- COMPOUND USED AS AUTOPHAGY REGULATOR, AND PREPARATION METHOD THEREFOR AND USES THEREOF
-
It is related to compounds used as autophagy modulators and a method for preparing and using the same, specifically providing a compound of general formula (I), or pharmaceutically acceptable salts thereof, which is a type of autophagy modulators, particularly mammalian ATG8 homologues modulators.
- -
-
Paragraph 0309; 0307
(2020/07/07)
-
- Regioselective synthesis of substituted piperidine-2,4-diones and their derivatives via Dieckmann cyclisations
-
Abstract A flexible route to piperidine-2,4-diones variously substituted at the 6-, 5,6- and 2,6-positions, both with and without 1-substitution, is described; no N-protective group is required. A related regioselective Dieckmann cyclisation is also described that uses Davies' α-methylbenzylamine auxiliary and affords 6-substituted piperidine-2,4-diones enantioselectively.
- Marson, Charles M.,Yau, Kin Cheung
-
p. 7459 - 7469
(2015/08/24)
-
- USE OF CONDENSED BENZO[B]THIAZINE DERIVATIVES AS CYTOPROTECTANTS
-
The present invention relates to arylthiazine compounds, metabolites, N-oxides, amides, esters,pharmaceutically acceptable salts, hydrates and solvates thereof and their use as cytoprotectants in the treatment or prophylaxis of diseases or states, either acute or chronic, involving aberrant cellular lipid peroxidation in the central nervous system or in the periphery of the body. The present invention also relates to a method for their preparation and to pharmaceutical composition comprising as an active ingredient one or more of the aforementioned compounds.
- -
-
Page/Page column 67
(2014/12/12)
-
- A new method of synthesis of 6-substituted piperidine-2,4-diones from homoallylamines
-
Mono- and dihomoallylamines serve as convenient precursors for the preparation of 6-substituted piperidine-2,4-diones. This transformation is based, on the one hand, on a simple and well-known halocyclocarbamation reaction proceeding by the addition of a
- Kuznetsov, Nikolai Yu.,Maleev, Victor I.,Khrustalev, Victor N.,Mkrtchyan, Anna F.,Godovikov, Ivan A.,Strelkova, Tatyana V.,Bubnov, Yuri N.
-
p. 334 - 344
(2012/02/16)
-
- Structure-activity relationship study of first selective inhibitor of excitatory amino acid transporter subtype 1: 2-Amino-4-(4-methoxyphenyl)-7- (naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4 H -chromene-3-carbonitrile (UCPH-101)
-
The excitatory amino acid transporters (EAATs) are expressed throughout the central nervous system, where they are responsible for the reuptake of the excitatory neurotransmitter (S)-glutamate (Glu).(1)Recently, we have reported the discovery of the first subtype selective EAAT1 inhibitor 2-amino-4-(4-methoxyphenyl)-7-(naphthalen-1-yl)-5-oxo-5,6,7,8-tetrahydro-4H- chromene-3-carbonitrile (UCPH-101) (1b) and presented an introductory structure-activity relationship (SAR) study.(2)Here, we present a detailed SAR by the design, synthesis, and pharmacological evaluation of analogues 1g-1t. By comparison of potencies of 1b, 1h, and 1i versus 1j, it is evident that potency is largely influenced by the chemical nature of the R1 substituent. The study also demonstrates that any chemical change of the functional groups or a change to the parental scaffold results in the complete loss of inhibitory activity of the compounds at EAAT1. Finally, a bioavailability study of UCPH-101 determined the half-life to be 30 min in serum (rats) but also that it was not able to penetrate the blood-brain barrier to any significant degree.
- Erichsen, Mette N.,Huynh, Tri H. V.,Abrahamsen, Bjarke,Bastlund, Jesper F.,Bundgaard, Christoffer,Monrad, Olja,Bekker-Jensen, Anders,Nielsen, Christina W.,Frydenvang, Karla,Jensen, Anders A.,Bunch, Lennart
-
experimental part
p. 7180 - 7191
(2010/12/25)
-
- Diastereoselective synthesis of 6-functionalized 4-aryl-1,3-oxazinan-2-ones and their application in the synthesis of 3-aryl-1,3-aminoalcohols and 6-arylpiperidine-2,4-diones
-
Halocyclocarbamation of benzyl N-(1-phenyl-3-butenyl)carbamates afforded 6-functionalized 4-aryl-1,3-oxazinan-2-ones with moderate to excellent diastereoselectivity depending on the N-substituent. Importantly, in contrast to reported cyclocarbamations of homoallylic carbamates, which are generally trans-diastereoselective, cyclization of N-unsubstituted Cbz-protected homoallylamines led to cis-1,3-oxazinan-2-ones, predominantly. The use of N-benzylated and in situ prepared N-silylated derivatives resulted however in trans-selectivity. Transition states are proposed to explain the stereochemical influence of the N-substituent on the cyclocarbamations. The functionalized 1,3-oxazinan-2-ones could be further elaborated towards biologically or synthetically important 6-arylpiperidine-2,4-diones and 3-aryl-1,3-aminoalcohols.
- Mangelinckx, Sven,Nural, Yahya,Dondas, H. Ali,Denolf, Bram,Sillanp??, Reijo,De Kimpe, Norbert
-
experimental part
p. 4115 - 4124
(2010/07/05)
-
- An expedient synthesis of 6-arylpiperidine-2,4-diones by chain-extension of β-aryl-β-aminoacids
-
The synthesis of novel 6-arylpiperidine-2,4-diones is described in five steps starting from β-aryl-β-aminoacids via the chain extension of the latter into δ-aryl-δ-amino-β-ketoacids. The chemical pathway involves an acylation of Meldrum's acid and yields useful building blocks for heterocyclic chemistry.
- Leflemme, Nicolas,Dallemagne, Patrick,Rault, Sylvain
-
p. 8997 - 8999
(2007/10/03)
-
- SYNTHESIS OF 6-ARYL-4-HYDROXYPIPERIDIN-2-ONES AND A POSSIBLE APPLICATION TO THE SYNTHESIS OF A NOVEL HMG-CoA REDUCTASE INHIBITOR
-
A series of 6-aryl-4-hydroxypiperidin-2-ones (11a-11g) were synthesised with the key step being a Dieckmann cyclisation of the appropriate methyl 3-(ethoxycarbonylacetylamino)-3-(substituted) propionate (8a-8g) and this new synthetic route was successfully applied to the synthesis of 4-hydroxy-6-(2-phenylethyl)piperidin-2-one (11h).The application of this strategy to the synthesis of the putative HMG-CoA reductase inhibitor 6--4-hydroxypiperidin-2-one (11i) was attempted, but failed during the Dieckmann cyclisation of methyl 3-(ethoxycarbonylacetylamino)- 3-propionate (8i).An alternative synthesis of a 1:1 diastereomeric mixture of (11i) was achieved by the reductive cleavage of the isoxazoline (24) with Raney nickel.The mixture of diastereoisomers (11i) was inactive in-vitro and in-vivo (rat) against HMG-CoA reductase
- Ashton, Michael J.,Hills, Susan J.,Newton, Christopher G.,Taylor, John B.,Tondu, Sylvie C. D.
-
p. 1015 - 1035
(2007/10/02)
-