- A high-efficacy and regenerable antimicrobial resin containing quaternarized N-halamine groups
-
A novel macroporous cross-linked antimicrobial resin containing quaternarized N-halamine groups, poly(1-chloro-5,5-dimethylhydantoinyl-3-ethyl- p-ethenylphenylmethyl dimethylammonium chloride) (Cl-PSQH), has been synthesized by a facile three-step reaction. The as-prepared resins were characterized by FT-IR, X-ray photoelectron spectroscopy, and zeta-potential measurement. Antimicrobial tests showed that Cl-PSQH was capable of about a 7-log inactivation of Staphylococcus aureus and Escherichia coli O157:H7 within 1 min of contact. Also, its regenerability and preliminary storage stability were investigated.
- Jie, Zhiqiang,Yan, Xiufang,Zhao, Lianhong,Worley,Liang, Jie
-
-
Read Online
- Sequential Selective C?H and C(sp3)?+P Bond Functionalizations: An Entry to Bioactive Arylated Scaffolds
-
Organophosphonium salts containing C(sp3)?+P bonds are among the most utilized reagents in organic synthesis for constructing C?C double bonds. However, their use as C-selective electrophilic groups is rare. Here, we explore an efficient and general transition-metal-free method for sequential chemo- and regioselective C?H and C(sp3)?+P bond functionalizations. In the present study, C?H alkylation resulting in the synthesis of benzhydryl triarylphosphonium salts was achieved by one-pot, four-component cross-coupling reactions of simple and commercially available starting materials. The utility of the resulting phosphonium salt building blocks was demonstrated by the chemoselective post-functionalization of benzylic C(sp3)?+PPh3 groups to achieve aminations, thiolations, and arylations. In this way, benzhydrylamines, benzhydrylthioethers, and triarylmethanes, structural motifs that are present in many pharmaceuticals and agrochemicals, are readily accessed. These include the synthesis of two anticancer agents from simple materials in only two to three steps. Additionally, a protocol for late-stage functionalization of bioactive drugs has been developed using benzhydrylphosphonium salts. This new approach should provide novel transformations for application in both academic and pharmaceutical research.
- Babu, K. Naresh,Masarwa, Ahmad,Massarwe, Fedaa,Shioukhi, Israa
-
supporting information
p. 26199 - 26209
(2021/11/09)
-
- RET INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
-
Provided herein are a RET inhibitor, a pharmaceutical composition thereof and uses thereof. In particular, provided is a compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Provided is a pharmaceutical composition comprising the compound, and uses of the compound and pharmaceutical composition thereof for the preparation of a medicament, in particular for treatment and prevention of RET-related diseases and conditions, including cancer, irritable bowel syndrome, and/or pain associated with irritable bowel syndrome.
- -
-
Paragraph 00230; 00410; 00658
(2020/07/05)
-
- The cubane paradigm in bioactive molecule discovery: Further scope, limitations and the cyclooctatetraene complement
-
The cubane phenyl ring bioisostere paradigm was further explored in an extensive study covering a wide range of pharmaceutical and agrochemical templates, which included antibiotics (cefaclor, penicillin G) and antihistamine (diphenhydramine), a smooth muscle relaxant (alverine), an anaesthetic (ketamine), an agrochemical instecticide (triflumuron), an antiparasitic (benznidazole) and an anticancer agent (tamibarotene). This investigation highlights the scope and limitations of incorporating cubane into bioactive molecule discovery, both in terms of synthetic compatibility and physical property matching. Cubane maintained bioisosterism in the case of the Chagas disease antiparasitic benznidazole, although it was less active in the case of the anticancer agent (tamibarotenne). Application of the cyclooctatetraene (COT) (bio)motif complement was found to optimize benznidazole relative to the benzene parent, and augmented anticancer activity relative to the cubane analogue in the case of tamibarotene. Like all bioisosteres, scaffolds and biomotifs, however, there are limitations (e.g. synthetic implementation), and these have been specifically highlighted herein using failed examples. A summary of all templates prepared to date by our group that were biologically evaluated strongly supports the concept that cubane is a valuable tool in bioactive molecule discovery and COT is a viable complement.
- Houston, Sevan D.,Fahrenhorst-Jones, Tyler,Xing, Hui,Chalmers, Benjamin A.,Sykes, Melissa L.,Stok, Jeanette E.,Farfan Soto, Clementina,Burns, Jed M.,Bernhardt, Paul V.,De Voss, James J.,Boyle, Glen M.,Smith, Maree T.,Tsanaktsidis, John,Savage, G. Paul,Avery, Vicky M.,Williams, Craig M.
-
supporting information
p. 6790 - 6798
(2019/07/22)
-
- Synthetic process of 2-dimethylaminoethyl chloride hydrochloride
-
The invention discloses a synthetic process of 2-dimethylaminoethyl chloride hydrochloride. The synthetic process comprises the following steps: taking dimethylethanolamine as a raw material, controlling the temperature to 10 to 15 DEG C and carrying out direct chlorination reaction on the dimethylethanolamine and thionyl chloride; adding absolute ethyl alcohol for carrying out a reflux reaction for one hour; filtering and drying to obtain a finished product. The synthetic process of the 2-dimethylaminoethyl chloride hydrochloride, provided by the invention, has the advantages of simple steps, high yield, good quality, low cost, mild reaction and convenience in operation; the purity of a product is high, i.e., the percentage of inorganic salt is less than 0.5 percent; three wastes are reduced, as hydrogen chloride gas and sulfur dioxide gas in the reaction are absorbed; a mother solution which is subjected to suction filtration does not need to be treated and is treated as waste liquid, so that environment protection is facilitated.
- -
-
Paragraph 0015; 0020-0022
(2018/04/01)
-
- Coumadin female phenol split-ring analogue and its medical use
-
The invention relates to the field of pharmaceutical chemistry, in particular to a coumestrol open-ring analogue with structures as shown in general formulae I and II and a medical application thereof, especially an application to the preparation of drugs as angiogenesis inhibition and vascular disruption agents.
- -
-
Paragraph 0036-0038
(2017/10/06)
-
- 5-AMINO-4-CARBAMOYL-PYRAZOLE COMPOUNDS AS SELECTIVE AND IRREVERSIBLE T790M OVER WT-EGFR KINASE INHIBITORS AND USE THEREOF????
-
Disclosed are compounds of Formula (I), pharmaceutical compositions comprising the same, processes for the preparation thereof, and the use thereof.
- -
-
Paragraph 0380
(2016/03/13)
-
- A two-step strategy to radiolabel choline phospholipids with99mTc in S180 cell membranes via strain-promoted cyclooctyne–azide cycloaddition reaction
-
As tumor markers, the radiolabeling of choline (Cho)-containing phospholipids in cellular membranes with99mTc is a challenge. The conventional strategy to combine the metallic radionuclide with Cho by large ligand damages the bioactivity of Cho, resulting in low tumor-to-nontumor ratios. Pretargeting strategy based on strain-promoted cyclooctyne–azide cycloaddition (SPAAC) reaction was applied to solve this general problem. Functional click synthons were synthesized as pretargeting components: azidoethyl-choline (AECho) serves as tumor marker and azadibenzocyclooctyne (ADIBO) conjugated to bis(2-pieolyl) amine (BPA) ligand (ADIBO-BPA) as99mTc(CO)3-labeling and azido-binding group. Both in vitro cell experiment and in vivo biodistribution experiment indicate that it is versatile to radiolabel Cho in cellular membranes via this two-step pretargeting strategy. We believe that this pretargeting strategy can indeed enhance the target-specificity and also reduce background signals to optimize imaging quality.
- Chen, Qingxin,Chu, Taiwei
-
supporting information
p. 5472 - 5475
(2016/11/09)
-
- Side chain impacts on pH- and thermo-responsiveness of tertiary amine functionalized polypeptides
-
The systemic investigation of the structural impacts of side chains on the pH- and thermo-responsiveness of tertiary amine functionalized poly(l-glutamate)s (TA-PGs) was carried out. The TA-PGs polymers were effectively synthesized by Cu(I)-catalyzed azide-alkyne cycloaddition click reaction of azido tertiary amines with poly(γ-propargyl-l-glutamate) (PPLG). Turbimetric measurements were performed to characterize the pH- and temperature-induced phase transition of TA-PGs in aqueous solution, which suggested a structural dependence of the properties on the N-substituted groups and the "linkers" between 1,2,3-triazole ring and the tertiary amine groups in the side chains. In detail, the pH responsive properties of TA-PGs were basically determined by the hydrophobicity of the N-substituted groups in the side chains and the pH transition point (pHt) decreased as the increasing hydrophobicity of the N-substituted groups, while the temperature-responsiveness of TA-PGs were affected by either the N-substituted groups or the "linkers." TA-PGs with a moderate N-substituted amine group (e.g., DEA, PR, and PD) or a branched "linker" (e.g., iso-propylene and 2-methylpropylene group) were more likely to express the LCST-type phase transition tuned by pH variation. These structure-property relationships revealed in this study would help to develop the applications of TA-PGs in smart drug delivery systems. Copyright
- Xiao, Chunsheng,Cheng, Yilong,Zhang, Yu,Ding, Jianxun,He, Chaoliang,Zhuang, Xiuli,Chen, Xuesi
-
p. 671 - 679
(2014/02/14)
-
- INDENOISOQUINOLINONE DERIVATIVES, MANUFACTURING METHOD AND MEDICAL USE THEREOF
-
Indenoisoquinolinone derivatives (I), the manufacturing method and the medical use thereof, which belong to pharmaceutical chemistry and organic chemistry field, are disclosed. These compounds can be used for treating several medical symptoms related to postmenopausal syndrome, uterine fibers deterioration and aortic smooth muscle cells proliferation, especially ER-(+) depend breast cancer. Meanwhile, these compounds can also be used for treating glioma and lung cancer, and have inhibiting effect on tumor metastasis effect on tumor metastasis.
- -
-
Paragraph 0056; 0057
(2013/04/13)
-
- PHENYLALANINE DIPEPTIDE DERIVATIVES, COMPOSITIONS AND USE THEREOF
-
Disclosed are a compound of formula I, stereoisomers, pharmaceutically acceptable salts or hydrates thereof, a pharmaceutical composition comprising the smae, a process for preparing the same and use thereof. The compound may also be used to prepare a medicament to treat viral infections, especially to prepare a medicament to treat hepatitis B virus and human immunodeficiency virus with little toxic side effects.
- -
-
Page/Page column 13
(2009/10/06)
-
- THE ISOFLAVONE DERIVATIVES OF TECTORIDIN, THE PREPARATION THEREOF AND THE ANTI-VIRUS MEDICINES CONTAINING THE SAME AS THE EFFECTIVE CONSTITUENTS
-
The present invention is related to an isoflavone derivative of tectorigenin compound as shown in formula (II), its preparation method and the antiviral medicine containing it as an effective constituent. The compound structure is shown as follows: Where:: R1 is H, NH2 or SO3M; R2 is OR' ; R3 is H or -CH2NR" ; where R' is H, -CH2COONa or -CH2CH2NMe2; NR" is or -NMe2; M is H, Na, K or N+H (CH2CH2OH)3.
- -
-
Page/Page column 7; 8; 12
(2008/06/13)
-
- Heterocyclic substituted 2-methyl-benzimidazole antiviral agents
-
The present invention concerns antiviral compounds, their methods of preparation and their compositions, and use in the treatment of viral infections. More particularly, the invention provides heterocyclic substituted 2-methylbenzimidazole derivatives for the treatment of respiratory syncytial virus infection.
- -
-
-
- Bolaform and Classical Cationic Metallomicelles as Catalysts of the Cleavage of p-Nitrophenyl Picolinate
-
Bolaform micelles made of ligand surfactants 6-(((12-(trimethylammonio)-n-dodecanoyl)amino)methyl)-2-(hydroxymethyl)pyridine bromide (1) or 6-(((10-(trimethylammonio)-n-decyl)thio)methyl)-2-(hydroxymethyl)pyridine bromide (3) in the presence of Cu(II) or Zn(II) ions are good catalysts of the hydrolysis of p-nitrophenyl picolinate (PNPP).In the presence of 4.6x1E-4 M Cu(II) at pH=6.25 and 25 deg C, 2x1E-3 M 1 and 3 cleave PNPP with kinetic advantages of 7.6x1E5 and 1.6x1E6, respectively, over the uncatalyzed hydrolysis of the substrate.Classical micelles made of surfactant 6-(((2-(n-hexadecyldimethylammonio)ethyl)thio)methyl)-2-(hydroxymethyl)pyridine bromide (5) are less efficient ligands for Cu(II) or Zn(II) ions and poorer catalysts of the cleavage of PNPP than 1 or 3 due to the proximity and hence to the electrostatic repulsion between the ammonium group and the metal ion coordination site.The critical feature of the catalytic process is, quite likely, the formation of a ternary complex (8) involving ligand, metal ion, and substrate.The (deprotonated) hydroxyl bound to the pyridine moiety of the catalyst in the ternary complex acts as a nucleophile leading to a transacylation intermediate that undergoes a rapid, metal ion assisted hydrolysis "turning over" the catalyst.In all cases the micellar systems are better catalysts than the corresponding neutral nonmicellar models.This indicates that concentration effects coupled with a more facile acid dissociation of the hydroxyl and, possibly, with an enhanced electrophilicity of the metal ion in the aggregates largely offset the adverse electrostatic interactions between the metal ions and the positively charged micellar surface.
- Fornasier, Roberto,Scrimin, Paolo,Tecilla, Paolo,Tonellato, Umberto
-
p. 224 - 229
(2007/10/02)
-
