- DEUTERATED FORMS OF AMINOSTEROLS AND METHODS OF USING THE SAME
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Described are deuterated forms of aminosterols, or a pharmaceutically acceptable salt thereof, wherein one or more hydrogen atoms at one or more positions selected from C1, C2, C3, C4, C5, C6, C7, C8, C9, C11, C12, C14, C15, C16, C17, C18, C19, C20, C21,
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Paragraph 0470-0472
(2020/08/30)
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- IMIDAZOQUINOLINE AMINE DERIVATIVES, PHARMACEUTICAL COMPOSITION, USE THEREOF
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The invention provides novel imidazoquinoline amine derivatives, having agonistic activities to Toll-like receptors (TLRs), in particular TLR7 and/or TLR8, pharmaceutical compositions thereof, and methods of treatment, reduction or prevention of certain d
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Paragraph 00156
(2020/08/22)
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- Synthesis method of double different protected amino acids
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The invention relates to a synthesis method of double different protected amino acids.The technical problems of harsh reaction conditions, inapplicability of production enlarging and the like in an existing synthesis method are mainly solved. According to the technical scheme, the synthesis method of double different protected amino acids comprises the following steps: one of Boc20, Alloc-Cl or Cbz-Osuis added to amino alcohol under the action of an alkaline reagent to obtain a compound 1; the compound 1 reacts with methanesulfonyl chloride or paratoluensulfonyl chloride to obtain an intermediate, then a halide is added into acetone, heating and refluxing are executed to obtain a compound 2; the compound 2 is condensed with diethyl acetamidomalonate under the action of an alkaline agent togenerate a compound 3; the compound 3 is dissolved in alcohol and water, an inorganic base is added, heating, hydrolyzing and decarboxylating are executed to obtain a compound 4; acetylase is added into deionized water to obtain a compound 5 through enzymolysis; amino acid protection is executed, wherein one of Fmoc-Osu, Cbz-OSu, Alloc-Cl or Boc20 is added into thecompound 5 under the action of an alkaline agent to generatea target compound A.
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Paragraph 0018
(2019/07/04)
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- Rapid Assembly of Saturated Nitrogen Heterocycles in One-Pot: Diazo-Heterocycle “Stitching” by N–H Insertion and Cyclization
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Methods that provide rapid access to new heterocyclic structures in biologically relevant chemical space provide important opportunities in drug discovery. Here, a strategy is described for the preparation of 2,2-disubstituted azetidines, pyrrolidines, pi
- Boddy, Alexander J.,Affron, Dominic P.,Cordier, Christopher J.,Rivers, Emma L.,Spivey, Alan C.,Bull, James A.
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supporting information
p. 1458 - 1462
(2019/01/04)
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- CYCLIC KETO-AMIDE COMPOUNDS AS CALPAIN MODULATORS AND METHODS OF PRODUCTION AND USE THEREOF
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The present technology relates to cyclic keto-amide compounds of general formulae I to XXXII, compositions and kits thereof as calpain modulators and methods useful for the treatment of various diseases or disorders such as fibrotic disease or cancer whic
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Paragraph 00405
(2017/09/27)
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- OLIGONUCLEOTIDE-LIGAND CONJUGATES AND PROCESS FOR THEIR PREPARATION
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The present invention relates to ligand conjugates of oligonucleotides (e.g., iRNA agents) and methods for their preparation. The ligands are derived primarily from monosaccharides These conjugates are useful for the in vivo delivery of oligonucleotides.
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Page/Page column 97; 98; 99
(2015/02/02)
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- HEPATITIS B CORE PROTEIN ALLOSTERIC MODULATORS
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ABSTRACT The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound.
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Paragraph 000344
(2015/10/05)
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- Magnetic beads having surface glycoconjugates and use thereof
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Magnetic beads that include polyvalent ligands comprising various carbohydrates are described. Methods for fabricating such magnetic beads are also provided as well as methods of their use to capture and enrich pathogen cell population for subsequent culture, lysis and identification.
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Page/Page column 27; 28
(2015/02/19)
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- LIPIDATED IMMUNE RESPONSE MODIFIER COMPOUND COMPOSITIONS, FORMULATIONS, AND METHODS
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The compound N-(4-{[4-amino-2-butyl-1H-imidazo[4,5-c]quinolin-1-yl]oxy}butyl)octadecanamide is a useful drug compound for enhancing immune response and can be used, for example, as a vaccine adjuvant and a cancer treatment.
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Page/Page column 5
(2012/03/11)
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- Asymmetric organocatalytic intramolecular aza-michael addition of enone carbamates: Catalytic enantioselective access to functionalized 2-substituted piperidines
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The synthetically useful functionalized 2-substituted piperidines containing a lateral ketone group have been strategically accessed via an organocatalytic enantioselective intramolecular aza-Michael addition of enone carbamates, in which a novel internal substrate combination of the enone moiety as Michael acceptor and the carbamate moiety as Michael donor was revealed in asymmetric bifunctional organocatalysis. This heteroatom conjugate addition, which was realized by using a catalytic chiral Cinchona-based primary-tertiary diamine and an achiral Bronsted acid, mostly proceeded in high yield and good to excellent stereocontrol (up to 99% ee). This reaction provides an alternative catalytic asymmetric method for installing the stereogenic nitrogen-containing carbon center in functionalized 2-substituted piperidines, leading to the development of a straightforward and expeditious synthesis of some naturally occurring bioactive 2-substituted piperidine alkaloids. Copyright
- Liu, Jian-Dong,Chen, Ying-Chun,Zhang, Guo-Biao,Li, Zhi-Qiang,Chen, Peng,Du, Ji-Yuan,Tu, Yong-Qiang,Fan, Chun-An
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p. 2721 - 2730
(2011/12/04)
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- Simple methodology for the preparation of amino alcohols from amino acid esters using nabh4-methanol in THF
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Amino alcohols constitute a very useful and versatile class of organic compounds, with important applications in synthetic and medicinal chemistry. However, in most of the procedures described in the literature for the obtainment of these compounds, considerable limitations can be found, such as drastic conditions, long time reactions, poor yields, and purification problems. The present article describes a methodology that gives amino alcohols and N-protected amino alcohols based on the reduction of amino acid esters under mild conditions, employing NaBH4 in the presence of methanol. The reactions occurred in a short time (15-20min) and provide yields of 50-95%.
- Goncalves,Pinheiro,Da Silva,Da Costa,Kaiser,De Souza
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experimental part
p. 1276 - 1281
(2011/05/04)
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- Dihydroxylation of vinyl sulfones: Stereoselective synthesis of (+)- and (-)-febrifugine and halofuginone
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(Chemical Equation Presented) The asymmetric dihydroxylation of amino-functionalized vinyl sulfone 19 has been used for the 3-step preparation of 3-hydroxylpiperidine 24 in 86% enantiomeric excess. This enantiomerically enriched building block was used then to synthesize the naturally occurring antimalarial alkaloid febrifugine 1 and its antiangiogenic analogue, halofuginone 3.
- McLaughlin, Noel P.,Evans, Paul
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supporting information; experimental part
p. 518 - 521
(2010/03/30)
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- Hydrogenation of N-acylcarbamates and N-acylsulfonamides catalyzed by a bifunctional [Cp*Ru(PN)] complex
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Awakening of the Cp one: the bifunctional complex 1 facilitates the interaction with substrates bearing less electrophilic carbon atoms than ketones, epoxides, and imides. The title reaction was applicable to the reduction of Evans' asymmetric alkylation products to the chiral alcohols along with gtood recovery of the chiral oxazolidinone auxiliary. EWG=electron- withdrawing group.
- Ito, Masato,Koo, Lee Wei,Himizu, Akio,Kobayashi, Chika,Sakaguchi, Ayaka,Ikariya, Takao
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scheme or table
p. 1324 - 1327
(2009/06/30)
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- Stereoselective syntheses of (E)-α,β-didehydroamino acid and peptide containing its residue utilizing oxazolidinone derivative
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Reaction of methyl N-Boc-N-phenoxycarbonylglycinate with various aldehydes afforded the corresponding cis-4,5-oxazolidinone derivatives, which were effectively converted to (E)-α,β-didehydroamino acids by means of a base. Furthermore, N-deprotection of the oxazolidinone derivatives and subsequent coupling reaction with Boc-amino acid furnished the corresponding dipeptides, which were transformed to dipeptide containing α,α- didehydroamino acid with high E selectivity.
- Kometani, Miki,Ihara, Kohki,Kimura, Rumi,Kinoshita, Hideki
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experimental part
p. 364 - 380
(2009/06/28)
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- A mild and efficient chemoselective: N-benzyloxycarbonylation of amines using TBAB a catalyst under solvent-free conditions
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We describe a mild and efficient method for the chemoselective N-benzyloxycarbonylation of amines by treatment amines and aminoesters with benzyloxycarbonyl chloride (Cbz-Cl) in the presence of TBAB under solvent-free in excellent yields. The method is ge
- Babu, Kothamasu Suresh,Rao, Vidadala Rama Subba,Rao, Ravu Ranga,Babu, Sakhamuri Sivaram,Rao, Janaswami Madhusudana
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experimental part
p. 393 - 396
(2009/10/17)
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- N-Benzyloxycarbonylation of amines in the ionic liquid [TPA][l-Pro] as an efficient reaction medium
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An efficient method for the N-benzyloxycarbonylation of amines is described. The reaction of amines with Cbz-Cl in the ionic liquid [TPA][l-Pro] afforded the corresponding N-Cbz derivatives in excellent yields. The method is versatile for the preparation
- Suryakiran,Chinni Mahesh,Ramesh,Jon Paul Selvam,Venkateswarlu
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p. 2607 - 2610
(2008/09/18)
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- Acyclic nucleoside analogues as inhibitors of Plasmodium falciparum dUTPase
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We report the discovery of novel uracil-based acyclic compounds as inhibitors of deoxyuridine 5′-triphosphate nucleotidohydrolase (dUTPase), an enzyme involved in nucleotide metabolism that has been identified as a promising target for the development of
- Nguyen, Corinne,Ruda, Gian Filippo,Schipani, Alessandro,Kasinathan, Ganasan,Leal, Isabel,Musso-Buendia, Alexander,Kaiser, Marcel,Brun, Reto,Ruiz-Pérez, Luis M.,Sahlberg, Britt-Louise,Johansson, Nils Gunnar,González-Pacanowska, Dolores,Gilbert, Ian H.
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p. 4183 - 4195
(2007/10/03)
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- Kinase-mediated trapping of bi-functional conjugates of paclitaxel or vinblastine with thymidine in cancer cells
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In the present work, we explore the possibility of introducing selectivity to existing chemotherapeutics via the design of non-pro-drug, bi-functional molecules comprising a microtubule-binding agent and a substrate for a disease-associated kinase. The design, synthesis, and in vitro biological evaluation of paclitaxel-thymidine and vinblastine-thymidine bi-functional conjugates are reported here. This work provides the first account of 'kinase-mediated trapping' of cancer therapeutics.
- Aspland, Simon E.,Ballatore, Carlo,Castillo, Rosario,Desharnais, Joel,Eustaquio, Trisha,Goelet, Philip,Guo, Zijian,Li, Qing,Nelson, David,Sun, Chengzao,Castellino, Angelo J.,Newman, Michael J.
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p. 5194 - 5198
(2008/02/02)
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- Study on the Structure Activity Relationships of NPTX-594, a Spider Toxin Belonging to the Type-B Acylpolyamine Structure
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In order to elucidate the structure activity relationships of the spider toxin termed NPTX-594, eleven toxin analogs were designed and synthesized, and their paralytic activities against cricket were tested. As a result of the present study, it was clarif
- Wakamiya, Tateaki,Kinoshita, Tomohiko,Hattori, Yoshihide,Yamaguchi, Yoshihiro,Naoki, Hideo,Corzo, Gerardo,Nakajimal, Terumi
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p. 331 - 340
(2007/10/03)
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- Toward Efficient Zn(II)-Based Artificial Nucleases
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A series of cis-cis-triaminocyclohexane Zn(II) complex-anthraquinone intercalator conjugates, designed in such a way to allow their easy synthesis and modification, have been investigated as hydrolytic cleaving agents for plasmid DNA. The ligand structure
- Boseggia, Elisa,Gatos, Maddalena,Lucatello, Lorena,Mancin, Fabrizio,Moro, Stefano,Palumbo, Manlio,Sissi, Claudia,Tecilla, Paolo,Tonellato, Umberto,Zagotto, Giuseppe
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p. 4543 - 4549
(2007/10/03)
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- Phosphonic acid derivatives having carboxypeptidase b inhibitory activity
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A compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof: wherein R1represents hydrogen atom, an alkyl group, a substituted alkyl group and the like; R2and R3represent hydrogen atom, an alkyl group, a substituted alkyl group, an alkoxyl group and the like; X represents —CH2—, —O—, or —NH—; A represents the following group (II): [in which R7and R8represent hydrogen atom, an alkyl group, an acyl group, an alkoxycarbonyl group and the like; R9and R10represents hydrogen atom, a halogen atom, hydroxyl group, phenyl group, an alkyl group and the like] and the like; and E represents hydrogen atom and the like, which has inhibitory activity against carboxypeptidase B and is useful for therapeutic and/or preventive treatment of a thrombotic disease.
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- Effect of spermine conjugation on the cytotoxicity and cellular transport of acridine
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Polyamines are believed to be potent vectors for the selective delivery of chemotherapeutic agents into cancer cells. In this paper, we report the effect of spermine conjugation on the cytotoxic and transport properties of acridine. Six derivatives, composed of a spermine chain attached at its N1 position to an acridine via an aliphatic chain, were synthesized. The aliphatic linker, comprised of 3-5 methylene units, was connected to the position-9 of the heterocycle through either an amide (amidoacridines 8-10) or an amine (aminoacridines 11-13) linkage. Independently of their architecture, all ligands showed a high affinity for DNA binding but a limited DNA sequence selectivity. In a whole cell assay with L1210 and Chinese hamster ovary (CHO) cells, the aminoacridines (IC50 values around 2 μM) were more potent than the amidoacridines (IC50 values between 20 and 40 μM). This was related to a less efficient transport for the latter. As determined from competitive uptake studies with [14C] spermidine, all conjugates had a high affinity for the polyamine transport system (PTS). However, on the basis of competitive studies with an excess of spermidine and on the differential effect on cell growth and accumulation in CHO and in the mutant PTS deficient CHO-MG cells, the accumulation of the conjugates through the PTS was found to be poor but still more efficient for the aminoacridines. α-Difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase, which induces an up-regulation of the activity of the PTS, enhanced accumulation of all acridine conjugates through the PTS and had a synergistic effect on the potency of the acridine conjugates to inhibit cell growth. Despite their high affinity for the PTS, the low amount of derivatives transiting through the PTS is likely to be related to their ability to repress rapidly and efficiently the activity of the PTS and, consequently, to inhibit their own uptake via this system.
- Delcros, Jean-Guy,Tomasi, Sophie,Carrington, Simon,Martin, Bénédicte,Renault, Jacques,Blagbrough, Ian S.,Uriac, Philippe
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p. 5098 - 5111
(2007/10/03)
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- Evaluation of diene hierarchies for Diels-Alder reactions en route to xestocyclamine A: Elaboration of an ansa bridge by B-alkyl Suzuki macrocyclization
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A double Michael addition of amine 2 to 1 was a key reaction in the synthesis of the isoquinuclidine core 4 of xestocyclamine A, a protein kinase C inhibitor. The first ansa bridge was formed efficiently by a B-alkyl Suzuki coupling in 3. TBDPS = tert-but
- Gagnon, Alexandre,Danishefsky, Samuel J.
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p. 1581 - 1584
(2007/10/03)
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- A microgonotropen pentaaza pentabutylamine and its interactions with DNA
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The central pyrrole of a site-selective DNA minor groove binding tripyrrole peptide (1) has been attached to N-protected pentaazapentacosanoic acid (17) via a (CH2)3 NHCO (CH2)3 linker to provide 19, subsequent deprotection provided the pentaaza microgonotropen 4. The polyamine moiety of 4 reaches out of the minor groove and binds to the phosphate backbone of DNA. We find when employing Hoechst 33258 (Ht) as a fluorescent titrant to follow binding of 4 to the hexadecameric duplex d(GGCGCAAATTTGGCGG)/(CCGCCAAATTTGCGCC) and by 1H NMR titration of d(CGCAAATTTGCG)2 with 4 that the latter forms both 1:1 and 2:1 dsDNA complexes. Certain aspects of the structure of 4:d(CGCAAATTTGCG)2 complex derived via 1H NMR are discussed. The electrophoretic mobilities of φX-174 DNA digested with HaeIII endonuclease restriction fragments complexed to 4 shows that the latter brings about a greater conformational change in the DNA fragments than observed previously with other microgonotropens.
- Sengupta, Dipanjan,Blasko, Andrei,Bruice, Thomas C.
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p. 803 - 813
(2007/10/03)
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- Oxime esters as acylating agents in the aminolysis reaction. A simple and chemoselective method for the preparation of amides from amino alcohols
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Oxime esters, such as acetone O-alkanoyl-, O-alkenoyl- or O-benzyloxycarbonyloximes, react with amines under extremely mild conditions to give the corresponding amides in very good yield. When amino alcohols are used a total chemoselectivity is observed.
- Fernandez,Menendez,Gotor
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p. 713 - 716
(2007/10/02)
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- Asymmetric Syntheses of the Naturally Ocurring β-Amino Acids, β-Lysine, β-Leucine and β-Phenyl-β-alanine via Nitrone Cycloaddition
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A general asymmetric synthesis of β-amino acids is based on the dipolar cycloaddition of nitrones 7 (R* chiral) with vinyl acetate 8a, ketene acetals 8b or α-chloroacrylonitrile 8c.The cycloadducts 9 are converted either directly (9b) or via the isoxazolidones 10 (9a, 9c) into the free β-amino acids 11.Diastereoselectivity at C-3 in the adducts 9 ranges between 2:1 and 11:1.The natural β-amino acids, β-lysine, β-leucine and β-phenyl-β-alanine, have been prepared in this way.
- Keirs, David,Moffat, David,Overton, Karl,Tomanek, Richard
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p. 1041 - 1051
(2007/10/02)
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- Enantioselective Synthesis of Optically Pure (R)- and (S)-β-Lysine via Nitrone Cycloaddition
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Optically pure (R)- and (S)-β-lysines have been obtained via cycloaddition of chiral nitrone (4) to vinyl acetate, followed by facile chromatographic separation of the four resulting acetates (5) into two pairs of C-5 epimers and conversion of each pair i
- Keirs, David,Moffat, David,Overton, Karl
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p. 654 - 655
(2007/10/02)
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- CONVENIENT SYNTHESES AND REACTIONS OF TWO KINDS OF BASIC α-DEHYDROAMINO ACID DERIVATIVES
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Two kinds of basic N-carboxy α-dehydroamino acid anhydrides (ΔNCA) were synthesized by the cyclization of N-benzyloxycarbonyl (Cbz)-α-dehydro-ornithine and -lysine (DHA), derived from Cbz-aminoaldehydes and N-Cbz-2-(diethoxyphosphinyl)glycine esters.Moreover, facile conversion of Cbz as Nα-protecting group in DHA to Boc via ΔNCA was also successful.
- Shin, Chung-gi,Obara, Takumi,Segami, Shigenori,Yonezawa, Yasuchika
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p. 3827 - 3830
(2007/10/02)
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- HYDROXY SUBSTITUTED UREIDO AMINO AND IMINO ACIDS
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Compounds of the formula STR1 are disclosed. These compounds are useful as hypotensive agents due to their angiotensin converting enzyme inhibition activity and depending upon the definition of X may also be useful as analgesics due to their enkephalinase
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- SUBSTITUTED PROLINE COMPOUNDS, COMPOSITION AND METHOD OF USE
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Compounds of the formula STR1 are disclosed. These compounds are useful as hypotensive agents due to their angiotensin converting enzyme inhibition activity and depending upon the definition of X may also be useful as analgesics due to their enkephalinase inhibition activity.
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- Semisynthetic Aminoglycoside Antibacterials. Part 10. Synthesis of Novel 1-N-Aminoalkoxycarbonyl and 1-N-Aminoalkylcarboxamido Derivatives of Sisomicin, Gentamicin B, Gentamicin C1a, and Kanamycin A
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Suitably protected derivatives of sisomicin, 5-epi-sisomicin, gentamicin B, gentamicin C1a, and kanamycin A have been converted into a series of 1-N-alkoxycarbonyl, 1-N-aminoalkoxycarbonyl, 1-N-carboxamido, 1-N-alkylcarboxamido, and 1-N-aminoal
- Mallams, Alan K.,Morton, James B.,Reichert, Paul
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p. 2186 - 2208
(2007/10/02)
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- 1-N-substituted derivatives of 4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitols
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Novel 1-N-aminoalkyl (oxycarbonyl or carboxamido or thiocarboxamido) derivatives of 4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitols, useful as antibacterial agents, are described.
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