- Fragment-Based Discovery of Novel Potent Sepiapterin Reductase Inhibitors
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Genome-wide-association studies in chronic low back pain patients identified sepiapterin reductase as a high interest target for developing new analgesics. Here we used 19F NMR fragment screening for the discovery of novel, ligand-efficient SPR
- Alen, Jo,Schade, Markus,Wagener, Markus,Christian, Frank,Nordhoff, Sonja,Merla, Beatrix,Dunkern, Torsten R.,Bahrenberg, Gregor,Ratcliffe, Paul
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p. 6391 - 6397
(2019/07/08)
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- ANTIBIOTIC COMPOUNDS
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The present invention relates to antibiotic compounds of formula (I), to compositions containing these compounds and to methods of treating bacterial diseases and infections using the compounds. The compounds find application in the treatment of infection with, and diseases caused by, Gram-positive and/or Gram-negative bacteria, and in particular in the treatment of infection with, and diseases caused by, Neisseria gonorrhoeae.
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- Discovery of a 7-arylaminobenzimidazole series as novel CRF1receptor antagonists
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A promising lead compound 1 of a benzimidazole series has been identified as a corticotropin-releasing factor 1 (CRF1) receptor antagonist. In this study, we focused on replacement of a 7-alkylamino group of 1, predicted to occupy a large lipophilic pocket of a CRF1receptor, with an aryl group. During the course of this examination, we established new synthetic approaches to 2,7-diarylaminobenzimidazoles. The novel synthesis of 7-arylaminobenzimidazoles culminated in the identification of compounds exhibiting inhibitory activities comparable to the alkyl analog 1. A representative compound, p-methoxyanilino analog 16g, showed potent CRF binding inhibitory activity against a human CRF1receptor and human CRF1receptor antagonistic activity (IC50?=?27?nM, 56?nM, respectively). This compound exhibited ex vivo125I-Tyr0(125I-CRF) binding inhibitory activity in mouse frontal cortex, olfactory bulb, and pituitary gland at 20?mg/kg after oral administration. In this report, we discuss the structure–activity-relationship of these 7-arylamino-1H-benzimidazoles and their synthetic method.
- Mochizuki, Michiyo,Kori, Masakuni,Kono, Mitsunori,Yano, Takahiko,Sako, Yuu,Tanaka, Maiko,Kanzaki, Naoyuki,Gyorkos, Albert C.,Corrette, Christopher P.,Aso, Kazuyoshi
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p. 4675 - 4691
(2016/09/13)
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- 2-AMINO PYRIMIDINE COMPOUNDS AS POTENT HSP-90 INHIBITORS
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The present invention is directed to compounds of formula (I), or pharmaceutically acceptable salts thereof, their synthesis, and their use as HSP-90 inhibitors.
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Page/Page column 24
(2010/03/04)
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- BENZIMIDAZOLE COMPOUNDS
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There is provided a compound of the formula (1) wherein R1 is an optionally substituted C1-10 alkyl; R2 is H, or a C1-6 alkyl which may be substituted with 1 to 3 substituents; R3 is a 5- or 6-membered aromatic group which may be substituted with 1 to 5 substituents, wherein the 5- or 6-membered aromatic group may be fused with a 5- or 6- membered ring which may be substituted with 1 to 3 C1-6 alkyls; R4 is a hydrogen, a halogen, a hydroxy, a cyano, a C1-6 alkyl or a C1-6 alkoxy; Z is -O-, -S-, -SO-, -SO2-, or - NR5- wherein R5 is a hydrogen or a C1-6 alkyl; or a salt thereof or a prodrug thereof, which have CRF receptor antagonist activity and use thereof.
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Page/Page column 93-94
(2008/12/05)
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