- Synthesis and inhibitory effects of triarylpyrazoles on LPS-induced NO and PGE2 productions in RAW 264.7 macrophages
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Abstract: The inhibition of nitric oxide and prostaglandin E2 productions is a very interesting research topic in the field of anti-inflammatory drug development. In the current study, a new series of 1,3,4-triarylpyrazole derivatives was synth
- Park, Byung-Jun,El-Gamal, Mohammed I.,Lee, Woo-Suck,Shin, Ji-Sun,Yoo, Kyung Ho,Lee, Kyung-Tae,Oh, Chang-Hyun
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- Discovery of highly potent V600E-B-RAF kinase inhibitors: Molecular modeling study
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A series of 20 triarylpyrazole derivatives containing amide or urea linker have been synthesized. Their in vitro antiproliferative activity against NCI-60 cancer cell lines panel has been reported. Upon investigating the mechanism of action at molecular l
- Tarazi, Hamadeh,El-Gamal, Mohammed I.,Oh, Chang-Hyun
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- Synthesis, in vitro antiproliferative activity, and kinase inhibitory effects of pyrazole-containing diarylureas and diarylamides
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Twenty pyrazole-containing diarylureas and diarylamides were designed and synthesized. They were tested for in vitro antiproliferative activity over a 58-cancer cell line panel at the NCI, USA. The diarylurea derivatives 1b-e and 1g exerted the strongest
- El-Gamal, Mohammed I.,Park, Byung-Jun,Oh, Chang-Hyun
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Read Online
- 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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- Synthesis of 1H-Pyrazole-1-carboxamide derivatives and their antiproliferative activity against melanoma cell line
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Synthesis of a new series of 1H-pyrazole-1-carboxamide derivatives is described. Their antiproliferative activity against A375 human melanoma cell line was tested and the effect of substituents on the diarylpyrazole scaffold was investigated. The pharmacological results indicated that most of the newly synthesized compounds showed moderate activity against A375, compared with sorafenib. Among all of these derivatives, compound IIe which has N-methylpiperazinyl and phenolic moieties showed the most potent antiproliferative activity against A375 human melanoma cell line.
- El-Gamal, Mohammed I.,Sim, Tae Bo,Hong, Jun Hee,Cho, Jung-Hyuck,Yoo, Kyung Ho,Oh, Chang-Hyun
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experimental part
p. 197 - 204
(2011/10/07)
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- Discovery and optimization of CRTH2 and DP dual antagonists
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A series of phenylacetic acid derivatives was discovered as CRTH2 antagonists. Modification of the series led to compounds that are also antagonists of DP. Since activation of CRTH2 and DP are believed to play key roles in mediating responses of asthma and other immune diseases, this series was optimized to increase the dual antagonistic activities and improve pharmacokinetic properties. These efforts led to selection of AMG 009 as a clinical candidate.
- Liu, Jiwen,Fu, Zice,Wang, Yingcai,Schmitt, Mike,Huang, Alan,Marshall, Derek,Tonn, George,Seitz, Lisa,Sullivan, Tim,Lucy Tang,Collins, Tassie,Medina, Julio
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scheme or table
p. 6419 - 6423
(2010/05/02)
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- Substituted Diphenylethers, -Amines, -Sulfides and -Methanes for the Treatment of Respiratory Disease
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The invention relates to substituted diphenylethers, -amines, -sulfides, and -methanes as useful pharmaceutical compounds for treating respiratory-disorders, pharmaceutical compositions containing them, and processes for their preparation.
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Page/Page column 25
(2009/01/20)
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- NOVEL COMPOUNDS
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The invention relates to substituted phenylacetic acids as useful pharmaceutical compounds for treating respiratory disorders, pharmaceutical compositions containing them, and processes for their preparation.
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Page/Page column 40
(2008/06/13)
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- Mandelic acid derivatives and their use as throbin inhibitors
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There is provided a compound of formula I wherein Ra, R1, R2, Y and R3 have meanings given in the description and pharmaceutically acceptable derivatives (including prodrugs) thereof, which compounds and derivatives are useful as, or are useful as prodrugs of, competitive inhibitors of trypsin-like proteases, such as thrombin, and thus, in particular, in the treatment of conditions where inhibition of thrombin is required (e.g. thrombosis) or as anticoagulants.
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(2008/06/13)
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- PHARMACEUTICAL COMBINATION
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There is provided a combination product comprising: (1) a compound of claim 1 in WO 02/44145 or a compound of claim 20 in WO 02/44145 (or derivative thereof)or a pharmaceutically-acceptable derivative thereof; and (1) a compound as defined in claim 1 of WO 01/28992 or (2) a compound of Claim 34 of WO 01/28992 or (3) Compound A or B or C or D (or pharmaceutically-acceptable salts thereof) for use in treating arrhythmia or a coagulation controlled complication thereof.
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- SYNTHESES OF PHENOLIC METABOLITES OF AN ANTIFUNGAL IMIDAZOLE DERIVATIVE (CLOCONAZOLE HYDROCHLORIDE)
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Syntheses of phenolic metabolites of antifungal vinylimidazole derivative 6*HCl (Cloconazole hydrochloride) are described.Phenolic compound 8 was prepared from 2 using selective mono THP protection, followed by imidazolation and deprotection. 10 was synth
- Takahashi, Kimio,Shimizu, Sumio,Ogata, Masaru
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p. 1483 - 1491
(2007/10/02)
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- Ring-substituted 1,2-dialkylated 1,2-bis(hydroxyphenyl)ethanes. 2. Synthesis and estrogen receptor binding affinity of 4,4'-, 5,5'-, and 6,6'-disubstituted metahexestrols
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The synthesis of symmetrically 4,4'-, 5,5'-, and 6,6'-disubstituted derivatives of the mammary tumor inhibiting antiestrogen metahexestrol [meso-3,4-bis(3-hydroxyphenyl)hexane] (1) are described [4,4'-disubstituents: F(2), Cl (3), Br (4), I (5), CH2N(CH3)2 (6), CH3 (7), CH2OCH3 (8), CH2OC2H5 (9), CH2OH (10), NO2 (11), NH2 (12), N(CH3)2 (13), COCH3 (14), and C2H5 (15); 5,5'-substituents: OH (16) and Cl (17); 6,6'-disubstituents: OH (18), F (19), Cl (20), and CH3 (21)]. The synthesis of 1-3, 16, and 19 was accomplished by reductive coupling of the propiophenones with TiCl4/Zn and subsequent hydrogenation of the cis-3,4-diphenylhex-3-enes. Compounds 17, 18, 20, and 21 were synthesized by coupling the 1-phenyl-1-propanols with TiCl3/LiAlH4 and separation of the meso diastereomers, while 4-15 were obtained by substitution of metahexestrol. The binding affinity of these compounds to the calf uterine estrogen receptor was measured relative to that of [3H]estradiol by a competitive binding assay. The test compounds showed relative binding affinity (RBA) values between 15 and 0.5% were evaluated in the mouse uterine weight test. They showed a similar (2 and 12), slightly increased (19 and 21), or strongly enhanced (7 and 20) estrogenicity compared to that of metahexestrol. Compounds 1, 2, 7, 12, and 21 exhibited antiestrogenic activity inhibiting the estrone-stimulated uterine growth (24 to 60% inhibition).
- Hartmann,Heindl,Schonenberger
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p. 577 - 585
(2007/10/02)
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- Reaction of Some 1,4-Benzoquinone Mono-oximes with Methanolic Hydrogen Chloride
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When 2-methyl-1,4-benzoquinone 4-oxime (1) reacted with methanolic hydrogen chloride at 25-30 deg C the product was 2-chloro-4,6-dimethoxy-3-methylaniline (2).Similarly 1,4-benzoquinone 4-oxime (7) gave 2-chloro-4,6-dimethoxyaniline (8), 3-methyl-1,4-benzoquinone 4-oxime (11) gave 2-chloro-4-methoxy-6-methoxymethylaniline (12) and 2-chloro-4-methoxy-6-methylaniline (13), and 2-methoxy-1,4-benzoquinone 4-oxime (19) gave 2-chloro-4,5-dimethoxyaniline (20).
- Sargent, Melvyn V.
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p. 1095 - 1098
(2007/10/02)
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