231287-89-1Relevant articles and documents
Discovery of Small-Molecule Cyclic GMP-AMP Synthase Inhibitors
Anderson, Rachel,Chen, Zhijian J.,Padilla-Salinas, Rosaura,Sun, Lijun,Yang, Xikang,Yin, Hang,Zhang, Shuting
, (2020/02/04)
Cyclic guanosine monophosphate-adenosine monophosphate (GMP-AMP) (cGAS), a cytosolic DNA sensor, plays an important role in the type I interferon response. DNA from either invading microbes or self-origin triggers the enzymatic activity of cGAS. Aberrant activation of cGAS is associated with various autoimmune disorders. Only one selective probe exists for inhibiting cGAS in cells, while others are limited by their poor cellular activity or specificity, which underscores the urgency for discovering new cGAS inhibitors. Here, we describe the development of new small-molecule human cGAS (hcGAS) inhibitors (80 compounds synthesized) with high binding affinity in vitro and cellular activity. Our studies show CU-32 and CU-76 selectively inhibit the DNA pathway in human cells but have no effect on the RIG-I-MAVS or Toll-like receptor pathways. CU-32 and CU-76 represent a new class of hcGAS inhibitors with activity in cells and provide a new chemical scaffold for designing probes to study cGAS function and development of autoimmune therapeutics.
NOVEL CYCLIC GMP-AMP SYNTHASE (CGAS) INHIBITORS AND THEIR METHOD OF USE
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Page/Page column 97, (2020/01/08)
Methods of treating diseases related to cGAS activation. Small molecule inhibitors of cGAS and pharmaceutical compositions and uses thereof in treating autoimmune diseases or inflammation.
2-(3,4-Dihydro-1H-isoquinolin-2yl)-pyridines as a novel class of NR1/2B subtype selective NMDA receptor antagonists
Buettelmann, Bernd,Alanine, Alexander,Bourson, Anne,Gill, Ramanjit,Heitz, Marie-Paule,Mutel, Vincent,Pinard, Emmanuel,Trube, Gerhard,Wyler, Rene
, p. 829 - 832 (2007/10/03)
Recently, we disclosed 4-aminoquinolines as structurally novel NR1/2B subtype selective NMDA receptor antagonists. We would now like to report our findings on structurally related pyridine analogues. The SAR developed in this series resulted in the discovery of high affinity antagonists which are selective (vs α1 and M1 receptors) and active in vivo.
Pyridine substituted isoquinoline derivatives
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, (2008/06/13)
The invention relates to compounds of formulae Compounds of the invention have a good affinity to the NMDA receptor and are useful for the treatment of diseases related to this receptor.
Conjugated aromatic compounds with a pyridine substituent
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, (2008/06/13)
The present invention relates to compounds of formulae The compounds of the present invention are NMDA (N-methyl-D-aspartate)-receptor subtype blockers and are used in the treatment of diseases related to this receptor.
BENZOSULFONE DERIVATIVES
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, (2008/06/13)
The present invention relates to novel compounds of the general formula STR1 wherein R 1 is hydrogen;R. sup.2 is hydrogen, trifluoromethyl or lower alkyl;R 3 is hydrogen or amino; or R 1 and R 2 or R 3 and R 2 taken together are--CH. dbd.CH--CH=CH--;Z is pyrimidin-4-yl, pyridin-4-yl, pyridin-2-yl or phenyl; R 4, R 5 are each independently hydrogen, lower alkyl, trifluoromethyl, halogen, lower alkoxy, nitrilo, amino, lower alkyl-amino, di-lower alkyl-amino, piperazinyl, morpholinyl, pyrrolidinyl, vinyl, C. sub.3-C 6 cycloalkyl, C 3-C 6 cycloalkenyl, t-buthylethinyl, hydroxyalkylethinyl, phenylethinyl, naphthyl, thiophenyl, or phenyl, which may be substituted by halogen, lower alkoxy, lower alkyl, trifluoromethyl or nitro, or a group--NH(CH. sub.2). sub.n NR 6 R 7,--N(CH 3)(CH 2) n NR 6 R. sup.7,--NH(CH 2) n-morpholin-4-yl or--NH(CH 2) n OH; n is 2-4R 6 and R 7 are each independently hydrogen or lower alkyl,and to their pharmaceutically acceptable salts. It has been found that the compounds of formula I possess a selective affinity to 5HT-6 receptors.
