62462-05-9Relevant academic research and scientific papers
N-((HETEROARYLMETHYL)-HETEROARYL-CARBOXAMIDE DERIVATIVES AS PLASMA KALLIKREIN INHIBITORS
-
Page/Page column 46, (2016/06/14)
The present invention provides a selection of compounds of formula (I): compositions comprising such compounds; the use of such compounds in therapy (for example in the treatment or prevention of a disease or condition in which plasma kallikrein activity is implicated); and methods of treating patients with such compounds.
ACYLAMINOCYCLOALKYL COMPOUNDS SUITABLE FOR TREATING DISORDERS THAT RESPOND TO MODULATION OF DOPAMINE D3 RECEPTOR
-
Page/Page column 45; 46, (2014/05/24)
The present invention relates to novel acylaminocycloalkyl compounds, in particular to the compounds of the formula (I) as described herein and to their salts and N-oxides. The compounds possess valuable therapeutic properties and are suitable, in particular, for treating diseases that respond to modulation of the dopamine D3 receptor. In formula (I), the variables have the following meanings: m is 1 or 2, n is 1 or 2, A is selected from the group consisting of CH2, CH2CH2, CHFCH2 and CF2CH2, R1 is hydrogen or C1-C3-alkyl, R2 is selected from the group consisting of hydrogen, and fluorine, R3a is selected from the group consisting of hydrogen and methyl, R3b is selected from the group consisting of hydrogen and methyl, R4 is branched C4-C6 alkyl or branched fluorinated C4-C6 alkyl, and R5 is an oxygen containing radical such as C1-C2-alkoxy-C1-C4-alkyl, fluorinated C1-C2-alkoxy-C1-C4-alkyl, hydroxy-C1-C4-alkyl, fluorinated hydroxy-C1-C4-alkyl, oxetanyl, fluorinated oxetanyl, oxolanyl, fluorinated oxolanyl, C3-C5 cycloalkyl, fluorinated C3-C5 cycloalkyl, C3-C5 cycloalkoxy-C1-C4-alkyl and fluorinated C3-C5 cycloalkoxy-C1-C4-alkyl.
Photodynamic antitumor agents: β-Methoxyethyl groups give access to functionalized porphycenes and enhance cellular uptake and activity
Richert,Wessels,Muller,Kisters,Benninghaus,Goetz
, p. 2797 - 2807 (2007/10/02)
Porphycene photosensitizers bearing two or four methoxyethyl side chains were synthesized in nine steps from commercially available starting materials. Ether cleavage led to (hydroxy-ethyl)- and (bromoethyl)porphycenes that were converted to vinyl and benzo derivatives. Five of the side chain- functionalized porphycenes were biologically studied in comparison with two tetra-n-propylporphycenes. Porphycenes were incorporated in small unilamellar liposomes and incubated with cultivated SSK2 murine fibrosarcoma cells. Cellular uptake and phototoxicity 24 h after 5 J/cm2 laser light treatment were determined. The porphycenes tested were between 17 and 220 times more photodynamically active than the currently clinically used sensitizer Photofrin, although extinction coefficients of the porphycenes' irradiated bands are only approximately 10-fold higher. The LD50 concentration for SSK2 cells in the incubation medium was as low as (8.5 ± 2.8) x 10-9 M for tetrakis(methoxyethyl)porphycene. Two methoxy or hydroxy groups enhanced cellular uptake, three or four methoxy groups both enhanced and accelerated cellular uptake of tetraalkylporphycenes. Half-life times of the uptake processes varied between (0.14 ± 0.04) and (14 ± 4) h and cellular saturation levels between (1.2 ± 0.2) and (26 ± 3) pmol/105 cells. When individual uptake rates were accounted for, all porphycenes had a similar 'cellular' phototoxicity, pointing toward a common mechanism of action. Evidence is presented for the assumption that cell membranes are the primary targets of the tested porphycenes and that membrane solubility may play a critical role in their photodynamic efficiency. The results show that nonionic polar side chain functionalities can strongly enhance cellular uptake and antitumor activity of lipophilic porphyrinoids and thus that the known lipophilicity/activity relationship can be reversed for very hydrophobic sensitizers.
IMPROVED SYNTHESIS OF METHYL 5-METHOXY-3-OXOPENTANOATE
Akhrem, A. A.,Chernov, Yu. G.
, p. 255 - 256 (2007/10/02)
Ethyl 5-methoxy-2-acetyl-3-oxopentanoate was obtained by the acylation of the magnesium enolate of acetoacetic ester with β-methoxypropionyl chloride.Its ketone cleavage led to methyl 5-methoxy-3-oxopentanoate.
FACILE SYNTHESIS OF ALKYL 5-ALKOXY-3-OXOPENTANOATES
Sanchez, Ignacio H.,Larraza, Maria Isabel,Brena, Francisco Kuri,Cruz, Adrian,Sotelo, Octavio,Flores, Humberto J.
, p. 299 - 308 (2007/10/02)
A facile synthesis of several alkyl 5-alkoxy-3-oxopentanoates, based on the reductive elimination of triphenylphosphine from the readily available alkyl 5-alkoxy-3-oxo-2-(triphenylphosphoranylidene) pentanoates, is described.
