- SHP2 PHOSPHATASE INHIBITORS AND METHODS OF USE THEREOF
-
The present disclosure relates to novel compounds including formula (X) and pharmaceutical compositions thereof, and methods for inhibiting the activity of SHP2 phosphatase with the compounds and compositions of the disclosure. The present disclosure further relates to, but is not limited to, methods for treating disorders associated with SHP2 deregulation with the compounds and compositions of the disclosure.
- -
-
Paragraph 0276
(2019/10/15)
-
- Solvent-Controlled, Site-Selective N-Alkylation Reactions of Azolo-Fused Ring Heterocycles at N1-, N2-, and N3-Positions, Including Pyrazolo[3,4- d]pyrimidines, Purines, [1,2,3]Triazolo[4,5]pyridines, and Related Deaza-Compounds
-
Alkylation of 4-methoxy-1H-pyrazolo[3,4-d]pyrimidine (1b) with iodomethane in THF using NaHMDS as base selectively provided N2-methyl product 4-methoxy-2-methyl-2H-pyrazolo[3,4-d]pyrimidine (3b) in an 8/1 ratio over N1-methyl product (2b). Interestingly, conducting the reaction in DMSO reversed selectivity to provide a 4/1 ratio of N1/N2 methylated products. Crystal structures of product 3b with N1 and N7 coordinated to sodium indicated a potential role for the latter reinforcing the N2-selectivity. Limits of selectivity were tested with 26 heterocycles which revealed that N7 was a controlling element directing alkylations to favor N2 for pyrazolo- and N3 for imidazo- and triazolo-fused ring heterocycles when conducted in THF. Use of 1H-detected pulsed field gradient-stimulated echo (PFG-STE) NMR defined the molecular weights of ionic reactive complexes. This data and DFT charge distribution calculations suggest close ion pairs (CIPs) or tight ion pairs (TIPs) control alkylation selectivity in THF and solvent-separated ion pairs (SIPs) are the reactive species in DMSO.
- Bookser, Brett C.,Weinhouse, Michael I.,Burns, Aaron C.,Valiere, Andrew N.,Valdez, Lino J.,Stanczak, Pawel,Na, Jim,Rheingold, Arnold L.,Moore, Curtis E.,Dyck, Brian
-
p. 6334 - 6353
(2018/06/01)
-
- FUSED HETEROARYL DERIVATIVES AS OREXIN RECEPTOR ANTAGONISTS
-
Fused heteroaryl derivative compounds which are antagonists of orexin receptors are provided. The compounds can be used in the potential treatment or prevention of neurological and psychiatric disorders and diseases in which orexin receptors are involved. Also provided is a composition which comprises the compound can be use to prevent or treat such diseases in which orexin receptors are involved.
- -
-
Page/Page column 99; 100
(2016/07/27)
-
- 2-n-butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine and analogues as A2A adenosine receptor antagonists. Design, synthesis, and pharmacological characterization
-
Two types of adenosine receptor ligands were designed, i.e., 9H-purine and 1H-imidazo[4,5-c]pyridines, to obtain selective A2A antagonists, and we report here their synthesis and binding affinities for the four adenosine receptor subtypes Asub
- Minetti, Patrizia,Tinti, Maria Ornella,Carminati, Paolo,Castorina, Massimo,Di Cesare, Maria Assunta,Di Serio, Stefano,Gallo, Grazia,Ghirardi, Orlando,Giorgi, Fabrizio,Giorgi, Luca,Piersanti, Giovanni,Bartoccini, Francesca,Tarzia, Giorgio
-
p. 6887 - 6896
(2007/10/03)
-
- IMIDAZOPYRIDINES AS MUSCARINIC AGENTS
-
The compound of the formula: STR1 where R 1 is H, alkyl, perhaloalkyl, arylalkyl, alkenyl or alkynyl; R 2 is H when R. sub.4 is other than H, and, when R 4 is H, R 2 is STR2 in which R 5 is hydrogen or alkyl; R 3 is hydrogen or halogen; R. sub.4 is H or STR3 X, Y and Z are, independently, nitrogen or carbon, at least one of X, Y or Z being nitrogen; n is 1 or 2; n 1 is 0, 1, 2, 3, 4, or 5; or a pharmaceutically acceptable salt thereof are centrally active muscarinic agents.
- -
-
-
