- New triarylpyrazoles as broad-spectrum anticancer agents: Design, synthesis, and biological evaluation
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A new series of diarylureas and diarylamides possessing 1,3,4-triarylpyrazole scaffold was designed and synthesized. Their in vitro antiproliferative activities against NCI-60 cell line panel were tested. Most of the compounds showed strong and broad-spec
- El-Gamal, Mohammed I.,Park, Yi Seul,Chi, Dae Yoon,Yoo, Kyung Ho,Oh, Chang-Hyun
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- Design, synthesis, in vitro potent antiproliferative activity, and kinase inhibitory effects of new triarylpyrazole derivatives possessing different heterocycle terminal moieties
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A new series of triarylpyrazole derivatives having different heterocycle terminal groups have been designed and synthesised. Compounds 1h–j and 1l exhibited the highest mean percentage inhibition against the 58 cancer cell lines at a concentration of 10 μ
- Gamal El-Din, Mahmoud M.,El-Gamal, Mohammed I.,Abdel-Maksoud, Mohammed S.,Yoo, Kyung Ho,Oh, Chang-Hyun
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- Design, synthesis, and in vitro antiproliferative and kinase inhibitory effects of pyrimidinylpyrazole derivatives terminating with arylsulfonamido or cyclic sulfamide substituents
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A novel series of substituted pyrimidine compounds bearing N-phenylpyrazole and terminating with aryl and cyclic sulfonamido moiety were designed, synthesized, and evaluated in vitro as antiproliferative agents against a panel of 53 cell lines of differen
- Gamal El-Din, Mahmoud M.,El-Gamal, Mohammed I.,Abdel-Maksoud, Mohammed S.,Yoo, Kyung Ho,Baek, Daejin,Choi, Jungseung,Lee, Huiseong,Oh, Chang-Hyun
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Read Online
- Evaluation of the inhibitory effects of pyridylpyrazole derivatives on lps-induced pge2 productions and nitric oxide in murine raw 264.7 macrophages
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A series of thirteen triarylpyrazole analogs were investigated as inhibitors of lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2 ) and nitric oxide (NO) production in RAW 264.7 macrophages. The target compounds 1a–m have first
- El-Din, Mahmoud M. Gamal,El-Gamal, Mohammed I.,Kwon, Young-Do,Kim, Su-Yeon,Han, Hee-Soo,Park, Sang-Eun,Oh, Chang-Hyun,Lee, Kyung-Tae,Kim, Hee-Kwon
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- Design, synthesis, biological evaluation, and docking studies of novel (imidazol-5-yl)pyrimidine-based derivatives as dual BRAFV600E/p38α inhibitors
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The synergistic effect of dual inhibition of serine/threonine protein kinases that are involved in the same signalling pathway of the diseases can exert superior biological benefits for treatment of these diseases. In the present work, a new series of (imidazol-5-yl)pyrimidine was designed and synthesized as dual inhibitors of BRAFV600E and p38α kinases which are considered as key regulators in mitogen-activated protein kinase (MAPK) signalling pathway. The target compounds were evaluated for dual kinase inhibitory activity. The tested compounds exhibited nanomolar scale IC50 values against BRAFV600E and low to sub-micromolar IC50 range against p38α. Compound 20h was identified as the most potent dual BRAFV600E/p38α inhibitor with IC50 values of 2.49 and 85 nM, respectively. Further deep investigation revealed that compound 20h possesses inhibitory activity of TNF-α production in lipopolysaccharide-induced RAW 264.7 macrophages with IC50 value of 96.3 nM. Additionally, the target compounds efficiently frustrated the proliferation of LOX-IMVI melanoma cell line. Compound 20h showed a satisfactory antiproliferative activity with IC50 value of 13 μM, while, compound 18f exhibited the highest cytotoxicity potency with IC50 value of 0.9 μM. Compound 18f is 11.11-fold more selective toward LOX-IMVI melanoma cells than IOSE-80PC normal cells. The newly reported compounds represent therapeutically promising candidates for further development of BRAFV600E/p38α inhibitors in an attempt to overcome the acquired resistance of BRAF mutant melanoma.
- Ali, Eslam M.H.,El-Telbany, Rania Farag A.,Abdel-Maksoud, Mohammed S.,Ammar, Usama M.,Mersal, Karim I.,Zaraei, Seyed-Omar,El-Gamal, Mohammed I.,Choi, Se-In,Lee, Kyung-Tae,Kim, Hee-Kwon,Lee, Kwan Hyi,Oh, Chang-Hyun
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- INHIBITORS OF THE YAP/TAZ-TEAD INTERACTION AND THEIR USE IN THE TREATMENT OF CANCER
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The invention relates to compounds of formula (I): wherein R1; R2, R3, R4, R5 and are as defined in the description. The compounds of formula (I) are inhibitors of the YAP/TAZ-TEAD interaction and thu
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Paragraph 0232
(2020/04/21)
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- IMIDAZOPYRIDAZINE DERIVATIVES AS MODULATORS OF THE GABAA RECEPTOR ACTIVITY.
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The present invention relates to imidazopyridazine derivatives. More particularly, it relates to 4-(biphenyl-3-yl)-7H-imidazo[4,5-c]pyridazine derivatives of formula (I) and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R and R6 are as defined in the description. The imidazopyridazine derivatives of the present invention modulate the activity of the GABAA receptor. They are useful in the treatment of a number of conditions, including pain.
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Page/Page column 73
(2016/01/01)
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- Antiproliferative diarylpyrazole derivatives as dual inhibitors of the ERK pathway and COX-2
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A series of 3,4-diarylpyrazole-1-carboxamide derivatives was designed and synthesized. A selected group of the target compounds was tested for in vitro antiproliferative activities over a panel of 60 cancer cell lines at the National Cancer Institute (NCI, Bethesda, MD, USA) at a single-dose concentration of 10 μm, and the four most active compounds 9a, 9l, 9n, and 10o were further tested in a five-dose testing mode to determine their IC50 values over the 60 cell lines. In addition, a selected group of target compounds were tested for inhibitory effect over cyclooxygenase isozymes. Compounds 9a, 9l, 9n, and 10o were also tested for MEK and ERK kinase inhibitory activity using Western blot assay. Compound 10o was selective toward melanoma cell line subpanel, and its antiproliferative activity may be attributed to selective cyclooxygenase-2 inhibition and ERK pathway inhibition.
- El-Gamal, Mohammed I.,Choi, Hong Seok,Yoo, Kyung Ho,Baek, Daejin,Oh, Chang-Hyun
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p. 336 - 347
(2013/09/12)
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- New diarylureas and diarylamides containing 1,3,4-triarylpyrazole scaffold: Synthesis, antiproliferative evaluation against melanoma cell lines, ERK kinase inhibition, and molecular docking studies
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Synthesis of a new series of diarylureas and diarylamides possessing 1,3,4-triarylpyrazole scaffold is described. Their in vitro antiproliferative activities against 9 human melanoma cell lines were tested. Compounds 12, 13, 15, and 21-23 showed the highe
- Choi, Won-Kyoung,El-Gamal, Mohammed I.,Choi, Hong Seok,Baek, Daejin,Oh, Chang-Hyun
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experimental part
p. 5754 - 5762
(2012/01/03)
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- Design, synthesis, and antiproliferative activity of 3,4-diarylpyrazole-1- carboxamide derivatives against melanoma cell line
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Synthesis of a new series of 3,4-diarylpyrazole-1-carboxamide derivatives is described. Their antiproliferative activity against A375P human melanoma cell line was tested and the effect of substituents on the diarylpyrazole scaffold was investigated. The
- El-Gamal, Mohammed I.,Choi, Hong Seok,Cho, Hae-Guk,Hong, Jun Hee,Yoo, Kyung Ho,Oh, Chang-Hyun
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experimental part
p. 745 - 754
(2012/06/30)
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- Synthesis of methyl-, fluoro-, and chloro-substituted 6-hydroxyisoindolin-1-ones
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The synthesis of a series of methyl-, fluoro-, and chloro-substituted 6-hydroxyisoindolin-1-ones is described.
- Powers, James J.,Favor, David A.,Rankin, Trent,Sharma, Rashmi,Pandit, Chetan,Jeganathan, Azhwarsamy,Maiti, Samarendra N.
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supporting information; experimental part
p. 1267 - 1269
(2009/09/05)
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- Piperidine derivatives and methods of use
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Compounds are provided that act as potent antagonists of the CCR1 receptor, and have in vivo anti-inflammatory activity. The compounds are generally monocyclic and bicyclic compounds and are useful in pharmaceutical compositions, methods for the treatment
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(2008/06/13)
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