- Discovery of a novel 2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide M4 positive allosteric modulator (PAM) chemotype
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This Letter details our efforts to discover structurally unique M4 PAMs containing 5,6-heteroaryl ring systems. In an attempt to improve the DMPK profiles of the 2,3-dimethyl-2H-indazole-5-carboxamide and 1-methyl-1H-benzo[d][1,2,3]triazole-6-carboxamide cores, we investigated a plethora of core replacements. This exercise identified a novel 2,3-dimethylimidazo[1,2-a]pyrazine-6-carboxamide core that provided improved M4 PAM activity and CNS penetration.
- Temple, Kayla J.,Engers, Julie L.,Long, Madeline F.,Watson, Katherine J.,Chang, Sichen,Luscombe, Vincent B.,Jenkins, Matthew T.,Rodriguez, Alice L.,Niswender, Colleen M.,Bridges, Thomas M.,Conn, P. Jeffrey,Engers, Darren W.,Lindsley, Craig W.
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- COMPOUNDS AND USES THEREOF
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The present invention features compounds useful in the treatment of neurological disorders and primary brain cancer. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders and primary brain cancer.
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- INDAZOLES AS LRRK2 INHIBITORS
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The present invention is directed to indazole compounds which are inhibitors of LRRK2 and are useful in the treatment of CNS disorders.
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Page/Page column 98
(2020/10/09)
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- COMPOUNDS AND USES THEREOF
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The present invention features compounds useful in the treatment of neurological disorders. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing neurological disorders.
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- Keeping it small, polar, and non-flat: diversely functionalized building blocks containing the privileged 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]- and [1,5-a]pyridine cores
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Six sets of functionalized building blocks based on 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridine as well as 5,6,7,8-tetrahydro[1,2,4]triazolo[1,5-a]pyridine cores have been prepared. These compounds are non-flat, bicyclic heterocycles that are likely to find utility as privileged motifs for lead-like compound design. One set of building blocks, (5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-6-ylmethyl)amines, proved useful as a scaffold for developing compounds that stimulate glucagon-like peptide-1 (GLP-1) secretion and are novel anti-diabetes drug leads.
- Mishchuk, Alexander,Shtil, Natalia,Poberezhnyk, Mykola,Nazarenko, Konstiantyn,Savchenko, Timur,Tolmachev, Andrey,Krasavin, Mikhail
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p. 1056 - 1059
(2016/02/16)
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