cas 4530-20-5, Boc-Glycine | Articles data

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Discovery of degradable niclosamide derivatives able to specially inhibit small cell lung cancer (SCLC)
Small cell lung cancer (SCLC) is exceedingly tough to treat and easy to develop resistance upon long use of the first-line drug carboplatin or radiotherapy. Novel medicines effective and specific against SCLC are greatly needed. Herein, we focused on the discovery of such a medicine by exploring a drug niclosamide with repurposing strategy. Initial screening efforts revealed that niclosamide, an anthelmintic drug, possessed the in vitro anticancer activity and an obvious sensitivity towards SCLC. This observation inspired the evaluation for two different kinds of niclosamide derivatives. 2 with a degradable ester as a linker exhibited the comparable activity but slightly inferior selectivity to SCLC, by contrast, the cytotoxicities of 4 and 5 with non-degradable ether linkages completely disappeared, clearly validating the importance of 2-free hydroxyl group or 2-hydroxyl group released in the antitumor activity. Mechanism study unfolded that, similar to niclosamide, 2 inhibited growth of cancer cells via p 53 activation and subsequent underwent cytochrome c dependent apoptosis. Further structural modification to afford phosphate sodium 8 with significantly enhanced aqueous solubility (22.1 mg/mL) and a good selectivity towards SCLC demonstrated more promising druggability profiles. Accordingly, niclosamide as an attractive lead hold a huge potential for developing targeted anti-SCLC drugs.
He, XingGang,Li, MaoLin,Ye, WenChong,Zhou, Wen
(2021)
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The 4-tert-butylphenyl group as a simple tag for solution phase synthesis
A solution phase synthesis strategy was investigated using 4-tert-butylphenyl group as the tag and a beta-cyclodextrin column as the affinity chromatographic support for the isolation of compounds containing the tag. It was found that compounds containing the tag have significantly longer retention times on the beta-cyclodextrin column than those compounds that do not have such a tag. The tag is chemically inert and can be introduced onto and removed from target compounds readily. This solution phase synthesis method was applied to the synthesis of some simple amino acid derivatives.
Blodgett, Jordan,Li, Tingyu
p. 6649 - 6652
(2004)
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Ligand-based rational design, synthesis and evaluation of novel potential chemical chaperones for opsin
Inherited blinding diseases retinitis pigmentosa (RP) and a subset of Leber's congenital amaurosis (LCA) are caused by the misfolding and mistrafficking of rhodopsin molecules, which aggregate and accumulate in the endoplasmic reticulum (ER), leading to photoreceptor cell death. One potential therapeutic strategy to prevent the loss of photoreceptors in these conditions is to identify opsin-binding compounds that act as chemical chaperones for opsin, aiding its proper folding and trafficking to the outer cell membrane. Aiming to identify novel compounds with such effect, a rational ligand-based approach was applied to the structure of the visual pigment chromophore, 11-cis-retinal, and its locked analogue 11-cis-6mr-retinal. Following molecular docking studies on the main chromophore binding site of rhodopsin, 49 novel compounds were synthesized according to optimized one-to seven-step synthetic routes. These agents were evaluated for their ability to compete for the chromophore binding site of opsin, and their capacity to increase the trafficking of the P23H opsin mutant from the ER to the cell membrane. Different new molecules displayed an effect in at least one assay, acting either as chemical chaperones or as stabilizers of the 9-cis-retinal-rhodopsin complex. These compounds could provide the basis to develop novel therapeutics for RP and LCA.
Bassetto, Marcella,Brancale, Andrea,Pasqualetto, Gaia,Pileggi, Elisa,Rozanowska, Malgorzata,Schepelmann, Martin,Varricchio, Carmine
supporting information

(2021/09/24)

Vorinostat skeleton-based anthranilamide compound as well as preparation and application thereof
The invention provides a vorinostat skeleton-based anthranilamide compound as well as preparation and application of the anthranilamide compound. The structural formula of the o-aminobenzamide compound based on a vorinostat skeleton is shown in the specification, wherein n is equal to 1-6, and R is methylamino, dimethylamino, hydroxyl, NH2 or the like. The anthranilamide compound based on the vorinostat skeleton has the effect of inhibiting gastric cancer cell proliferation through MTT method determination, and can be used for preparing anti-gastric cancer drugs.
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Paragraph 0025

(2021/08/06)

PRODRUGS OF ABIRATERONE
The present invention relates to compounds of formula (I), or their isotopic forms, stereoisomers, tautomers, or pharmaceutically acceptable salt(s) thereof as prodrugs of abiraterone. The present invention also describes method of making such compounds, pharmaceutical compositions comprising such compounds and the use of the compounds of formula (I).
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Page/Page column 20

(2021/05/29)

TRPV1 agonist, preparation method and application thereof
The present invention relates to a compound represented by a formula I, a stereoisomer, a tautomer, a solvate, a polymorph or a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the compound, and a preparation method and a medical use of the compound, wherein the structure of the formula I is shown in the specification.
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Paragraph 0160-0164

(2021/03/31)

PHOTOLYTIC COMPOUNDS AND TRIPLET-TRIPLET ANNIHILATION MEDIATED PHOTOLYSIS
The invention provides novel photolytic compounds and prodrugs, nanoparticles and compositions thereof, and methods of conducting photolysis mediated by triplet-triplet annihilation.
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Paragraph 0026; 00203

(2021/04/17)

Substituted aza five-membered ring derivative and application thereof in medicine
The invention discloses a substituted aza-five-membered ring derivative and application thereof to medicines. , The invention provides a substituted aza five-membered ring compound or a stereoisomer, a tautomer, an oxynitride, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and a pharmaceutical composition containing the compound of the present invention. The invention also discloses application of the compound or the pharmaceutical composition of the compound in preparation of a medicament for treating PDE4 related diseases such as atopic dermatitis (AD) or chronic obstructive pulmonary disease (COPD).
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Paragraph 0466; 0471-0473

(2021/10/30)

Composition for promoting differentiation of skin keratinocyte comprising a SAC derivatives or a SMC derivatives
The present invention relates to a composition for promoting keratinocyte differentiation. More specifically, SAC derivative or SMC derivatives as an active ingredient promotes differentiation of keratinocytes to promote skin keratinocyte differentiation, has excellent anti-wrinkling effect, skin barrier recovery effect, and is applicable to pharmaceutical, cosmetic, soap, body, shampoo and pack.
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Paragraph 0028-0031; 0041-0043; 0057-0060; 0070-0072

(2021/02/02)

Amino acid substrate and preparation method and purpose thereof
The invention discloses an amino acid substrate. A structural formula of the substrate is shown in Figure 1. By means of development and innovation of a synthetic process of dipeptide in the amino acid substrate and a coupling process of the dipeptide and chromogen and innovation and application verification of an extraction and purification process, the reaction yield of each step of a product isgreatly improved, the color is close to white, the influence of the substrate color in the identification process is reduced, and the sensitivity and the accuracy of the aerobic flora vaginitis detection process are improved to a greater extent. The substrate is in the form of hydrochloride, and the solubility of the substrate can be greatly improved when the detection is carried out in the formof the hydrochloride. In a detection application, the corresponding preparation work is conducted according to the preparation requirement of the aerobic flora vaginitis detection, and the color rendering performance of the synthetic substrate is compared with the color rendering performance of the existing aerobic flora vaginitis detection in the market according to a detection standard. The color rendering performance is better than that of an aerobic flora vaginitis detection reagent in the market.
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Paragraph 0019

(2019/02/10)

Synthesis and anti-tumor activity evaluation of novel 7-fluoro-4-(1-piperazinyl) quinolines
Background: Three series of new 7-fluoro-4-(1-piperazinyl) quinolines (I1~I6, II1~II2 and IV1~IV4) were synthesized. Their anti-tumor activity was evaluated in vitro against three human carcinoma cell lines, namely SGC-7901 cells, BEL-7402 cells and A549 cells expressing high levels of EGFR by Methyl Thiazolyl Terazolium (MTT) assay. Methods: Three series of quinoline derivatives were synthesized, characterized and evaluated for their in vitro anti-tumor activities. Results and Discussion: Structures of the newly synthesized compounds were confirmed by spectral analysis. The preliminary bioassay indicated that compounds I1, I10 and II1 exhibited better anti-tumor activity than the rest of the target compounds and gefitinib against A549 cell based assay, which demonstrated that compounds I1, I10 and II1 are potential agents for cancer therapy. Results suggested that the substitutes on piperazinyl influenced anti-tumor activities remarkably. Conclusion: These results are useful for discovering more potent novel anti-tumor compounds and further studies are ongoing.
Liu, Dan,Xue, Aiqi,Liu, Zhixin,Zhang, Yi,Peng, Penghui,Wang, Haifeng
p. 663 - 669
(2019/06/24)

Hydrogen-Bonding-Regulated Supramolecular Nanostructures and Impact on Multivalent Binding
Herein we describe the H-bonding-regulated nanostructure, thermodynamics, and multivalent binding of two bolaamphiphiles NDI-1 and NDI-2 consisting of a hydrophobic naphthalene diimide connected to a hydrophilic wedge by a H-bonding group and a glucose mo
Sikder, Amrita,Ray, Debes,Aswal, Vinod K.,Ghosh, Suhrit
supporting information
p. 1606 - 1611
(2019/01/04)

SYNTHESIS OF (2S,3R,4R)-4,5-DIHYDROXYISOLEUCINE AND DERIVATIVES
The invention relates to a method for the preparation of a 4,5-dihydroxyisoleucine derivative comprising the steps of asymmetric Claisen rearrangement of a Z-aminocrotyl-glycin ester and subsequent kinetic resolution of the product diastereomer mix by acylase, and subsequent Sharpless dihydroxylation of the resulting 2-amino-3-methylpent-4-enoicacid derivative.
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Page/Page column 24-25

(2019/10/19)

Spontaneous Single-Crystal-to-Single-Crystal Evolution of Two Cross-Laminated Polymers
Two cases of spontaneous evolution of monomers to linear polymers having novel cross-laminated topology are reported. We synthesized two peptide monomers N3-Gly-Gly-NH-CH2-CCH and N3-Gly-Gly-Gly-CH2-CCH and solved their crystal structures by single-crystal X-ray diffraction. They adopt H-bonded crisscrossed layered packing in their crystals such that: (a) the monomers are aligned head-to-tail in 1D-chain-like arrays and parallel arrangement of such arrays forms a layer; (b) the proximally placed azide and alkyne motifs are in an orientation apt for their regiospecific cycloaddition; (c) each monomer having x peptide bonds is H-bonded with 2x monomers disposed in intersecting arrangement, which pre-organize 1D-chain-like arrays in adjacent layers in perpendicular orientation. These crystals underwent spontaneous single-crystal-to-single-crystal (SCSC) polymerization via azide–alkyne cycloaddition reaction to form triazolyl-polyglycines, at room temperature. The crisscrossed arrangement of monomers in adjacent layers ensured the formation of cross-laminated polymers.
Athiyarath, Vignesh,Sureshan, Kana M.
supporting information
p. 612 - 617
(2018/12/13)

Synthesis and application of tanshinone IIA derivatives
The invention discloses a tanshinone IIA derivative containing amino acid fragments and synthesis and application of the tanshinone IIA derivative. After tanshinone IIA is modified with amino acids, the compound has excellent water solubility and stabilit
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Paragraph 0037-0038

(2019/03/06)

Anticancer intermediate based on PKI-587 and polyethylene glycol coupled anticancer drug, and preparation methods and application thereof
The invention provides an anticancer intermediate based on PKI-587 and a polyethylene glycol coupled anticancer drug, and preparation methods and application thereof, belonging to the field of treatment of cancers. The anticancer intermediate has a general structural formula as described in the specification, and at least one AC in the general structural formula is the anticancer drug PKI-587. Thepolyethylene glycol coupled anticancer drug has a general structural formula as described in the specification. The above two drugs can realize combined medication of the targeting anticancer drug PKI-587 and a plurality of other anticancer drugs, so toxic response caused by mutual influence and pharmacokinetics of a plurality of other anticancer drugs can be prevented during individual administration of the anticancer drugs, multidrug resistance of cancers is overcome, and synergistic effect is exerted; and the two drugs can be used for preparing anticancer drugs with targeting effect and have critical clinical value and wide market prospects.
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Paragraph 0120; 0121; 0122

(2018/03/09)

With synergistic anti-cancer activity of the intermediate drug and polyethylene glycol coupled synergistic anti-cancer drug, and its preparation method and application (by machine translation)
The present invention provides synergistic anti-cancer activity of the intermediate drug and polyethylene glycol coupled synergistic anti-cancer drug, and its preparation method and application, which belongs to the field of cancer treatment. The has a synergistic anti-cancer activity of the general structural formula of intermediate drug The polyethylene glycol coupled synergistic anti-cancer drug the general structural formula of This two categories of drugs can realize a plurality of anticancer drug between the combination, to avoid a separate taking a plurality of anti-cancer drugs owing to the mutual influence between the pharmacokinetics and caused toxic reaction, and helps overcome the cancer of the multi-drug resistance, has synergistic effects, can be used for the preparation of anticancer drugs, has significant clinical value and broad market prospect. (by machine translation)
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Paragraph 0121; 0122; 0123

(2018/03/09)

The novel anti-tumor medicine synthetic method and a pharmaceutically acceptable salt thereof and solid preparation (by machine translation)
The invention discloses a method for synthesis of antineoplastic agent, the chemical name is 5 - chloro - N2 - (3 - amino-acetyl aminophenyl) - N4 - (2 - [...] phenyl) pyrimidine - 2, 4 - diamine. At the same time, its salt, crystalline form research, select and suitable for further development as a preparation of the maleate, tartrate and succinate and its corresponding crystalline form. The invention also provides a to the antineoplastic agent as the active ingredient of the solid preparation, wherein the supplemented with one or more solubilising. The invention solid preparation dissolution characteristic and excellent stability, with clinical application prospect. (by machine translation)
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Paragraph 0050; 0051; 0052

(2018/09/08)

Synthesis of Histidine-Containing Oligopeptides via Histidine-Promoted Peptide Ligation
Histidine-containing peptides are valuable therapeutic agents for a treatment of neurodegenerative diseases. However, the synthesis of histidine-containing peptides is not trivial due to the potential of imidazole sidechain of histidine to act as a nucleophile if unprotected. A peptide ligation method utilizing the imidazole sidechain of histidine has been developed. The key imidazolate intermediate that acts as an internal acyl transfer catalyst during ligation is generated by deprotonation. Transesterification with amino acids or peptides tethered with C-terminal thioester followed by N→N acyl shifts led to the final ligated products. A range of histidine-containing dipeptides could be synthesized in moderate to good yields via this method without protecting the imidazole sidechain. The protocol was further extended to tripeptide synthesis via a long-range N→N acyl transfer, and tetrapeptide synthesis.
Huang, Kai-Jin,Huang, Yi-Chen,Lin, Yuya A.
supporting information
p. 400 - 403
(2018/02/21)

Antiplasmodial activity of hydroxyethylamine analogs: Synthesis, biological activity and structure activity relationship of plasmepsin inhibitors
Malaria, particularly in endemic countries remains a threat to the human health and is the leading the cause of mortality in the tropical and sub-tropical areas. Herein, we explored new C2 symmetric hydroxyethylamine analogs as the potential inhibitors of Plasmodium falciparum (P. falciparum; 3D7) in in-vitro cultures. All the listed compounds were also evaluated against crucial drug targets, plasmepsin II (Plm II) and IV (Plm IV), enzymes found in the digestive vacuole of the P. falciparum. Analog 10f showed inhibitory activities against both the enzymes Plm II and Plm IV (Ki, 1.93 ± 0.29 μM for Plm II; Ki, 1.99 ± 0.05 μM for Plm IV). Among all these analogs, compounds 10g selectively inhibited the activity of Plm IV (Ki, 0.84 ± 0.08 μM). In the in vitro screening assay, the growth inhibition of P. falciparum by both the analogs (IC50, 2.27 ± 0.95 μM for 10f; IC50, 3.11 ± 0.65 μM for 10g) displayed marked killing effect. A significant growth inhibition of the P. falciparum was displayed by analog 12c with IC50 value of 1.35 ± 0.85 μM, however, it did not show inhibitory activity against either Plms. The hemolytic assay suggested that the active compounds selectively inhibit the growth of the parasite. Further, potent analogs (10f and 12c) were evaluated for their cytotoxicity towards mammalian HepG2 and vero cells. The selectivity index (SI) values were noticed greater than 10 for both the analogs that suggested their poor toxicity. The present study indicates these analogs as putative lead structures and could serve as crucial for the development of new drug molecules.
Kumar Singh, Amit,Rajendran, Vinoth,Singh, Snigdha,Kumar, Prashant,Kumar, Yogesh,Singh, Archana,Miller, Whelton,Potemkin, Vladimir,Poonam,Grishina, Maria,Gupta, Nikesh,Kempaiah, Prakasha,Durvasula, Ravi,Singh, Brajendra K.,Dunn, Ben M.,Rathi, Brijesh
p. 3837 - 3844
(2018/07/13)

IONIZABLE CATIONIC LIPID FOR RNA DELIVERY
What is described is a compound of formula I consisting of a compound in which R1 is a branched chain alkyl consisting of 10 to 31 carbons; R2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons; L1 and L2 are the same or different, each a linear alkylene of 1 to 20 carbons or a linear alkenylene of 2 to 20 carbons; X1 is S or O; R3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.
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Paragraph 0029; 0492-0495

(2018/07/04)

IONIZABLE CATIONIC LIPID FOR RNA DELIVERY
What is described is a compound of formula I consisting of a compound in which R1 is a branched chain alkyl consisting of 10 to 31 carbons;R2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons, or a branched chain alkyl consisting of 10 to 31 carbons;L1 and L2 are the same or different, each a linear alkane of 1 to 20 carbons or a linear alkene of 2 to 20 carbons;X1 is S or O;R3 is a linear or branched alkylene consisting of 1 to 6 carbons; andR4 and R5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.
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Paragraph 0534; 0535; 0536; 0537

(2018/07/05)

Photolytic release of bioactive carboxylic acids from fused pyran conjugates
New ester cages bearing the coumarin (2H-benzopyran-2-one) skeleton with extended π-systems as phototriggers, for glycine and β-alanine, as models of carboxylic acid bifunctional molecules with biological relevance, were evaluated under photolysis conditions at 254, 300, 350 and 419 nm of irradiation in a RPR-100 photochemical reactor. The processes were followed by HPLC-UV detection and 1H NMR with collection of kinetic data. The results showed a correlation between the photolysis efficiency and the increasing extension of the conjugation for both glycine and β-alanine, showing that the 7-aminocoumarin afforded the best results at all wavelengths tested. From a study of the time-resolved fluorescence behaviour, these compounds were also found to exhibit more complex fluorescence decay kinetics. This was attributed to the presence of conjugated and non-conjugated coumarin species.
Concei??o, Rafaela,Hungerford, Graham,Costa, Susana P.G.,Gon?alves, M. Sameiro T.
p. 368 - 379
(2017/09/26)

Synthesis and evaluation of chirally defined side chain variants of 7-chloro-4-aminoquinoline to overcome drug resistance in malaria chemotherapy
A novel 4-aminoquinoline derivative [(S)-7-chloro-N-(4-methyl-1-(4-methyl-piperazin-1-yl)pentan-2-yl)-quinolin-4-amine triphosphate] exhibiting curative activity against chloroquine-resistant malaria parasites has been identified for preclinical development as a blood schizonticidal agent. The lead molecule selected after detailed structure-activity relationship (SAR) studies has good solid-state properties and promising activity against in vitro and in vivo experimental malaria models. The in vitro absorption, distribution, metabolism, and excretion (ADME) parameters indicate a favorable drug-like profile.
Dola, Vasantha Rao,Soni, Awakash,Agarwal, Pooja,Ahmad, Hafsa,Raju, Kanumuri Siva Rama,Rashid, Mamunur,Wahajuddin, Muhammad,Srivastava, Kumkum,Haq,Dwivedi,Puri,Katti
(2017/03/09)

Copper(I)-Mediated Denitrogenative Macrocyclization for the Synthesis of Cyclic α3β-Tetrapeptide Analogues
A copper(I)-mediated denitrogenative reaction has been successfully developed for the preparation of cyclic tetrapeptides. The key reactive intermediate, ketenimine, triggers intramolecular cyclization through attack of the terminal amine group to generate an internal β-amino acid with an amidine linkage. The chemistry developed herein provides a new synthetic route for the preparation of cyclic α3β-tetrapeptide analogues that contain important biological properties and results in rich structural information being obtained for conformational studies. With the success of this copper(I)-catalyzed macrocyclization, two histone deacetylase inhibitor analogues consisting of the cyclic α3β-tetrapeptide framework have been successfully synthesized.
Chen, Chun-Chi,Wang, Sheng-Fu,Su, Yung-Yu,Lin, Yuya A.,Lin, Po-Chiao
p. 1326 - 1337
(2017/06/23)

Enhanced Spacer Length between Mannose Mimicking Shikimoyl and Quinoyl Headgroups and Hydrophobic Region of Cationic Amphiphile Increases Efficiency of Dendritic Cell Based DNA Vaccination: A Structure-Activity Investigation
In the field of dendritic cell based genetic immunization, previously we showed that liposomes of cationic amphiphiles containing mannose-mimicking shikimoyl headgroup are promising DNA vaccine carriers for dendritic cell (DC) transfection. The present structure-activity study reports on the influence of spacer length (between mannose-mimicking headgroups and quaternary nitrogen centers) in modulating the DC-transfection efficiencies. Further, we report on the anti-melanoma immune response inducing properties of the promising cationic amphiphiles in syngeneic C57BL/6J mice under prophylactic settings.
Voshavar, Chandrashekhar,Meka, Rakesh C. R.,Samanta, Sanjoy,Marepally, Srujan,Chaudhuri, Arabinda
p. 1605 - 1610
(2017/03/08)

Synthesis, characterization, and biological studies of diosgenyl analogs
A series of diosgenyl analogs were prepared from diosgenin to evaluate their anticancer activity and antithrombotic property. Analog 4, which had a spiroketal structure with a 6-aminohexanoic acid residue, exhibited the highest potency against all five tumor cell lines. It significantly blocked tumor growth, induced cell apoptosis and autophagy, and regulated cellular calcium concentration, mitochondrial membrane potential, adenosine triphosphate, and cell cycle. In addition, fluorescence-tagged compounds indicated that the analogs could rapidly accumulate in the cytoplasm, but no specific localization in the nucleus of cancer cells was observed. Furthermore, preliminary structure–activity relationship studies demonstrated that spiroketal analogs exhibit better antithrombotic activity than furostanic analogs, which exhibit the opposite effect by promoting thrombosis. Our study indicates that compound 4 may be a promising anticancer drug candidate for cancer patients with thromboembolism.
Huang, Bao-Zhan,Xin, Guang,Ma, Li-Mei,Wei, Ze-Liang,Shen, Yan,Zhang, Rui,Zheng, Hua-Jie,Zhang, Xiang-Hua,Niu, Hai,Huang, Wen
p. 272 - 298
(2017/03/17)

Darbey adds the group derivative and its preparation and use
The invention belongs to the field of medicines, and specifically relates to dabigatran derivatives or the pharmaceutical salts thereof, a preparation method for the derivatives, a medicine composition containing the dabigatran derivatives, and an application of the derivatives and the medicine composition in preparation for anticoagulant medicines and treatment for related diseases.
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Paragraph 0054; 0055

(2017/07/23)

2-OXO-1,2-DIHYDROPYRIDINE-3-CARBOXAMIDE COMPOUNDS AND THEIR USE AS DUAL INHIBITORS OF PDK1/AURA
The present invention concern a 2-oxo-1,2-dihydropyridine-3-carboxamide compound of Formula (I) in the treatment of pathologies which require a dual inhibitor of PDK1/AurA enzymes such as for instance tumours, particularly glioblastoma.
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Page/Page column 19-20

(2018/01/15)

New reagent for the introduction of Boc protecting group to amines: Boc-OASUD
A new reagent, tert-butyl (2,4-dioxo-3-azaspiro [5,5] undecan-3-yl) carbonate (Boc-OASUD) for the preparation of N-Boc-amino acids is described. The Boc-OASUD reacts with amino acids and their esters at room temperature in the presence of a base and gives N-Boc-amino acids and their esters in good yields and purity. Introduction of the Boc group takes place without racemization. The Boc-OASUD, being a solid and more stable, is a better alternative to di-tert-butyl dicarbonate which is low melting and has to be dispensed in plastic containers than glass because of its poor stability.
Maheswara Rao, B. Leela,Nowshuddin, Shaik,Jha, Anjali,Divi, Murali K.,Rao
supporting information
p. 2127 - 2132
(2017/10/31)

Bimane: A Visible Light Induced Fluorescent Photoremovable Protecting Group for the Single and Dual Release of Carboxylic and Amino Acids
A series of ester conjugates of carboxylic and amino acids were synthesized based on bimane fluorescent photoremovable protecting group (FPRPG). The photorelease of single and dual (same as well as different) carboxylic and amino acids is demonstrated from a single bimane molecule on irradiation with visible light (λ ≥ 410 nm). The detailed mechanistic study of photorelease revealed that the release of two caged acids is simultaneous but in a stepwise pathway.
Chaudhuri, Amrita,Venkatesh, Yarra,Behara, Krishna Kalyani,Singh, N. D. Pradeep
supporting information
p. 1598 - 1601
(2017/04/13)

Synthesis of Met-enkephalin by solution-phase peptide synthesis methodology utilizing para-toluene sulfonic acid as N-terminal masking of l-methionine amino acid
The Met-enkephalin, Tyr-Gly-Gly-Phe-Met, was synthesized by the solution-phase synthesis (SPS) methodology employing -OBzl group as carboxyls' protection, while the t-Boc groups were employed for the N-terminal α-amines' protection for the majority of the amino acids of the pentapeptide sequence. The l-methionine (l-Met) amino acid was used as PTSA.Met-OBzl obtained from the simultaneous protection of the α-amino, and carboxyl group with para-toluene sulfonic acid (PTSA) and as-OBzl ester, respectively in a C-terminal start of the 2?+?2?+?1 fragments condensation convergent synthetic approach. The protection strategy provided a short, single-step, simultaneous, orthogonal, nearly quantitative, robust, and stable process to carry through the protected l-methionine and l-phenylalanine coupling without any structural deformities during coupling and workups. The structurally confirmed final pentapeptide product was feasibly obtained in good yields through the current approach.
Khan, Riaz A.
p. 884 - 888
(2016/11/11)

Bisindolyl maleimide derivative and preparation method and application thereof
The invention provides a bisindolyl maleimide derivative and a preparation method and application thereof. The bisindolyl maleimide derivative has an excellent alpha-glucosidase inhibition effect and can be used for preventing and treating diabetes.
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Paragraph 0280; 0281

(2017/01/02)

Design, synthesis, and in vitro antiplasmodial activity of 4-aminoquinolines containing modified amino acid conjugates
Abstract: A new series of side chain-modified 4-aminoquinolines were synthesized and screened for in vitro antiplasmodial activity against both chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. Among the series, compounds 30 and 31 showed significant inhibition of parasite growth against K1 strain of P. falciparum with IC50 values 0.28 and 0.31?μM, respectively, whereas compounds 34, 35, and 38 exhibited superior activity against K1 strain with IC50 values 0.18, 0.22, and 0.17?μM, respectively, as compared to 0.255?μM for chloroquine (CQ). All the compounds displayed good resistance factor between 1.54 and >34.48 as against 51.0 for CQ. All these analogues were found to form strong complex with hematin and inhibited the β-hematin formation in vitro, suggesting that this class of compounds act on a heme polymerization target. Overall results suggest that present series of compounds appear to be promising for further lead optimization to obtain compounds active against drug-resistant parasites. Graphical Abstract: [Figure not available: see fulltext.]
Srinivasarao, Kondaparla,Agarwal, Pooja,Srivastava, Kumkum,Haq,Puri, Sunil K.,Katti
p. 1148 - 1162
(2016/07/06)

A kind of amino acid tanshinone phenolic derivative and its preparation method
The invention relates to amino acid tanshinone phenolic ester derivatives and a preparation method thereof. The derivatives are obtained by reducing tanshinone compounds and performing esterified modification on the reduced tanshinone compounds and an amino acid into prodrugs, wherein the tanshinone compounds are phenanthrenequinone compounds which exist in salvia miltiorrhiza and have an o-quinone structure; the esterified amino acid is alpha-amino acid. The amino acid tanshinone phenolic ester derivatives are compounds having a structure of a general formula (I) or medicinal salts thereof, wherein R1 and R2 represent H or acyl alpha-amino acid and a salt thereof, and R1 and R2 are not H at the same time. The amino acid tanshinone phenolic ester derivatives have the beneficial effects that firstly, the new tanshinone derivatives are provided and the new substances have potential treatment effect on some serious diseases such as tumors, and secondly, amino acid tanshinone phenolic ester derivatives have excellent water solubility and thus can be prepared into injections conveniently in addition to various oral preparations, and therefore, the amino acid tanshinone phenolic ester derivatives are capable of quickly taking effect in disease treatment. As important prodrugs, the amino acid tanshinone phenolic ester derivatives have important application value.
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Paragraph 0045; 0135; 0145; 0155

(2016/10/09)

Design and synthesis of novel HDAC8 inhibitory 2,5-disubstituted-1,3,4-oxadiazoles containing glycine and alanine hybrids with anti cancer activity
Oxadiazole is a heterocyclic compound containing an oxygen atom and two nitrogen atoms in a five-membered ring. Of the four oxadiazoles known, 1,3,4-oxadiazole has become an important structural motif for the development of new drugs and the compounds containing 1,3,4-oxadiazole cores have a broad spectrum of biological activity. Herein, we describe the design, synthesis and biological evaluation of a series of novel 2,5-disubstituted 1,3,4-oxadiazoles (10a–10j) as class I histone deacetylase (HDAC) inhibitors. The compounds were designed and evaluated for HDAC8 selectivity using in silico docking software (Glide) and the top 10 compounds with high dock score and obeying Lipinski's rule were synthesized organically. Further the biological HDAC inhibitory and selectivity assays and anti-proliferative assays were carried out. In in silico and in vitro studies, all compounds (10a–10j) showed significant HDAC inhibition and exhibited HDAC8 selectivity. Among all tested compounds, 10b showed substantial HDAC8 inhibitory activity and better anticancer activity which is comparable to the positive control, a FDA approved drug, vorinostat (SAHA). Structural activity relation is discussed with various substitutions in the benzene ring connected on 1,3,4-oxadizole and glycine/alanine. The study warranted further investigations to develop HDAC8-selective inhibitory molecule as a drug for neoplastic diseases. Novel 1,3,4-oxadizole substituted with glycine/alanine showed HDAC8 inhibition.
Pidugu, Vijaya Rao,Yarla, Nagendra Sastry,Pedada, Srinivasa Rao,Kalle, Arunasree M.,Satya, A. Krishna
p. 5611 - 5617
(2016/10/24)

Locking PDK1 in DFG-out conformation through 2-oxo-indole containing molecules: Another tools to fight glioblastoma
The phosphoinositide-dependent kinase-1 (PDK1) is one of the main components of the PI3K/Akt pathway. Also named the master kinase of the AGC family, PDK1 plays a critical role in tumorigenesis, by enhancing cell proliferation and inhibiting apoptosis, as well as in cell invasion and metastasis formation. Although there have been done huge efforts in discovering specific compounds targeting PDK1, nowadays no PDK1 inhibitor has yet entered the clinic. With the aim to pick out novel and potent PDK1 inhibitors, herein we report the design and synthesis of a new class of molecules obtained by merging the 2-oxo-indole nucleus with the 2-oxo-pyridonyl fragment, two moieties with high affinity for the PDK1 hinge region and its DFG-out binding site, respectively. To this purpose, a small series of compounds were synthesised and a tandem application of docking and Molecular Dynamic (MD) was employed to get insight into their mode of binding. The OXID-pyridonyl hybrid 8, possessing the lower IC50 (IC50 Combining double low line 112 nM), was also tested against recombinant kinases involved in the PI3K/PDK1/Akt pathway and was subjected to vitro studies to evaluate the cytotoxicity and the inhibition of tumour cell migration. All together the results let us to consider 8, as a lead compound of a new generation of PDK1 inhibitors and encourage us to further studies in this direction.
Sestito, Simona,Daniele, Simona,Nesi, Giulia,Zappelli, Elisa,Di Maio, Danilo,Marinelli, Luciana,Digiacomo, Maria,Lapucci, Annalina,Martini, Claudia,Novellino, Ettore,Rapposelli, Simona
supporting information
p. 47 - 63
(2016/05/09)

Paliperidone amino acid ester and its preparation method
The invention discloses a preparation method of a paliperidone amino-acid ester compound or medicinal salt thereof used for treating mental disease, wherein the structural formula of the compound is shown as a formula (I) (described in the specification). The compound can be an optical isomer and also can be a racemic mixture. The paliperidone amino-acid ester can be metabolized and converted into paliperidone (II) with pharmacological activity in vivo after being ingested in a human body, the paliperidone (II) is taken as an antagonist for neurotransmission substance to play a pesticide effect, and the paliperidone (II) is used for treating related mental diseases such as schizophrenia.
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Paragraph 0014; 0015; 0016; 0017

(2017/01/12)

2-OXO-1,2-DIHYDROPYRIDINE-3-CARBOXAMIDE COMPOUNDS AND THEIR USE AS INHIBITORS OF PDK1
The present invention concern a 2-oxo-1,2-dihydropyridine-3-carboxamide compound of Formula (I) and new 2-oxo-1,2-dihydropyridine-3-carboxamide compounds of Formula (II) in the treatment of pathologies which require an inhibitor of PDK1 enzyme such as diabetes, neurodegenerative diseases such as Alzheimer's and Prion Diseases, and tumours such as breast, and pancreatic cancers and glioblastoma, particularly glioblastoma.
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Page/Page column 21; 22

(2016/12/26)

Bisindolylmaleimide derivative, and preparation method and use thereof
The invention provides a bisindolylmaleimide derivative, and a preparation method and a use thereof. The bisindolylmaleimide derivative has a good tumor treatment effect, especially has a good treatment effect on some drug-resistant tumors, and can realize accurate treatment of the drug-resistant tumors.
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Paragraph 0284; 0285

(2017/04/03)

Synthesis of 1,3,6-Trisubstituted Azulenes Based on the 1-Acyloxyazulene Scaffold
An efficient synthetic route to 1,3,6-trisubstituted azulenes based on the 1-acyloxyazulene scaffold was developed. The 1-position in azulene was substituted in the ring-formation step with a functionalized acyloxy group. Additionally, the 3- and 6-positions of azulene were functionalized with versatile synthetic handles, a halogen atom and a formyl group.
Leino, Teppo O.,Johansson, Niklas G.,Devisscher, Lars,Sipari, Nina,Yli-Kauhaluoma, Jari,Wallén, Erik A. A.
p. 5539 - 5544
(2016/11/25)

Photocaging of Single and Dual (Similar or Different) Carboxylic and Amino Acids by Acetyl Carbazole and its Application as Dual Drug Delivery in Cancer Therapy
A new fluorescent photoremovable protecting group (FPRPG) based on acetylcarbazole framework has been explored for the first time release of single and dual (similar or different) substrates from single chromophore. Mechanistic studies of the photorelease process revealed that photorelease of two (similar or different) substrates from acetyl carbazole proceeds via a stepwise pathway. Further, we constructed photoresponsive dual drug delivery system (DDS) to release two different anticancer drugs (caffeic acid and chlorambucil, 1 equiv each). In vitro study reveals that our DDS exhibit excellent properties like biocompatibility, cellular uptake, and photoregulated dual drug release.
Venkatesh, Yarra,Rajesh,Karthik,Chetan,Mandal, Mahitosh,Jana, Avijit,Singh, N.D. Pradeep
supporting information
p. 11168 - 11175
(2016/11/28)

Study of the Paternò–Büchi type photolabile protecting group and application to various acids
An efficient photolabile protecting group, thiochromone S,S-dioxides with the diazomethyl group for phosphate derivatives, amino acids and sulfonic acids was developed. Protection and photodeprotection reactions proceeded smoothly under mild conditions without any catalyst.1H NMR and HPLC spectra studies demonstrated the photolysis properties of the photolabile protecting group and gave an exact quantification of the released substrates. Specially, the photoproduct derived from the thiochromone derivatives following Paternò–Büchi type photo-cycloaddition showed high fluorescence intensity. This fluorescent characteristic demonstrated the photodeprotection progress also can be monitored by fluorescence spectra.
Zhang, Youlai,Zhang, Huan,Ma, Chi,Li, Junru,Nishiyama, Yasuhiro,Tanimoto, Hiroki,Morimoto, Tsumoru,Kakiuchi, Kiyomi
supporting information
p. 5179 - 5184
(2016/11/13)

Support Functionalization with a Phosphine-Containing Hyperbranched Polymer: A Strategy to Enhance Phosphine Grafting and Metal Loading in a Hydroformylation Catalyst
We present the design of a hydroformylation catalyst through the immobilization of air-stable Rh nanoparticles (NPs) on a magnetic support functionalized with a hyperbranched polymer that bears terminal phosphine groups. The catalyst modification with the hyperbranched polymer improved the metal–support interaction, the metal loading, and the catalytic activity. The catalyst was active for the hydroformylation of natural products, such as estragole, and could be used in successive reactions with negligible metal leaching. The phosphine grafting played a key role in the recyclability of Rh NPs under hydroformylation conditions. The catalytic activity was maintained in successive reactions, even if the catalyst was exposed to air during each recovery procedure. The modification of the support with hyperbranched polyester allowed us either to increase the number of Rh active species or to obtain more active Rh species on the catalyst surface.
Garcia, Marco A. S.,Heyder, Rodrigo S.,Oliveira, Kelley C. B.,Costa, Jean C. S.,Corio, Paola,Gusevskaya, Elena V.,dos Santos, Eduardo N.,Bazito, Reinaldo C.,Rossi, Liane M.
p. 1951 - 1960
(2016/07/06)

MULTI-TARGETED UBENIMEX PRODRUG DERIVATIVE AND PREPARATION METHOD AND USE THEREOF
The present invention relates to the design, synthesis, and biological study of multi-targeted Ubenimex pro-drug derivative. More particularly, provided in the present invention is a compound as shown by general structural formula (I) (wherein the definit
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Paragraph 0070

(2015/12/08)

Kilogram-Scale Synthesis of Osteogenic Growth Peptide (10-14) Using a Fragment Coupling Approach
Kilogram-scale synthesis of a bioactive pentapeptide in solution by "3 + 2" fragment coupling strategy has been successively accomplished in the development of OGP (10-14), a minimal OGP-derived sequence that retains the full proliferative activity of the osteogenic growth peptide. The synthetic scheme, coupling conditions, and scaling-up of the process are systematically studied; the epimerization of the tripeptide fragment and pentapeptide are also evaluated.
Zhang, Teng,Chen, Zhenxing,Tian, Yan,Han, Bin,Zhang, Ning,Song, Wei,Liu, Zhulan,Zhao, Jinli,Liu, Jianli
supporting information
p. 1257 - 1262
(2015/09/28)

Efficient transfer hydrogenation reactions with quinazoline-based ruthenium complexes
(4-Phenylquinazolin-2-yl)methanamine was synthesized in high yield by starting from naturally and commercially available glycine in a few steps. The ligand was reacted with RuCl2(PPh3)3 and RuCl2(PPh3)dppb to obtain N-heterocyclic ruthenium(II) complexes. We have examined these catalysts in transfer hydrogenation of acetophenone derivatives and excellent conversions of up to 99% and high TOF values of up to 118,800 h-1 using 0.1 mol % of catalyst were achieved.
Karabuga, Semistan,Bars, Songul,Karakaya, Idris,Gumus, Selcuk
supporting information
p. 101 - 104
(2015/02/02)

Novel NO-releasing derivatives of betulinic acid with antitumor activity
Abstract Thirteen novel NO-releasing derivatives of betulinic acid (BA) bearing two types of NO-donors (nitrates and furoxans) were synthesized and evaluated for their antitumor activity. The results showed that furoxan-based derivatives exhibited higher antitumor activity than nitrate-based derivatives, with compounds 11a and 11b displaying promising potency against B16 cell lines and HepG2 cell lines (IC50 1 μmol/L). We supposed that NO-releasing amount of these derivatives which can be detected by Griess method may contribute more to their antitumor activity. As a result, furoxan-based derivatives released larger amount of NO than that of nitrate-based derivatives, which partially explained the higher anti-tumor activity of the former.
Liu, Jin-Hong,Zhu, Zi-Fei,Tang, Jia,Jiang, Ai-Qin,Hu, Liu-Fang,Chen, Li
supporting information
p. 759 - 762
(2015/08/03)

Multiple-stimulus-responsive supramolecular gels and regulation of chiral twists: The effect of spacer length
Abstract A new class of homologous gelators, LG12-(CH2)n-BSA, composed of bipyridinyl groups, L-glutamic moieties having double dodecyl chains, and linked alkyl spacers with different lengths were synthesized. It was found that these gelators could immobilize medium-polarity solvents readily and the behaviors of these gels showed a dependence on the spacer length. Of all the gels, the LG12-(CH2)11-BSA gels exhibited self-healing property and multiple-stimulus responsibility, such as heating, shaking, and sonication. The investigation of CD spectra indicated that the supramolecular chirality, which was attributed to the chiral transfer from the chiral center to the assemblies, was also closely related to the length of methylene spacers. The longer the alkyl spacers, the weaker the transmitted supramolecular chirality. Only LG12-(CH2)1-BSA gelators, which had the shortest spacers, formed right-handed nanoscale chiral twists owing to crowded hydrogen bonding interactions. Moreover, the high-polarity solvent DMF was found to be able to regulate the chiral twist as well as its pitch length readily. A new twist on healing: Self-healing supramolecular gels that are responsive to multiple stimuli were developed. The formation of nanoscale twists could be controlled by the length of the methylene spacers of the gelator molecules. The pitch of these twists could be regulated by DMF.
Miao, Wangen,Yang, Dong,Liu, Minghua
p. 7562 - 7570
(2015/05/13)

Site-Specific Amphiphilic Magnetic Copolymer Nanoaggregates for Dual Imaging
Molecular imaging along with combinations of imaging modalities can provide a thorough understanding of disease, in particular, tumors. Magnetic resonance imaging (MRI) offers exceptional tissue contrast and resolution; whereas optical imaging provides high sensitivity. Hence a norbornene based copolymer (Nor-Cob-Py-Fol) is reported in this paper as a dual-imaging agent. Nor-Cob-Py-Fol having Co2+ complex, pyrene and poly(ethylene glycol) derived folate, have been synthesized using ring-opening metathesis polymerization (ROMP). All the monomers and polymers are characterized by 1H NMR, IR, GPC, and TGA techniques. The morphology of the copolymer nanoaggregates has been evaluated with DLS, TEM, and SEM techniques. The functionalization of Co2+ to the polymer is monitored by FTIR, 1H NMR, and 13C NMR spectroscopy. Furthermore, the presence of Co2+ in the nanoaggregates is confirmed by the EDX (SEM) technique. To prove the MRI capabilities nature of copolymer nanoaggregates, NMR experiment is performed at room temperature. Cell viability studies suggest the biocompatibility nature of the copolymer. Flow cytometry as well as epifluoroscence microscope experiments clearly demonstrate the dual-imaging ability of the newly designed copolymer. The much higher relaxivity ratio (r2/r1) of the present method clearly establishes the superiority of our system as one of the best contrast agents known to the practitioners of magnetic resonance imaging.
Mukherjee, Saikat,Dinda, Himadri,Shashank, Litesh,Chakraborty, Ipsita,Bhattacharyya, Rangeet,Das Sarma, Jayasri,Shunmugam, Raja
p. 6791 - 6800
(2015/10/28)

Selective Allosteric Antagonists for the G Protein-Coupled Receptor GPRC6A Based on the 2-Phenylindole Privileged Structure Scaffold
G protein-coupled receptors (GPCRs) represent a biological target class of fundamental importance in drug therapy. The GPRC6A receptor is a newly deorphanized class C GPCR that we recently reported for the first allosteric antagonists based on the 2-arylindole privileged structure scaffold (e.g., 1-3). Herein, we present the first structure-activity relationship study for the 2-arylindole antagonist 3, comprising the design, synthesis, and pharmacological evaluation of a focused library of 3-substituted 2-arylindoles. In a FRET-based inositol monophosphate (IP1) assay we identified compounds 7, 13e, and 34b as antagonists at the GPRC6A receptor in the low micromolar range and show that 7 and 34b display >9-fold selectivity for the GPRC6A receptor over related GPCRs, making 7 and 34b the most potent and selective antagonists for the GPRC6A receptor reported to date.
Johansson, Henrik,Boesgaard, Michael Worch,N?rskov-Lauritsen, Lenea,Larsen, Inna,Kuhne, Sebastiaan,Gloriam, David E.,Br?uner-Osborne, Hans,Sejer Pedersen, Daniel
p. 8938 - 8951
(2015/12/09)