- 5-Imino-1,2,4-thiadiazoles: First small molecules As substrate competitive inhibitors of glycogen synthase kinase 3
-
Cumulative evidence strongly supports that glycogen synthase kinase-3 (GSK-3) is a pathogenic molecule when it is up-dysregulated, emerging as an important therapeutic target in severe unmet human diseases. GSK-3 specific inhibitors might be promising effective drugs for the treatment of devastating pathologies such as neurodegenerative diseases, stroke, and mood disorders. As GSK-3 has the ability to phosphorylate primed substrates, small molecules able to bind to this site should be perfect drug candidates, able to partially block the activity of the enzyme over some specific substrates. Here, we report substituted 5-imino-1,2,4-thiadiazoles as the first small molecules able to inhibit GSK-3 in a substrate competitive manner. These compounds are cell permeable, able to decrease inflammatory activation and to selectively differentiate neural stem cells. Overall, 5-imino-1,2,4-thiadiazoles are presented here as new molecules able to decrease neuronal cell death and to increase endogenous neurogenesis blocking the GSK-3 substrate site
- Palomo, Valle,Perez, Daniel I.,Perez, Concepcion,Morales-Garcia, Jose A.,Soteras, Ignacio,Alonso-Gil, Sandra,Encinas, Arantxa,Castro, Ana,Campillo, Nuria E.,Perez-Castillo, Ana,Gil, Carmen,Martinez, Ana
-
experimental part
p. 1645 - 1661
(2012/04/04)
-
- SUBSTITUTED 5-IMINO-1,2,4-THIADIAZOLES THAT CAN BE USED TO TREAT NEURODEGENERATIVE DISEASES
-
The present invention is based on the use of a broad family of 5-imino-1,2,4-thiadiazoles as potential new drugs for the treatment of diseases in which PDE7 inhibition is important, specially inflammatory diseases, autoimmune and neurodegenerative disorde
- -
-
Page/Page column 8
(2012/09/11)
-
- SUBSTITUTED 5-IMINO-1,2,4-THIADIAZOLES THAT CAN BE USED TO TREAT NEURODEGENERATIVE DISEASES
-
The present invention relates to the use of a broad family of substituted 5-imino-1,2,4-thiadiazoles as potential novel drugs for treating diseases in which PDE7 inhibition is relevant, especially inflammatory, autoimmune and neurodegenerative diseases. F
- -
-
Page/Page column 11
(2012/08/14)
-
- Synthesis of a few novel bioactive 2-substituted amino-5-indol-3-oyl-4- phenylthiazoles
-
The 2-amino-4-arylthiazole motif is an important structural element in a variety of bioactive molecules. The (4+1) thiazole construction strategy adopted involves the synthesis of the [C-N-C-S] precursors, namely 1-aryl-3-(N- phenylbenzimidoyl) thiourea or 1-alkyl-3-(N-phenylbenzimidoyl) thiourea and the preparation of the C5 synthone, the halo acetylhetaroyl derivative. The optimized reaction conditions developed have thus lead to the preparation of five 2-(N-arylamino)-5-(indol-3-oyl)-4-phenylthiazoles and three 2-(N,N-dialkylamino)-5-(indol-3-oyl)-4-phenylthiazoles. The structure of these new compounds were assigned on the basis of elemental analysis, FTIR, 1H NMR and 13C NMR and screened for their antimicrobial activity.
- Thomas,Reshmy,Ushadevi
-
p. 1016 - 1019
(2008/09/19)
-
- Synthesis and biological evaluation of a new series of 2,3,5-substituted [1,2,4]-thiadiazoles as modulators of adenosine A1 receptors and their molecular mechanism of action
-
We synthesized two series (7a-i and 8a-i) of 2,3,5-substituted [1,2,4]-thiadiazole analogues of SCH-202676 (7a, 2,3-diphenyl-5-N-methylimino- 2H-[1,2,4]-thiadiazole) with emphasis on the N-imino substituent. Compounds 7a-g,i and 8a-g at a final concentrat
- G?bly?s, Anikó,De Vries, Henk,Brussee, Johannes,Ijzerman, Adriaan P.
-
p. 1145 - 1151
(2007/10/03)
-
- 2,3-Diaryl-5-anilino[1,2,4]thiadiazoles as melanocortin MC4 receptor agonists and their effects on feeding behavior in rats
-
The melanocortin-4 receptor (MC4) modulates physiological functions such as feeding behavior, nerve regeneration, and drug addiction. Using a high throughput screen based on 125I-NDP-MSH binding to the human MC4 receptor, we discovered 2,3-diar
- Pan, Kevin,Scott, Malcolm K.,Lee, Daniel H. S.,Fitzpatrick, Louis J.,Crooke, Jeffery J.,Rivero, Ralph A.,Rosenthal, Daniel I.,Vaidya, Anil H.,Zhao, Boyu,Reitz, Allen B.
-
p. 185 - 192
(2007/10/03)
-
- Synthesis and regioselective [4+2] cycloaddition/nucleophilic reactions of N-arylamino-1:3-diaza-1:3-butadienes with ketenes and accompanying rearrangements
-
N-Arylamino-1:3-diaza-1:3-butadienes 4 are shown to undergo regioselective reactions with phenyl- and chloroketenes resulting in high yields of 3-aryl-2-methylthio6-phenyl-4(3H)-pyrimidinones 7. Similar reactions with bromo- and iodoketenes, resulted, via
- Dey, Paramita D.,Sharma, Arun K.,Rai, Sachchida N.,Mahajan, Mohinder P.
-
p. 7459 - 7468
(2007/10/02)
-
- Reactions of Phenylbenzamidines with Isocyanates and Isothiocyanates
-
The reaction of N-aryl benzamidines with phenyl isocyanate (phenyl isothiocyanate) yields the normal adducts, quinazoline-4-ones (4-thiones) or diphenyl ureas (thioureas) depending on the substituent on the aryl group and the reaction conditions.The mechanisms of the various transformations are discussed.
- Nair, M. D.,Desai, J. A.
-
-