- Functionalized Chiral Bambusurils: Synthesis and Host-Guest Interactions with Chiral Carboxylates
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Bambusurils are a class of macrocyclic anion receptors that exhibit notable anion recognition properties, able to bind various inorganic anions as well the carboxylates or sulfonates. Recently, we reported enantioselective recognition of chiral carboxylates using non-functionalized chiral bambusuril derivatives. Herein, we report the synthesis and host-guest properties of two new representatives of chiral bambusuril macrocycles bearing ester functional groups, differing by the substituents attached to their portals. Their supramolecular properties in terms of carboxylate binding were studied by means of NMR in DMSO-d6. The reported bambusurils bind selected chiral carboxylates with enantioselectivity factors up to 3.1. The results indicated that the selectivity towards different carboxylates is governed by the steric constraint of the substituents surrounding bambusuril portals. No clear trend in the binding affinities and their enantioselectivities was found.
- ?indelá?, Vladimír,?tefek, Adam,Sokolov, Jan
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p. 1307 - 1314
(2020/07/04)
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- Design, synthesis and biological evaluation of novel 1-phenyl phenanthridin-6(5H)-one derivatives as anti-tumor agents targeting TOPK
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T–lymphokine-activated killer cell–originated protein kinase (TOPK) is a serine-threonine mitogen-activated protein kinase that is highly expressed in many types of human cancer. Due to its important role in cancer progression, TOPK is becoming an attractive target in chemotherapeutic drug design. In this study, a series of 1-phenyl phenanthridin-6(5H)-one derivatives have been identified as a novel chemical class of TOPK inhibitors. Some of them displayed very potent anti-cancer activity with IC50s less than 100 nM, superior than reference compound OTS964. The most potent compound, 9g suppressed the growth of cancer cells by apoptosis and specifically inhibited the activities of TOPK. Oral administration of 9g effectively suppressed tumor growth with TGI >79.7% in colorectal cancer xenograft models, demonstrating superior efficacy compared to OTS964. Pharmacokinetic studies reveal its good oral bioavailability. Our findings therefore show that 9g is a specific inhibitor of TOPK both in vitro and in vivo that may be further developed as a potential therapeutic agent against colorectal cancer.
- Hu, Quan-Fang,Gao, Tian-Tao,Shi, Yao-Jie,Lei, Qian,Liu, Zhi-Hao,Feng, Qiang,Chen, Zhen-Jia,Yu, Luo-Ting
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p. 407 - 422
(2018/11/24)
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- 6 - Phenanthridone derivative and its preparation and use (by machine translation)
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The invention belongs to the chemical field, and in particular relates to 6 - phenanthridone derivative and its preparation and use. The invention provides a 6 - phenanthridone derivatives, its structural formula as formula I shown. In addition, the inven
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Paragraph 0094; 0096-0098
(2019/06/05)
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- Highly Enantiospecific Borylation for Chiral α-Amino Tertiary Boronic Esters
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Herein we report a highly efficient and enantiospecific borylation method to synthesize a wide range of enantiopure (>99 % ee) α-amino tertiary boronic esters. The configurationally stable α-N-Boc substituted tertiary organolithium species and pinacolborane (HBpin) underwent enantiospecific borylation at ?78 °C with the formation of a new stereogenic C?B bond. This reaction has a broad scope, enabling the synthesis of various α-amino tertiary boronic esters in excellent yields and, importantly, with universally excellent enantiospecificity (>99 % es) and complete retention of configuration.
- Qi, Qingqing,Yang, Xuena,Fu, Xiaoping,Xu, Shiqing,Negishi, Ei-ichi
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supporting information
p. 15138 - 15142
(2018/10/26)
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- ISOQUINOLINE COMPOUNDS, A PROCESS FOR THEIR PREPARATION, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM
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A compound of formula (I): wherein the substituents are as defined in the description. Medicinal products containing the same which are useful in treating or preventing pathologies which are the result of activation of the RhoA/ROCK pathway and phosphorylation of the myosin light chain.
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Paragraph 0243; 0256; 0257; 0258; 0259; 0366; 0367-0369
(2017/06/12)
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- Discovery and optimization of a novel series of potent mutant B-Raf V600E selective kinase inhibitors
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B-Raf represents an attractive target for anticancer therapy and the development of small molecule B-Raf inhibitors has delivered new therapies for metastatic melanoma patients. We have discovered a novel class of small molecules that inhibit mutant B-Raf
- Vasbinder, Melissa M.,Aquila, Brian,Augustin, Martin,Chen, Huawei,Cheung, Tony,Cook, Donald,Drew, Lisa,Fauber, Benjamin P.,Glossop, Steve,Grondine, Michael,Hennessy, Edward,Johannes, Jeffrey,Lee, Stephen,Lyne, Paul,M?rtl, Mario,Omer, Charles,Palakurthi, Sangeetha,Pontz, Timothy,Read, Jon,Sha, Li,Shen, Minhui,Steinbacher, Stefan,Wang, Haixia,Wu, Allan,Ye, Minwei
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p. 1996 - 2015
(2013/05/09)
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- CYCLOBUTYL CARBOXYLIC ACID DERIVATIVES
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The invention relates to compounds of formula (I) and to pharmaceutically acceptable salts, prodrugs, solvates or hydrates thereof. This invention also relates to a method of using such compounds in the treatment of hyperproliferative diseases and autoimm
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Page/Page column 48
(2009/06/27)
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- Pyrrolopyrimidines and Pyrrolopyridines
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Compounds of formula I in free or salt or solvate form, wherein X, T1, T3 and T4 have the meanings as indicated in the specification, are useful for treating diseases mediated by the ALK-5 and/or ALK-4 receptor. Pharmaceutical compositions that contain the compounds and processes for preparing the compounds are also described.
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Page/Page column 54-55
(2009/07/25)
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- CHEMICAL COMPOUNDS-576
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The invention relates to chemical compounds of the formula (I): or pharmaceutically or pharmaceutically acceptable salts thereof, which possess B-Raf inhibitory activity and are accordingly useful for their anti-cancer activity and thus in methods of trea
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Page/Page column 57
(2008/12/06)
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- Compounds with medicinal effects due to interaction with the glucocorticoid receptor
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The invention provides for compounds having the structure according to the formula I
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Page/Page column 6-7
(2010/11/27)
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- INHIBITORS OF HEPATITIS C VIRUS RNA-DEPENDENT RNA POLYMERASE, AND COMPOSITIONS AND TREATMENTS USING THE SAME
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The present invention provides compounds of formula (4), and their pharmaceutically acceptable salts and solvates, which are useful as inhibitors of the Hepatitis C virus (HCV) polymerase enzyme and are also useful for the treatment of HCV infections in HCV-infected mammals. The present invention also provides pharmaceutical compositions comprising compounds of formula (4), their pharmaceutically acceptable salts and solvates. Furthermore, the present invention provides intermediate compounds and methods useful in the preparation of compounds of formula (4).
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Page/Page column 176
(2008/06/13)
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- ALPHA-HYDROXY AMIDES AS BRADYKININ ANTAGONISTS OR INVERSE AGONISTS
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α-Hydroxy amide derivatives of the general formula (I) are bradykinin B1 antagonists or inverse agonists useful in the treatment or prevention of symptoms such as pain and inflammation associated with the bradykinin B1 pathway. R2a is selected from (1) a group selected from Ra. (2) (CH2)nNRbC(O)Ra. (3)(CH2)nNRbSO2Rd.(4)(CH2)nNRbCO2Ra.(5)(CH2)k-heterocycle optionally substituted with 1 to 3 groups independently selected from halogen.nitro, cyano.ORa.SRa.C1-4 alkyl and C1-3 haloakyl wherein said heterocycle is (a) a 5-membered heteroaromatic ring having a ring heteroatom selected from N.O and S. and optionally having up to 3 additional ring nitrogen atoms wherein said ring is optionally benzo-fused; or(b) a 6-membered heteromatic ring containing from 1 to 3 ring nitrogen atoms and N-oxydes thereof. Wherein said ring is optionally benzo-fused. (6)(CH2)kCO2Ra.and (7)(CH2)C(O)NRbRc. R2b is OH or a group selected from R2a; or R2a and R2b together with the carbon atom to which they are attached form a 3-to 7-membered carbocyclic ring optionally substituted with 1 to 4 groups independently selected from halogen. ORa. C1-4 alkyl and C1-4 haloalkyl;
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Page/Page column 27
(2008/06/13)
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- Preparation of novel 3H-trifluoromethyldiazirine-based photoactivatable potassium channel antagonists
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The preparation of a series of photoactivatable precursors for use in photoaffinity labelling of potassium channels is described. 3H-Diazirine functionalities were incorporated into the previously described potassium channel antagonists 1-3. The ability to perform enantioselective reductions and Wittig reactions in the presence of 3H-diazirines was central to this work.
- Sanderson, John M.,Findlay, John B. C.,Fishwick, Colin W. G.
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p. 11244 - 11252
(2007/10/03)
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