- The reaction of prop-2-ynylsulfonium salts and sulfonyl-protected β-amino ketones to epoxide-fused 2-methylenepyrrolidines and S-containing pyrroles
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A novel divergent domino annulation reaction of prop-2-ynylsulfonium salts with sulfonyl-protected β-amino ketones has been developed, affording various epoxide-fused 2-methylenepyrrolidines and S-containing pyrroles in moderate to excellent yields. Prop-2-ynylsulfonium salts act as C2synthons in the reactions providing a promising epoxide-fused skeleton in a single operation with readily accessible starting materials.
- Jia, Tingting,Zeng, Gongruixue,Zhang, Chong,Zeng, Linghui,Zheng, Wenya,Li, Siyao,Wu, Keyi,Shao, Jiaan,Zhang, Jiankang,Zhu, Huajian
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supporting information
p. 2657 - 2660
(2021/03/16)
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- Synthesis, characterization, COX1/2 inhibition and molecular modeling studies on novel 2-thio-diarylimidazoles
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Heterocyclic compounds with diaryl substituents have been a milestone approach for selective cyclooxygenase 2 (COX 2) inhibition by bioisosteric replacements and modifications. It is also known that thiazole derivatives have different pharmacological acti
- ?ahin, Zafer,Bender, Ceysu,Berk, Bark?n,Biltekin Kaleli, Sevde Nur,Demirayak, ?eref,Ko?o?lu Kalkan, Melike,Yurtta?, Leyla
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p. 1841 - 1853
(2022/01/08)
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- Structural Basis for EGFR Mutant Inhibition by Trisubstituted Imidazole Inhibitors
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Acquired drug resistance in epidermal growth factor receptor (EGFR) mutant non-small-cell lung cancer is a persistent challenge in cancer therapy. Previous studies of trisubstituted imidazole inhibitors led to the serendipitous discovery of inhibitors that target the drug resistant EGFR(L858R/T790M/C797S) mutant with nanomolar potencies in a reversible binding mechanism. To dissect the molecular basis for their activity, we determined the binding modes of several trisubstituted imidazole inhibitors in complex with the EGFR kinase domain with X-ray crystallography. These structures reveal that the imidazole core acts as an H-bond acceptor for the catalytic lysine (K745) in the "αC-helix out" inactive state. Selective N-methylation of the H-bond accepting nitrogen ablates inhibitor potency, confirming the role of the K745 H-bond in potent, noncovalent inhibition of the C797S variant. Insights from these studies offer new strategies for developing next generation inhibitors targeting EGFR in non-small-cell lung cancer.
- Heppner, David E.,Günther, Marcel,Wittlinger, Florian,Laufer, Stefan A.,Eck, Michael J.
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p. 4293 - 4305
(2020/05/27)
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- Design, synthesis and biological evaluation of new Axl kinase inhibitors containing 1,3,4-oxadiazole acetamide moiety as novel linker
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Using the principle of bioisosteric replacement, we present a structure-based design approach to obtain new Axl kinase inhibitors with significant activity at the kinase and cellular levels. Through a stepwise structure-activity relationships exploration, a series of 6,7-disubstituted quinoline derivatives, which contain 1,3,4-oxadiazol acetamide moiety as novel Linker, were ultimately synthesized with Axl as the primary target. Most of them exhibited moderate to excellent activity, with IC50 values ranging from 0.032 to 1.54 μM against the tested cell lines. Among them, the most promising compound 47e, as an Axl kinase inhibitor (IC50 = 10 nM), shows remarkable cytotoxicity against A549, HT-29, PC-3, MCF-7, H1975 and MDA-MB-231 cell lines. More importantly, 47e also shows a significant inhibitory effect on EGFR-TKI resistant NSCLC cell lines H1975/gefitinib. Meanwhile, this study provides a novel type of linker for Axl kinase inhibitors, namely 1,3,4-oxadiazol acetamide moiety, which is out of the scope of the “5- atoms role ".
- Xu, Congjun,Han, Yufei,Xu, Sicong,Wang, Ruxin,Yue, Ming,Tian, Yu,Li, Xiaofan,Zhao, Yanfang,Gong, Ping
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- Combating fluconazole-resistant fungi with novel β-azole-phenylacetone derivatives
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A series of β-azole-phenylacetone derivatives with novel structures were designed and synthesized to combat the increasing incidence of susceptible fungal infections and drug-resistant fungal infections. The antifungal activity of the synthesized compounds was assessed against five susceptible strains and five fluconazole-resistant strains. Antifungal activity tests showed that most of the compounds exhibited excellent antifungal activities against five pathogenic strains with MIC values in the range of 0.03–1 μg/mL. Compounds with R1 = 3-F substituted and 15o and 15ae exhibited moderate antifungal activities against fluconazole-resistant strains 17# and CaR with MIC values in the range of 1–8 μg/mL. Compounds with R1 = H or 2-F (such as 15a, 15o, 15p) displayed moderate to good antifungal activity against fluconazole-resistant strains 632, 901 and 904 with MIC values in the range of 0.125–4 μg/mL. Notably, 15o and 15ae exhibited antifungal activity against five susceptible strains and five fluconazole-resistant strains. Preliminary mechanistic studies showed that the potent antifungal activity of compound 15ae stemmed from inhibition of C. albicans CYP51. Compounds 15o, 15z and 15ae were nearly nontoxic to mammalian A549 cells.
- Zhao, Liyu,Sun, Nannan,Tian, Linfeng,Sun, Yin,Chen, Yixuan,Wang, Xinran,Zhao, Shizhen,Su, Xin,Zhao, Dongmei,Cheng, Maosheng
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-
- DOPAMINE D3 RECEPTOR ANTAGONISTS HAVING A MORPHOLINE MOIETY
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The disclosure provides compounds of formula (I) or pharmaceutically acceptable salts thereof: The disclosure also provides processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them, and their use
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Paragraph 0244
(2018/11/21)
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- CYCLOPROPYL DERIVATIVES AS ROR-GAMMA MODULATORS
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The present invention provides compounds which are modulators of RORγ and their use for the treatment of diseases or conditions mediated by RORγ. Further, the present invention relates to processes of preparing such compounds, their tautomeric forms, novel intermediates involved in their synthesis, their pharmaceutically acceptable salts, methods for using such compounds and pharmaceutical compositions containing them (Formula I).
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Page/Page column 38
(2018/03/02)
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- 3,4-diaryl maleimide derivative and preparation method and application thereof
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The invention discloses a 3,4-diaryl maleimide derivative represented by a general formula I and a medicinal salt form thereof. The invention further discloses a preparation method of the mentioned 3,4-diaryl maleimide derivative and application of the 3,
- -
-
Paragraph 0067; 0068
(2017/08/23)
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- 3. 4 - diaryl maleic imide derivative and its preparation method and application
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The invention discloses a 3,4-diarylmaleimide derivative and a preparation method as well as application thereof. The general formula of the 3,4-diarylmaleimide derivative is shown in the specification. The 3,4-diarylmaleimide derivative can be applied to
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-
Paragraph 0079; 0080
(2017/07/07)
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- Discovery of 2-azetidinone and 1H-pyrrole-2,5-dione derivatives containing sulfonamide group at the side chain as potential cholesterol absorption inhibitors
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Cholesterol absorption inhibitor (CAI) targeting Niemann-Pick C1-like1 protein was developed for the treatment of hyperlipidaemia and only ezetimibe was approved so far. For developing novel CAIs, we synthesized sixteen 2-azetidinone derivatives and thirt
- Yuan, Xinrui,Lu, Peng,Xue, Xiaojian,Qin, Hui,Fan, Chen,Wang, Yubin,Zhang, Qi
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supporting information
p. 849 - 853
(2016/05/24)
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- SUBSTITUTED PHENYL IMIDAZOLYL PIPERIDYL COMPOUNDS AS P70S6K1 INHIBITORS
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The present invention relates to novel substituted phenyl imidazolyl piperidyl compounds that inhibit activity ofP70S6KI, pharmaceutical compositions comprising the compounds, and methods of using the compounds to treat physiological disorders, such as dyslipidemia, preferably hyperlipidemia, more preferably hypercholesterolemia and/ or hypertriglyceridemia.
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Page/Page column 6
(2016/06/01)
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- COMPOUNDS USEFUL AS MODULATORS OF TRPM8
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The present invention includes compounds useful as modulators of TRPM8, such as compounds of Formulae (Ia), (Ib) and (Ic), and the subgenus and species thereof; personal products containing those compounds; and the use of those compounds and the personal products, particularly the use of increasing or inducing chemesthetic sensations, such as cooling or cold sensations.
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Paragraph 0853
(2016/03/29)
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- Discovery and synthesis of a novel series of liver X receptor antagonists
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Fourteen novel compounds were prepared and their antagonistic activities against liver X receptors (LXR) α/β were tested in vitro. Compound 26 had an IC50 value of 6.4 μM against LXRα and an IC50 value of 5.6 μM against LXRβ. Docking studies and the results of structure-activity relationships support the further development of this chemical series as LXRα/β antagonists.
- Nian, Siyun,Gan, Xia,Tan, Xiangduan,Yu, Zhenpeng,Wang, Panfeng,Chen, Xing,Wang, Guoping
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p. 628 - 635
(2015/09/07)
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- NOVEL SUBSTITUTED IMIDAZOLES AS CASEIN KINASE 1 δ/ε INHIBITORS
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The invention provides compounds of Formula (I) and pharmaceutically acceptable salts thereof. The compounds of Formula (I) inhibit protein kinase activity thereby making them useful as anticancer agents.
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Page/Page column 72; 73
(2014/07/08)
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- New 1,3-oxazolo[4,5-c]quinoline derivatives: Synthesis and evaluation of antibacterial and antituberculosis properties
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A new class of fused oxazoloquinoline derivatives was synthesized starting from 2-bromo-1-phenylethanones 1a-b through multi-step reactions. The newly synthesized compounds were evaluated for their in vitro antibacterial against Escherichia coli (ATTC-259
- Eswaran, Sumesh,Adhikari, Airody Vasudeva,Ajay Kumar
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experimental part
p. 957 - 966
(2010/04/26)
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- Pyrrolo [3,2-C] Pyridine-4-One 2-Indolinone Protein Kinase Inhibitors
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The present invention relates to pyrrolo[3,2-c]pyridine-4-one 2-indolinone compounds of Formula (I) and their pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8X, Y and have the meaning cited in the specification.
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Page/Page column 73
(2010/02/16)
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- SMALL MOLECULE INHIBITORS OF PLASMODIUM FALCIPARUM DIHYDROOROTATE DEHYDROGENASE
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Inhibitors of dihydroorotate dehydrogenase (DHODH) for the Plasmodium enzyme have been identified and characterized. The inhibitors have high specificity, submicromolar efficacy against cultured parasite strains, exhibit drug-like properties, and are not overtly cytotoxic.
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Page/Page column 49-50
(2010/01/29)
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- Ion channel modulators
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The invention relates to compounds, compositions comprising the compounds, and methods of using the compounds and compound compositions. The compounds, compositions, and methods described herein can be used for the therapeutic modulation of ion channel fu
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Page/Page column 94
(2008/06/13)
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- Ion Channel Modulators
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The invention relates to compounds, compositions comprising the compounds, and methods of using the compounds and compound compositions. The compounds, compositions, and methods described herein can be used for the therapeutic modulation of ion channel function, and treatment of disease and disease symptoms, particularly those mediated by certain calcium channel subtype targets.
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Page/Page column 37; 40
(2010/11/29)
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- PYRROLO [3,2-C] PYRIDINE-4-ONE 2-INDOLINONE PROTEIN KINASE INHIBITORS
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The present invention relates to pyrrolo[3,2-c]pyridine-4-one 2-indolinone compounds of Formula (I) and their pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8 X , Y and …. have the meaning cited in the specifica
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Page/Page column 112
(2010/11/28)
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- Indole, indazole and indoline derivatives as CETP inhibitors
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The present invention relates to compounds of formula (I): wherein —X—Y—, R1 to R11 and n are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prevention of diseases which are mediated by CETP inhibitors.
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Page/Page column 29
(2010/02/15)
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- Ion channel modulators
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The invention relates to compounds, compositions comprising the compounds, and methods of using the compounds and compound compositions. The compounds, compositions, and methods described herein can be used for the therapeutic modulation of ion channel fu
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Page/Page column 44
(2008/06/13)
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- Concise synthesis of 1H-pyrazin-2-ones and 2-aminopyrazines
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Convenient syntheses of 1H-pyrazin-2-ones and 2-aminopyrazines are described. By coupling Boc-protected amino acids with α-amino ketones or with amino alcohols and subsequent oxidation, 1H-pyrazin-2-ones were obtained. Transformation into the corresponding pyrazine triflates and substitution with primary or secondary amines led to 2-aminopyrazines. Since these syntheses take advantage of the use of readily available starting materials (e.g., amino acids, aminoalcohols and amines) a variety of the entitled structures can be obtained in few, high yielding steps.
- Adam, Isabelle,Orain, David,Meier, Peter
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p. 2031 - 2033
(2007/10/03)
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- ANTIBACTERIAL BENZOIC ACID DERIVATIVES
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The invention provides antimicrobial agents and methods of using the agents for sterilization, sanitation, antisepsis, disinfection, and treatment of infections in mammals.
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-
- A QUINOLINE AMIDE DERIVATIVE AS AGENT AGAINST DISORDERS OF THE CNS
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A compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, is provided (Formula I) as is a process for its preparation and methods for its use in therapy, particularly in treating CNS or CNS-mediated disorders.
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-
- Syntheses and Photophysical Properties of Some 5(2)-Aryl-2(5)-(4-pyridyl)oxazoles and Related Oxadiazoles and Furans
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A number of 5-aryl-2-(4-pyridyl)oxazoles, a 2-aryl-5-(4-pyridyl)oxazole, the related oxadiazole and furan, several 2-(4-pyridyl)cycloalkanooxazoles, and many of their quaternary salts were prepared.No single standard synthesis was effective for preparation of more than a few of the 25 free bases described; methods often unique to a base were employed.Minor variations in structure sometimes produced large differences in absorption and emission wavelengths, as well as in the magnitude of the extinction coefficient.The salts are of interest as laser dyes, scintillation fluors, biological stains, and shifters for luminescent solar concentrators.
- Hall, J. Herbert,Chien, Joseph Yuming,Kauffman, Joel M.,Litak, Peter T.,Adams, Jeffrey K.,et al.
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p. 1245 - 1273
(2007/10/02)
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- New Anticancer Agents: Synthesis of 1,2-Dihydropyridopyrizines (1-Deaza-7,8-dihydropteridines)
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Reaction of α-aminoacetophenone oximes (2) with ethyl 6-amino-4-chloro-5-nitropyridine-2-carbamate (1) gave ethyl 6-amino-5-nitro-4-pyridine-2-carbamate oximes (3), which were hydrolyzed under acidic conditions to give the corresponding ketones (4).Related pyridines substituted with keto side chain were prepared from 1 and 1,3-diaminopropanone oximes and by oxidation of the side-chain hydroxy group of ethyl 6-amino-4-amino>-5-nitropyridine-7-carbamates (6).Catalytic hydrogenation of the nitro group of 4 over Raney nickel in a large volume of ethanol gave the 1-deaza-7,8-dihydropteridines (7).Several of the oximes 3 were successfully hydrogenated to give 7 directly.The resulting 1-deaza-7,8-dihydropteridines showed potent cytotoxicity against cultured L1210 cells and significant anticancer activity against lymphocytic leukemia P-388 in mice.THese biological activities are attributed to the accumulation of cells at mitosis.
- Temple, Carroll,Wheeler, Glynn P.,Elliott, Robert D.,Rose, Jerry D.,Kussner, Conrad L.,et al.
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p. 1045 - 1050
(2007/10/02)
-
- 1-[[[5-(Substituted phenyl)-2-oxazolyl]methylene]amino]-2,4-imidazolidinediones
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A series of 1-[[[5-(substituted phenyl-2-oxazolyl]methylene]amino]-2,4-imidazolidinediones are useful as muscle relaxants.
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