- Total synthesis of two isoflavone C-glycosides (6-tert-butyl puerarin and 6-tert-butyl-4′-methoxypuerarin) through the deoxybenzoin pathway
-
The total synthesis of two isoflavone C-glycosides (6-tert-butylpuerarin and 6-tert-butyl-4′-methoxypuerarin) was achieved through the deoxybenzoin pathway with overall yields of 14.6% and 14.2%. The key intermediate 12 was obtained by de-tert-butylation
- Zou, Yunpeng,Zhang, Shouguo,Wen, Xiaoxue,wang, Gang,sun, Yunbo,Liu, Shuchen,Peng, Tao,Gao, Yue,Wang, Lin
-
-
Read Online
- An efficient total synthesis of a natural Penipanoid A
-
Natural products with heterocyclic core units are ample and widespread in nature, with many compounds exhibiting promising therapeutic properties. Penipanoid A (1) is a triazole based natural product isolated from the marine sediment derived fungus Penici
- Basavaiah, K.,Rao, G. Nageswara,Reddy, A. Satyanarayana,Reddy, V. Krishna
-
-
- R - alpha - amino -4 - methoxybenzene b amide synthesis method
-
The invention relates to a preparing method of a compound, in particular to a compounding method of R-alpha-amino-4-anisyl phenyl acetamide, which comprises the following steps: acidylation, methylation and aminolysis. In the step of acidylation, raw mate
- -
-
Page/Page column 5-8
(2019/03/28)
-
- Enantioselective 1,2-Anionotropic Rearrangement of Acylsilane through a Bisguanidinium Silicate Ion Pair
-
Highly enantioselective bisguanidinium-catalyzed tandem rearrangements of acylsilanes are reported. The acylsilanes were activated via an addition of fluoride on the silicon to form a penta-coordinate anionic silicate intermediate. The silicate then underwent alkyl or aryl group migration from the silicon atom to the neighboring carbonyl carbon atom (1,2-anionotropic rearrangement), followed by [1,2]-Brook rearrangement to provide the secondary alcohols in high yields with excellent enantioselectivities (up to 95% ee). The isolation of an α-silylcarbinol intermediate as well as DFT calculations revealed that the 1,2-anionotropic rearrangement occurred via a bisguanidinium silicate ion pair, which is the stereodetermining step. The chiral center formed is then retained without inversion through the subsequent [1,2]-Brook rearrangement. Crotyl acylsilanes were smoothly transformed into homoallylic linear crotyl alcohols with retention of E/Z geometry, and no branched alcohols were detected. This clearly suggested that the 1,2-anionotropic rearrangement occurred through a three-membered instead of a five-membered transition state.
- Cao, Weidi,Tan, Davin,Lee, Richmond,Tan, Choon-Hong
-
supporting information
p. 1952 - 1955
(2018/02/17)
-
- Diastereoselective Electrophilic Trifluoromethylthiolation of Chiral Oxazolidinones: Access to Enantiopure α-SCF3 Alcohols
-
Lithium imide enolates featuring Evans’ chiral oxazolidinone auxiliary were involved in diastereoselective α-trifluoromethylthiolation with electrophilic SCF3 donors. Diastereopure products were isolated and converted to enantiopure α-SCF3 alcohols without racemisation. (Figure presented.).
- Chachignon, Hélène,Kondrashov, Evgeniy V.,Cahard, Dominique
-
supporting information
p. 965 - 971
(2018/01/27)
-
- A chiral pool approach for asymmetric syntheses of both antipodes of equol and sativan
-
For the first time, both antipodes of the isoflavans, equol and sativan were synthesized in >98% ee with good overall yields starting from readily available starting materials. The chiral isoflavan, (?)-equol is produced from soy isoflavones, formonentin and daidzein by the action of intestinal bacteria in certain groups of population and other chiral isoflavans are reported from various phytochemical sources. To produce these chiral isoflavans in gram quantities, Evans’ enantioselective aldol condensation was used as a chiral-inducing step to introduce the required chirality at the C-3 position. Addition of chiral boron-enolate to substituted benzaldehyde resulted in functionalized syn-aldol products with >90% yield and excellent diastereoselectivity. Functional group transformations followed by intramolecular Mitsunobu reaction and deprotection steps resulted the target compounds, S-(?)-equol and S-(+)-sativan, with high degree of enantiopurity. By simply switching the chiral auxiliary to (S)-4-benzyloxazolidin-2-one and following the same synthetic sequence the antipodes, R-(+)-equol and R-(?)-sativan were achieved. Both enantiomers are of interest from a clinical and pharmacological perspective and are currently being developed as nutraceutical and pharmacological agents. This flexible synthetic process lends itself quite readily to the enantioselective syntheses of other biologically active C-3 chiral isoflavans.
- Yalamanchili, Chinni,Chittiboyina, Amar G.,Chandra Kumar Rotte, Sateesh,Katzenellenbogen, John A.,Helferich, William G.,Khan, Ikhlas A.
-
p. 2020 - 2029
(2018/03/21)
-
- Directed Remote Lateral Metalation: Highly Substituted 2-Naphthols and BINOLs by In Situ Generation of a Directing Group
-
A general synthesis of highly substituted 2-naphthols based on a new carbanionic reaction sequence is demonstrated. The reaction exploits the dual nature of lithium bases consisting of consecutive ring opening of readily available coumarins with either LiNEt2 or LiNiPr2 into Z-cinnamamides, thus generating a directing group in situ and allowing, by conformational freedom, a lateral directed remote metalation for ring closure to give the aryl 2-naphthols in good to excellent yields. These transformations can be combined to provide a more efficient one-pot process. Mechanistic insight into the remote lateral metalation step, demonstrating the requirement of Z-cinnamamide, is described. Application of this methodology to the synthesis of highly substituted 3,3′-diaryl BINOL ligands is also reported.
- Patel, Jignesh J.,Laars, Marju,Gan, Wei,Board, Johnathan,Kitching, Matthew O.,Snieckus, Victor
-
supporting information
p. 9425 - 9429
(2018/07/29)
-
- Synthesis and peripheral substituent effects of bay-annulated indigo derivatives
-
In this study, indolo-naphthyridine-6,13-diones (5a–d) with four different peripheral substituents were prepared via bay-annulation reactions of indigo. The resulting compounds (5a–d) exhibited fluorescence in the red to near-IR region, while the parent indigo molecule showed no fluorescence. Although the peripheral substituents were oriented to the exterior of the π-conjugated system, the electronic structure affected the absorption and fluorescence spectra. Moreover, calculated molecular orbitals and absorption spectra successfully reproduced the experimental absorption spectra and cyclic voltammograms.
- Furuyama, Taniyuki,Tamura, Daichi,Maeda, Hajime,Segi, Masahito
-
p. 2913 - 2916
(2018/06/25)
-
- Heterocyclic pyrrolizinone and indolizinones derived from natural lactam as potential antifungal agents
-
With the aim to develop highly potential active heterocyclic compounds, two series of multi-substituted pyrrolizinone and indolizinones derived from lactam were designed, synthesized and evaluated for their potential antifungal activities against six species of the plant pathogen fungi (Fusarium graminearum, Sclerotinia sclerotiorum, Phomopsis adianticola, Gloeosporium theae-sinensis, Alternaria tenuis Nees, Magnaporthe oryzae). The structure of all the newly molecules were confirmed by analytical spectroscopic data, including 1H NMR, 13C NMR and ESI-MS. According to the preliminary studies on bio-evaluation assay, some of the obtained compounds exhibited moderate and broad-spectrum activities against six fungi compared to the intermediates 6a, 6f and the hymexazol. Particularly, the inhibition rate of compounds 7l, 7m and 7t reached 69.25%, 74.76%, 65.38% against Phomopsis adianticola and Magnaporthe oryzae in vitro activity. Furthermore, compounds 7l and 7t displayed obviously inhibition activities against Phomopsis adianticola compared to the hymexazol. Consequently, compounds 7l and 7t with six-membered alkane ring could be used as new motifs for further investigation.
- Wang, Shuangshuang,Bao, Longzhu,Wang, Wenda,Song, Di,Wang, Jingjing,Cao, Xiufang
-
p. 257 - 266
(2018/08/04)
-
- Straightforward α-Amino Nitrile Synthesis Through Mo(CO)6-Catalyzed Reductive Functionalization of Carboxamides
-
The selective reduction of amides into an intermediate hemiaminal catalyzed by Mo(CO)6 together with the inexpensive and easy to handle TMDS (1,1,3,3-tetramethyldisiloxane) as reducing agent, followed by subsequent trapping of the hemiaminal with a cyanide source, allows for the straightforward synthesis of α-amino nitriles. The methodology presented here, displays high levels of chemoselectivity allowing for the reduction of amides in the presence of functional groups such as ketones, imines, aldehydes, and acids, which affords a simple route for the synthesis of α-amino nitriles with a broad scope of functionalities in high yields. Furthermore, the applicability of this methodology is demonstrated by scale up experiments and by derivatization of the target compounds into synthetically interesting products. The selective cyanation is successfully applied in late stage functionalizations of amide containing drugs and prolinol derivatives.
- Trillo, Paz,Slagbrand, Tove,Adolfsson, Hans
-
supporting information
p. 12347 - 12351
(2018/09/10)
-
- Microwave-Assisted Synthesis, In Vivo Anti-Inflammatory and In Vitro Anti-Oxidant Activities, and Molecular Docking Study of New Substituted Schiff Base Derivatives
-
In view of considerable interest in the design and synthesis of new heterocyclic compounds with promising biological activities for medical and biological applications, a series of eight imine derivatives have been synthesized through microwave-assisted S
- Hanif, Muhammad,Hassan, Mubashir,Rafiq, Muhammad,Abbas, Qamar,Ishaq, Ansa,Shahzadi, Saba,Seo, Sung-Yum,Saleem, Muhammad
-
p. 424 - 437
(2018/09/14)
-
- Facile synthesis, biological evaluation and molecular docking studies of novel substituted azole derivatives
-
In this study, we synthesized the series of novel azole derivatives and evaluated for enzyme inhibition assays, corresponding kinetic analysis and molecular modeling. Among the investigated bioassays, the oxadiazole derivatives 4a-k were found potent α-glucosidase inhibitors while the Schiff base derivatives 7a-k exhibited considerable potential toward urease inhibition. The inhibition kinetics for the most active compounds were analyzed by the Lineweaver–Burk plots to investigate the possible binding modes of the synthesized compounds toward the tested proteins. Moreover, the detailed docking studies were performed on the synthesized library of 4a-k and 7a-k to study the molecular interaction and binding mode in the active site of the modeled yeast α-glucosidase and Jack Bean Urease, respectively. It could be inferred from docking results that theoretical studies are in close agreement to that of the experimental results. The structure of one of the compound 7k was characterized by the single crystal X-ray diffraction analysis in order to find out the predominant conformation of the molecules.
- Rafiq, Muhammad,Saleem, Muhammad,Jabeen, Farukh,Hanif, Muhammad,Seo, Sung-Yum,Kang, Sung Kwon,Lee, Ki Hwan
-
p. 177 - 191
(2017/03/15)
-
- Carboxamides as N-Alkylating Reagents of Secondary Amines in Indium-Catalyzed Reductive Amination with a Hydrosilane
-
A method for the catalytic reductive N-alkylation of amines by using secondary amides as the alkyl source was developed. A versatile type of carboxamide functioned as an N-alkylation reagent in the presence of an indium(III) catalyst and a hydrosilane to provide alkylated tertiary amines efficiently. This amide-based catalytic N-alkylation strategy is considered to be a highly useful protocol to access unsymmetrical tertiary amines.
- Ogiwara, Yohei,Shimoda, Wataru,Ide, Keisuke,Nakajima, Takumi,Sakai, Norio
-
supporting information
p. 2866 - 2870
(2017/06/06)
-
- N-(4-alkyl-5-benzylthiazol-2-yl)phenylalkylamide and application of same as anticancer drug
-
The invention relates to N-(4-alkyl-5-benzylthiazol-2-yl)phenylalkylamide with a chemical structural formula I as shown in the specification or a salt thereof. In the formula I, R is selected from a group consisting of C1-C2 alkyl groups and C3-C4 straight-chain or branched-chain alkyl groups; X, X, Y and Y are selected from a group consisting of hydrogen, a methyl group, an ethyl group, a hydroxyl group, a methoxy group, an ethoxy group, fluorine, chlorine, bromine and iodine; X, X, X, Y and Y are selected from a group consisting of hydrogen, a methyl group and an ethyl group; n is one selected from a group consisting of 1, 2 and 3; and the salt is one selected from a group consisting of hydrochloride, hydrobromide, sulfate, phosphate, mesylate, benzene sulfonate and tosilate. The invention also provides application of N-(4-alkyl-5-benzylthiazol-2-yl)phenylalkylamide and the salt thereof to preparation of drugs used for resisting human mammary gland cells MCF-7.
- -
-
Paragraph 0022; 0025; 0026
(2017/07/12)
-
- NEW TRIAZOLOTHIADIAZOLE COMPOUND, USES THEREOF, AND ORGANIC ELECTROLUMINESCENT DEVICES HAVING THE SAME
-
The present invention refers to are the novel it will doze with the mote Oh D Oh it will doze compound to formula 1 (wherein, R is substituted or unsubstituted aryl group or polycyclic of 10 - 25 carbon atoms with three Neel metal among others) to are dis
- -
-
Paragraph 0106; 0107
(2017/08/02)
-
- Vanadium-Catalyzed Oxidative C(CO)-C(CO) Bond Cleavage for C-N Bond Formation: One-Pot Domino Transformation of 1,2-Diketones and Amidines into Imides and Amides
-
A novel vanadium-catalyzed one-pot domino reaction of 1,2-diketones with amidines has been identified that enables their transformation into imides and amides. The reaction proceeds by dual acylation of amidines via oxidative C(CO)-C(CO) bond cleavage of 1,2-diketones to afford N,N′-diaroyl-N-arylbenzamidine intermediates. In the reaction, these intermediates are easily hydrolyzed into imides and amides through vanadium catalysis. This method provides a practical, simple, and mild synthetic approach to access a variety of imides as well as amides in high yields. Moreover, one-step construction of imide and amide bonds with a long-chain alkyl group is an attractive feature of this protocol.
- Digwal, Chander Singh,Yadav, Upasana,Ramya, P. V. Sri,Sana, Sravani,Swain, Baijayantimala,Kamal, Ahmed
-
p. 7332 - 7345
(2017/07/26)
-
- Synthesis of gibberellic acid derivatives and their effects on plant growth
-
A series of novel C-3-OH substituted gibberellin derivatives bearing an amide group were designed and synthesized from the natural product gibberellic acid (GA3). Their activities on the plant growth regulation of rice and Arabidopsis were evaluated in vivo. Among these compounds, 10d and 10f exhibited appreciable inhibitory activities on rice (48.6% at 100 μmol/L) and Arabidopsis (41.4% at 100mol/L), respectively. These results provide new insights into the design and synthesis of potential plant growth regulators.
- Tian, Hao,Xu, Yiren,Liu, Shaojin,Jin, Dingsha,Zhang, Jianjun,Duan, Liusheng,Tan, Weiming
-
-
- Ruthenium-catalysed one-pot regio- and diastereoselective synthesis of pyrrolo[1,2-a] indoles via cascade C-H functionalization/annulation
-
A cascade approach has been developed towards dual C-C bond formation via consecutive C-H functionalization/cyclization giving access to pyrrolo[1,2-a]indoles in a highly regio- and diastereoselective manner using catalytic [Ru(p-cymene)Cl2]2. The methodology was further expanded to attain pentacyclic structures involving manifold C-C bond creation.
- Singh, Sukhdev,Butani, Himanshu H.,Vachhani, Dipak D.,Shah, Anamik,Van Der Eycken, Erik V.
-
supporting information
p. 10812 - 10815
(2017/10/10)
-
- Stereoselective synthesis of Z-vinylsilanes via palladium-catalyzed direct intermolecular silylation of C(sp2)-H bonds
-
An efficient and convenient palladium-catalyzed direct intermolecular silylation of C(sp2)-H bonds by using disilanes as the silicon source with the assistance of a readily removable bidentate directing group is reported. This strategy provided a regio- and stereoselective protocol for exclusive synthesis of Z-vinylsilanes with reasonable to excellent yields and good functional group compatibility. Silylation of the isolated palladacycle intermediate revealed the Z-stereoselective pathway. Moreover, the practicality and effectiveness of this method were illustrated by a gram-scale experiment and further functionalization of the silylation product.
- Pan, Jin-Long,Chen, Chao,Ma, Zhi-Gang,Zhou, Jia,Wang, Li-Ren,Zhang, Shu-Yu
-
supporting information
p. 5216 - 5219
(2017/11/06)
-
- Discovery of a Potent, Selective T-type Calcium Channel Blocker as a Drug Candidate for the Treatment of Generalized Epilepsies
-
We report here the discovery and pharmacological characterization of N-(1-benzyl-1H-pyrazol-3-yl)-2-phenylacetamide derivatives as potent, selective, brain-penetrating T-type calcium channel blockers. Optimization focused mainly on solubility, brain penetration, and the search for an aminopyrazole metabolite that would be negative in an Ames test. This resulted in the preparation and complete characterization of compound 66b (ACT-709478), which has been selected as a clinical candidate.
- Bezen?on, Olivier,Heidmann, Bibia,Siegrist, Romain,Stamm, Simon,Richard, Sylvia,Pozzi, Davide,Corminboeuf, Olivier,Roch, Catherine,Kessler, Melanie,Ertel, Eric A.,Reymond, Isabelle,Pfeifer, Thomas,De Kanter, Ruben,Toeroek-Schafroth, Michael,Moccia, Luca G.,Mawet, Jacques,Moon, Richard,Rey, Markus,Capeleto, Bruno,Fournier, Elvire
-
supporting information
p. 9769 - 9789
(2017/12/26)
-
- Pyrrole marine alkaloid Neolamellarin A analogs and its preparation method and application
-
The invention relates to pyrrole ocean alkaloids Neolamellarin A analogues as shown in the formula I and a preparation method and application thereof. Experiments show that, some of the pyrrole ocean alkaloids Neolamellarin A analogues have strong inhibitory effect on tumor cell lines; some of the pyrrole ocean alkaloids Neolamellarin A analogues have very good neuro cell protective effect; and some of the pyrrole ocean alkaloids Neolamellarin A analogues have very strong inhibitory effect on heat shock protein Hsp90.
- -
-
Paragraph 0394-0396
(2017/10/27)
-
- Cytotoxic 1,3-thiazole and 1,2,4-thiadiazole alkaloids from Penicillium oxalicum: Structural elucidation and total synthesis
-
Two new thiazole and thiadiazole alkaloids, penicilliumthiamine A and B (2 and 3), were isolated from the culture broth of Penicillium oxalicum, a fungus found in Acrida cinerea. Their structures were elucidated mainly by spectroscopic analysis, total synthesis and X-ray crystallographic analysis. Biological evaluations indicated that compound 1, 3a and 3 exhibit potent cytotoxicity against different cancer cell lines through inhibiting the phosphorylation of AKT/PKB (Ser 473), one of important cancer drugs target.
- Yang, Zheng,Huang, Nianyu,Xu, Bang,Huang, Wenfeng,Xie, Tianpeng,Cheng, Fan,Zou, Kun
-
-
- Lewis acid-promoted [2 + 2] cycloadditions of alkenes with aryl ketenes
-
A method for the [2 + 2] cycloaddition of aryl ketenes and alkenes is presented. The process involves the in situ generation of a ketene in the presence of a Lewis acid. The utility of products is demonstrated towards the synthesis of a common scaffold fo
- Rigsbee,Zhou,Rasik,Spitz,Nichols,Brown
-
supporting information
p. 5477 - 5480
(2016/07/06)
-
- Hybrids of coumarin-indole: Design, synthesis and biological evaluation in Triton WR-1339 and high-fat diet induced hyperlipidemic rat models
-
In this study, a series of coumarin-indole hybrids have been synthesized and evaluated for their lipid lowering activity. Preliminary biological screening of the synthesized compounds was undertaken in an in vitro model of the HMG-CoA reductase enzyme, an
- Sashidhara, Koneni V.,Rao, K. Bhaskara,Sonkar, Ravi,Modukuri, Ram K.,Chhonker, Yashpal S.,Kushwaha, Pragati,Chandasana, Hardik,Khanna,Bhatta, Rabi S.,Bhatia, Gitika,Suthar, Manish Kumar,Saxena, Jitendra Kumar,Kumar, Vikash,Siddiqi, Mohammad Imran
-
p. 1858 - 1869
(2016/09/28)
-
- Copper-catalyzed base-accelerated direct oxidation of C-H bond to synthesize benzils, isatins, and quinoxalines with molecular oxygen as terminal oxidant
-
We describe herein an efficient and general copper (II)-catalyzed base-accelerated oxidation of the C-H bond to synthesize benzils and isatins. With similar oxidation system an efficient one-pot procedure for the synthesis of quinoxaline derivatives was realized. The two protocols feature using molecular oxygen as terminal oxidant, low catalyst loading, wide substrate scope, and high functional-group tolerance.
- Yu, Jing-Wen,Mao, Shuai,Wang, Yong-Qiang
-
supporting information
p. 1575 - 1580
(2015/03/14)
-
- 6,7-dimethoxyquinazolines as potential cytotoxic agents: Synthesis and in vitro activity
-
It has been reported that 6,7-dimethoxyquinazoline derivatives have cytotoxic potential independent of their a1-adrenoceptor blocking potential. Bioisosteres of 2-arylquinazolines are considered to have anti-tumor properties. In the present study, we have synthesized the 2-aryl and 2-arylmethyl derivatives of quinazolin-4(3H)-one while retaining the 6,7-dimethoxy substituents. Derivatives with n-butyl group attached to position-3 of quinazolinone nucleus were synthesized with the aim of increasing their lipophilicity. The potential of these synthesized compounds was evaluated against NCI (National Cancer Institute) 60 cell panel using the NCI disease oriented antitumor screen protocol. Based on the results of this screening we generalized that compounds having aryl groups directly attached to the quinazoline ring are less active than those which have one atom linker in between the two ring systems. Substitution of a lipophilic group like nbutyl decreases cytotoxic activity among the compounds and 4-aminoquinazolines showed better activity than 4-quinazolinones. Lipophilic groups in the aromatic ring yielded more active compounds as cytotoxic agents. Among the selected compounds, 4h and 13b were found to be potential lead compounds which could be further optimized as potential anti-neoplastic agents.
- Yadav, Mange Ram,Chauhan, Bishram Singh,Naik, Prashant,Gandhi, Hardik,Giridhar, Rajani
-
p. 190 - 205
(2015/04/14)
-
- Designing new analogs for streamlining the structure of cytotoxic lamellarin natural products
-
Despite the therapeutic potential of marine-derived lamellarin natural products, their preclinical development has been hampered by their lipophilic nature, causing very poor aqueous solubility. In order to develop more drug-like analogs, their structure was streamlined in this study from both the cytotoxic activity and lipophilicity standpoints. First, a modified total synthetic route was successfully devised to construct a library of 59 systematically designed lamellarin analogs, which were then subjected to cytotoxicity and log P determinations. Along with the 25 first-generation lamellarins previously synthesized in our laboratory, the structure-activity and structure-lipophilicity relationships were extensively evaluated. Our results clearly indicated the additional structural requirements around the lamellarin skeleton which, when combined with those reported previously, can provide invaluable guidance for further modifications to increase the aqueous solubility of these compounds.
- Tangdenpaisal, Kassrin,Worayuthakarn, Rattana,Karnkla, Supatra,Ploypradith, Poonsakdi,Intachote, Pakamas,Sengsai, Suchada,Saimanee, Busakorn,Ruchirawat, Somsak,Chittchang, Montakarn
-
p. 925 - 937
(2015/03/31)
-
- Design of dual MMP-2/HDAC-8 inhibitors by pharmacophore mapping, molecular docking, synthesis and biological activity
-
Recent analyses have highlighted the promotion of cancer migration and invasion, mediated through HDAC via MMP-2 and MMP-9. Since both class 1 HDACs and MMP-2/9 are involved in the migration and invasion of cancer, an attempt has been taken to design dual MMP-2/HDAC-8 inhibitors by pharmacophore mapping and molecular docking approaches. The designed molecules were synthesized and showed a range of inhibitory activity against different MMP subtypes. Most of these designed compounds were selective towards MMP-2 but less potent against anti-targets like MMP-8, -12, etc. The highly active MMP-2 inhibitors were also found to be active towards HDAC-8 but less potent against other class 1 HDACs (HDAC-1 and -2). Molecular dynamics simulations revealed that the designed compounds may be acting through a distinct mechanism of action in the 'acetate ion channel' of HDAC-8. Some potent dual MMP-2/HDAC-8 inhibitors were further explored for in vitro cellular assays against human lung carcinoma cell line A549. These analyses revealed that some of these dual inhibitors have considerable anti-migratory and anti-invasive properties. The work may help to obtain some useful dual inhibitors.
- Halder, Amit K.,Mallick, Sumana,Shikha, Deep,Saha, Achintya,Saha, Krishna D.,Jha, Tarun
-
p. 72373 - 72386
(2015/09/08)
-
- SUBSTITUTED BENZOTHIAZOLES AND THERAPEUTIC USES THEREOF FOR THE TREATMENT OF HUMAN DISEASES
-
The invention relates to a family of differently substituted benzothiazoles having an inhibitory activity against the enzyme casein kinase 1 (CK1), as a result of which they are suitable for use in the treatment or prevention of diseases caused by this enzyme, particularly diseases associated with circadian rhythm and inflammatory, autoimmune, psychiatric, neurodegenerative, neurological or ophthalmological diseases, as well as for inducing cell regeneration.
- -
-
Paragraph 0087
(2015/12/18)
-
- Enantioselective Oxidative Aerobic Dealkylation of N-Ethyl Benzylisoquinolines by Employing the Berberine Bridge Enzyme
-
N-Dealkylation methods are well described for organic chemistry and the reaction is known in nature and drug metabolism; however, to our knowledge, enantioselective N-dealkylation has not been yet reported. In this study, exclusively the (S)-enantiomers o
- Gandomkar, Somayyeh,Fischereder, Eva-Maria,Schrittwieser, Joerg H.,Wallner, Silvia,Habibi, Zohreh,Macheroux, Peter,Kroutil, Wolfgang
-
supporting information
p. 15051 - 15054
(2016/01/25)
-
- Protein kinase CK-1 inhibitors as new potential drugs for amyotrophic lateral sclerosis
-
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease where motor neurons in cortex, brain stem, and spinal cord die progressively, resulting in muscle wasting, paralysis, and death. Currently, effective therapies for ALS are lacking; however, identification of pathological TAR DNA-binding protein 43 (TDP-43) as the hallmark lesion in sporadic ALS suggests new therapeutic targets for pharmacological intervention. Pathological TDP-43 phosphorylation appears to drive the onset and progression of ALS and may result from upregulation of the protein kinase CK-1 in affected neurons, resulting in postranslational TDP-43 modification. Consequently, brain penetrant specific CK-1 inhibitors may provide a new therapeutic strategy for treating ALS and other TDP-43 proteinopathies. Using a chemical genetic approach, we report the discovery and further optimization of a number of potent CK-1δ inhibitors. Moreover, these small heterocyclic molecules are able to prevent TDP-43 phosphorylation in cell cultures, to increase Drosophila lifespan by reduction of TDP-43 neurotoxicity, and are predicted to cross the blood-brain barrier. Thus, N-(benzothiazolyl)-2-phenyl-acetamides are valuable drug candidates for further studies and may be a new therapeutic approach for ALS and others pathologies in which TDP-43 is involved.
- Salado, Irene G.,Redondo, Miriam,Bello, Murilo L.,Perez, Concepción,Liachko, Nicole F.,Kraemer, Brian C.,Miguel, Laetitia,Lecourtois, Magalie,Gil, Carmen,Martinez, Ana,Perez, Daniel I.
-
p. 2755 - 2772
(2014/04/17)
-
- Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1
-
The treatment of Human African trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important; pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp., has been identified as a candidate target, and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from Trypanosoma brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. Eight compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus, although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development.
- Khalaf, Abedawn I.,Huggan, Judith K.,Suckling, Colin J.,Gibson, Colin L.,Stewart, Kirsten,Giordani, Federica,Barrett, Michael P.,Wong, Pui Ee,Barrack, Keri L.,Hunter, William N.
-
supporting information
p. 6479 - 6494
(2014/10/16)
-
- Synthesis, crystal structure, anti-inflammatory and anti-hyperglycemic activities of novel 3,4-disubstituted 1,2,4-triazol-5(4H)-one derivatives
-
A new series of 3,4-disubstituted 1,2,4-triazol-5(4H)-one 5a-r, bearing various methoxyphenyl, fluorophenyl, tolyl and phenyl groups, was synthesized by the dehydrocyclization of hydrazinecarboxamides 4a-r by refluxing in a 2 N sodium hydroxide solution. Hydrazinecarboxamides 4a-r was synthesized via the condensation of the corresponding aralkanoic acid hydrazides, 3a-g, with fluoro-, tolyl- and methoxyphenylisocyanates. The newly synthesized compounds (5ar) were characterized by IR, 1H NMR and 13C NMR analyses. The structure of one compound 5a was determined by single crystal X-ray diffraction analysis. All of the synthesized compounds were screened for their anti-inflammatory and anti-diabetic (α-glucosidase and α-amylase inhibition) activity to identify new drugs that might be useful in preventing damage related to diabetes and inflammation. Compounds 5j, 5k and 5m decrease the expression of type II collagen in a dose dependent manner; similarly 5l decrease the COX-2 expression of rabbit articular chondrocytes in a dose dependent manner possessing potent anti-inflammatory potential while some of derivatives including 5c, 5e, 5g and 5h cause inflammation. Meanwhile, excellent α-glucosidase and moderate α-amylase inhibitory profiles against carbohydrate modulating enzymes were demonstrated by compounds 5b, 5f, 5k and 5q compared to the reference standard acarbose, and compounds 5g, 5h, 5i, 5j, 5l and 5o exhibited moderate to low enzyme inhibition potential among the series.
- Saleem, Muhammad,Yu, Seon-Mi,Rafiq, Muhammad,Kim, Song-Ja,Seo, Sung-Yum,Lee, Ki Hwan
-
p. 810 - 823
(2015/04/14)
-
- USE OF THE AMINOALKYLINDOLE JWH-073-M4 AND RELATED COMPOUNDS AS NEUTRAL CB1 RECPTOR ANTAGONISTS FOR THE TREATMENT OF ALCOHOLISM, DRUG ABUSE, OBESITY, AND OBESITY-RELATED DISEASES
-
Novel alkylindoles that bind tightly to cannabinoid receptors and are neutral antagonists for the cannabinoid 1 receptor and agonists for the cannabinoid 2 receptor are provided. These compounds are useful for treating alcoholism and drug abuse and for treating obesity.
- -
-
Page/Page column 52; 53
(2013/07/25)
-
- Design, synthesis and insecticidal activity of novel anthranilic diamides with benzyl sulfide scaffold
-
A series of novel anthranilic diamides with benzyl sulfide scaffold were synthesized, in which N-pyridylpyrazole moiety generally regarded as key pharmacophore was abandoned. The target compounds were characterized by 1H NMR, 13C NMR, 19F NMR and HRMS. The preliminary bioassays indicated that half of the title compounds were endowed with good insecticidal activities against armyworm (Mythimna sepatara) at the concentration of 500 mg/L. Exhilaratingly, the synthesized compound 3a was also active against Tetranychus cinnabarinus at 100 mg/L. The difference in activities between the target compounds was influenced by the substituents, which provided some hints for further investigation on structure modifications.
- Chen, Yin-Bo,Li, Ji-Ling,Shao, Xu-Sheng,Xu, Xiao-Yong,Li, Zhong
-
p. 673 - 676
(2013/07/26)
-
- An optimized RAD51 inhibitor that disrupts homologous recombination without requiring michael acceptor reactivity
-
Homologous recombination (HR) is an essential process in cells that provides repair of DNA double-strand breaks and lesions that block DNA replication. RAD51 is an evolutionarily conserved protein that is central to HR. Overexpression of RAD51 protein is
- Budke, Brian,Kalin, Jay H.,Pawlowski, Michal,Zelivianskaia, Anna S.,Wu, Megan,Kozikowski, Alan P.,Connell, Philip P.
-
p. 254 - 263
(2013/02/23)
-
- Pd(ii)-catalyzed decarboxylative acylation of phenylacetamides with α-oxocarboxylic acids via C-H bond activation
-
A palladium-catalyzed decarboxylative acylation of phenylacetamides with α-oxocarboxylic acids via C-H bond activation is described. This protocol provides efficient access to a range of ortho-acyl phenylacetamides, which can be easily converted to 3-isochromanone derivatives. The Royal Society of Chemistry 2013.
- Park, Jihye,Kim, Minyoung,Sharma, Satyasheel,Park, Eonjeong,Kim, Aejin,Lee, Sang Hwi,Kwak, Jong Hwan,Jung, Young Hoon,Kim, In Su
-
supporting information
p. 1654 - 1656
(2013/03/14)
-
- α-Diazo-β-ketonitriles: Uniquely reactive substrates for arene and alkene cyclopropanation
-
An investigation of the intramolecular cyclopropanation reactions of α-diazo-β-ketonitriles is reported. These studies reveal that α-diazo-β-ketonitriles exhibit unique reactivity in their ability to undergo arene cyclopropanation reactions; other similar acceptor-acceptor- substituted diazo substrates instead produce mixtures of C-H insertion and dimerization products. α-Diazo-β-ketonitriles also undergo highly efficient intramolecular cyclopropanation of tri- and tetrasubstituted alkenes. In addition, the α-cyano-α-ketocyclopropane products are demonstrated to serve as substrates for SN2, SN2′, and aldehyde cycloaddition reactions.
- Nani, Roger R.,Reisman, Sarah E.
-
supporting information
p. 7304 - 7311
(2013/06/27)
-
- Total syntheses of eudistomins Y1-Y7 by an efficient one-pot process of tandem benzylic oxidation and aromatization of 1-benzyl-3,4-dihydro-β-carbolines
-
The first total synthesis of eudistomin Y7 (7) and total syntheses of eudistomins Y1-Y6 (1-6) are described. An efficient room-temperature conversion of 1-benzyl-3,4-dihydro-β-carbolines (11) into 1-benzoyl-β-carbolines (14) by a one-pot process of tandem benzylic oxidation and aromatization as the key step of these total syntheses was also studied in detail. The first total synthesis of eudistomin Y 7 (7) and total syntheses of eudistomins Y1-Y6 (1-6) are described. An efficient room-temperature conversion of 1-benzyl-3,4-dihydro-β-carbolines (11) into 1-benzoyl-β-carbolines (14) by a one-pot process of tandem benzylic oxidation and aromatization as the key step of these total syntheses was also studied in detail. Copyright
- Trieu, Tien Ha,Dong, Jing,Zhang, Qiang,Zheng, Bo,Meng, Tian-Zhuo,Lu, Xia,Shi, Xiao-Xin
-
p. 3271 - 3277
(2013/07/05)
-
- Synthesis and structure activity relationship of tetrahydroisoquinoline- based potentiators of GluN2C and GluN2D containing N-Methyl-D-aspartate receptors
-
We describe here the synthesis and evaluation of a series of tetrahydroisoquinolines that show subunit-selective potentiation of NMDA receptors containing the GluN2C or GluN2D subunits. Bischler-Napieralski conditions were employed in the key step for the
- Santangelo Freel, Rose M.,Ogden, Kevin K.,Strong, Katie L.,Khatri, Alpa,Chepiga, Kathryn M.,Jensen, Henrik S.,Traynelis, Stephen F.,Liotta, Dennis C.
-
supporting information
p. 5351 - 5381
(2013/07/26)
-
- Vaulted biaryls in catalysis: A structure-activity relationship guided tour of the immanent domain of the VANOL ligand
-
The active site in the BOROX catalyst is a chiral polyborate anion (boroxinate) that is assembled in situ from three equivalents of B(OPh) 3 and one of the VANOL ligand by a molecule of substrate. The substrates are bound to the boroxinate by Hbonds to oxygen atoms O1-O3. The effects of introducing substituents at each position of the naphthalene core of the VANOL ligand are systematically investigated in an aziridination reaction. Substituents in the 4,4′- and 8,8′-positions have a negative effect on catalyst performance, whereas, substituents in the 7- and 7′-positions have the biggest impact in a positive direction. VANOL destination: The active site in the BOROX catalyst is a chiral polyborate anion (boroxinate; see figure) that is assembled in situ from three equivalents of B(OPh)3 and one of the VANOL ligand by a molecule of substrate. The effects of introducing substituents at each position of the naphthalene core of the VANOL ligand are systematically investigated in an aziridination reaction. Copyright
- Guan, Yong,Ding, Zhensheng,Wulff, William D.
-
supporting information
p. 15565 - 15571
(2013/11/19)
-
- Discovery of 4,6-substituted-(diaphenylamino)quinazolines as potent c-Src inhibitors
-
A series of 4,6-substituted-(diaphenylamino)quinazolines as c-Src inhibitors have been prepared and their biological activity has also been evaluated. All the compounds displayed potential antiproliferation activities, with IC50 values ranging from 3.42 μM to 118.81 μM in five human tumor cell lines. Particularly, compound 15 exhibited higher cytotoxicity against the tested five tumor cell lines compared to the other small molecules. Generally, most of these compounds showed selectivity between the A549 cells and the other four cells, according to their corresponding IC50 values. The results obtained from the in vitro enzyme assay indicated compound 15 has remarkable inhibitory activity against c-Src kinase with an IC50 value of 27.3 nM, which is comparable to the control compounds. Furthermore, molecular docking and QSAR study by means of DS 3.5 (Discovery Studio 3.5, Accelrys, Co. Ltd) explored the binding modes and the structure and activity relationship (SAR) of these derivatives.
- Li, Jing-Ran,Li, Dong-Dong,Fang, Fei,Du, Qian-Ru,Lin, Lin,Sun, Jian,Qian, Yong,Zhu, Hai-Liang
-
p. 8375 - 8386
(2013/12/04)
-
- Asymmetric hydrogenation of α- Or β-acyloxy α,β- unsaturated phosphonates catalyzed by a Rh(i) complex of monodentate phosphoramidite
-
The Rh(i) complex of a monodentate phosphoramidite bearing a primary amine moiety (DpenPhos) has been disclosed to be highly efficient for the asymmetric hydrogenation of a variety of α- or β-acyloxy α,β- unsaturated phosphonates, providing the corresponding biologically important chiral α- or β-hydroxy phosphonic acid derivatives with excellent enantioselectivities (90->99% ee).
- Zhang, Jinzhu,Dong, Kaiwu,Wang, Zheng,Ding, Kuiling
-
supporting information; scheme or table
p. 1598 - 1601
(2012/03/22)
-
- Enantioselective activation of stable carboxylate esters as enolate equivalents via N-heterocyclic carbene catalysts
-
The first N-Heterocyclic Carbene (NHC) mediated activation of stable carboxylate esters to generate enolate intermediates is disclosed. The catalytically generated arylacetic ester enolates undergo enantioselective reactions with α,β-unsaturated imines.
- Hao, Lin,Du, Yu,Lv, Hui,Chen, Xingkuan,Jiang, Huishen,Shao, Yaling,Chi, Yonggui Robin
-
supporting information; experimental part
p. 2154 - 2157
(2012/07/14)
-
- Synthesis of novel 2-[4-(4-substitutedbenzamido/phenylacetamido) phenyl]benzothiazoles as antimicrobial agents
-
A new series of 2-[4-(4-substitutedbenzamido/ phenylacetamido)phenyl] benzothiazole derivatives (6a-k) were synthesized and evaluated for antibacterial and antifungal activities against Staphylococcus aureus, Bacillus subtilis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli with their drug-resistant isolates and a yeast Candida albicans. Microbiological results indicated that the compounds possessed a broad spectrum of activity against the tested microorganisms at minimum inhibitory concentration (MIC) values between 100 and 6.25 lg/ml. Compounds 6d and 6k exhibited significant antibacterial activity showing 6.25 lg/ml MIC values against drugresistant S. aureus and P. aeruginosa isolates, respectively. Springer Science+Business Media, LLC 2011.
- Bolelli, Kayhan,Yalcin, Ismail,Ertan-Bolelli, Tugba,?zgen, Selda,Kaynak-Onurdag, Fatma,Yildiz, Ilkay,Aki, Esin
-
p. 3818 - 3825
(2013/02/23)
-
- Deracemization of α-aryl hydrocoumarins via catalytic asymmetric protonation of ketene dithioacetals
-
An unprecedented catalytic asymmetric protonation of ketene dithioacetals is described. Various racemic α-aryl hydrocoumarin derivatives are transformed into enantioenriched dithioacetal-protected hydrocoumarins in the presence of a chiral Br?nsted acid catalyst. A newly developed phosphoric acid, featuring the 3,5-bis(pentafluorothio)phenyl (3,5-(SF5) 2C6H3) substituent, is introduced. The obtained products can be easily converted into either hydrocoumarins or the corresponding chromans via simple hydrolysis or hydrogenation, respectively.
- Lee, Ji-Woong,List, Benjamin
-
supporting information
p. 18245 - 18248
(2013/01/15)
-
- Thiophene inhibitors of PDE4: Crystal structures show a second binding mode at the catalytic domain of PDE4D2
-
PDE4 inhibitors have been identified as therapeutic targets for a variety of conditions, particularly inflammatory diseases. We have serendipitously identified a novel class of phosphodiesterase 4 (PDE4) inhibitor during a study to discover antagonists of the parathyroid hormone receptor. X-ray crystallographic studies of PDE4D2 complexed to four potent inhibitors reveal the atomic details of how they inhibit the enzyme and a notable contrast to another recently reported thiophene-based inhibitor.
- Nankervis, Jacob L.,Feil, Susanne C.,Hancock, Nancy C.,Zheng, Zhaohua,Ng, Hooi-Ling,Morton, Craig J.,Holien, Jessica K.,Ho, Patricia W.M.,Frazzetto, Mark M.,Jennings, Ian G.,Manallack, David T.,John Martin,Thompson, Philip E.,Parker, Michael W.
-
supporting information; experimental part
p. 7089 - 7093
(2012/01/06)
-
- Synthesis, spasmolytic activity and structure-activity relationship study of a series of polypharmacological thiobenzanilides
-
Recently we presented a series of benzanilide derivatives with a selective spasmolytic effect on terminal ileum preparations of the guinea pig. In this report we demonstrate a further development of these compounds. The exchange of the amide oxygen agains
- Brunhofer, Gerda,Studenik, Christian,Ecker, Gerhard F.,Erker, Thomas
-
experimental part
p. 37 - 44
(2012/03/08)
-
- Structural diversity-guided convenient construction of functionalized polysubstituted butenolides and lactam derivatives
-
A molecular diversity-oriented convenient access to multi-substituted butenolides and lactam scaffolds via four different methods from various phenylacetic acid derivatives is described. The target molecules have been identified on the basis of analytical spectra data, and are useful synthons in the fields of medicine and agrochemicals.
- Ke, Shaoyong,Zhang, Ya-Ni,Shu, Wenming,Zhang, Zhigang,Shi, Liqiao,Liang, Ying,Wang, Kaimei,Yang, Ziwen
-
experimental part
p. 1071 - 1079
(2012/03/12)
-
- N-SULFONYL THIAZOLYLPIPERAZINE DERIVATIVES AND RELATED N-SULFONYL HETEROCYCLIC DERIVATIVES FOR THE TREATMENT OF NEURO DEGENERATIVE DISEASES
-
This invention provides thiazolylpiperazine derivatives, and N-sulfonyl heterocyclic derivatives including phenyl- and benzyl-thiazolylpiperidine derivatives, and pharmaceutically acceptable salts thereof, which are useful active ingredients for administration in a method for the treatment of an α-synucleopathy such as Parkinson's disease, diffuse Lewy body disease, traumatic brain injury, amyotrophic lateral sclerosis, Niemann-Pick disease, Hallervorden-Spatz syndrome, Down syndrome, neuroaxonal dystrophy, multiple system atrophy and Alzheimer's disease. This invention also provides methods for making such derivatives, and pharmaceutical compositions including such derivatives together with pharmaceutically acceptable excipients.
- -
-
Page/Page column 80; sheet 4
(2010/08/08)
-