- Diaminopyrimidines, diaminopyridines and diaminopyridazines as histamine H4 receptor modulators
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Previously disclosed H4 receptor modulators, the triamino substituted pyridines and pyrimidines, contain a free primary amino (-NH2) group. In this Letter we demonstrate that an exocyclic amine (NH2) is not needed to maintain affinity, and also show a significant divergence in the SAR of the pendant diamine component. These des-NH2 azacycles also show a distinct functional spectrum, that appears to be influenced by the diamine component; in the case of the 1,3-amino pyrimidines, the preferred diamine is the amino pyrrolidine instead of the more common piperazines. Finally, we introduce 3,5-diamino pyridazines as novel histamine H4 antagonists.
- Savall, Brad M.,Meduna, Steven P.,Tays, Kevin,Cai, Hui,Thurmond, Robin L.,McGovern, Patricia,Gaul, Michael,Zhao, Bao-Ping,Edwards, James P.
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Read Online
- Discovery and SAR studies of novel 2-anilinopyrimidine-based selective inhibitors against triple-negative breast cancer cell line MDA-MB-468
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Triple-negative breast cancers (TNBCs) are characterized as an invasive and intractable subtype of breast cancers. Overexpression of epidermal growth factor receptor (EGFR) has been considered to be an important target for TNBC therapy, but efficacies of
- Jo, Jeyun,Kim, Sou Hyun,Kim, Heegyu,Jeong, Myeonggyo,Kwak, Jae-Hwan,Taek Han, Young,Jeong, Jee-Yeong,Jung, Young-Suk,Yun, Hwayoung
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supporting information
p. 62 - 65
(2018/11/23)
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- SAR optimization studies on a novel series of 2-anilinopyrimidines as selective inhibitors against triple-negative breast cancer cell line MDA-MB-468
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Triple-negative breast cancers (TNBCs) account for approximately 15% of breast cancer cases and exhibit an aggressive clinical behavior. In this study, we designed and synthesized two series of 2-anilinopyrimidines based on the structure of our previously
- Jo, Jeyun,Kim, Heegyu,Oh, Ji Youn,Kim, Soyeong,Park, Yeong Hye,Choi, Hyeonjin,Jeong, Jee-Yeong,Jung, Young-Suk,Yun, Hwayoung
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- Novel Derivatives of 2-Anilinopyrimidine and Composition Comprising the Same
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The present invention relates to a 2-anilinopyrimidine derivative represented by chemical formula 1 and a composition containing the 2-anilinopyrimidine derivative as an active ingredient for preventing or treating cancer. According to the present inventi
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Paragraph 0064; 0070-0071; 0088-0089
(2018/09/08)
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- BICYCLIC COMPOUND AND USE THEREOF FOR INHIBITING SUV39H2
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The present invention directs to a compound represented by formula (I).
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Page/Page column 394; 395
(2017/08/01)
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- One-pot synthesis and antiproliferative activity of novel 2,4-diaminopyrimidine derivatives bearing piperidine and piperazine moieties
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A series of novel 2,4-diaminopyrimidines containing piperidine and piperazine moieties were synthesized via an efficient one-pot methodology. The bioassay tests demonstrated that compounds 27 and 28 displayed much stronger antitumor activities against four human cancer cell lines (HepG2, A549, MDA-MB-231 and MCF-7) than positive control fluorouracil. Particularly, compound 28 showed a two-fold improvement compared to fluorouracil in inhibiting MDA-MB-231 and A549 cell proliferation with IC50 values of 7.46 and 12.78 μM, respectively. Further flow-activated cell sorting analysis revealed that the most promising compound 28 displayed a significant effect on G 2/M cell-cycle arrest in a dose-dependent manner in MDA-MB-231 cells.
- Ma, Wei-Feng,Yang, Hai-Kui,Hu, Meng-Jin,Li, Qian,Ma, Tian-Zhu,Zhou, Zhong-Zhen,Liu, Rui-Yuan,You, Wen-Wei,Zhao, Pei-Liang
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p. 127 - 134
(2014/07/22)
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- Triazine-pyrimidine based molecular hybrids: Synthesis, docking studies and evaluation of antimalarial activity
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A series of novel triazine-pyrimidine hybrids have been synthesized and evaluated for their in vitro antimalarial activity. Some of the compounds showed promising antimalarial activity against both CQ-sensitive and CQ-resistant strains at micromolar level with a high selectivity index. All the compounds displayed better activity (IC50 = 1.32-10.70 μM) than the standard drug pyrimethamine (>19 μM) against the chloroquine-resistant strain W2. All the tested compounds were nontoxic against mammalian cell lines. Further, docking studies of the most active compounds were performed on both wild type and quadruple mutant (N51I, C59R, S108N, I164L) PfDHFR-TS using Glide to analyse the interaction of the compounds with the binding site of the protein. The binding poses of compounds 14 and 19, having a high Glide XP score and the lowest Glide energies, show an efficient binding pattern similar to that of the DHFR substrate (dihydrofolate) in the wild type and mutant DHFR active site. The analysis of the pharmacokinetic properties of the most active compounds using ADMET prediction attests to the possibility of developing compound 14 as a potent antimalarial lead. This journal is
- Kumar, Deepak,Khan, Shabana I.,Ponnan, Prija,Rawat, Diwan S.
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supporting information
p. 5087 - 5095
(2015/02/19)
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- Substituted nitrogen-containing heteroaryl derivatives useful as modulators of the histamine H4 receptor
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The present invention relates to substituted nitrogen-containing heteroaryl derivatives, pharmaceutical compositions containing them, and methods of using any of these derivatives and compositions for H4 receptor activity modulation and the tre
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Page/Page column 49; 52
(2009/04/24)
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- N-substituted 2′-(aminoaryl)benzothiazoles as kinase inhibitors: Hit identification and scaffold hopping
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Starting with a hit from vHTS attained by a docking procedure of virtual compounds into ATP pockets of different kinases applying the 4SCan technology, variations of the adenine mimic resulted in the identification of promising scaffolds, giving rise to in vitro IC50 values in the nanomolar range on different kinases down to 63 nM.
- Tasler, Stefan,Mueller, Oliver,Wieber, Tanja,Herz, Thomas,Krauss, Rolf,Totzke, Frank,Kubbutat, Michael H.G.,Schaechtele, Christoph
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scheme or table
p. 1349 - 1356
(2009/11/30)
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- 2-arylbenzothiazole analogues and uses thereof
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The present invention relates to compounds of the general formula (I) and salts, prodrugs, and stereoisomers thereof, wherein Y independently represents S, O, NR2, SO, SO2; A independently represents a fife- or six-membered aromatic carbocycle or heterocycle and wherein R1 to R20 in formula (I) represent independently of each other a variety of different substituents comprising alkyl, aryl, aralkyl, alkylaryl, heteroaryl groups and monofunctional moieties.
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Page/Page column 15
(2008/06/13)
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- 2-Arylbenzothiazole analogues and uses thereof in the treatment of cancer
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The present invention relates to anticancer compounds of the general formula (I) and salts and physiologically functional derivatives thereof, wherein Y independently represents S, O, NR 2 , SO, SO 2 ; A independently represents a five- or six-membered aromatic carbocycle or heterocycle and wherein R 1 in formula (I) represents one of the heteroaryl groups defined in the claims.
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Page/Page column 26
(2010/11/25)
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- Benzazole analogues and uses thereof
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The present invention relates to compounds of the general formulas (I), (Ia) and (II) and salts and physiologically functional derivatives thereof, wherein the substituents —Y are attached to the 5- or 6-position of the benzazole.
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Page/Page column 17
(2008/06/13)
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- 2,5- and 2,6-disubstituted benzazole analogues useful as protein kinase inhibitors
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The present invention relates to compounds of the general formulas (I), (Ia) and (II) and salts and physiologically functional derivatives thereof, wherein the substituents -Y are attached to the 5- or 6- position of the benzazole. These compounds are useful as protein kinase inhibitors in the treatment of i.a. cancer.
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Page/Page column 27
(2008/06/13)
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- Regioselective synthesis of new pyrimidine derivatives using organolithium reagents
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2,4-Dichloro-6-phenylpyrimidine (3) and 2-chloro-4-(1′, 3′dithian2′-yl)pyrimidine (7) were prepared using organolithium reagents. Nucleophilic attack on pyrimidines 1, 3 and 9 using N-methylpiperazine was shown to be highly regioselective, favouring the f
- Abdou, Ibrahim M.
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p. 785 - 787
(2007/10/03)
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- NOVEL COMPOUNDS
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The invention relates to pyridine derivatives of formula (I) where the variables are defined in the specification.Processes for the preparation of these compounds together with pharmaceutical compositions containing them and their use in therapy in particular in the modulation of autoimmune disease is also described.
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