- COMPOUNDS
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Disclosed are novel compounds that inhibit LRRK2 kinase activity, processes for their preparation, compositions containing them and their use in the treatment of or prevention of diseases characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis(ALS).
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Page/Page column 77
(2017/02/09)
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- Synthesis and evaluation of hedgehog signaling inhibitor with novel core system
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As we previously reported, N-methylpyrrolo[3,2-c]pyridine derivatives 1 (TAK-441) was discovered as a clinical candidate of hedgehog (Hh) signaling inhibitor by modification of the upper part. We next focused on modification of the lower part including core skeletons to discover new Hh signaling inhibitors with novel core rings. Efforts to find novel chemotypes by using X-ray single crystal structure analysis led to some potent Hh signaling inhibitors (2c, 2d, 2e, 2f) with novel core ring systems, which had benzamide moiety at the 5-position as a key component for potent activity. The suppression of Gli1 expression with these new Hh signaling inhibitors were weaker than that of compound 1 (TAK-441) because of low pharmacokinetic property. We recognized again TAK-441 is a good compound as clinical candidate with good structural and pharmacokinetic advantages.
- Ohashi, Tomohiro,Tanaka, Yuta,Shiokawa, Zenyu,Banno, Hiroshi,Tanaka, Toshio,Shibata, Sachio,Satoh, Yoshihiko,Yamakawa, Hiroko,Yamamoto, Yukiko,Hattori, Harumi,Kondo, Shigeru,Miyamoto, Maki,Tojo, Hideaki,Baba, Atsuo,Sasaki, Satoshi
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p. 4777 - 4791
(2015/08/03)
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- PYRIMIDINE PDE10 INHIBITORS
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The present invention is directed to pyrimidine compounds which are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10). The present invention also relates to the use of such compounds for treating neurological and psychiatric disorders, such as schizophrenia, psychosis or Huntington's disease, and those associated with striatal hypofunction or basal ganglia dysfunction.
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Page/Page column 63; 64
(2013/03/26)
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- FUSED HETEROCYCLIC RING DERIVATIVE AND USE THEREOF
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The present invention provides a fused heterocycle derivative having a strong Smo inhibitory activity, and use thereof. Specially, the present invention relates to a compound represented by the formula wherein each symbol is as defined in the specification, or salt thereof, and a medicament containing the compound or a prodrug thereof, which is an Smo inhibitor or an agent for the prophylaxis or treatment of cancer.
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Page/Page column 48
(2012/07/14)
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- Pyrimidines substituted by nitrogen-containing heterocyclic rings as intermediates
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1,2,4-Triazolo[4,3-c]pyrimidines substituted at the 5 or 7 position through a nitrogen atom which is part of a heterocyclic ring have been found to have potent bronchodilator activity and to be useful synthetic intermediates in the preparation of 1,2,4-triazolo[1,5-c]pyrimidines. Methods for inducing bronchodilation, pharmaceutical compositions, and synthetic processes and intermediates are also described.
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- Triazolo [4,3-c]pyrimidines substituted by nitrogen-containing heterocyclic rings
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1,2,4-Triazolo[4,3-c]pyrimidines substituted at the 5 or 7 position through a nitrogen atom which is part of a heterocyclic ring have been found to have potent bronchodilator activity and to be useful synthetic intermediates in the preparation of 1,2,4-triazolo[1,5-c]-pyrimidines. Methods for inducing bronchodilation, pharmaceutical compositions, and synthetic processes and intermediates are also described.
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