99-6

Usage

Uses

Used in Pharmaceutical Industry:
trans-2-(Hydroxymethyl)-1-phenylcyclopropanecarboxylic acid is used as an impurity in the synthesis of Milnacipran (M344600) for its role in the development of an antidepressant medication. Milnacipran is a selective norepinephrine and serotonin reuptake inhibitor, which is approved for the management of fibromyalgia. The presence of trans-2-(Hydroxymethyl)-1-phenylcyclopropanecarboxylic acid in the synthesis process is crucial for the effectiveness of the final product, as it contributes to the overall chemical structure and activity of the antidepressant.

InChI:InChI=1/C11H12O3/c12-7-9-6-11(9,10(13)14)8-4-2-1-3-5-8/h1-5,9,12H,6-7H2,(H,13,14)/t9-,11-/m0/s1

Upstream product

• 67843-74-7 (S)-epichlorohydrin 
• 140-29-4 phenylacetonitrile 
• 51594-55-9 (R)-(-)-epichlorohydrin 
• 63106-93-4 (1S,5R)-1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one 

Downstream Products

• 101152-94-7 (1S,2R)-milnacipran hydrochloride 
• 63106-93-4 (1S,5R)-1-phenyl-3-oxabicyclo[3.1.0]hexan-2-one 
• 1237261-65-2 (1S,2R)-2-((1,3-dioxoisoindolin-2-yl)methyl)-N,N-diethyl-1-phenylcyclopropanecarboxamide-cyclopropanecarboxamide 
• 175131-61-0 C₁₅H₂₂N₂O*ClH 

Relevant academic research and scientific papers

Preparation method of levomilnacipran diastereoisomer

The invention provides a preparation method of a levomilnacipran diastereoisomer. The preparation method comprises the following steps: taking benzyl cyanide and R-epichlorohydrin or S-epichlorohydrinas starting materials, performing cycloalkylation on th

(+)-Methyl (1 R, 2S)-2-{[4-(4-Chlorophenyl)-4-hydroxypiperidin-1-yl]methyl}-1-phenylcyclopropanecarboxylate [(+)-MR200] derivatives as potent and selective sigma receptor ligands: Stereochemistry and pharmacological properties

Methoxycarbonyl-1-phenyl-2-cyclopropylmethyl based derivatives cis-(+)-1a [cis-(+)-MR200], cis-(-)-1a [cis-(-)-MR201], and trans-(±)-1a [trans-(±)-MR204], have been identified as new potent sigma (σ) receptor ligands. In the present paper, novel enantiomerically pure analogues were synthesized and optimized for their σ receptor affinity and selectivity. Docking studies rationalized the results obtained in the radioligand binding assay. Absolute stereochemistry was unequivocally established by X-ray analysis of precursor trans-(+)-5a as camphorsulfonyl derivative 9. The most promising compound, trans-(+)-1d, showed remarkable selectivity over a panel of more than 15 receptors as well as good chemical and enzymatic stability in human plasma. An in vivo evaluation evidenced that trans-(+)-1d, in contrast to trans-(-)-1d, cis-(+)-1d, or cis-(-)-1d, which behave as σ1 antagonists, exhibited a σ1 agonist profile. These data clearly demonstrated that compound trans-(+)-1d, due to its σ1 agonist activity and favorable receptor selectivity and stability, provided an useful tool for the study of σ1 receptors.

PROCESS FOR THE PREPARATION OF (1S,2R)-MILNACIPRAN

The invention relates to a process for the preparation of Levomilnacipran, a compound useful in the treatment of depression, comprising the following steps: a) directly converting the enantiomerically enriched form of alcohol (D) into the enantiomerically enriched form of the phthalimido derivative (C) by treatment with phthalimide in the presence of a trialkyl or triarylphosphine and of a dialkyl azodicarboxylate, formula (I) wherein the amount of phthalimide is comprised between 1 and 1.3 equivalents with respect to the molar amount of alcohol (D) used, and the amounts of both the phosphine and the azodicarboxylate are comprised, independently from each other, between 1 and 1.5 equivalents with respect to the molar amount of alcohol (D) used; b) deblocking the enantiomerically enriched form of the phthalimido derivative (C) to obtain Levomilnacipran, formula (II).

Conformational restriction approach to β-Secretase (BACE1) inhibitors: Effect of a cyclopropane ring to induce an alternative binding mode

Improvement of a drugs binding activity using the conformational restriction approach with sp3 hybridized carbon is becoming a key strategy in drug discovery. We applied this approach to BACE1 inhibitors and designed four stereoisomeric cyclopropane compounds in which the ethylene linker of a known amidine-type inhibitor 2 was replaced with chiral cyclopropane rings. The synthesis and biologic evaluation of these compounds revealed that the cis-(1S,2R) isomer 6 exhibited the most potent BACE1 inhibitory activity among them. X-ray structure analysis of the complex of 6 and BACE1 revealed that its unique binding mode is due to the apparent CH-π interaction between the rigid cyclopropane ring and the Tyr71 side chain. A derivatization study using 6 as a lead molecule led to the development of highly potent inhibitors in which the structure-activity relationship as well as the binding mode of the compounds clearly differ from those of known amidine-type inhibitors.