- COMPOUNDS AND METHODS FOR INHIBITING VIRAL REPLICATION AND METHODS OF TREATING AND PREVENTING FLAVIVIRAL INFECTIONS
-
The present disclosure relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof. The present disclosure further relates to methods of inhibiting viral replication including contacting one or more cells that have been infected wit
- -
-
-
- Compound used as CDK7 kinase inhibitor and application thereof
-
The invention relates to a compound used as a CDK7 kinase inhibitor and application thereof. Specifically, the compound disclosed by the invention has a structure shown as a formula I, and the definitions of all groups and substituents are as described in the specification. The compounds of the present invention are useful as inhibitors of cyclin-dependent kinase 7 (CDK7) for the treatment or prevention of proliferative diseases such as cancer, especially for modulating and treating diseases associated with abnormal activity of cyclin-dependent kinase 7 (CDK7).
- -
-
Paragraph 0216-0219; 0471-0479
(2021/04/17)
-
- AMIDE-SUBSTITUTED HETEROCYCLIC COMPOUNDS FOR THE TREATMENT OF CONDITIONS RELATED TO THE MODULATION OF IL-12, IL-23 AND/OR IFN-ALPHA
-
Compounds having the following formula I: or a stereoisomer or pharmaceutically-acceptable salt thereof, where R1, R2, R3, R4, and R5 are as defined herein, are useful in the modulation of IL-12, IL-2
- -
-
Page/Page column 94
(2020/05/29)
-
- JMX0207, a Niclosamide Derivative with Improved Pharmacokinetics, Suppresses Zika Virus Infection Both in Vitro and in Vivo
-
Flaviviruses causes significant human disease. Recent outbreaks of the Zika virus highlight the need to develop effective therapies for this class of viruses. Previously we identified niclosamide as a broad-spectrum inhibitor for flaviviruses by targeting
- Butler, David,Chen, Haiying,D'Brant, Lianna,Fan, Xiaoyu,Hu, Saiyang,Koetzner, Cheri A.,Kramer, Laura D.,Kuo, Lili,Lang, Yuekun,Li, Hongmin,Li, Zhong,Rugenstein, Natasha,Samrat, Subodh Kumar,Tharappel, Anil M.,Trudeau, Nicole,Xu, Jimin,Zhang, Jing,Zhang, Qing-Yu,Zhou, Jia
-
p. 2616 - 2628
(2020/11/09)
-
- Drug Design Targeting T-Cell Factor-Driven Epithelial-Mesenchymal Transition as a Therapeutic Strategy for Colorectal Cancer
-
Metastasis is the cause of 90% of mortality in cancer patients. For metastatic colorectal cancer (mCRC), the standard-of-care drug therapies only palliate the symptoms but are ineffective, evidenced by a low survival rate of ～11%. T-cell factor (TCF) transcription is a major driving force in CRC, and we have characterized it to be a master regulator of epithelial-mesenchymal transition (EMT). EMT transforms relatively benign epithelial tumor cells into quasi-mesenchymal or mesenchymal cells that possess cancer stem cell properties, promoting multidrug resistance and metastasis. We have identified topoisomerase IIα (TOP2A) as a DNA-binding factor required for TCF-transcription. Herein, we describe the design, synthesis, biological evaluation, and in vitro and in vivo pharmacokinetic analysis of TOP2A ATP-competitive inhibitors that prevent TCF-transcription and modulate or reverse EMT in mCRC. Unlike TOP2A poisons, ATP-competitive inhibitors do not damage DNA, potentially limiting adverse effects. This work demonstrates a new therapeutic strategy targeting TOP2A for the treatment of mCRC and potentially other types of cancers.
- Abraham, Adedoyin D.,Esquer, Hector,Zhou, Qiong,Tomlinson, Nicholas,Hamill, Brayden D.,Abbott, Joshua M.,Li, Linfeng,Pike, Laura A.,Rinaldetti, Sébastien,Ramirez, Dominique A.,Lunghofer, Paul J.,Gomez, Jose D.,Schaack, Jerome,Nemkov, Travis,D'Alessandro, Angelo,Hansen, Kirk C.,Gustafson, Daniel L.,Messersmith, Wells A.,Labarbera, Daniel V.
-
supporting information
p. 10182 - 10203
(2019/11/29)
-
- SULFONAMIDE DERIVATIVE AND PHARMACEUTICALLY ACCEPTABLE ACID ADDITION SALT THEREOF
-
The present invention aims to provide a novel low-molecular-weight compound exhibiting an orexin receptor agonist activity and expected to be useful as a prophylactic or therapeutic agent for narcolepsy and the like. The present invention provides a compo
- -
-
Paragraph 0765
(2018/07/15)
-
- ALKYL-AMIDE-SUBSTITUTED PYRIDYL COMPOUNDS USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFNα RESPONSES
-
Compounds having the following formula I: or a stereoisomer or a pharmaceutically-acceptable salt thereof, wherein R1, R2, R3, R4, and R5 are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNα by acting on Tyk-2 to cause signal transduction inhibition.
- -
-
Page/Page column 73
(2017/09/02)
-
- ALKYL-AMIDE-SUBSTITUTED PYRIDYL COMPOUNDS USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFNALPHA RESPONSES
-
Compounds having the following formula (I): or a stereoisomer or a pharmaceutically-acceptable salt thereof, wherein R1, R2, R3, R4, and R5 are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNα by acting on Tyk-2 to cause signal transduction inhibition.
- -
-
Paragraph 00161
(2015/05/26)
-
- AMIDE-SUBSTITUTED HETEROCYCLIC COMPOUNDS USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFN ALPHα RESPONSES
-
Compounds having the following formula I: or a stereoisomer or pharmaceutically-acceptable salt thereof, where R1, R2, R3, R4, and R5 are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNa, by acting on Tyk-2 to cause signal transduction inhibition.
- -
-
Paragraph 00211
(2014/05/24)
-
- ALKYL-AMIDE-SUBSTITUTED PYRIDYL COMPOUNDS USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFNα RESPONSES
-
Compounds having the following formula (I): or a stereoisomer or pharmaceutically-acceptable salt thereof, where R1, R2, R3, R4, and R5 are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNα, by acting on Tyk-2 to cause signal transduction inhibition.
- -
-
Paragraph 00243
(2014/05/24)
-
- Patterned recognition of amines and ammonium ions by a stimuli-responsive foldamer-based hexameric oligophenol host
-
A stimuli-responsive hexameric oligophenol host undergoes amine-induced co-operative folding from a more fluorescent, more linear structure into less fluorescent, more curved or helically folded states, enabling easy identification and classification of the bound amine guests. The Royal Society of Chemistry 2013.
- Sun, Chang,Ren, Changliang,Wei, Yuchen,Qin, Bo,Zeng, Huaqiang
-
supporting information
p. 5307 - 5309
(2013/06/27)
-
- Melanin-concentrating hormone receptor 1 antagonists. Synthesis and structure-activity relationships of novel 3-(aminomethyl)quinolines
-
It was found that 3-(aminomethyl)quinoline derivatives showed high binding affinities for melanin-concentrating hormone receptor 1 (MCHR1) with reduced affinity for serotonin receptor 2c (5-HT2c) when the dihydronaphthalene nucleus of compound 1 (human MCHR1, IC50 = 1.9 nM; human 5-HT2c receptor, IC50 = 0.53 nM) was replaced by other bicyclic core scaffolds. Among the synthesized compounds, 8-methylquinoline derivative 5v especially showed high binding affinity (IC50 = 0.54 nM), potent in vitro antagonistic activity (IC50 = 2.8 nM) for MCHR1, and negligible affinity for 5-HT2c receptor (IC50 > 1000 nM). Oral administration of 5v significantly and dose-dependently suppressed nocturnal food intake in diet-induced obese rats and did not affect food intake in MCHR1-deficient mice. These results and rat pharmacokinetic study findings suggested that compound 5v is a highly potent, orally bioavailable, and centrally acting nonpeptide MCHR1 antagonist.
- Kamata, Makoto,Yamashita, Toshiro,Imaeda, Toshihiro,Tanaka, Toshio,Masada, Shinichi,Kamaura, Masahiro,Kasai, Shizuo,Hara, Ryoma,Sasaki, Shigekazu,Takekawa, Shiro,Asami, Asano,Kaisho, Tomoko,Suzuki, Nobuhiro,Ashina, Shuntaro,Ogino, Hitomi,Nakano, Yoshihide,Nagisa, Yasutaka,Kato, Koki,Kato, Kaneyoshi,Ishihara, Yuji
-
experimental part
p. 2353 - 2366
(2012/05/05)
-
- Synthesis of symmetric diester-functionalised Troeger's base analogues
-
The yields of ester-functionalised Troeger's base analogues are dramatically improved by incorporating an electron-donating group on the aromatic ring and/or enhancing solubil- ity of the aniline unit. In addition to 2,8-diester compounds, 1,7-, 3,9- and 4,10-diester-functionalised Troeger's base analogues have been prepared for the first time.
- Bhuiyan, M. Delower H.,Zhu, Kai-Xian,Jensen, Paul,Try, Andrew C.
-
supporting information; experimental part
p. 4662 - 4670
(2010/10/19)
-
- Synthesis, structural investigations, hydrogen-deuterium exchange studies, and molecular modeling of conformationally stablilized aromatic oligoamides
-
Biasing the conformational preferences of aromatic oligoamides by internally placing intramolecular hydrogen bonds has led to a series of stably folded molecular strands. This article presents the results from extensive solid-state, solution, and computational studies on these folding oligomers. Depending on its backbone length, an oligoamide adopts a crescent or helical conformation. Surprisingly, despite the highly repetitive nature of the backbone, the internally placed, otherwise very similar intramolecular hydrogen bonds showed significantly different stabilities as demonstrated by hydrogen-deuterium exchange data. It was also observed that the hydrogen-bonding strength can be tuned by adjusting the substituents attached to the exterior of the aromatic backbones. Examining the amide hydrogen-deuterium exchange rates of trimers revealed that a six-membered hydrogen bond nearing the ester end is the weakest among all the four intramolecular hydrogen bonds of a molecule. This observation was verified by ab initio quantum mechanical calculations at the level of B3LYP/6-31G. Such a "weak point" creates the "battle of the bulge" where backbone twisting is centered, which is consistently observed in the solid-state structures of the four trimer molecules studied. In the solid state, the oligomers assemble into interesting one-dimensional structures. A pronounced columnar packing of short oligomers (i.e., dimers, trimers, and tetramer) and channel-like, potentially ion-conducting stacks of longer oligomers (i.e., tetramer, pentamer, and hexamer) were observed.
- Yan, Yan,Qin, Bo,Ren, Changliang,Yip, Yeow Kwan,Ye, Ruijuan,Zeng, Huaqiang,Chen, Xiuying,Su, Haibin,Zhang, Dawei
-
supporting information; experimental part
p. 5869 - 5879
(2010/07/13)
-
- Helical organization in foldable aromatic oligoamides by a continuous hydrogen-bonding network
-
Introduction of a continuous internal hydrogen-bonding network suppressed the conformational flexibility of a series of oligoaromatic foldamers with a lengthened backbone. The helical ordering over up to six aromatic repeating units was established in solution by a 2D NOESY study and in the solid state by an X-ray diffraction method. Computational molecular modeling further corroborates the experimentally observed helical propagation in this class of foldable molecular strands.
- Yan, Yan,Qin, Bo,Shu, Yingying,Chen, Xiuying,Yip, Yeow Kwan,Zhang, Dawei,Su, Haibin,Zeng, Huaqiang
-
supporting information; experimental part
p. 1201 - 1204
(2009/08/07)
-
- Crystallographic evidence of an unusual, pentagon-shaped folding pattern in a circular aromatic pentamer
-
(Figure Presented) Introduction of a continuous hydrogen-bonding network suppressed the conformational flexibility of an oligomeric backbone. Cyclization of a rigidified, suitably sized oligomer led to a circular aromatic pentamer. Its crystal structure d
- Qin, Bo,Chen, Xiuying,Fang, Xiao,Shu, Yingying,Yip, Yeow Kwan,Yan, Yan,Pan, Siyan,Ong, Wei Qiang,Ren, Changliang,Su, Haibin,Zeng, Huaqiang
-
supporting information; experimental part
p. 5127 - 5130
(2009/05/30)
-
- Synthesis of novel analogues of antimycin A3
-
Four novel analogues of antimycin A3, 1a-d, were synthesized in good overall yields.
- Hu, Zilun,Jiang, Xiangjun,Han, Wei
-
p. 5192 - 5195
(2008/12/20)
-
- NOVEL CONDENSED IMIDAZOLE DERIVATIVE
-
Disclosed is a compound represented by the formula (1) below which has a high DPP-IV inhibitory activity and is improved in safety, toxicity and the like. Also disclosed is a prodrug of such a compound and pharmaceutically acceptable salts of them. (In the formula, R1 represents a hydrogen atom, an optionally substituted alkyl group or the like; R2 and R3 independently represent a hydrogen atom, an optionally substituted alkyl group or the like; R4 and R5 independently represent a hydrogen atom, an optionally substituted alkyl group or the like: R6 represents a hydrogen atom, an optionally substituted aryl group or the like; and -Y-NH2, represents a group represented by the following formula (A): (wherein m is 0, 1 or 2; and R7 may not exist or one or two R7 may exist and independently represent an optionally substituted alkyl group or the like) or the like.]
- -
-
Page/Page column 175
(2010/11/23)
-
- QUINOLINE COMPOUND
-
A compound, which has a melanin-concentrating hormone antagonistic action and useful as an agent for preventing or treating obesity, and which is represented by the formula: wherein Aris a cyclic group optionally having substituent(s) ;Xis a bond or a spacer having a main chain of 1 to 6 atoms;R1 and R2are the same or different and each is a hydrogen atom or a hydrocarbon group optionally having substituent(s), or R1 and R2 may form, together with the adjacent nitrogen atom, a nitrogen-containing heterocycle optionally having substituent(s);Yis a divalent hydrocarbon group optionally having substituent(s) (except CO);R3is a hydrogen atom or a hydrocarbon group optionally having substituent(s); andring A and ring Bmay further have substituents, and when ring B further has a substituent, the substituent may be linked to R1 to form a ring, or a salt thereof, or a prodrug thereof, is provided.
- -
-
-
- Antibiotic compounds
-
The present invention relates to carbapenems and provides a compound of the formula (I): STR1 or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof wherein: R1 is 1-hydroxyethyl, 1-fluoroethyl or hydroxymethyl; R2 is hydrogen or C1-4 alkyl; R3 is hydrogen or C1-4 alkyl; R4 and R5 are the same or different and are selected from hydrogen, halo, cyano, C1-4 alkyl, nitro, hydroxy, carboxy, C1-4 alkoxy, C1-4 alkoxycarbonyl, aminosulphonyl, C1-4 alkylaminosulphonyl, di-C1-4 alkylaminosulphonyl, carbamoyl, C1-4 alkylcarbamoyl, di-C1-4 alkylcarbamoyl, trifluoromethyl, sulphonic acid, amino, C1-4 alkylamino, di-C1-4 alkylamino, C1-4 alkanoylamino, C1-4 alkanoyl(N-C1-4 alkyl)amino, C1-4 alkanesulphonamido and C1-4 alkylS(O)n -- wherein n is zero, one or two: with the proviso that there is no hydroxy or carboxy substituent in a position ortho to the --NR2 --. Processes for their preparation, intermediates in their preparation, their use as therapeutic agents and pharmaceutical compositions containing them.
- -
-
-
- (S)-N--5-iodo-2-methoxybenzamide Hydrochloride, a New Selective Radioligand for Dopamine D-2 Receptors
-
From salicylic acid, the two enantiomers of N--5-iodo-2-methoxybenzamide (6b) were prepared in a five-step synthesis.With use of Heindel's triazene method for introduction of the radionuclide, the iodine-125-labeled substit
- Paulis, Tomas de,Janowsky, Aaron,Kessler, Robert M.,Clanton, Jeffrey A.,Smith, Howard E.
-
p. 2027 - 2033
(2007/10/02)
-
