- NOVEL COMPOUNDS AND USES
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The present invention relates to compounds of formula (I): wherein Q is O or S; R1 is a cyclic group substituted with at least one group X, wherein R1 may optionally be further substituted; X is any group comprising a carbonyl group; and R2 is a cyclic group substituted at the α-position, wherein R2 may optionally be further substituted. The present invention further relates to salts, solvates and prodrugs of such compounds, to pharmaceutical compositions comprising such compounds, and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by the dual action of NLRP3 inhibition and the stimulation of insulin secretion.
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Page/Page column 60-62
(2018/12/13)
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- SULFONYLUREAS AND RELATED COMPOUNDS AND USE OF SAME
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ABSTRACT The present invention provides for certain sulfonyl ureas and related compounds which have advantageous properties and show useful activity in the inhibition of activation of the NLRP3 inflammasome. Such compounds are useful in the treatment of a wide range of disorders in which the inflammation process, or more specifically the NLRP3 inflammasome, have been implicated as being a key factor.
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Page/Page column 149
(2016/09/15)
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- Novel tricyclic indeno[5,6-b]furan-imidazole hybrid compounds: Design, synthesis and antitumor activity
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A series of novel hybrid compounds between tricyclic indeno[5,6-b]furan and imidazole has been prepared and evaluated in vitro against a panel of human tumor cell lines. The results suggest that the existence of benzimidazole ring and substitution of the imidazolyl-3-position with a naphthylacyl group were vital for modulating cytotoxic activity. In particular, hybrid compound 26 was found to be the most potent compound against 5 strains human tumor cell lines and more active than cisplatin (DDP), while compound 18 was more selective towards breast carcinoma (MCF-7) and colon carcinoma (SW480) with IC50 value 3.4-fold and 4.3-fold more sensitive to DDP.
- Chen, Wen,Yang, Li-Juan,Li, Yan,Wang, Xue-Quan,Wang, Shao-Jie,Wan, Wei-Chao,Zhang, Hong-Bin,Yang, Xiao-Dong
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p. 561 - 571
(2013/08/23)
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- Synthesis of a novel series of tricyclic indan derivatives as melatonin receptor agonists
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To develop a new therapeutic agent for sleep disorders, we synthesized a novel series of tricyclic indan derivatives and evaluated them for their binding affinity to melatonin receptors. In our previous paper, we proposed a conformation of the methoxy group favorable for the binding of the MT1 receptor. To fix the methoxy group in an active conformation, we decided to synthesize conformationally restricted tricyclic indan analogues with the oxygen atom in the 6-position incorporated into a furan, 1,3-dioxane, oxazole, pyran, morpholine, or 1,4-dioxane ring system. Among these compounds, indeno[5,4-b]furan analogues were found to be the most potent and selective MT1 receptor ligands and to have superior metabolic stability. The optimization of substituents led to (S)-(-)-22b, which showed very strong affinity for human MT1 (Ki = 0.014 nM), but no significant affinity for hamster MT3 (Ki = 2600 nM) or other neurotransmitter receptors. The pharmacological effects of (S)-(-)-22b were studied in experimental animals, and it was found that a dose of 0.1 mg/kg, po promoted a sleep in freely moving cats, as demonstrated by a decrease in wakefulness and increases in slow wave sleep and rapid eye movement sleep, which lasted for 6 h after administration. Melatonin (1 mg/kg, po) also had a sleep-promoting effect, though it lasted only 2 h. A new chiral method for the synthesis of (S)-(-)-22b starting from 60, which was prepared from 59 employing asymmetric hydrogenation with the (S)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl-Ru complex, was developed. (S)-(-)-22b (TAK-375) is currently under clinical trial for the treatment of insomnia and circadian rhythm disorders.
- Uchikawa, Osamu,Fukatsu, Kohji,Tokunoh, Ryosuke,Kawada, Mitsuru,Matsumoto, Kiyoharu,Imai, Yumi,Hinuma, Shuji,Kato, Koki,Nishikawa, Hisao,Hirai, Keisuke,Miyamoto, Masaomi,Ohkawa, Shigenori
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p. 4222 - 4239
(2007/10/03)
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