28697-07-6Relevant articles and documents
A short enantioselective synthesis of pipecolic acid
Fernandez-Garcia,McKervey
, p. 2905 - 2906 (1995)
A simple enantioselective route to pipecolic acid is described. The key step involves the Sharpless asymmetric epoxidation of an N-protected aminoheptenol which spontaneously cyclises to a piperidine derivative on deprotection.
TUBULYSIN DERIVATIVES AND METHODS FOR PREPARING THE SAME
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Page/Page column 29, (2020/02/16)
The invention relates to novel means and methods for the synthesis of tubulysin and derivatives thereof, which find their use e.g. as cytotoxic agents in targeted drug delivery. Provided is a method for preparing a tubulysin derivative, comprising reacting compounds A, B and C in a 3- component Passerini reaction, wherein compound A is a carboxylic acid according to the general formula (A); wherein compound B is an aldehyde according to the general formula (B); and wherein compound C is an isocyanide according to the general formula (C).
Pipecolic esters as minimized templates for proteasome inhibition
Giletto, Matthew B.,Osmulski, Pawel A.,Jones, Corey L.,Gaczynska, Maria E.,Tepe, Jetze J.
, p. 2734 - 2746 (2019/03/12)
Allosteric regulators of clinically important enzymes are gaining popularity as alternatives to competitive inhibitors. This is also the case for the proteasome, a major intracellular protease and a target of anti-cancer drugs. All clinically used proteasome inhibitors bind to the active sites in catalytic chamber and display a competitive mechanism. Unfortunately, inevitable resistance associated with this type of inhibition drives the search for non-competitive agents. The multisubunit and multicatalytic “proteolytic machine” such as the proteasome is occasionally found to be affected by agents with other primary targets. For example the immunosuppressive agent rapamycin has been shown to allosterically inhibit the proteasome albeit at levels far higher than its mTOR related efficacy. As part of an ongoing program to search for novel proteasome-targeting pharmacophores, we identified the binding domain of rapamycin as required for proteasome inhibition even without the macrocyclic context of the parent compound. By subsequent structure-activity relationship studies, we generated a pipecolic ester derivative compound 3 representing a new class of proteasome inhibitors. Compound 3 affects the core proteasome activities and proliferation of cancer cells with low micromolar/high nanomolar efficacy. Molecular modeling, atomic force microscopy imaging and biochemical data suggest that compound 3 binds into one of intersubunit pockets in the proteasomal α ring and destabilizes the α face and the gate. The α face is used as a docking area for proteasome-regulating protein modules and the gate is critical for controlling access to the catalytic chamber. Thus, the pipecolic ester template elicits a new and attractive mechanism for proteasome inhibition distinct from classical competitive drugs.
PIPECOLIC ESTERS FOR INHIBITION OF THE PROTEASOME
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Paragraph 00274; 00276, (2019/08/26)
The present disclosure relates to chemical compounds that modulate proteasome activity, pharmaceutical compositions containing such compounds, and use of these compounds and compositions for the treatment of disorders of uncontrolled cellular proliferation such as, for example, a cancer. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
PROCESS FOR THE PRODUCTION OF COBIMETINIB
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Page/Page column 33, (2019/05/22)
The present invention relates to a novel route of synthesis for the production of enantiomerically pure Cobimetinib, new intermediates in the synthesis of Cobimetinib and an amorphous Cobimetinib hemifumarate salt comprising a high salt content.
Synthesis method of bupivacaine
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Paragraph 0010; 0015, (2016/10/10)
The invention belongs to a synthesis method of bupivacaine. The method comprises: adding 2 piperidinecarboxylicacid into aqueous alkali, dropwise adding Cbz and alkaline water, after finishing dropwise adding at normal temperature, reacting for 12 hours, after reaction, extracting with diethyl ether, washing a water layer to be weak-acid with 18% of diluted hydrochloric acid, extracting with the diethyl ether again, combining an diethyl ether layer, drying and filtering, and concentrating to obtain a dried product; adding the dried product into a DMF solvent, then adding a catalyst for reaction for 1 hour at normal temperature, then adding 2,6-dimethylaniline, reacting for 18hours at normal temperature, adding water and ethyl acetate for washing, taking an organic layer, drying and filtering, and concentrating to obtain a dried concentrated product; adding the dried concentrated product into a solvent, then adding a catalyst, pressurizing and introducing hydrogen, filtering after reaction and concentrating to obtain a dried product; adding the product in the above step into a solvent, dropwise adding bromo-n-butane at normal temperature, after dropwise adding, rising temperature to 80 DEG C for reacting for 12 hours, adding diluted hydrochloric acid, slowing cooling to normal temperature, and crystallizing, filtering and drying to obtain the product. The synthesis method has the advantages of higher yield, smaller pollution and low equipment requirement.
Ring-Strain Effects in Base-Induced Sommelet–Hauser Rearrangement: Application to Successive Stereocontrolled Transformations
Tayama, Eiji,Watanabe, Kazutoshi,Matano, Yoshihiro
supporting information, p. 3631 - 3641 (2016/07/29)
The base-induced Sommelet–Hauser (S–H) rearrangement of azetidine-2-carboxylic acid ester-derived ammonium salts into 2-aryl-substituted derivatives was demonstrated. The ring-strain of four-membered N-heterocycles enables efficient generation of the desired ylide intermediate and enhances the rate of the S–H rearrangement. The asymmetric version of the rearrangement was characterized by excellent levels of successive chirality transmissions. The regio- and stereo-controlled nucleophilic ring opening of the rearrangement products produced quaternary α-aryl amino acid esters with excellent enantiopurities.
A short enantioselective total synthesis of (R)- and (S)-pipecolic acid
Chavan, Subhash P.,Khairnar, Lalit B.,Chavan, Prakash N.,Kalbhor, Dinesh B.
, p. 1246 - 1251 (2015/02/19)
A convenient and practical total synthesis of (R)- and (S)-pipecolic acid has been achieved by utilizing chiral cis-aziridine-2-carboxylate as the common synthetic precursor. The synthesis involves regioselective reductive cleavage of the aziridine ring and Wittig olefination as key reactions.
CONDENSED HETEROCYCLIC COMPOUNDS HAVING 5-HT6 RECEPTOR AFFINITY
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Page/Page column 106, (2010/04/03)
The present disclosure provides compounds having affinity for the 5-HT6 receptor which are of the formula (I) wherein R1, A, B, D, E, G, Q, Ar, n, m, and p are as defined herein. The disclosure also relates to methods of preparing such compounds, compositions containing such compounds, and methods of use thereof.
Formation of N-acyl-N,N'-dicyclohexylureas from DCC and arenecarboxylic acids in the presence of hydroxybenzotriazole in CH2CI2 at room temperature
Kaiser, Carlos R.,Pinheiro, Alessandra C.,De Souza, Marcus V. N.,Wardell, James L.,Wardell, Solange M.S.V.
experimental part, p. 468 - 472 (2009/08/15)
The syntheses of N-acyl-N',N'-dicyclohexylureas from 1,3- dicyclohexylcarbodiimide and arenecarboxylic acids [p-XC6H 4CO2H (X = H or NO2), 2-, 3- or 4-pyridinecarboxylic acid and pyrazinecarboxylic acid] in the
