- Discovery of New Imidazo[2,1- b]thiazole Derivatives as Potent Pan-RAF Inhibitors with Promising in Vitro and in Vivo Anti-melanoma Activity
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BRAF is an important component of MAPK cascade. Mutation of BRAF, in particular V600E, leads to hyperactivation of the MAPK pathway and uncontrolled cellular growth. Resistance to selective inhibitors of mutated BRAF is a major obstacle against treatment of many cancer types. In this work, a series of new (imidazo[2,1-b]thiazol-5-yl)pyrimidine derivatives possessing a terminal sulfonamide moiety were synthesized. Pan-RAF inhibitory effect of the new series was investigated, and structure-activity relationship is discussed. Antiproliferative activity of the target compounds was tested against the NCI-60 cell line panel. The most active compounds were further tested to obtain their IC50 values against cancer cells. Compound 27c with terminal open chain sulfonamide and 38a with a cyclic sulfamide moiety showed the highest activity in enzymatic and cellular assay, and both compounds were able to inhibit phosphorylation of MEK and ERK. Compound 38a was selected for testing its in vivo activity against melanoma. Cellular and animal activities are reported.
- Abdel-Maksoud, Mohammed S.,El-Gamal, Mohammed I.,Lee, Bong S.,Gamal El-Din, Mahmoud M.,Jeon, Hong R.,Kwon, Dow,Ammar, Usama M.,Mersal, Karim I.,Ali, Eslam M. H.,Lee, Kyung-Tae,Yoo, Kyung Ho,Han, Dong Keun,Lee, Jae Kyun,Kim, Garam,Choi, Hong Seok,Kwon, Young Jik,Lee, Kwan Hyi,Oh, Chang Hyun
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p. 6877 - 6901
(2021/06/25)
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- Carbazole-containing sulfonamides and sulfamides: Discovery of cryptochrome modulators as antidiabetic agents
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A series of novel carbazole-containing sulfonamides and sulfamides were synthesized. A structure-activity relationship study of these compounds led to the identification of potent cryptochrome modulators. Based on the results of efficacy studies in diet-induced obese (DIO) mice, and the desired pharmacokinetic parameters, compound 41 was selected for further profiling.
- Humphries, Paul S.,Bersot, Ross,Kincaid, John,Mabery, Eric,McCluskie, Kerryn,Park, Timothy,Renner, Travis,Riegler, Erin,Steinfeld, Tod,Turtle, Eric D.,Wei, Zhi-Liang,Willis, Erik
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p. 757 - 760
(2016/05/24)
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- HETEROARYLS AND USES THEREOF
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The present invention provides a compound of formula I: and pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3, R4, R5, L1, L2, m, and n, are as described in the specification. Such compounds are inhibitors of VPS34 and thus useful for treating proliferative, inflammatory, or cardiovascular disorders.
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Paragraph 00401
(2015/08/03)
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- HETEROARYLS AND USES THEREOF
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The present invention provides a compound of formula I: and pharmaceutically acceptable salts thereof, wherein X, R1, R2, R3, R4, R5, L1, L2, m, and n, are as described in the specification. Such compounds are inhibitors of VPS34 and thus useful for treating proliferative, inflammatory, or cardiovascular disorders.
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Paragraph 0555-0556
(2015/09/22)
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- Carbazole-Containing Sulfonamides as Cryptochrome Modulators
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The subject matter herein is directed to carbazole-containing sulfonamide derivatives and pharmaceutically acceptable salts or hydrates thereof of structural formula I wherein the variable R1, R2, R3, R4, R5, R6, R7, A, B, C, D, E, F, G, H, a, and b are accordingly described. Also provided are pharmaceutical compositions comprising the compounds of formula I to treat a Cry-mediated disease or disorder, such as diabetes, obesity, metabolic syndrome, Cushing's syndrome, and glaucoma.
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Paragraph 0405-0406
(2013/11/19)
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- Novel lβ-methylcarbapenems having cyclic sulfonamide moieties: Synthesis and evaluation of in-vitro biological activity - Part II
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The synthesis of a new series of 1β-methylcarbapenems having cyclic sulfonamide moieties is described. Their in-vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of a substituent on the pyrroli
- Seong, Jong Kim,Cho, Jung-Hyuck,Oh, Chang-Hyun
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scheme or table
p. 528 - 532
(2009/12/06)
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- Synthesis and antibacterial activities of novel oxazolidinones having cyclic sulfonamide moieties
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The synthesis of a new series of oxazolidinones having cyclic sulfonamide moieties is described. Their in vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of substituents on the oxazolidinone
- Kim, Seoung Jong,Jung, Myung-Ho,Yoo, Kyung Ho,Cho, Jung-Hyuck,Oh, Chang-Hyun
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scheme or table
p. 5815 - 5818
(2009/11/30)
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- Novel lβ-methylcarbapenems having cyclic sulfonamide moieties: Synthesis and evaluation of in vitro antibacterial activity
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The synthesis of a new series of 1β-methylcarbapenems having cyclic sulfonamide moieties is described. Their in vitro antibacterial activities against both Gram-positive and Gram-negative bacteria were tested and the effect of substituent on the pyrrolidi
- Kim, Seong Jong,Park, Hyeong Beom,Lee, Jae Seoung,Jo, Nam Hyun,Yoo, Kyung Ho,Baek, Daejin,Kang, Byoung-won,Cho, Jung-Hyuck,Oh, Chang-Hyun
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p. 1176 - 1183
(2008/03/17)
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- Aza- and polyaza-naphthalenyl carboxamides useful as HIV integrase inhibitors
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Aza- and polyaza-naphthalenyl carboxamide derivatives including certain quinoline carboxamide and naphthyridine carboxamide derivatives are described. These compounds are inhibitors of HIV integrase and inhibitors of HIV replication, and are useful in the
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- Synthesis and Biological Activity of 3--5--1H-indole and Analogues: Agonists for the 5-HT1D Receptor
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A novel series of 5-(1,1-dioxo-1,2,5-thiadiazolidin-2-yl)tryptamines was designed, synthesized, and evaluated as 5-HT1D receptor agonists.Compounds such as 8d,f,k were identified which had comparable affinity, potency, and receptor selectivity
- Castro, Jose L.,Baker, Raymond,Guiblin, Alexander R.,Hobbs, Sarah C.,Jenkins, Matthew,et al.
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p. 3023 - 3032
(2007/10/02)
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