- SPIRO-LACTAM COMPOUNDS AND METHODS OF TREATING VIRAL INFECTIONS USING THE SAME
-
Disclosed are compounds, and pharmaceutically acceptable salts thereof, that can ameliorate or treat a viral infection in a subject in need thereof. The disclosure also includes conjugates of such compounds with a protease.
- -
-
Page/Page column 100; 106
(2021/12/28)
-
- Highly Stable Zr(IV)-Based Metal-Organic Frameworks for Chiral Separation in Reversed-Phase Liquid Chromatography
-
Separation of racemic mixtures is of great importance and interest in chemistry and pharmacology. Porous materials including metal-organic frameworks (MOFs) have been widely explored as chiral stationary phases (CSPs) in chiral resolution. However, it remains a challenge to develop new CSPs for reversed-phase high-performance liquid chromatography (RP-HPLC), which is the most popular chromatographic mode and accounts for over 90% of all separations. Here we demonstrated for the first time that highly stable Zr-based MOFs can be efficient CSPs for RP-HPLC. By elaborately designing and synthesizing three tetracarboxylate ligands of enantiopure 1,1′-biphenyl-20-crown-6, we prepared three chiral porous Zr(IV)-MOFs with the framework formula [Zr6O4(OH)8(H2O)4(L)2]. They share the same flu topological structure but channels of different sizes and display excellent tolerance to water, acid, and base. Chiral crown ether moieties are periodically aligned within the framework channels, allowing for stereoselective recognition of guest molecules via supramolecular interactions. Under acidic aqueous eluent conditions, the Zr-MOF-packed HPLC columns provide high resolution, selectivity, and durability for the separation of a variety of model racemates, including unprotected and protected amino acids and N-containing drugs, which are comparable to or even superior to several commercial chiral columns for HPLC separation. DFT calculations suggest that the Zr-MOF provides a confined microenvironment for chiral crown ethers that dictates the separation selectivity.
- Jiang, Hong,Yang, Kuiwei,Zhao, Xiangxiang,Zhang, Wenqiang,Liu, Yan,Jiang, Jianwen,Cui, Yong
-
supporting information
p. 390 - 398
(2021/01/13)
-
- Cytotoxic activity of synthetic chiral amino acid derivatives
-
Cancer is a chronic degenerative disease considered one of the most important causes of death worldwide. In this context, a series of dual-protected amino acid derivatives was synthesized and evaluated as potential novel anticancer agents. The 40 derivatives were prepared in up to three reaction steps. The cytotoxic activities were screened in vitro against a panel of tumor and non-tumor cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Among the synthesized derivatives, three of them showed promising activity against cancer cells with half-maximal inhibitory concentration (IC50) ranging between 1.7-6.1 μM. The most promising derivative, bearing both a lipophilic N-alkyl diamine moiety and a protected amino acid scaffold showed a selectivity index of 3.4 towards tumor cells. The N-alkyl diamine moiety seems to play a crucial role in the enhancement of the anticancer activity. On the other hand, the incorporation of an amino acid scaffold resulted in increase in the selectivity towards cancer cell lines.
- de Castro, Pedro P.,Siqueira, Raoni P.,Conforte, Luiza,Franco, Chris H.J.,Bressan, Gustavo C.,Amarante, Giovanni W.
-
p. 193 - 200
(2019/12/28)
-
- PEPTIDE AMIDE COMPOUND AND PREPARATION METHOD AND MEDICAL USE THEREOF
-
The invention provides a peptide amide compound represented by the general general formula (I), a preparation method thereof, and a medical application thereof. The compound has a novel structure, better biological activity, and better analgesic effect.
- -
-
Paragraph 0228
(2020/06/15)
-
- Alanine derivative and preparation method and application thereof
-
The invention discloses an alanine derivative and a preparation method and application thereof. The preparation comprises the following steps: taking biphenylpyridine as a hinge region binding fragment, introducing L-alanine as a flexible linker by adopting a fragment drug design strategy to construct a compound library with kinase inhibitory activity, and discovering a tyrosine kinase inhibitor with Bcr-Abl kinase inhibitory activity through ADP-Glo kinase activity screening. The compound can be used for preparing anti-tumor (chronic myelogenous leukemia) drugs, inhibits kinase activity of Bcr-Abl and Bcr-AblT315I, and has the activity of inhibiting cell proliferation of K562 cells. The introduction of an alanine structure has an important effect on the inhibitory activity of the compound, the structural diversity of the kinase inhibitor can be expanded, and the activity result shows that the structure can be used as a Linker pharmacodynamic fragment of the Bcr-Abl tyrosine kinase inhibitor.
- -
-
Paragraph 0044; 0048
(2019/07/04)
-
- INHIBITORS OF FIBROBLAST ACTIVATION PROTEIN
-
Compounds and compositions for modulating fibroblast activation protein (FAP) are described. The compounds and compositions may find use as therapeutic agents for the treatment of diseases, including hyperproliferative diseases.
- -
-
Paragraph 1047-1048
(2019/07/03)
-
- GLUCOPYRANOSYL DERIVATIVE AND USE THEREOF
-
Provided are a glucopyranosyl derivative as a sodium-dependent glucose transporters inhibitor, especially as a SGLT1 inhibitor, a pharmaceutically acceptable salt or a stereoisomer thereof, a pharmaceutical composition thereof, and the uses of the compound and pharmaceutical composition thereof in the preparation of drugs for the treatment of diabetes and diabetes-related diseases.
- -
-
Paragraph 00227; 00283
(2019/08/12)
-
- Mandelic acid aminoacid aminopeptidase N inhibitor and synthesis method
-
The invention relates to a mandelic acid aminoacid aminopeptidase N inhibitor, the general chemical formula of which is in the drawing (The formula is shown in the description.), wherein R1, R2, R3 and R4 are H, F, Cl, Br, NO2, OCH3, CH3 or CH(CH3)3; and R5 is CH3 or CH2CH(CH3)2. Thiosemicarbazide and substituted benzoic acid are utilized to carry out condensation reaction, so that a substituted phenylthiadiazole derivative is produced, the substituted phenylthiadiazole derivative is connected with Boc-protected amino acid by acylation reaction, the protecting group is then removed under the effect of strong acid, and finally, after acylation with trimethylsiloxylphenylacetyl chloride, the target compound is obtained. The route of the synthesis process is short, the raw materials are easyto obtain, and the production cost is low.
- -
-
Paragraph 0037; 0038
(2018/07/15)
-
- Synthesis and molecular simulation study of furoic peptidomimetic derivatives as potent aminopeptodase N inhibitors
-
The aminopeptidase N (APN) plays a critical role in angiogenesis and is over-expressed in tumor cells. In this paper, we report the synthesis and enzyme inhibition assay of furoic peptidomimetic compounds. These new compounds exhibit potent inhibitory ability toward APN with IC50 values lying in the micromolar level. The binding mode of inhibitors in APN active site was explained by a molecular simulation study. These data reveal that ligand coordinating with the catalytic Zn-ion is very important for inhibitory activities.
- Gao, Min,He, Junhua,Xu, Weidong,Lai, Xiaoping,Liu, Fen,Tu, Guogang
-
p. 123 - 127
(2018/03/25)
-
- Amine compound for inhibiting SSAO/VAP-1 and application thereof in medicines
-
The present invention relates to an amine compound for inhibiting SSAO/VAP-1 and application thereof in medicines. In particular, the present invention relates to an amine compound for inhibiting a semicarbazide-sensitive oxidase (SSAO) and/or vascular adhesion protein-1 (VAP-1) inhibitor, or a pharmaceutically acceptable salt thereof, a stereoisomer or an/a E/Z isomer, further relates to a pharmaceutical composition containing the amine compound. The invention further relates to the application of the amine compound and the pharmaceutical composition in manufacture of the medicines for treatment of inflammation, inflammation-related diseases and immune diseases.
- -
-
Paragraph 0317; 0319; 0320; 0321
(2018/09/08)
-
- Synthesis method for nitro group-containing natural product chrysamides B and diastereoisomer-compound thereof
-
The invention belongs to the technical fields of medicinal chemistry and organic synthesis, and relates to a synthesis method for a nitro group-containing natural product chrysamides B, a chrysamidesB diastereoisomer-compound and a synthesis method and application thereof. According to the invention, a convergent synthesis method is adopted to condense chiral epoxy carboxylic acid and chiral dimethylpiperazine ring, and thereby the nitro group-containing natural product chrysamides B with a symmetrical structure and the chrysamides B diastereoisomer-compound are easily and efficiently synthesized. By three-step continuous oxidation, chiral epoxy carboxylic acid is prepared from p-nitrobenzaldehyde which is easy to obtain commercially, and dimethylpiperazine ring is prepared by reduction after alanine dimerization. The compound shows inhibitory activity on pasteurella multocida. Such a convergent synthesis route can be applied to the chemical synthesis of compounds with the similar structure and related derivatives, opening up a broad development space for novel antibiotic drugs.
- -
-
Paragraph 0026; 0027
(2018/11/22)
-
- Metal-induced supramolecular chirality inversion of small self-assembled molecules in solution
-
A non-covalent self-assembled chiral alanyl aminopyridine ligand exhibits supramolecular chirality in solution, independent of the organic solvent used. The supramolecular chirality of the assemblies is completely inverted by complexation to zinc ions. To date, such a supramolecular metal-ligand system has not been reported in the literature.
- Kokan, Zoran,Peri?, Berislav,Vazdar, Mario,Marini?, ?eljko,Viki?-Topi?, Dra?en,Me?trovi?, Ernest,Kirin, Sre?ko I.
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supporting information
p. 1945 - 1948
(2017/02/15)
-
- Antiviral nucleoside phosphoramidate and pharmaceutical composition and applications thereof
-
The invention provides an antiviral nucleoside phosphoramidate and a pharmaceutical composition and applications thereof. The nucleoside phosphoramidate compound is prepared by connecting nucleoside with phosphate through phosphorus-oxygen bonds. The structural formulas of the nucleoside phosphoramidate compound are represented by a, a1, a2, b, b1, and b2. The invention also discloses stereoisomers, pharmaceutically acceptable salts, hydrates, solvates, or crystals of the nucleoside phosphoramidate compound. The anti-hepatitis C activity of the provided novel nucleoside phosphoramidate is obviously better than that of sofosbuvir used in clinic. On the saccharide ring, the fluorine atoms are replaced by chlorine atoms, and the cytotoxicity of measure cell lines is prominently reduced. By systematically modifying and optimizing the basic groups, saccharide rings, and prodrugs, the anti-hepatitis C activity of partial synthesized compounds is 2 to 10 times higher than that of sofosbuvir. At the same time, the key parts of metabolism are optimized, the metabolism stability and chemical stability of synthesized compounds in plasma are better, compared with those of sofosbuvir.
- -
-
Paragraph 0092-0095
(2017/05/06)
-
- Efficient N-Boc protection of amines by a reusable heterogeneous solid acid nanocatalyst at room temperature
-
An efficient and rapid protocol for chemoselective N-Boc protection of various structurally different aryl, aliphatic, and heterocyclic amines is reported with (Boc)2O using mesoporous silica phenylsulfonic acid (SBA-15-Ph-SO3H) as a recyclable and heterogeneous solid acid nanocatalyst under solvent-free condition at ambient temperature. The catalyst can be easily recovered and reused for ten reaction cycles for protection of amines without considerable loss of activity. The advantages of this green method are simplicity, easy workup, chemoselectivity, short reaction time, and excellent yield.
- Veisi, Hojat,Sedrpoushan, Alireza,Ghazizadeh, Habibollah,Hemmati, Saba
-
p. 1451 - 1461
(2016/04/26)
-
- 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.
- -
-
Paragraph 0022; 0023; 0024
(2017/01/12)
-
- Enantioselective hydrolysis of amino acid esters by non-chiral copper complexes equipped with bis (β-cyclodextrin)s
-
Two non-chiral copper(II) complexes equipped with bis(β-cyclodextrin)s (bisCDs) were explored as hydrolase models for the enantioselective hydrolysis of two pairs of alkyl chain-possessing amino acid ester enantiomers. The two bisCD complexes are pyridine-linked with different CD cavity orientations, denoted as CuL1 (L1?=?2,6-bis(6-mono-amino-β-cyclodextrin-methyl)-pyridine) and CuL2 (L2?=?2,6-bis(3-mono-amino-β-cyclodextrin-methyl)-pyridine). Kinetic studies indicated that the “back-to-back” bisCD complex CuL1 showed higher catalytic efficiency and more pronounced enantioselectivity for all substrates than the “face-to-face” bisCD complex CuL2. Overall preference of L-isomers was observed for both complexes. In the presence of CuL1, the formation of catalyst-substrate Michaelis complexes during the hydrolysis was demonstrated by saturation kinetic study and Electrospray ionization mass spectrometry (ESI–MS) analysis. Enantiomer selectivity (vmaxL/vmaxD) value for N-Boc-N'-Boc-Lysine 4-nitrophenyl esters (Boc-Lys(Boc)-ONp), the longer alkyl-chain analogs, is twice of that for N-Boc-Alanine 4-nitrophenyl esters (Boc-Ala-ONp). The enantioselective hydrolysis of Boc-Lys(Boc)-ONp promoted by CuL1 was confirmed by chiral high-performance liquid chromatography (HPLC) analysis. The participation of CD cavities during enantioselective hydrolysis was investigated through inhibition assay. The enantioselectivity in hydrolyzing different amino acid esters promoted by CuL1 was compared. The mechanism involved in the cooperation of two adjacent CD cavities of bisCD was proposed.
- Xue, Shan-Shan,Zhao, Meng,Lan, Jing-Xing,Ye, Rui-Rong,Li, Yi,Ji, Liang-Nian,Mao, Zong-Wan
-
p. 297 - 303
(2016/09/19)
-
- Phase I metabolites of mephedrone display biological activity as substrates at monoamine transporters
-
Background and Purpose: 4-Methyl-N-methylcathinone (mephedrone) is a synthetic stimulant that acts as a substrate-type releaser at transporters for dopamine (DAT), noradrenaline (NET) and 5-HT (SERT). Upon systemic administration, mephedrone is metabolized to several phase I compounds: the N-demethylated metabolite, 4-methylcathinone (nor-mephedrone); the ring-hydroxylated metabolite, 4-hydroxytolylmephedrone (4-OH-mephedrone); and the reduced keto-metabolite, dihydromephedrone. Experimental Approach: We used in vitro assays to compare the effects of mephedrone and synthetically prepared metabolites on transporter-mediated uptake and release in HEK293 cells expressing human monoamine transporters and in rat brain synaptosomes. In vivo microdialysis was employed to examine the effects of i.v. metabolite injection (1 and 3?mg·kg?1) on extracellular dopamine and 5-HT levels in rat nucleus accumbens. Key Results: In cells expressing transporters, mephedrone and its metabolites inhibited uptake, although dihydromephedrone was weak overall. In cells and synaptosomes, nor-mephedrone and 4-OH-mephedrone served as transportable substrates, inducing release via monoamine transporters. When administered to rats, mephedrone and nor-mephedrone produced elevations in extracellular dopamine and 5-HT, whereas 4-OH-mephedrone did not. Mephedrone and nor-mephedrone, but not 4-OH-mephedrone, induced locomotor activity. Conclusions and Implications: Our results demonstrate that phase I metabolites of mephedrone are transporter substrates (i.e. releasers) at DAT, NET and SERT, but dihydromephedrone is weak in this regard. When administered in vivo, nor-mephedrone increases extracellular dopamine and 5-HT in the brain whereas 4-OH-mephedrone does not, suggesting the latter metabolite does not penetrate the blood–brain barrier. Future studies should examine the pharmacokinetics of nor-mephedrone to determine its possible contribution to the in vivo effects produced by mephedrone.
- Mayer,Wimmer,Dillon-Carter,Partilla,Burchardt,Mihovilovic,Baumann,Sitte
-
supporting information
p. 2657 - 2668
(2016/10/19)
-
- SPIROCYCLIC HAT INHIBITORS AND METHODS FOR THEIR USE
-
Compounds having a structure of Formula (IX) or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein R1, R2a, R2b, R3a, R3b, R4a, R4b, Q1----Q2, R6, R7, A, B, W, x, and y are as defined herein and are provided. Pharmaceutical compositions comprising such compounds and methods for treating various HAT-related conditions or diseases, including cancer, by administration of such compounds are also provided.
- -
-
Page/Page column 698
(2016/04/10)
-
- Efinaconazole intermediate and preparation method thereof
-
The invention provides an efinaconazole intermediate compound (VI) and a preparation method thereof and relates to the field of pharmaceutical technology. The preparation method comprises the following steps: a compound (V) reacts with trimethylsulfoxonium iodide to obtain a compound (VV); and the compound (VV) experiences a ring-opening reaction with 1,2,4-triazole to obtain the compound (VI). The method has the advantages of easiness in operation, low production cost and good product quality and is suitable for industrial production.
- -
-
Paragraph 0046; 0047; 0048
(2016/10/10)
-
- 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
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p. 5611 - 5617
(2016/10/24)
-
- Benzo[a]acridinylmethyl esters as pH sensitive fluorescent photoactive precursors: Synthesis, photophysical, photochemical and biological applications
-
A newsworthy class of carboxylate esters based on the (benzo[a]acridin-12- yl)methyl (BAM) chromophore has been shown to perform dual functions as a "pH sensitive fluorescent probe" and a "phototrigger" for acids. The photophysical properties of all the BAM ester conjugates were investigated and found to be highly sensitive to solvent polarity, H-bonding capability and pH of the environment. On irradiation using UV light (≥410 nm), BAM ester conjugates underwent heterolytic cleavage of C-O bonds resulting in efficient release of carboxylic and amino acids. Interestingly, the newly synthesized BAM chromophore was also explored for the construction of a drug delivery system (DDS). In the current DDS, the BAM chromophore plays two important roles: (i) a "fluorophore" for cell imaging and (ii) a "phototrigger" for the drug release. In vitro biological studies revealed that the newly developed BAM based DDS has a good biocompatibility, cellular uptake properties and efficient photoregulated anticancer drug release ability. the Partner Organisations 2014.
- Ikbal,Saha, Biswajit,Barman, Shrabani,Atta, Sanghamitra,Banerjee, Deb Ranjan,Ghosh, Sudip Kumar,Singh, N. D. Pradeep
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p. 3459 - 3469
(2014/05/20)
-
- Novel Isobaric Tandem Mass Tags for Quantitative Proteomics and Peptidomics
-
Compositions and methods of tagging peptides and other molecules using novel isobaric tandem mass tagging reagents, including novel N,N-dimethylated amino acid 8-plex and 16-plex isobaric tandem mass tagging reagents. The tagging reagents comprise: a) a reporter group having at least one atom that is optionally isotopically labeled; b) a balancing group, also having at least one atom that is optionally isotopically labeled, and c) an amine reactive group. The tagging reagents disclosed herein serve as attractive alternatives for isobaric tag for relative and absolute quantitation (iTRAQ) and tandem mass tags (TMTs) due to their synthetic simplicity, labeling efficiency and improved fragmentation efficiency.
- -
-
Paragraph 0197
(2013/04/10)
-
- NOVEL TRIFLUOROMETHYL-OXADIAZOLE DERIVATIVES AND THEIR USE IN THE TREATMENT OF DISEASE
-
The invention relates to novel trifluoromethyl-oxadiazole derivatives of formula (I), and pharmaceutically acceptable salts thereof, (I) in which all of the variables are as defined in the specification, pharmaceutical compositions thereof, pharmaceutical combinations thereof, and their use as medicaments, particularly for the treatment of neurodegeneration, muscle atrophy or metabolic syndrome via inhibition of HDAC4.
- -
-
Page/Page column 93
(2013/03/26)
-
- BORONIC ACID CATALYSTS AND METHODS OF USE THEREOF FOR ACTIVATION AND TRANSFORMATION OF CARBOXYLIC ACIDS
-
The present application provides methods and catalysts for activation of carboxylic acids for organic reactions. In particular, methods are disclosed for direct nucleophilic addition reactions, such as, amidation reactions with amines, cycloadditions, and conjugate additions, using boronic acid catalysts of formula I, II or III: Also included are novel boronic acid catalysts of formula IV, V and III:
- -
-
Page/Page column 46-47
(2012/09/10)
-
- Synthesis and cytotoxic activity of methyl glycyrrhetinate esterified with amino acids
-
Methyl glycyrrhetinate was esterified at position C3 of ring A using different amino acids. A short, unbranched chain of four carbon atoms with two amino groups in positions 2 and 4 was shown to be the most active compound of this series (IC50 = 0:8 M on liposarcoma Lipo cells). These compounds trigger apoptosis as shown by an acridine orange/ethidium bromide assay, trypan blue tests and DNAladdering experiments.
- Csuk, Rene,Schwarz, Stefan,Siewert, Bianka,Kluge, Ralph,Stroehl, Dieter
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p. 731 - 746
(2012/11/13)
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- Zinc chloride promoted efficient and facile BOC protection of amines
-
Amines are efficiently protected as their BOC derivatives under mild reaction conditions when reacted with BOC anhydride in presence of ZnCl2. The present method is applicable to a variety of amines including aliphatic, aromatic as well as heteroaromatic amines. This protocol appears to be competitive and in some cases superior to previously reported procedures that work under basic conditions.
- Arifuddin, M.,Lakshmikant, N.,Rajasekar, N.,Shinde, D. B.
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p. 1168 - 1172,5
(2020/08/31)
-
- Ferric chloride-promoted efficient and facile BOC protection of amines
-
Amines are efficiently protected as their tertiary butyloxycarbonyl (BOC) derivatives under mild reaction condition when reacted with (BOC)2O in the presence of FeCl3. The present method is applicable to a variety of amines including aliphatic, aromatic, and hetero aromatic amines.
- Tasneem,Rajanna
-
experimental part
p. 715 - 719
(2011/04/12)
-
- Novel synthesis and biological evaluation of enigmols as therapeutic agents for treating prostate cancer
-
Enigmol is a synthetic, orally active 1-deoxysphingoid base analogue that has demonstrated promising activity against prostate cancer. In these studies, the pharmacologic roles of stereochemistry and N-methylation in the structure of enigmols were examined. A novel enantioselective synthesis of all four possible 2S-diastereoisomers of enigmol (2-aminooctadecane-3,5-diols) from l-alanine is reported, which features a Liebeskind-Srogl cross-coupling reaction between l-alanine thiol ester and (E)-pentadec-1-enylboronic acid as the key step. In vitro biological evaluation of the four enigmol diastereoisomers and 2S,3S,5S-N-methylenigmol against two prostate cancer cell lines (PC-3 and LNCaP) indicates that all but one diastereomer demonstrate potent oncolytic activity. In nude mouse xenograft models of human prostate cancer, enigmol was equally effective as standard prostate cancer therapies (androgen deprivation or docetaxel), and two of the enigmol diastereomers, 2S,3S,5R-enigmol and 2S,3R,5S-enigmol, also caused statistically significant inhibition of tumor growth. A pharmacokinetic profile of enigmol and N-methylenigmol is also presented.
- Garnier-Amblard, Ethel C.,Mays, Suzanne G.,Arrendale, Richard F.,Baillie, Mark T.,Bushnev, Anatoliy S.,Culver, Deborah G.,Evers, Taylor J.,Holt, Jason J.,Howard, Randy B.,Liebeskind, Lanny S.,Menaldino, David S.,Natchus, Michael G.,Petros, John A.,Ramaraju, Harsha,Reddy, G. Prabhakar,Liotta, Dennis C.
-
supporting information; experimental part
p. 438 - 443
(2011/08/06)
-
- IMIDAZOLIDINEDIONE DERIVATIVES
-
The invention provides a compound of formula (Ia), and pharmaceutically acceptable salts thereof. The invention also provides use of the compounds or salts as modulators of Kv3.1 and/or Kv3.2, and in the treatment of diseases or disorders where a modulator of Kv3.1 and/or Kv3.2 is required, such as depression and mood disorders, hearing disorders, schizopherenea, substance abuse disorders, sleep disorders or epilepsy.
- -
-
Page/Page column 50
(2011/06/26)
-
- Optically active helical substituted polyacetylenes as chiral seeding for inducing enantioselective crystallization of racemic N -(tert -butoxycarbonyl)alanine
-
Helical substituted polyacetylenes were investigated for inducing enantioselective crystallization of racemic N-(tert-butoxycarbonyl)alanine (BOC-alanine) enantiomers. For this purpose, helical substituted polyacetylenes [(R)-PSA and (S)-PSA)] were dissolved in supersaturated racemic BOC-alanine solutions. Upon cooling the solutions, (R)-PSA preferentially induced BOC-l-alanine to crystallize, while (S)-PSA facilitated the enantioselective crystallization of BOC-d-alanine, according to the characterizations by circular dichroism, XRD, SEM, and optical rotation analyses. As expected, no enantioselective crystallization was observed in such cases: racemic BOC-alanine enantiomers in the absence of optically active helical PSA and racemic BOC-alanine enantiomers in the presence of equal amount of (R)-PSA and (S)-PSA. The present study provides the first direct evidence for the role of artificially synthetic helical polymers in inducing efficiently enantioselective crystallization.
- Chen, Bo,Deng, Jianping,Cui, Xin,Yang, Wantai
-
experimental part
p. 7109 - 7114
(2012/04/04)
-
- Highly enantioselective fluorescent recognition of amino acid derivatives by unsymmetrical salan sensors
-
Novel unsymmetrical salan fluorescent sensors 2a and 2b have been designed and synthesized. The chiral recognition of N-Boc-protected amino acids by 2a and 2b has been investigated. Sensor 2a possesses higher sensitivity and enantioselectivity than sensor 2b does. Job analysis and nonlinear regression results show that 2a can form a 1:1 stoichiometric complex with a N-Boc-protected amino acid. The obtained response selectivities and the association constants indicate that 2a is a highly enantioselective and sensitive fluorescent sensor toward N-Boc-protected amino acids.
- Yang, Xia,Shen, Kang,Liu, Xuechao,Zhu, Chengjian,Cheng, Yixiang
-
scheme or table
p. 4611 - 4614
(2011/10/01)
-
- Enantiomeric resolution of α-amino acid derivatives on two diastereomeric chiral stationary phases based on chiral crown ethers incorporating two different chiral units
-
Two diastereomeric chiral stationary phases (CSPs) were applied to the liquid chromatographic resolution of various racemic a-amino methyl esters, α-amino N,N-diethylamides and α-amino N-propylamides. The CSP incorporating (R)-3,3' -diphenyl-1,1' -binaphtyl and (R,R)-tartaric acid unit as chiral barriers did not show any chiral recognition. In contrast, the CSP incorporating (R)-3,3'-diphenyl-1,1'-binaphtyl and (S,S)-tartaric acid unit as chiral barriers was found to show excellent chiral recognition especially for the two enantiomers of a-amino N-propylamides. Some of a-amino methyl esters and α-amino N,N-diethylamides were also resolved on the CSP incorporating (R)-3,3'-diphenyl-1,1'-binaphtyl and (S,S)-tartaric acid unit. From these results it was concluded that the two chiral units composing the diastereomeric CSPs can show "matched" or "mismatched" effect on the chiral recognition according to their absolute stereochemistry.
- Kim, Hee Jin,Choi, Hee Jung,Cho, Yoon Jae,Hyun, Myung Ho
-
body text
p. 1551 - 1554
(2010/10/20)
-
- Synthesis and antitumour activity of glycyrrhetinic acid derivatives
-
Glycyrrhetinic acid (GA) is one of many interesting triterpenoic acids showing anticancerogenic potential. GA is known to trigger apoptosis in tumour cell lines, although GA has a low cytotoxicity. In our study we were able to prepare derivatives of GA that show lowered the IC50 values as determined by a sulforhodamine B (SRB) assay using 15 different human tumour cell lines. Thus, combining an ester group combined with the presence of an amino acid moiety led to a ca. 60-fold improved antitumor activity. Experiments on mouse embryonic fibroblasts (NiH3T3) revealed that these compounds showed a better selectivity for tumour cells compared to the parent compound GA. An apoptotic effect of some of these compounds was determined using an acridine orange/ethidium bromide (AO/EB) test and DNA laddering experiments.
- Schwarz, Stefan,Csuk, René
-
experimental part
p. 7458 - 7474
(2011/01/04)
-
- Atlantic cod trypsin-catalyzed peptide synthesis with inverse substrates as acyl donor components
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Atlantic cod trypsin-catalyzed peptide synthesis has been studied by using p-amidino- and p-guanidinophenyl esters of N-(tert-butyloxycarbonyl)amino acid as acyl donor components. The reaction temperature was optimized at 0 °C. The method was shown to be successful as effectively for synthesizing the peptide and useful for preparing dipeptide between D-amino acid with D-amino acid and β-amino acid with β-amino acid, respectively. The enzymatic hydrolysis of the resulting products was negligible.
- Fuchise, Tomoyoshi,Kishimura, Hideki,Yang, Zhi-Hong,Kojoma, Mareshige,Toyota, Eiko,Sekizaki, Haruo
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experimental part
p. 484 - 487
(2010/08/19)
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- Merrifield resin supported dipeptides: Efficient and recyclable organo-catalysts for asymmetric aldol reactions under neat reaction conditions
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A number of Merrifield resin supported dipeptide and tripeptide catalysts have been developed of which Pro-Ala-O-P, catalyst A, was found to be an efficient catalyst for asymmetric direct aldol reactions. Aldehydes and ketones underwent smooth aldol reaction in the presence of a catalytic amount of A at room temperature under neat reaction conditions and generated the corresponding products with excellent isolated yields (≤98%), good diastereoselectivities (dr ≥ 90:10) and enantioselectivities (≤95% ee). In addition, catalyst A could be used seven times without loss of its catalytic activity. Thieme Stuttgart.
- Yan, Jincan,Wang, Lei
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experimental part
p. 2065 - 2072
(2009/04/03)
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- Cooling Compounds
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A cooling composition comprising at least one compound of the Formula I in which R is selected from the group of moieties consisting of (CH2)nCOOR″; (CH2)nCONMe2; (CH2)nOR″; and CHNH2CH3; where n is 1-3 and R″ is independently selected from hydrogen, methyl and ethyl; and R′ is selected from the group consisting of the moieties fenchyl, D-bornyl, L-bornyl, exo-norbornyl, 2-methylisobornyl, 2-ethylfenchyl, 2-methylbornyl, cis-pinan-2-yl, verbanyl and isobornyl. The compositions are useful in providing cooling sensations to the skin or mucous membranes of the body.
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- Synthesis of 3,5-disubstituted 1,2,4-oxadiazoles as peptidomimetic building blocks
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Twelve new 1,2,4-oxadiazole based compounds have been synthesized. Their structures contain a protected amine and a carboxyl or an ester group, and thus serve as potential peptidomimetic building blocks. The synthetic route is simple and mild conditions are used so that the chirality of the starting amino acids is retained.
- Jakopin, ?iga,Ro?kar, Robert,Dolenc, Marija Sollner
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p. 1465 - 1468
(2008/02/02)
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- Acid- and base-stable esters: A new protecting group for carboxylic acids
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An acid- and base-stable protecting group for carboxylic acids is described. The esters of (2,6-dichloro-4-methoxyphenyl)(2,4-dichlorophenyl) methanol are stable to Bransted and Lewis acids, Bronsted bases, and a wide variety of nucleophiles; however, the esters can be conveniently deprotected by a solvolytic displacement reaction with 20% trifluoroacetic acid. Georg Thieme Verlag Stuttgart.
- Kurosu, Michio,Biswas, Kallolmay,Narayanasamy, Prabagaran,Crick, Dean C.
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p. 2513 - 2516
(2008/02/13)
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- A facile synthesis of p- and m-(amidinomethyl)phenyl esters derived from amino acid and tryptic hydrolysis of these synthetic inverse substrates
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A facile synthetic method for p- and m-(amidinomethyl)phenyl esters derived from a variety of amino acids is presented. We analyzed the kinetic behavior of trypsin towards these synthetic esters, which are inverse substrates. The substituent (meta- and para-isomers) and isosteric effects of (amidinomethyl)phenyl esters are discussed.
- Sekizaki, Haruo,Itoh, Kunihiko,Shibuya, Akiyoshi,Toyota, Eiko,Tanizawa, Kazutaka
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p. 1514 - 1517
(2008/03/12)
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- Synthesis and biological evaluation of chiral α-aminoanilides with central antinociceptive activity
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Tocainide and related optically active chiral α-aminoanilides were synthesized and tested in vivo via the hot plate test to evaluate their central analgesic action. The aims of the study were to verify if a) the increase in lipophilicity, obtained by the introduction of an alkyl group on the steric center (3f-i), and the replacement of the C=O group with the C=S (10) group as well as the introduction of a methyl or ethyl group on the amidic nitrogen atom (8a-c) would produce an increase in central analgesic efficacy with respect to Tocainide; b) the 2,6-xylidide moiety is crucial for high analgesic activity (3b-e); c) the hydrogen atom bonded to the amidic nitrogen moiety is an essential pharmacophoric element for analgesic activity. Among all the synthesized compounds, 3f showed antinociceptive properties with a good enantioselective index.
- Corbo, Filomena,Franchini, Carlo,Lentini, Giovanni,Muraglia, Marilena,Ghelardini, Carla,Matucci, Rosanna,Galeotti, Nicoletta,Vivoli, Elisa,Tortorella, Vincenzo
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p. 1907 - 1915
(2008/02/01)
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- Useful reagents for introduction of Boc and Fmoc protective groups to amines: Boc-DMT and Fmoc-DMT
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New amino-protecting reagents, Boc-DMT and Fmoc-DMT, were prepared, and found to be useful for the introduction of Boc and Fmoc groups into amines. Both the reagents can protect various amines including amino acids in good yield in aqueous media. Since the reagents are neither unstable nor irritating, they are practically useful. Georg Thieme Verlag Stuttgart.
- Hioki, Kazuhito,Kinugasa, Mizuho,Kishimoto, Michiko,Fujiwara, Miho,Tani, Shohei,Kunishima, Munetaka
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p. 1931 - 1933
(2007/10/03)
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- Enzymatic removal of carboxyl protecting groups. 1. Cleavage of the tert-butyl moiety
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(Chemical Equation Presented) A recent discovery that a certain amino acid motif (GGG-(A)X-motif) in lipases and esterases determines their activity toward tertiary alcohols prompted us to investigate the use of these biocatalysts in the mild and selective removal of tert-butyl protecting groups in amino acid derivatives and related compounds. An esterase from Bacillus subtilis (BsubpNBE) and lipase A from Candida antarctica (CAL-A) were identified as the most active enzymes, which hydrolyzed a range of tert-butyl esters of protected amino acids (e.g., Boc-Tyr-OtBu, Z-GABA-OtBu, Fmoc-GABA-O tBu) in good to high yields and left Boc, Z, and Fmoc-protecting groups intact.
- Schmidt, Marlen,Barbayianni, Efrosini,Fotakopoulou, Irene,Hoehne, Matthias,Constantinou-Kokotou, Violetta,Bornscheuer, Uwe T.,Kokotos, George
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p. 3737 - 3740
(2007/10/03)
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- METHOD FOR PRODUCING SOLUTION CONTAINING N-t-BUTYLOXYCARBONYLAMINO ACID
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PROBLEM TO BE SOLVED: To provide a method for producing a solution containing an N-t-butyloxycarbonylamino acid (BOCA) with which the production efficiency is good. SOLUTION: The method for producing the solution containing the BOCA comprises the following steps (a) to (c). (a) A step of reacting di-t-butyl dicarbonate with an amino acid in an amount of equivalent based on the carbonate in the presence of an organic solvent immiscible with water, a base and water and affording a reaction mixture containing a salt of the BOCA, (b) a step of adding an acid to the reaction mixture, producing the free BOCA and extracting the produced BOCA with the organic solvent immiscible with water and (c) a step of separating an organic phase containing the BOCA obtained in the step (b) and the organic solvent immiscible with water from an aqueous phase containing a salt produced by a neutralizing reaction of the acid with the base.
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Page/Page column 7;8
(2008/06/13)
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- Enantioselective ester hydrolysis catalyzed by β-cyclodextrin conjugated with β-hairpin peptides
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Designed cyclodextrin-peptide conjugates, which have one or two β-hairpin peptides, have been synthesized as catalysts for ester hydrolysis. One or two β-hairpin peptides were located at the primary hydroxyl group side of β-cyclodextrin so as to arrange t
- Tsutsumi, Hiroshi,Ikeda, Hiroshi,Mihara, Hisakazu,Ueno, Akihiko
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p. 723 - 726
(2007/10/03)
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- Copolymerization of chiral amino acid-based acetylenes and helical conformation of the copolymers
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The present study deals with the copolymerization of an amino acid-based acetylene, N-(tert-butoxycarbonyl)-L-alanine N′-propargylamide (L-1A) with the optical isomer (D-1A), achiral hexanoic acid N-propargylamide (2A), and pivalic acid N-propargylamide (3A), and chiroptical properties of the copolymers. The copolymerization catalyzed by (nbd)Rh+[η6-C6H5B- (C6H5)3] afforded copolymers with number-average molecular weights over 104 in good yields. Nonlinear relationships were observed in the specific rotation and CD and UV-vis spectroscopies with respect to the L-1A content in feed. For instance, poly(L-1A-co-D-1A)s incorporated with 12.5% of either optical isomer (75% ee) exhibited almost the same optical properties as those of the homopolymers. Chiral amplification was observed in the copolymerization of L-1A with the achiral monomers. The specific rotation of poly(L-1A-co-2A) with 45% L-1A unit was practically the same as that of poly(L-1A). The copolymers of L-1A and 3A with an L-1A content in feed as low as 12% exhibited nearly the same helix content as the homopolymer of L-1A did.
- Gao, Guangzheng,Sanda, Fumio,Masuda, Toshio
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p. 3938 - 3943
(2007/10/03)
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- Employing the structural diversity of nature: Development of modular dipeptide-analogue ligands for ruthenium-catalyzed enantioselective transfer hydrogenation of ketones
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A library of novel dipeptideanalogue ligands based on the combination of tert-butoxycarbonyl(N-Boc)-protected a-amino acids and chiral vicinal amino alcohols were prepared. These highly modular ligands were combined with [{RuCl2(p-cymene)}2 and the resulting metal complexes were screened as catalysts for the enantioselective reduction of acetophenone under transfer hydrogenation conditions using 2-propanol as the hydrogen donor. Excellent enantioselectivity of 1-phenylethanol (up to 98% ee) was achieved with several of the novel catalysts. Although most of the ligands contained two stereocenters, it was demonstrated that the absolute configuration of the product alcohol was determined by the configuration of the amino acid part of the ligand. Employing ligands based on L-amino acids generated S-configured products, and catalysts based on Damino acids favored the formation of the R-configured alcohol. The combination N-Boc-L-alanine and (R)-phenylglycinol (Boc-L-Ab) or its enantiomer (N-Boc-D-alanine and (S)-phenylglycinol, Boc-D-Aa) proved to be the best ligands for the reduction process. Transfer hydrogenation of a number of aryl alkyl ketones were evaluated and excellent enantioselectivity, up to 96 % ee, was obtained.
- Pastor, Isidro M.,Vaestilae, Patrik,Adolfsson, Hans
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p. 4031 - 4045
(2007/10/03)
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- N-acylamino benzyl ether derivatives
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This invention relates to N-acylamino aryl derivatives of the formula 1where R1, R21, R22, R23, R3, R4, R5 R6, R7, R8, R, and n are as defined herein and where X is —CHRO, —OCHR—, —CH2S—, —SCH2—, —CH2CH2—, —CH=CH— or —C≡C—. The compounds of the invention are selective monoamine oxidase B inhibitors, and they are therefore useful in the treatment of diseases mediated by monoamine oxidase B, for example, for the treatment of Alzheimer's disease or senile dementia.
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- π-deficient 2-(arylsulfonyl)ethyl esters as protecting groups for carboxylic acids
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Several π-deficient 2-(arylsulfonyl)ethyl groups have been studied as carboxylic acid protecting groups. The 2-[3,5-bis(trifluoromethyl)phenylsulfonyl]ethyl group is the most easily removed protecting group for acids under mild basic conditions using aqueous NaHCO3.
- Alonso, Diego A.,Nájera, Carmen,Varea, Montserrat
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p. 277 - 287
(2007/10/03)
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- Synthesis of chiral α-amino acids
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A novel method for the synthesis of chiral α-amino acids has been developed where the acid functionality was constructed by oxidizing a hydroxymethyl group introduced by Evans' method in the α-position of an appropriate acid substrate and the amino part came from the amide of the original carboxyl group following a modified Hofmann rearrangement reaction.
- Chakraborty, Tushar K.,Ghosh, Animesh
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p. 9691 - 9693
(2007/10/03)
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- Enantioselective hydrolysis of amino acid esters by apomyoglobin: Perfect kinetic resolution of a phenylalanine derivative
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Apoprotein of horse-heart myoglobin promoted enantioselective hydrolysis of 4-nitrophenyl esters of amino acids, which allowed nearly perfect kinetic resolution of racemic N-Boc-phenylalanine ester (Boc-Phe-ONp).
- Tomisaka,Ishida,Konishi,Aida
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p. 133 - 134
(2007/10/03)
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