- Lipase sensing by naphthalene diimide based fluorescent organic nanoparticles: a solvent induced manifestation of self-assembly
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The precise control of supramolecular self-assembly is gaining utmost interest for the demanding applications of manifested nano-architecture across the scientific domain. This study delineates the morphological transformation of naphthalene diimide (NDI) derived amphiphiles with varying water content in dimethyl sulfoxide (DMSO) and the selective sensing of lipase using its aggregation-induced emission (AIE) properties. To this end, NDI-based, benzyl alcohol protected alkyl chain (C1, C5, and C10) linked amphiphilic molecules (NDI-1,2,3) were synthesized. Among the synthesized amphiphiles, benzyl ester linked C5 tailored naphthalene diimide (NDI-2) exhibited AIE with an emission maximum at 490 nm in a DMSO-water binary solvent system fromfw= 30% and above water content. The fibrous morphology ofNDI-2atfw= 30% got gradually transformed to spherical aggregated particles along with steady increment in the emission intensity upon increasing the amount of water in DMSO. Atfw= 99% water in DMSO, complete transformation to fluorescent organic nanoparticles (FONPs) was observed. Microscopic and spectroscopic techniques demonstrated the solvent driven morphological transformation and the AIE property ofNDI-2. Moreover, this AIE ofNDI-2FONPs was employed in the selective turn-off sensing of lipase against many other enzymes including esterase, through hydrolysis of a benzyl ester linkage with a limit of detection 10.0 ± 0.8 μg L?1. TheNDI-2FONP also exhibited its lipase sensing efficiencyin vitrousing a human serum sample.
- Chakraborty, Debayan,Sarkar, Deblina,Ghosh, Anup Kumar,Das, Prasanta Kumar
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p. 2170 - 2180
(2021/03/14)
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- MACROCYCLIZATION OF PEPTIDOMIMETICS
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The invention provides an improved method of macrocyclization of peptidomimetics, as measured by isolated yields and product distribution, which comprises substitution of one or more of the backbone amide C=O bonds with a turn-inducing motif. The method is general with enhancements seen across a range of ring sizes (e.g. tri-, tetra-, penta- and hexapeptides). Specifically, the invention provides a peptidomimetic macrocycle comprising a carbonyl bioisosteric turn-inducing element having the structure: (I) wherein X is a heteroatom; and wherein R1 to R6 are each independently selected from alkyl, aryl, heteroaryl and H.
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Page/Page column 61
(2019/10/19)
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- DRUGS TO TREAT OCULAR DISORDERS
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The present invention provides new prodrugs of therapeutically active loop diuretics, including oligomeric prodrugs, and compositions to treat medical disorders, for example, ocular disorders such as glaucoma, a disorder or abnormality related to an increase in intraocular pressure (IOP), a disorder requiring neuroprotection, age-related macular degeneration, or diabetic retinopathy.
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- 11,13-MODIFIED SAXITOXINS FOR THE TREATMENT OF PAIN
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Provided herein are compounds, pharmaceutical compositions comprising the compounds, methods of preparing the compounds, and methods of using the compounds and compositions in treating conditions associated with voltage-gated sodium channel function where the compounds are 11,13-modified saxitoxins according to Formula (I): where R4, R4a, R7, R7a, and X2 are as described herein.
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Paragraph 00200; 00274
(2018/10/25)
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- METHOD FOR INHIBITING GROWTH OF CANCER CELLS
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1 A method of inhibiting the growth of cancer cells is disclosed in which cancer cells that contain an enhanced amount relative to non-cancerous cells of one or more of phosphorylated mTOR, Aktl, ERK2 and serine2152-phosphorylated filamin A are contacted
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- Synthesis of poly(ester-amide) dendrimers based on 2,2-Bis(hydroxymethyl) propanoic acid and glycine
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Water-soluble, biodegradable, and biocompatible poly(ester-amide) dendrimers with hydroxyl functional groups are synthesized from previously prepared AB2 adduct of 2,2-bis(hydroxymethyl) propanoic acid (bis-MPA) and glycine as a repeating unit. Two esterification procedures using different coupling reagent/catalyst systems (DCC/DPTS or EDC/DMAP) are studied with respect to efficiency, ease of products purification, and quality of the final products. Both procedures have their own benefits and drawbacks, depending on dendrimer generation. The synthesized poly(ester-amide) dendrimers as well as commercially available bis-MPA dendrimers, poly(ester-amide) hyperbranched polymer, and poly(vinyl alcohol) are used for preparation of solid dispersions of sulfonylurea antidiabetic drug glimepiride to improve its poor water-solubility. In vitro dissolution studies show in comparison with pure glimepiride in crystalline or amorphous form, to the same extent improved glimepiride solubility for solid dispersions based on dendritic polymers, but not for poly(vinyl alcohol). The amount of glimepiride complexed with both dendrimer types increases with dendrimer generation.
- Pahovnik, David,?usak, Anja,Reven, Sebastjan,?agar, Ema
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p. 3292 - 3301
(2016/02/18)
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- SUBSTITUTED PYRROLIDINE-2-CARBOXAMIDES
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There are provided compounds of the formula wherein X, Y, Z, R1, R2, R3 and R4 are as described herein and enantiomers and pharmaceutically acceptable salts and esters thereof. The compounds are useful as anticancer agents.
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Paragraph 0153
(2013/09/26)
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- A self-assembled complex with a Titanium(IV) catecholate core as a potential bimodal contrast agent
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A ditopic chelating ligand (H64) that bears catechol and diethylenetriamine-N,N,N',N',N'-pentaacetate (DTPA) has been designed and shown to specifically bind lanthanide(III) ions at the DTPA core ([Ln(H 24)(H2O)]-/su
- Dehaen, Geert,Eliseeva, Svetlana V.,Kimpe, Kristof,Laurent, Sophie,Vanderelst, Luce,Muller, Robert N.,Dehaen, Wim,Binnemans, Koen,Parac-Vogt, Tatjana N.
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experimental part
p. 293 - 302
(2012/03/09)
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- RADIOLABELLING METHOD USING CYCLOALKYL GROUPS
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This invention relates to novel cyclo alkyl compounds suitable for labeling by 18F, methods of preparing such a compound, compositions comprising such compounds, kits comprising such compounds or compositions and uses of such compounds, compositions or kits for diagnostic imaging by positron emission tomography (PET).
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Page/Page column 47
(2011/02/24)
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- PIPERAZINE DERIVATIVES FOR BINDING AND IMAGING AMYLOID PLAQUES AND THEIR USE
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The invention relates to compounds of formula (I), their synthesis and their use, in particular for detecting amyloid deposits in a patient.
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Page/Page column 34
(2010/04/06)
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- A class of novel conjugates of substituted purine and Gly-AA-OBzl: Synthesis and evaluation of orally analgesic activity
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Aimed at the chemotherapy of chronic pain two kinds of analgesic pharmacophores, substituted purine and Gly-AA-OBzl, were coupled via a five-step-reaction procedure and 19 novel conjugates N-[2-chloro-9- (tetrahydropyran-2-yl)-9H-purin-6-yl]-N-cyclopropylglycylamino acid benzylesters were provided. On mouse-tail flick model their in vivo analgesic activities were assayed. The results indicate that introducing Gly-OC2H 5 into the 6-position of the substituted purine leads to ambiguous increase of the analgesic activity, while introducing Gly-AA-OBzl into this position leads to significant increase of the analgesic activity.
- Kang, Guifeng,Zhao, Ming,Zhang, Xiaoyi,Peng, Li,Li, Chunbo,Mao, Wei,Ye, Weidong,Peng, Shiqi
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supporting information; experimental part
p. 6157 - 6160
(2010/12/19)
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- NOVEL CASCADE POLYMER COMPLEXES, PROCESSES FOR THEIR PREPARATION AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM
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The invention relates to novel cascade polymer complexes, to compositions comprising these compounds, to the use of the complexes in NMR diagnosis, and to processes for preparing these compounds and compositions. The complex-forming cascade polymer comple
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Page/Page column 24
(2008/12/04)
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- Process For Preparing Porphyrin Derivatives, Such As Protoporphyrin (IX) And Synthesis Intermediates
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The present invention relates to a process for preparing a porphyrin of formula (I), optionally in the form of a salt with an alkali metal and/or in the form of a metal complex: in which: R and R′ are as defined in claim 1, comprising: a step of condensation, in an acidic medium, between a dipyrromethane of formula (II): in which R′b is as defined above for (I), and a dipyrromethane of formula (III): in which R″ is as defined in claim 1, and also the compounds of formula (III).
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Page/Page column 16-17
(2008/12/07)
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- A novel naphthylmethyleneimino-type photocleavable protecting group for primary amines
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A novel naphthylmethyleneimino-type protecting group for aliphatic and aromatic primary amines including α-amino acids was devised and its introduction was accomplished in good to excellent yields. This type of protecting group was found to be cleanly removed photochemically to regenerate the primary amines in good to high yields, regardless of steric and electronic properties. Georg Thieme Verlag Stuttgart.
- Igarashi, Tetsutaro,Shimokawa, Masaru,Iwasaki, Miyuki,Nagata, Kensaku,Fujii, Masato,Sakurai, Tadamitsu
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p. 1436 - 1440
(2008/02/13)
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- CHEMICAL COMPOUNDS
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The present invention provides novel compounds that demonstrate protective effects on target cells from HIV infection in a manner as to bind specifically to the chemokine receptor, and which affect the binding of the natural ligand or chemokine to a receptor such as CXCR4 and/or CCR5 of a target cell.
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Page/Page column 105; 106
(2010/10/20)
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- Synthesis and cytotoxic activities of β-carboline amino acid ester conjugates
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β-Carboline represents a class of compounds with potent anti-tumor activity by intercalating with DNA. To further enhance the cytotoxic potency and bioavailability of β-carboline, a series of novel β-carboline amino acid ester conjugates were designed and synthesized, and the cytotoxic activities of these compounds were tested using a panel of human tumor cell lines. In addition, the membrane permeability of these compounds was evaluated in vitro using a Caco-2 cell monolayer model. The β-carboline amino acid ester conjugates demonstrated improved cytotoxic activity compared to the parental β-carbolines. In particular, the Lys/Arg conjugates were the most potent analogs with an IC50 value of 4 and 1 μM against human cervical carcinoma cells. The low interaction energy of Arg conjugate based on molecular modeling may contribute to its enhanced cytotoxicity. Taken together, this study provided new insights into structure-activity relationships in the β-carboline amino acid ester conjugates and identified the β-carboline Lys/Arg conjugates as promising lead compounds for further in vivo biological and molecular evaluation.
- Zhao, Ming,Bi, Lanrong,Wang, Wei,Wang, Chao,Baudy-Floc'h, Michele,Ju, Jingfang,Peng, Shiqi
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p. 6998 - 7010
(2007/10/03)
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- Structural studies of racecadotril and its process impurities by NMR and mass spectroscopy
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Three unknown impurities in racecadotril bulk drug at levels below 0.5% were detected by simple reverse phase isocratic high performance liquid chromatography (HPLC). Structures for these impurities were proposed by molecular ion information and their fragmentation pattern obtained by LC-MS and these impurities were confirmed by NMR spectroscopy. The impurities I, II and III were characterized as benzyl 2-methyl carboximido acetate, benzyl 2-phenyl ethyl carboximido acetate, and benzyl 2-(1-benzyl vinyl carboximido) acetate. These structures were further confirmed by co-injecting of synthetic standards of impurities with racecadotril. The mechanism of the formation of these process related impurities is discussed.
- Mallikarjun Reddy,Moses Babu,Sudhakar,Sharma,Sudershan Reddy,Vyas
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p. 994 - 998
(2007/10/03)
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- Chemoselective conversion of azides to t-butyl carbamates and amines
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Azides were converted to the corresponding carbamates using a system of 20 mol% of decaborane (B10H14) and 20 weight% of 10% Pd/C in methanol in the presence of di-tert-butyl dicarbonate at rt in high yields and to the corresponding amines using a system of 10 mol% of decaborane and 20 weight% of 10% Pd/C in methanol in the absence of di-tert-butyl dicarbonate at rt in high yields.
- Jung, Yeon Joo,Chang, Yu Mi,Lee, Ji Hee,Yoon, Cheol Min
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p. 8735 - 8739
(2007/10/03)
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- Indium Mediated Reduction of Nitro and Azide Groups in the Presence of HCl in Aqueous Media
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Indium mediated reduction of azide and nitro groups in the presence of HCl (1.5 equiv based on indium) at room temperature in aqueous THF successfully provided the corresponding amine in high to quantitative yields. Under the some reaction conditions, selective reduction of azide and nitro group in the presence of vinyl group could be accomplished.
- Lee, Jung Gyu,Choi, Kyung Il,Koh, Hun Yeong,Kim, Youseung,Kang, Yonghan,Cho, Yong Seo
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- The 9-xanthenylmethyl group: A novel photocleavable protecting group for amines
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The 9-xanthenylmethyl group has been investigated as a photocleavable protecting group for amines. Several amines, including two amino acids, were protected in good to very good yield. Irradiation of the protected substrates in neutral solution regenerated the starting amines in good to excellent yield.
- Du, Hong,Boyd, Mary K
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p. 6645 - 6647
(2007/10/03)
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- Application of a unique automated synthesis system for solution-phase peptide synthesis
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An automated synthesis system, which is suitable for repetitive syntheses using similar reaction procedures, was used to synthesize systematically a library of all possible dipeptides (25) and tripeptides (125) from 5 protected amino acids. The apparatus has also been applied to the automated synthesis of 10 fragment tripeptide derivatives that are constituents of the hormone PACAP-27. The measured molecular optical rotation values of the library of 125 tripeptides were found to correlate well with calculated values obtained by summation of the molecular optical rotation values for the constituent amino acids.
- Sugawara,Kobayashi,Okamoto,Kitada,Fujino
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p. 1272 - 1280
(2007/10/02)
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- The synthesis of pure Amadori rearrangement products
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The term "Maillard reaction" is used to describe a complex set of reactions in foods leading to flavour generation and non-enzymatic browning.The first step in this process is the so-called Amadori rearrangement: a reducing saccharide and a peptide fragment react to form an Amadori Rearrangement Product (ARP).To be able to do model studies on flavour generation, gram amounts of pure ARP are required.In the present study, glucose-derived ARPs were synthesised from specifically protected and activated starting compounds.After deprotection and purification, pure ARPs were obtained.This is the first time that ARPs of dipeptides have been isolated.
- Noomen, S. N.,Breel, G. J.,Winkel, C.
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p. 321 - 324
(2007/10/02)
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- Nonprostanoid Prostacyclic Mimetics. 5. Structure-Activity Relationships Associated with phenoxy>acetic Acid
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cis-phenoxy>acetic acid (3) was previously identified as a nonprostanoid prostacyclin (PGI2) mimetic that potently inhibits ADP-induced aggregation of human platelets with an IC50 of 0.18 μM.As part of an effort to further explore structure-activity relationships for this class of platelet inhibitor and to provide additional insight into the nonprostanoid PGI2 mimetic pharmacophore, the effect of constraining the cis-olefin moiety of 3 into various ring systems was examined.Incorporation of the cis-olefin of 3 into either an oxazole (26) or an unsubstituted pyrazole (35) heterocycle provided compounds that are eqipotent with progenitor 3.However, the oxazole 11f, which is isomeric with 26, inhibits ADP-induced human platelet aggregation in vitro with an IC50 of 0.027 μM, 6-fold more potent than 3, 26, or 35.These results suggest that the central oxazole ring of 11f is functioning as more than a simple scaffold that provides optimal stereodefinition for interaction with the PGI2 receptor.The nitrogen atom of the central heterocycle of 11f is postulated to engage in hydrogen-bond formation with a donor moiety in the PGI2 receptor protein, an interaction not available to 26 due to the markedly different topology.In support of this contention, the crystal structures of 11f and 26 contain strong intermolecular hydrogen bonds between the carboxylic acid hydrogen atom and the nitrogen atom of the central oxazole ring.Although 11f and 26 are exact isosteres and could, in principle, adopt the same molecular packing arrangement in the solid state, this is not the case, and the intermolecular hydrogen-bonding interactions in 11f and 26 are accommodated by entirely different molecular packing arrangements.Incorporation of the olefin moiety of 3 into a benzene ring provided a compound, 40, over 60-fold weaker with an IC50 of 11.1 μM.The affinitites of 11f, 26, 31, 32, and 40 for the human platelet PGI2 receptor, determined by displacement of iloprost, correlated with inhibition of platelet function.The solid-state structures of 11f, 26, 31, 32, and 40 were determined and revealed that the more potent compounds 11f and 26 adopt a relatively planar overall topography.In contrast, the central phenyl ring and the phenoxy ring of the weakly active compound 40 are rotated by 53 deg from planarity.The chemical shifts of the protons of the phenoxy rings of 3, 11f, 18, 26, 31, 32, and 40 suggest that in solution 3, 11f, 18, and 26 adopt a planar conformation while 40 does not.Taken together, these data suggest that the more potent nonprostanoid PGI2 mimetics are those in which elements of the side chain are able to adopt a relatively planar topographical arrangement.
- Meanwell, Nicholas A.,Romine, Jeffrey L.,Rosenfeld, Michael J.,Martin, Scott W.,Trehan, Ashok K.,et al.
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p. 3884 - 3903
(2007/10/02)
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- Synthesis and spectroscopic properties of azaglutamine amino acid and peptide derivatives
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tert-Butyl carbazate and Boc-amino acid hydrazides undergo a Michael addition with acrylamide to give substituted carbazates having the side-chain of glutamine on nitrogen. These carbazates may react with chloroformates to give protected azaglutamine esters, and N-activated amino acid esters to give azaglutamine peptides.
- Gray,Quibell,Jiang,Baggett
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p. 141 - 146
(2007/10/02)
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