- Catalytic Asymmetric Disulfuration by a Chiral Bulky Three-Component Lewis Acid-Base
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A three-component Lewis acid–base (Lewis trio) involving a bulky chiral primary amine, B(C6F5)3 and a bulky tertiary amine has been developed as an effective enamine catalyst for enantioselective disulfuration reactions. The bulky tertiary amine was found to activate a bulky primary–tertiary diamine–borane Lewis pair for enamine catalysis via frustrated interaction. The resulted chiral bulky Lewis trio (BLT) allows for the construction of chiral disulfides via direct disulfuration with β-ketocarbonyls or α-branched aldehydes in a practical and highly stereocontrolled manner.
- Zhang, Qi,Li, Yao,Zhang, Long,Luo, Sanzhong
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Read Online
- Hydrotropic polymer-based paclitaxel-loaded self-assembled nanoparticles: Preparation and biological evaluation
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The poor compatibility of carrier materials with drugs is one of the main obstacles in the drug encapsulation of nano-drug delivery system (NDDS), hindering the clinical translation of NDDS. In this study, using paclitaxel (PTX) as the insoluble model drug, we conjugated N,N-diethylniacinamide (DENA), a hydrotropic agent of PTX, to the backbone of poly(l-γ-glutamyl-glutamine) (PGG), a water-soluble polymer, to prepare the "hydrotropic polymer" PGG-DENA to improve its compatibility with PTX. By virtue of the hydrotropic effect of the DENA group, PTX was encapsulated by PGG-DENA to obtain the hydrotropic polymeric nanoparticles (PGG-DENA/PTX NPs). PTX-conjugated poly(l-γ-glutamyl-glutamine) acid (PGG-PTX) NPs previously reported were used as the control in the study. The PGG-DENA/PTX NPs showed a z-average hydrodynamic diameter of about 70 nm, and good long-term stability in PBS solution at 4 °C. The cumulative release rate of PTX from PGG-DENA/PTX NPs reached 79.10% at 96 h, while that of PGG-PTX NPs was 22.96%. PGG-DENA/PTX NPs showed significantly increased in vitro cytotoxicity on NCI-H460 lung cancer cells compared with PGG-PTX NPs. The hemolysis study proved that the PGG-DENA/PTX NPs has good biocompatibility. These results indicated that by introducing the hydrotropic agent DENA, the hydrotropic polymer PGG-DENA becomes an effective carrier material of PTX. This study provides a solution to increase the compatibility of carrier materials with insoluble drugs, and also may provide an effective way to develop a series of personalized carrier materials suitable for different insoluble drugs.
- Gao, Lipeng,Gao, Liefang,Fan, Mingxue,Li, Qilong,Jin, Jiyu,Wang, Jing,Lu, Weiyue,Yu, Lei,Yan, Zhiqiang,Wang, Yiting
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Read Online
- Reaction of Diisobutylaluminum Borohydride, a Binary Hydride, with Selected Organic Compounds Containing Representative Functional Groups
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The binary hydride, diisobutylaluminum borohydride [(iBu)2AlBH4], synthesized from diisobutylaluminum hydride (DIBAL) and borane dimethyl sulfide (BMS) has shown great potential in reducing a variety of organic functional groups. This unique binary hydride, (iBu)2AlBH4, is readily synthesized, versatile, and simple to use. Aldehydes, ketones, esters, and epoxides are reduced very fast to the corresponding alcohols in essentially quantitative yields. This binary hydride can reduce tertiary amides rapidly to the corresponding amines at 25 °C in an efficient manner. Furthermore, nitriles are converted into the corresponding amines in essentially quantitative yields. These reactions occur under ambient conditions and are completed in an hour or less. The reduction products are isolated through a simple acid-base extraction and without the use of column chromatography. Further investigation showed that (iBu)2AlBH4 has the potential to be a selective hydride donor as shown through a series of competitive reactions. Similarities and differences between (iBu)2AlBH4, DIBAL, and BMS are discussed.
- Amberchan, Gabriella,Snelling, Rachel A.,Moya, Enrique,Landi, Madison,Lutz, Kyle,Gatihi, Roxanne,Singaram, Bakthan
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supporting information
p. 6207 - 6227
(2021/05/06)
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- Rapid assembly of phosphate-bridged tetra-mannose by ionic liquid-supported oligosaccharide synthesis
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An efficient ionic liquid-supported oligosaccharide synthesis (ILSOS) strategy was described for the synthesis of linear oligo-phosphomannan. A new cleavable benzyl carbamate-type IL supporter containing 5-aminopentanyl linker was designed as an acceptor IL tag to facilitate this synthesis. The chain elongation on IL tag was achieved by H-phosphonate chemistry, including condensation with α-mannosyl H-phosphonate, in situ oxidation reaction and subsequent deprotection. After four cycles, linear α-(1 → 6)-tetra-mannan phosphate was obtained with a total yield of 52.7% within 45 h. The IL tagged product exhibited a tunable solubility in polar and non-polar solvent systems that facilitate a chromatography-free purification in the assembly process. The IL tag could be easily removed after hydrogenolysis treatment after the final step, to afford an amine terminated linker at the reducing end of phosphoglycan for further conjugation with a carrier protein. This methodology offered an efficient and chromatography-free approach for the synthesis of phosphoglycan.
- Yang, Guangyi,Mei, Guodong,Shen, Peng,Hong, Haofei,Wu, Zhimeng
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- [...] derivatives
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PROBLEM TO BE SOLVED: To provide a dibenzyl trithiocarbonate derivative having various functional groups at both terminals of the molecule and to provide a method for producing the same.SOLUTION: There is provided a dibenzyl trithiocarbonate derivative represented by the following general formula (1): wherein, Ar is a phenylene group or a naphthylene group; R is an acetoxy group, a hydroxy group, a hydroxymethyl group, or a methoxycarbonyl group having a substituent represented by the formula, -C(O)-O-CH-R(wherein, Ris a Cto Calkyl or a Cto Calkenyl group having a substituent). There is provided a method for producing a dibenzyl trithiocarbonate derivative represented by the general formula (1) in which a compound represented by the formula (3) (wherein X is a halogen atom) is reacted with a trithiocarbonate in an amide-based solvent to trithiocarbonate.
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Paragraph 0070
(2018/01/02)
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- ORGANIC COMPOUNDS TO TREAT HEPATITIS B VIRUS
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The disclosure relates to compositions comprising a HBV RNAi agent. In some embodiments, the HBV RNAi agent comprises a sense and an anti-sense strand, each strand being an 18-mer and the strands together forming a blunt-ended duplex, wherein the 3′ end of at least one strand terminates in a phosphate or modified internucleoside linker and further comprises, in 5′ to 3′ order: a spacer; a second phosphate or modified internucleoside linker; and a 3′ end cap. In some embodiments, the 3′ end of both the sense and anti-sense strand further comprise, in 5′ to 3′ order: a spacer; a second phosphate or modified internucleoside linker; and a 3′ end cap. The two strands can have the same or different spacers, phosphates or modified internucleoside linkers, and/or 3′ end caps. The strands can be ribonucleotides, or, optionally, one or more nucleotide can be modified or substituted. Optionally, at least one nucleotide comprises a modified internucleoside linker. Optionally, the RNAi agent can be modified on one or both 5′ end. Optionally, the sense strand can comprise a 5′ end cap which reduces the amount of the RNA interference mediated by this strand. Optionally, the RNAi agent is attached to a ligand. This format can be used to devise RNAi agents to a variety of different targets and sequences. The disclosure also relates to processes for making such compositions, and methods and uses of such compositions, e.g., to mediate RNA interference. The disclosure also pertains to methods of treating, ameliorating and preventing HBV in a patient involving the step of administering to the patient a therapeutic amount of a HBV RNAi agent.
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Paragraph 0602; 0611
(2016/08/17)
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- CURABLE COMPOUND WITH HIGH REFRACTIVE INDEX, ADHESIVE COMPOSITION FOR OPTICAL MEMBER COMPRISING THE SAME AND COMPOSITION FOR OPTICAL SHEET COMPRISING THE SAME
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Provided are a compound represented by chemical formula 1, a compound represented by chemical formula 4, an adhesive composition for optical members including the same, and a composition for optical sheets including the same. More specifically, the purpose of the present invention is to provide a compound which is curable and has a high refractive index.COPYRIGHT KIPO 2016
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Paragraph 0144-0147
(2017/04/11)
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- Smaller, faster, better: Modular synthesis of unsymmetrical ammonium salt-tagged NHC-gold(i) complexes and their application as recyclable catalysts in water
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Facile access towards a small library of unsymmetrical ammonium salt-tagged N-heterocyclic carbene gold(i) complexes is described, and their application as recyclable catalysts in cyclization reactions of acetylenic carboxylic acids and amides to lactones and lactams, respectively, in aqueous media is demonstrated. Catalyst 1ab was applied in the synthesis of 2-epi-clausemarine A (16).
- Belger, Katrin,Krause, Norbert
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supporting information
p. 8556 - 8560
(2015/08/06)
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- 3'END CAPS FOR RNAi AGENTS FOR USE IN RNA INTERFERENCE
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The disclosure relates to novel compounds and compositions comprising a RNAi agent comprising a novel compound as a 3' end cap. The disclosure also relates to processes for making such compositions, and methods and uses of such compositions, e.g., to mediate RNA interference.
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Page/Page column 161-162
(2015/04/22)
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- Novel analogues of resveratrol: Metabolism and inhibition of colon cancer cell proliferation
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Resveratrol is a phytochemical present in the skin of red grapes, and hence red wine as well as a variety of berries and nuts. It is an anti-oxidant, which has shown cancer chemopreventive properties in preclinical rodent models of carcinogenesis. The bioavailability of resveratrol is low, as it is rapidly metabolised to glucuronides and sulfates. The pharmacological activities of conjugate metabolites of phenols are often much lower than those of their metabolic progenitors. Therefore chemical synthetic manipulations aimed at slowing the rate of metabolic conjugation of phenols may generate analogues with increased bioavailability and efficacy. Here we describe the synthesis using the Wittig-Horner-Emmons reaction of a new series of resveratrol analogues in which the phenol moieties were systematically replaced by hydroxymethyl and/or methoxy groups. Incubation of analogues, which lack phenol groups with phase II metabolising enzyme preparations generated hardly any, or only small amounts of, conjugates. Four of the new analogue inhibited the growth of human-derived HCA-7 colon cancer cells, but with much less potency than resveratrol.
- Simon, Charles,Britton, Robert G.,Cai, Hong,Gescher, Andreas J.,Brown, Karen,Jenkins, Paul R.
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p. 6203 - 6212
(2013/07/19)
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- Synthesis and evaluation of isoxazole derivatives as lysophosphatidic acid (LPA) antagonists
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A series of isoxazole derivatives were synthesized and their antagonistic activities against LPA stimulation on both LPA1/CHO cells and rHSC cells were evaluated. Among them, 3-(4-{4-[1-(2-chloro-cyclopent-1-enyl)-ethoxycarbonylamino]-isoxazol-3- yl}-benzylsulfanyl)-propionic acid (34) showed the most potent activities.
- Yamamoto, Takashi,Fujita, Koichi,Asari, Sayaka,Chiba, Akira,Kataba, Yuka,Ohsumi, Koji,Ohmuta, Naoko,Iida, Yuko,Ijichi, Chiori,Iwayama, Satoshi,Fukuchi, Naoyuki,Shoji, Masataka
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p. 3736 - 3740
(2008/02/07)
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- Design, synthesis, and discovery of stilbene derivatives based on lithospermic acid B as potent protein tyrosine phosphatase 1B inhibitors
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Dihydroxy stilbene derivatives were designed based on lithospermic acid B and were prepared from 4-(chloromethyl)benzoic acid. The inhibitory activities of the novel compounds against protein tyrosine phosphatase 1B (PTP1B) were evaluated. 3,4-Dihydroxy stilbene carbonyl compounds (7, 11b, 27b) inhibited PTP1B with IC50 values comparable to molybdate, while the conjugation-extended compound (15b) showed inhibition 3-fold better than preclinical RK682. The introduction of electron withdrawing groups or amides into the second phenyl ring, or extension of the conjugation into the stilbene molecule may increase stability of the generated radicals.
- Jung, Mankil,Lee, Yongnam,Park, Moonsoo,Kim, Hanjo,Kim, Heekyeong,Lim, Eunyoung,Tak, Jungae,Sim, Minjoo,Lee, Dongeun,Park, Namsoo,Oh, Won Keun,Hur, Kyu Yeon,Kang, Eun Seok,Lee, Hyun-Chul
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p. 4481 - 4486
(2008/02/13)
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- Novel azole compound
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Azole compounds represented by formula I: wherein ring A is isoxazole and the like, R1 is a substituted or unsubstituted aryl group and the like, R2 is a hydrogen atom and the like, and R3 is a substituted or unsubstituted alkyl group and the like, and pharmaceutically acceptable salts thereof inhibit the physiological activity of lysophosphatidic acid (LPA), and are useful as for the prophylaxis or treatment of diseases in which inhibition of the physiological activity of LPA is useful for the prophylaxis or treatment thereof, such as diseases involving the LPA receptor.
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Page/Page column 30
(2008/06/13)
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- New NO-releasing pharmacodynamic hybrids of losartan and its active metabolite: Design, synthesis, and biopharmacological properties
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In a preliminary work, we reported two NO-sartans, possessing the characteristics of an AT1 antagonist and a "slow NO donor", obtained by adding NO-donor side chains to losartan 1. The NO release from an NO-sartan should be modulated in order to strengthen the antihypertensive activity of the native drug and to ensure additional effects, such as the antiplatelet and anti-ischemic ones. To obtain a collection of proto-typical NO-sartans, showing different rates of NO release, new NO-donor moieties have been linked to 1 or its active metabolite 2 (EXP 3174). Almost all the synthesized compounds exhibited both AT1-antagonist and NO-mediated vasorelaxing properties, with a wide range of NO-releasing rates. Further pharmacological investigation on compound 4a showed that it possessed antihypertensive and cardiac antihypertrophic effects similar to those of the reference AT1-blocking or ACE-inhibiting drugs. Furthermore, the additional anti-ischemic cardio-protective properties and antiplatelet effects of 4a have been preliminarily investigated.
- Breschi, Maria C.,Calderone, Vincenzo,Digiacomo, Maria,Macchia, Marco,Martelli, Alma,Martinotti, Enrica,Minutolo, Filippo,Rapposelli, Simona,Rossello, Armando,Testai, Lara,Balsamo, Aldo
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p. 2628 - 2639
(2007/10/03)
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- Novel alkyl/aryl hydroxy or keto thiepine compounds as inhibitors of apical sodium co-dependent bile acid transport (ASBT) and taurocholate uptake
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Thiepine apical sodium co-dependent bile acid transport (ASBT) inhibitors are disclosed together with methods of making the same, methods of using the same to treat hyperlipidemic conditions as well as pharmaceutical compositions containing the same compounds.
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- CARBOXAMIDES DERIVATIVES
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The present invention relates to carboxamides which are useful as an active ingredient of pharmaceutical preparations. The carboxamides of the present invention have IP receptor antagonistic activity, and can be used for the prophylaxis and treatment of diseases associated with IP receptor antagonistic activity.Such diseases include urological diseases or disorder as follows: bladder outlet obstruction, overactive bladder, urinary incontinence, detrusor hyper-reflexia, detrusor instability, reduced bladder capacity, frequency of micturition, urge incontinence, stress incontinence, bladder hyperreactivity, benighn prostatic hypertrophy (BPH), prostatitis, urinary frequency, nocturia, urinary urgency, pelvic hypersensitivity, urethritis, pelvic pain syndrome, prostatodynia, cystitis, or idiophatic bladder hypersensitivity.The compounds of the present invention are also useful for treatment of pain including, but not limited to inflammatory pain, neuropathic pain, acute pain, chronic pain, dental pain, premenstrual pain, visceral pain, headaches, and the like; hypotension;hemophilia and hemorrhage; and inflammation, since the diseases are alleviated by treatment with an IP receptor antagonist.
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- Method for the preparation of tetrahydrobenzothiepines
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Among its several embodiments, the present invention provides an improved process for the preparation of tetrahydrobenzothiepine-1,1-dioxide compounds; the provision of a process for preparing a diastereomeric mixture of tetrahydrobenzothiepine-1,1-dioxide compounds from a single diastereomer of such compounds; the provision of a process for the preparation of 3-bromo-2-substituted propionaldehyde compounds; and the provision of a process for the preparation of 3-thio-2-substituted propionaldehyde compounds.
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- Method for preparing alkylating agents and their use for alkylating cyclic ureas
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This invention relates to methods for preparing alkylating agents and use of the agents prepared. In particular, this invention relates to preparation methods for hydroxy halide and organooxy halide alkylating agents and their use for alkylating cyclic urea compounds.
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- Stereoselective synthesis of HIV-1 protease inhibitor, DMP 323
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DMP 323, a potent HIV-1 protease inhibitor, has been synthesized by an efficient stereoselective process, amenable to large scale preparations. The core C2 symmetric diol was synthesized by a stereoselective pinacol coupling of CBZ protected D-phenylalanine. Judicious selection of protecting groups allowed cyclic urea formation under mild conditions, enhanced the ease of bis-alkylation, and led te intermediates which were easily purified without chromatography. Additionally, a one-pot, high yield process was developed te prepare the alkylating agent, 4-[(triphenylmethoxy)methyl]benzyl chloride from 1,4-benzenedimethanol.
- Pierce,Pierce, Michael E.,Harris,Harris, Gregory D.,Islam,Islam, Qamrul,Radesca,Radesca, Lilian A.,Storace,Storace, Louis,Waltermire,Waltermire, Robert E.,Wat,Wat, Ed,Jadhav,Jadhav, Prabhakar K.,Emmett,Emmett, George C.
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p. 444 - 450
(2007/10/02)
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- Substituted sulfonamides, process of preparation and medicines containing same
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The present invention concerns new substituted sulfonamides, and the physiologically acceptable salts possibly in the form of complexes, esters and amides thereof, represented by the formula: STR1
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