- Probing the Intracellular Dynamics of Nitric Oxide and Hydrogen Sulfide Using an Activatable NIR II Fluorescence Reporter
-
Understanding the complex interplay among gasotransmitters is of great significance but remains technically challenging. In this study, we present the design and synthesis of a dually responsive BOD-NH-SC reporter for probing the dynamic and alternating existence of NO and H2S in living cells. This designed reporter can repeatedly cycle S-nitrosation and transnitrosation reactions when successively treated with NO and H2S, thus affording the interchange of NIR fluorescence at 645 nm (NO) and NIR II fluorescence at 936 nm (H2S). In light of this unique fluorescence alternation between two colors, we synthesized water-soluble BOD-NH-SC dots to visualize the intracellular dynamics of NO and H2S. These molecular probes thus provide a toolbox to elucidate the interplaying roles of NO and H2S in the complex interaction networks of various signal transduction pathways.
- Zhu, Tianli,Ren, Ning,Liu, Xia,Dong, Yan,Wang, Rongchen,Gao, Jinzhu,Sun, Jie,Zhu, Ying,Wang, Lihua,Fan, Chunhai,Tian, He,Li, Jiang,Zhao, Chunchang
-
supporting information
p. 8450 - 8454
(2021/03/08)
-
- Diphenyl-aminopyrimidine compound for inhibiting kinase activity
-
The invention relates to a diphenyl-aminopyrimidine compound with an inhibiting function on protein tyrosine kinase, a pharmaceutical composition containing the diphenyl-aminopyrimidine compound, andpreparation and application of the diphenyl-aminopyrimidine compound, in particular to a compound shown as the formula (I) and pharmaceutically acceptable salt or crystal forms or prodrugs or metabolin or aquo-complex or solvate or isotope derivatives thereof, wherein R1, R2, R5, R6, R7, R8 and W are defined as the description. The compound can be used for treating ALK-mediated cancer related symptoms, such as non-small cell lung cancer or breast cancer or neural tumors or esophagus cancer or soft tissue cancer or lymphoma or leukemia. The formula is shown in the specification.
- -
-
-
- PISTON FOR AN INTERNAL COMBUSTION ENGINE AND METHOD FOR PRODUCING THE PISTON FOR AN INTERNAL COMBUSTION ENGINE
-
The present invention relates to compounds of general formula (I), wherein A represents an optionally substituted heterocycle group, B represents an aryl or heteroaryl group and wherein X, R1, R2, R3, R4 and R5 are as defined in the description. Compounds of formula (I) are useful to destroy, inhibit, or prevent the growth or spread of cells, especially malignant cells, into surrounding tissues implicated in a variety of human and animal diseases.
- -
-
-
- Affinity-Driven Covalent Modulator of the Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH) Cascade
-
Traditional medicines provide a fertile ground to explore potent lead compounds, yet their transformation into modern drugs is fraught with challenges in deciphering the target that is mechanistically valid for its biological activity. Herein we reveal that (Z)-(+)-isochaihulactone (1) exhibited significant inhibition against multiple-drug-resistant (MDR) cancer cell lines and mice xenografts. NMR spectroscopy showed that 1 resisted an off-target thiolate, thus indicating that 1 was a target covalent inhibitor (TCI). By identifying the pharmacophore of 1 (α,β-unsaturated moiety), a probe derived from 1 was designed and synthesized for TCI-oriented activity-based proteome profiling. By MS/MS and computer-guided molecular biology approaches, an affinity-driven Michael addition of the noncatalytic C247 residue of GAPDH was found to control the “ON/OFF” switch of apoptosis through non-canonically nuclear GAPDH translocation, which bypasses the common apoptosis-resistant route of MDR cancers.
- Chern, Jeffy,Lu, Chun-Ping,Fang, Zhanxiong,Chang, Ching-Ming,Hua, Kuo-Feng,Chen, Yi-Ting,Ng, Cheng Yang,Chen, Yi-Lin Sophia,Lam, Yulin,Wu, Shih-Hsiung
-
supporting information
p. 7040 - 7045
(2018/05/29)
-
- FUSED-RING OR TRICYCLIC ARYL PYRIMIDINE COMPOUND USED AS KINASE INHIBITOR
-
Disclosed is a fused-ring or tricyclic aryl pyrimidine compound used as a mutation selectivity EGFR inhibitor. Specifically, disclosed is a compound represented by formula (I) and used as an EGFR inhibitor or a pharmaceutically acceptable salt thereof.
- -
-
Paragraph 0176; 0177
(2018/03/25)
-
- A novel anti-Alzheimer agent inhibiting oligomerization and fibriliation of beta-amyloid protects neuronal cell from Aβ-induced cytotoxicity
-
The present invention relates to development of a novel treatment agent for Alzheimerandprime;s disease, having ability of protecting neural cells and inhibiting fibrosis and oligomerization of beta-amyloid. A compound of the present invention is capable of, while maintaining therapeutic effects on Alzheimerandprime;s disease, recovering ability of directly inhibiting oligomerized and fibrous amyloid beta, which is inherent activities of existing curcumin, thereby being useful as a novel inhibitor.COPYRIGHT KIPO 2017
- -
-
Paragraph 0042; 0043
(2017/04/25)
-
- Discovery of a Tetrahydrobenzisoxazole Series of γ-Secretase Modulators
-
The design and synthesis of a new series of tetrahydrobenzisoxazoles as modulators of γ-secretase activity and their structure-activity relationship (SAR) will be detailed. Several compounds are active γ-secretase modulators (GSMs) with good to excellent selectivity for the reduction of Aβ42 in the cellular assay. Compound 14a was tested in vivo in a nontransgenic rat model and was found to significantly reduce Aβ42 in the CNS compartment compared to vehicle-treated animals (up to 58% reduction of cerebrospinal fluid Aβ42 as measured 3 h after an acute oral dosing at 30 mg/kg).
- Zhao, Zhiqiang,Pissarnitski, Dmitri A.,Huang, Xianhai,Palani, Anandan,Zhu, Zhaoning,Greenlee, William J.,Hyde, Lynn A.,Song, Lixin,Terracina, Giuseppe,Zhang, Lili,Parker, Eric M.
-
supporting information
p. 1002 - 1006
(2017/10/18)
-
- COMPOUNDS WITH ANTI-TUMORAL ACTIVITY
-
The present invention relates to compounds of general formula (I), wherein A represents an optionally substituted heterocycle group, B represents an aryl or heteroaryl group and wherein X, R1, R2, R3, R4 and R5 are as defined in the description. Compounds of formula (I) are useful to destroy, inhibit, or prevent the growth or spread of cells, especially malignant cells, into surrounding tissues implicated in a variety of human and animal diseases.
- -
-
Page/Page column 62; 63
(2016/09/22)
-
- Dicyanovinyl-substituted J147 analogue inhibits oligomerization and fibrillation of β-amyloid peptides and protects neuronal cells from β-amyloid-induced cytotoxicity
-
A series of novel J147 derivatives were synthesized, and their inhibitory activities against β-amyloid (Aβ) aggregation and toxicity were evaluated by using the oligomer-specific antibody assay, the thioflavin-T fluorescence assay, and a cell viability assay in the transformed SH-SY5Y cell culture. Among the synthesized J147 derivatives, 3j with a 2,2-dicyanovinyl substituent showed the most potent inhibitory activity against Aβ42 oligomerization (IC50 = 17.3 μM) and Aβ42 fibrillization (IC50 = 10.5 μM), and disassembled the preformed Aβ42 fibrils with an EC50 of 10.2 μM. Finally, we confirmed that 3j is also effective at preventing neurotoxicity induced by Aβ42-oligomers as well as Aβ42-fibrils.
- Kim, Kyoungdo,Park, Kwang-Su,Kim, Mi Kyoung,Choo, Hyunah,Chong, Youhoon
-
supporting information
p. 9564 - 9569
(2015/09/28)
-
- PHARMACEUTICAL COMPOUNDS
-
This invention relates to compounds that inhibit or modulate the activity of Chk-1 kinase. Also provided are pharmaceutical compositions containing the compounds and the therapeutic uses of the compounds.
- -
-
Page/Page column 91; 128; 129
(2015/09/23)
-
- Glutamate receptor photomodulators
-
The present invention relates to the discovery of particular aromatic compounds of formula (1), possessing activity as modulators of metabotropic glutamate receptors (mGIuR) whose modulatory activity on the receptor may be controlled by irradiation with suitable light resulting in the optical control of receptor biological function, to the use of said compounds as a medicament, and to pharmaceutical compositions comprising said compounds of formula (1).
- -
-
Paragraph 0220
(2015/04/15)
-
- Chemoselective reduction and self-immolation based FRET probes for detecting hydrogen sulfide in solution and in cells
-
Hydrogen sulfide (H2S) has been regarded as the third gaseous transmitter. Based on the mechanism of chemoselective azido reduction and self-immolation, five fluorescence resonance energy transfer (FRET) probes for the detection of H2S were designed and synthesized. The effect of functional substitution of the self-immolative moiety on azido reduction and quinone-methide rearrangement were investigated. Their fluorescence responses and chemoselectivity for H2S detection were evaluated in solutions and in cells. This strategy may provide a general route for designing H 2S probes with many commercially available FRET pairs. the Partner Organisations 2014.
- Chen, Bifeng,Wang, Peng,Jin, Qingqing,Tang, Xinjing
-
p. 5629 - 5633
(2014/07/22)
-
- FSH RECEPTOR ANTAGONISTS
-
The invention relates to FSH receptor antagonist according to general formula (I) or a pharmaceutically acceptable salt thereof and to a pharmaceutical composition containing the same. The compounds can be used for the treatment and prevention of endometriosis, for the treatment and prevention of pre-menopausal and peri-menopausal hormone-dependent breast cancer, for contraception, and for the treatment of uterine fibroids and other menstrual-related disorders
- -
-
Page/Page column 63
(2013/04/10)
-
- PYRAZOLOPYRIDINE DERIVATIVES, PREPARATION PROCESS THEREFOR AND THERAPEUTIC USE THEREOF
-
The invention relates to FGF-inhibiting pyrazolopyrimidine derivatives of general formula (I) to a process for preparing them and to the therapeutic use thereof.
- -
-
Page/Page column 23
(2013/07/05)
-
- GAMMA SECRETASE MODULATORS
-
Disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein each of the substituents is given the definition as set forth in the specification and claims. Also disclosed are pharmaceutical compositions containing compounds of Formula (I) and use of the compounds in the treatment of neurodegenerative diseases or conditions such as Alzheimer's disease.
- -
-
Page/Page column 18
(2013/05/22)
-
- COMPOUNDS FOR INHIBITING CELL PROLIFERATION IN EGFR-DRIVEN CANCERS
-
The invention features compounds, pharmaceutical compositions and methods for treating patients who have an EGFR-driven cancer of Formula (I), wherein the variables are as defined herein.
- -
-
Page/Page column 84
(2013/12/03)
-
- COMPOUNDS FOR INHIBITING CELL PROLIFERATION IN EGFR-DRIVEN CANCERS
-
The invention features compounds, pharmaceutical compositions and methods for treating patients who have an EGFR-driven cancer of formula (I), wherein the variables are as defined herein.
- -
-
Page/Page column 71
(2012/11/14)
-
- (DIHYDRO) IMIDAZOISO (5, 1-A) QUINOLINES AS FSH RECEPTOR AGONISTS FOR THE TREATMENT OF FERTILITY DISORDERS
-
The invention relates to imidazoiso[5,1-a]quinoline and 5,6-dihydro-imidazoiso[5,1-a]quinoline derivatives according to general Formula (1) or a pharmaceutically acceptable salt thereof. The compounds can be used for the treatment of infertility.
- -
-
Page/Page column 30
(2010/12/26)
-
- (DIHYDRO)IMIDAZOISO[5,1-A]QUINOLINES
-
The invention relates to imidazoiso[5,1-a]quinoline and 5,6-dihydro-imidazoiso[5,1-a]quinoline derivatives according to general Formula I or a pharmaceutically acceptable salt thereof. The compounds can be used for the treatment of infertility.
- -
-
Page/Page column 11; 12
(2010/12/31)
-
- NOVEL CURCUMIN DERIVATIVE
-
The present invention provides a novel compound that is structurally similar to curcumin and has a suppressive effect on Aβ aggregation, a degradative effect on Aβ aggregates, an inhibitory effect on β-secretase, and a protective effect on neurons. The novel compound is a compound represented by the following general formula (Ia) or a salt thereof: wherein R1 represents a 4-hydroxy-3-methoxyphenyl group or the like, and R2 represents a 1H-indol-6-yl group or the like.
- -
-
Page/Page column 19
(2009/12/07)
-
- (DIHYDRO)PYRROLO[2,1-A]ISOQUINOLINES
-
The invention relates to 5,6 - dihydropyrrolo [2,1-a] isoquinoline and pyrrolo[2,1-a] isoquinoline derivatives according to general formula (I) or a pharmaceutically acceptable salt thereof. The compounds can be used for the treatment of infertility.
- -
-
Page/Page column 100
(2009/10/09)
-
- Effect of aldehyde and methoxy substituents on nucleophilic aromatic substitution by [18F]fluoride
-
For a series of benzaldehydes only with a leaving group or with both a leaving group and a single methoxy substituent 18F-fluorination via nucleophilic aromatic substitution (SNAr) was studied in DMF and Me2SO. In general, the radiochemical yields were clearly higher in DMF than in Me2SO. In the fluorodehalogenation reaction (leaving group: halogen = Br, Cl), extremely low radiochemical yields were observed in Me2SO (2SO (within 3 min reaction time, 90% of the precursor was consumed; radiochemical yield = 1.0 ± 0.5%); however, in DMF oxidation was always kept at a low level during the entire reaction (13C-NMR ppm values of the aromatic carbon atom bearing the leaving group.
- Shen, Bin,L?ffler, Dirk,Zeller, Klaus-Peter,übele, Michael,Reischl, Gerald,Machulla, Hans-Jürgen
-
p. 1461 - 1468
(2008/09/18)
-
- Synthesis and biological evaluation of aryl azide derivatives of combretastatin a-4 as molecular probes for tubulin
-
Two new aryl azides, (Z)-1-(3'-azido-4'-methoxyphenyl)-2-(3'',4'',5''-trimethoxyphenyl)ethene 9 and (Z)-1-(4'-azido-3'-methoxyphenyl)-2-(3'',4'',5''-trimethoxyphenyl)ethene 5, modeled after the potent antitumor, antimitotic agent combretastatin A-4 (CA-4)
- Pinney, Kevin G.,Mejia, Maria P.,Villalobos, Victor M.,Rosenquist, Brent E.,Pettit, George R.,Verdier-Pinard, Pascal,Hamel, Ernest
-
p. 2417 - 2425
(2007/10/03)
-
- 13C NMR Spectra of Substituted o-Nitroanisoles and n-Butyl o-Nitrophenyl Ethers
-
13C NMR analyses of substituted o-nitroanisoles and n-butyl o-nitrophenyl ethers are reported. Key Words: 13C NMR - o-Nitroanisoles - n-Butyl o-nitrophenyl ethers
- Zeegers, Petrus J.,Thompson, Malcolm J.
-
p. 497 - 499
(2007/10/02)
-