- COMBINED TREATMENT WITH A TLR7 AGONIST AND AN HBV CAPSID ASSEMBLY INHIBITOR
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The present invention is directed to compositions and methods for treating hepatitis B virus infection. In particular, the present invention is directed to a combination therapy comprising administration of a TLR7 agonist and an HBV capsid assembly inhibi
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Page/Page column 29; 30
(2018/04/13)
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- NOVEL CYCLICSULFONIMIDOYLPURINONE COMPOUNDS AND DERIVATIVES FOR THE TREATMENT AND PROPHYLAXIS OF VIRUS INFECTION
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The present invention relates to compounds of formula (I), wherein R1, R2 and R3 and n are as described herein, or pharmaceutically acceptable salt, enantiomer or diastereomer thereof, and compositions including the compounds and methods of using the compounds.
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Page/Page column 19
(2018/05/24)
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- Amide compound, pharmaceutical composition, preparation method and application thereof
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The invention provides an amide compound, a pharmaceutical composition, a preparation method and application thereof and belongs to the field of medicine. Structure of the amide compound is shown as aformula I. The preparation method includes: in an alkaline condition and in an organic solvent, allowing a compound I and a compound II to be in condensation reaction. The amide compound or pharmaceutically acceptable salt thereof have long-acting sensory and/or motion blocking activity, can be used for preparing long-acting local anesthetic or analgesic and is long in efficacy lasting time, little side effect and high in medication safety.
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Paragraph 0244-0247
(2018/09/11)
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- Design and Synthesis of 4-Alkylidene-β-lactams: Benzyl- and Phenethyl-carbamates as Key Fragments to Switch on Antibacterial Activity
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The emergence of multidrug-resistant bacterial strains is particularly important in chronic pathologies such as cystic fibrosis (CF), in which persistent colonization and selection of resistant strains is favored by the frequent and repeated use of antibacterial agents. Staphylococcus aureus is a common pathogen in CF patients that has an associated increased multidrug resistance. In previous studies we demonstrated that the presence of a 4-alkylidene side chain directly linked to a β-lactam appeared to strengthen the potency against S. aureus, especially against methicillin-resistant S. aureus (MRSA) strains. In the present study, 21 new 4-alkylidene-β-lactams were synthesized and evaluated for antibacterial activity. We designed the new compounds to have aryl, benzyl, or phenethyl-carbamate groups on the C3 hydroxyethyl side chain. We found a correlation between biological activity and the nitrogen substituent of the carbamate group, and two phenethyl-carbamate β-lactams were shown to be valuable antibacterial agents against selected linezolid-resistant strains, with a minimum inhibitory concentrations of 2–4 mg L?1.
- Giacomini, Daria,Martelli, Giulia,Piccichè, Miriam,Calaresu, Enrico,Cocuzza, Clementina Elvezia,Musumeci, Rosario
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p. 1525 - 1533
(2017/09/25)
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- Development of synthetic aminopeptidase N/CD13 inhibitors to overcome cancer metastasis and angiogenesis
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Cancer metastasis is a major barrier to its treatment and an important cause of patient death. Antimetastatic agents hold promise for patients with advanced metastatic tumors. Aminopeptidase N/CD13 (APN) is being pursued by many as an important target against cancer metastasis and angiogenesis, but there are few reports on the in vivo evaluation of synthetic APN inhibitors. Herein, a series of compounds targeting APN were synthesized and evaluated for their antimetastasis and antiangiogenesis potency both in vitro and in vivo. Excitingly, compounds 4m, 4t, and 4cc, with the most potent APN inhibitory activities, displayed significant antimetastasis and antiangiogenesis effects in vitro and in vivo, suggesting that those synthetic APN inhibitors have the potential to overcome cancer metastasis and angiogenesis.
- Su, Li,Cao, Jiangying,Jia, Yuping,Zhang, Xiaonan,Fang, Hao,Xu, Wenfang
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supporting information
p. 959 - 964
(2013/02/23)
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- (Tosylimino)phenyl-λ3-iodane as a reagent for the synthesis of methyl carbamates via hofmann rearrangement of aromatic and aliphatic carboxamides
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A new, mild procedure for the Hofmann rearrangement of aromatic and aliphatic carboxamides using (tosylimino)phenyl-λ3-iodane, PhINTs, as a reagent is reported. Because of the mild reaction conditions, this method is particularly useful for the Hofmann rearrangement of substituted benzamides, which usually afford complex reaction mixtures with other hypervalent iodine oxidants. The mild reaction conditions and high selectivity in the reaction of carboxamides with PhINTs allow the isolation of the initially formed labile isocyanates or their subsequent conversion to stable carbamates by treatment with alcohols.
- Yoshimura, Akira,Luedtke, Matthew W.,Zhdankin, Viktor V.
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experimental part
p. 2087 - 2091
(2012/05/05)
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- "TRPV1 VANILLOID RECEPTOR ANTAGONISTS WITH A BICYCLIC PORTION"
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The invention discloses compounds of formula I wherein Y is a group of formula A, B, C, D, or E: and W, Q, n, R1, R2, R3, U1-U5, J and K have the meanings given in the description. The compounds of formula I are TRPV1 antagonists and are useful as active
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Page/Page column 47; 48
(2011/10/13)
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- TRPV1 vanilloid receptor antagonists with a bicyclic portion
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The invention discloses compounds of formula I wherein Y s selected from a group of formula and W, Q, n, R1, R2, R3, U1-U5 have the meanings given in the description. The compounds of formula I are TRPV1 antagonists and are useful as active ingredients of pharmaceutical compositions for the treatment of pain and other conditions ameliorated by the inhibition of the vanilloid receptor TRPV1. 1.
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Page/Page column 17-18
(2011/11/01)
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- Organosilicon synthesis of isocyanates: II. Synthesis of aliphatic, carbocyclic, and fatty-aromatic isocyanates
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Silylation of a series of aliphatic, carbocyclic, and fatty-aromatic amines gave the corresponding silyl derivatives whose yield depended on the electronic and steric structure of the substrate and the nature of the silylating agent. The yield of isocyanates obtained by phosgenation of the silyl derivatives under mild conditions decreased in going from aliphatic amines to benzylamines and rose as the length of the alkyl chain in fatty-aromatic amines extended. The most convenient procedure for the synthesis of low-boiling alkyl isocyanates was found to be based on the transformation of amines or ammonium salts into silyl or silyl silyl-carabamates, followed by pyrolysis of the latter in the presence of trichloro(phenyl)silane. Pleiades Publishing, Inc., 2006.
- Lebedev,Lebedeva,Sheludyakov,Ovcharuk,Kovaleva,Ustinova
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p. 469 - 477
(2008/02/07)
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- Efficient synthesis of 2,9-disubstituted 8-hydroxyadenine derivatives
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An efficient and general method for the synthesis of 2,9-disubstituted 8-hydroxyadenines, which are expected to have various biological activities, was realized. 5-amino-4-cyano-2-hydroxyimidazoles(1) were prepared from aminomalononitrile and isocyanates as key intermediates. The condensation of 1a with amidines, imidates, guanidine, urea and thioureas afforded 8-hydroxyadenines (2-6) possessing various substituents at the 2-position. Furthermore, selective alkylation of 2-amino- and 2-hydroxyadenines (4 and 6) successively proceeded to give the corresponding 2-alkylamino- and 2-alkoxyadenines (5 and 7), respectively. 2-Alkythioadenines (15) were prepared by an analogous reaction of 1a with benzoyl isothiocyanate and subsequent S-alkylation. The imidazoles 1 are most useful intermediated for the synthesis of 8-hydroxyadenine derivatives.
- Hirota, Kosaku,Kazaoka, Kazunori,Niimoto, Itaru,Sajiki, Hironao
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p. 1354 - 1365
(2007/10/03)
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- Inhibition of serine proteases: Activity of 1,3-diazetidine-2,4-diones
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The present work demonstrates that the 1,3-diazetidine-2,4-dione nucleus is effective as a scaffold of serine protease inhibitors. Compound 1 displayed high activity against human cathepsin G and α-chymotrypsin (0.39, 0.69 nM). Compound 6 exhibited 0.85 nM inhibition of human chymase. Compound 10 was a selective inhibitor against human neutrophil elastase.
- Aoyama, Yasunori,Uenaka, Masaaki,Konoike, Toshiro,Hayasaki-Kajiwara, Yoko,Naya, Noriyuki,Nakajima, Masatoshi
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p. 1691 - 1694
(2007/10/03)
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- Orally Active β-Lactam Inhibitors of Leukocyte Elastase-1. Activity of 3,3-Diethyl-2-azetidinones
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A thorough analysis of the mechanism of inhibition of human leukocyte elastase (HLE) by a monocyclic β-lactam and the mechanism of β-lactam hydrolysis led to the preparation of potent and highly stable inhibitors of HLE.This work led to the identification of 4--3,3-diethyl-1-carbonyl>-2-azetidinone (2) as the first orally active inhibitor of human leukocyte elastase (HLE).Analogs of 2 with different substituents on the urea N were synthesized and evaluated for their activity in vitro against HLE as well as in vivo in a hamster lung hemorrhage model.Compounds with a methyl or a methoxy group in the para position of the benzene ring were very potent in both assays.The results are discussed on the basis of the proposed model for the binding of this class of inhibitors to HLE and a possible mechanism of inhibition is presented.
- Shah, Shrenik K.,Dorn, Conrad P.,Finke, Paul E.,Hale, Jeffrey J.,Hagmann, William K.,et al.
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p. 3745 - 3754
(2007/10/02)
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- ARYLMETHYL ISOCYANATES
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Chloromethyl isocyanate reacts readily with aromatic hydrocarbons in the presence of anhydrous ferric chloride or other catalysts of the Friedel-Crafts reaction with the formation of arylmethyl isocyanates.The latter add alcohols and amines readily, being converted into the corresponding substituted urethanes and ureas.When heated in the presence of catalytic amounts of 1,3-dimethylphosphol-3-ene they give substituted carbodiimides.
- Kozhushko, B. N.,Lomakina, A. V.,Paliichuk, Yu. A.,Shokol, V. A.
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p. 654 - 660
(2007/10/02)
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