14676-00-7Relevant articles and documents
2-Aminohydroxamic acid derivatives as inhibitors of Bacillus cereus phosphatidylcholine preferred phospholipase C PC-PLCBc
González-Bulnes, Patricia,González-Roura, Albert,Canals, Daniel,Delgado, Antonio,Casas, Josefina,Llebaria, Amadeu
supporting information; experimental part, p. 8549 - 8555 (2011/02/25)
Phosphatidylcholine preferring phospholipase C (PC-PLC) is an important enzyme that plays a key role in a variety of cellular events and lipid homoeostases. Bacillus cereus phospholipase C (PC-PLCBc) has antigenic similarity with the elusive mammalian PC-PLC, which has not thus far been isolated and purified. Therefore the discovery of inhibitors of PC-PLC Bc is of current interest. Here, we describe the synthesis and biological evaluation of a new type of compounds inhibiting PC-PLCBc. These compounds have been designed by evolution of previously described 2-aminohydroxamic acid PC-PLCBc inhibitors that block the enzyme by coordination of the zinc active site atoms present in PC-PLCBc [Gonzalez-Roura, A.; Navarro, I.; Delgado, A.; Llebaria, A.; Casas, J. Angew. Chem. Int. Ed. 2004, 43, 862]. The new compounds maintain the zinc coordinating groups and possess an extra trimethylammonium function, linked to the hydroxyamide nitrogen by an alkyl chain, which is expected to mimic the trimethylammonium group of the phosphatidylcholine PC-PLCBc substrates. Some of the compounds described inhibit the enzyme with IC 50's in the low micromolar range. Unexpectedly, the most potent inhibitors found are those that possess a trimethylammonium group but have chemically blocked the zinc coordinating functionalities. The results obtained suggest that PC-PLCBc inhibition is not due to the interaction of compounds with the phospholipase catalytic zinc atoms, but rather results from the inhibitor cationic group recognition by the PC-PLCBc amino acids involved in choline lipid binding.
Synthesis of a library of polycationic lipid core dendrimers and their evaluation in the delivery of an oligonucleotide with hVEGF inhibition
Parekh, Harendra S.,Marano, Robert J.,Rakoczy, Elizabeth P.,Blanchfield, Joanne,Toth, Istvan
, p. 4775 - 4780 (2007/10/03)
This article follows on from our previous work in the area of non-viral gene delivery using polycationic dendrimers (PCDs). Herein we report on the synthesis and efficacy of a new library of lipid core PCDs in the delivery of the anti-angiogenic oligonucleotide (ODN-1) to retinal pigment epithelial cells. ELISA was used to monitor hVEGF levels in cells transfected with dendriplexes, Cytofectin GSV and control (non-transfected). At 48 h, hVEGF titres had returned to that of the untransfected control for Cytofectin GSV however, a number of dendriplexes continued to exhibit a marked reduction in hVEGF titres.
Derivatives of heterocycles with 5 members, their preparation and their use as medicaments
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, (2008/06/13)
The invention relates to thiazole, oxazole, imidazole, isoxazole and isoxazoline derivatives of general formula (I) wherein Het is thiazole, oxazole, imidazole, isoxazole or isoxazoline, n is an integer from 0 to 6, A is notably selected from various optionally substituted aromatic radicals, B is notably hydrogen, alkyl or phenyl, R1 and R2 are notably independently hydrogen, alkyl or cycloalkyl or R1 and R2, taken together with the carbon atom which carries them, form a carbocycle with 3 to 7 members and Ω is —NR46R47 or —OR48, R46 and R47 are notably independently hydrogen, alkyl, cycloalkyl or —(CH2)k—COOR51, R51 is notably alkyl or haloalkyl and R48 is notably hydrogen or alkyl. These compounds have advantageous pharmacological properties which allow their use in therapeutics, notably for treating neurodegenerative disorders or pain.
Derivatives of heterocycles with 5 members, their preparation and their use as medicaments
-
, (2008/06/13)
The invention relates to thiazole, oxazole, imidazole, isoxazole and isoxazoline derivatives of general formula (I) wherein Het is thiazole, oxazole, imidazole, isoxazole or isoxazoline, n is an integer from 0 to 6, A is notably selected from various optionally substituted aromatic radicals, B is notably hydrogen, alkyl or phenyl, R1 and R2 are notably independently hydrogen, alkyl or cycloalkyl and Ω is —NR46R47 or —OR48 R46 and R47 are notably independently hydrogen, alkyl, cycloalkyl or —(CH2)k—COOR51, R51 is notably alkyl or haloalkyl and R48 is notably hydrogen or alkyl. These compounds have advantageous pharmacological properties which allow their use in therapeutics, notably for treating neurodegenerative disorders or pain.
Alkylamide compounds
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, (2008/06/13)
The invention provides compounds of formula (I) wherein R1 is optionally substituted C1-6alkyl, optionally substituted carbocyclyl, optionally substituted heterocyclyl, C1-6alkoxy, —NR2R3 or —NR4SO2R5; n is 2 to 6; X is oxygen, sulfur or —CH2—; Y is C1-6alkyl which may be branched- or straight-chain, and may be independently substituted by one or more halo, C1-4alkoxy, hydroxy or C3-7cycloalkyl; wherein the linkage —(CH2)n— and the linkage when X is —CH2—, may be substituted by C1-4alkyl, C1-4haloalkyl, hydroxy, C1-4alkoxy, C1-4haloalkoxy, hydroxyC1-4alkyl, C1-4alkoxyC1-4alkyl, C1-4haloalkoxyC1-4alkyl, C3-7cycloalkyl or C3-7cycloalkylC1-4alkyl. The compounds of the invention are useful in the treatment of sexual dysfunction, particularly female sexual dysfunction.
