- Anti-influenza virus compound as well as preparation method and application thereof
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The invention provides an anti-influenza virus pharmaceutical compound, and a preparation method and application thereof. The compound provided by the invention is a prodrug, has remarkably improved bioavailability and antiviral activity compared with a parent drug, is suitable for treating/prepaid influenza virus infection related diseases, has improved pharmacokinetic characteristics, and is particularly suitable for being developed into an oral preparation.
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Paragraph 0131; 0134; 0135
(2021/05/01)
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- New orally active dual enkephalinase inhibitors (DENKIs) for central and peripheral pain treatment
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Protecting enkephalins, endogenous opioid peptides released in response to nociceptive stimuli, is an innovative approach for acute and neuropathic pain alleviation. This is achieved by inhibition of their enzymatic degradation by two membrane-bound Zn-metallopeptidases, neprilysin (NEP, EC 3.4.24.11) and aminopeptidase N (APN, EC 3.4.11.2). Selective and efficient inhibitors of both enzymes, designated enkephalinases, have been designed that markedly increase extracellular concentrations and half-lives of enkephalins, inducing potent antinociceptive effects. Several chemical families of Dual ENKephalinase Inhibitors (DENKIs) have previously been developed but devoid of oral activity. We report here the design and synthesis of new pro-drugs, derived from co-drugs combining a NEP and an APN inhibitor through a disulfide bond with side chains improving oral bioavailability. Their pharmacological properties were assessed in various animal models of pain targeting central and/or peripheral opioid systems. Considering its efficacy in acute and neuropathic pain, one of these new DENKIs, 19-IIIa, was selected for clinical development.
- Poras, Hervé,Bonnard, Elisabeth,Dangé, Emilie,Fournié-Zaluski, Marie-Claude,Roques, Bernard P.
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supporting information
p. 5748 - 5763
(2014/08/05)
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- NOVEL BETULINIC ACID DERIVATIVES AS HIV INHIBITORS
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(I)The invention relates to novel novel betulinic acid derivatives and related compounds, and pharmaceutical compositions useful for therapeutic treatment of viral diseases and particularly HIV mediated diseases.
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Paragraph 0167
(2013/11/18)
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- Catalysis of the photodecomposition of carbon tetrachloride in ethanol by an Amberlite anion exchange resin
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The chloride form of the polystyrene-divinylbenzene anion exchange resin Amberlite IRA-900 was found to catalyze the photodecomposition of carbon tetrachloride in ethanol at wavelengths above 350 nm. With sulfate, bromide, and perchlorate as counterions, the resin was inactive. The major products are acetaldehyde, phosgene, chloroform, and hydrogen chloride. The photoreaction is much slower under 1.0 atm O2 than under air, while in deoxygenated solutions it is also much slower and produces no phosgene. Much of the observed behavior can be explained by a model in which the poly(styrene-co- divinylbenzene) matrix absorbs light and transfers energy to CCl4, which undergoes photodissociation, assisted by a chloride ion to stabilize the chlorine atom as Cl2-. Two major reaction channels for the trichloromethyl radicals produced by photodissociation are proposed, one in which CCl3 abstracts hydrogen from ethanol and the other involving addition of O2 to form trichloromethylperoxy radicals.
- Hoggard, Patrick E.,Maldotti, Andrea
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experimental part
p. 243 - 249
(2011/02/16)
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- METHOD FOR PRODUCTION OF CANDESARTAN
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The invention relates to novel methods for the production of Candesartan, or a protected form of Candesartan, a Candesartan salt or ester, compounds of application in said method, methods for production thereof, use thereof in said method, a novel polymorph of Candesartan cilexetil, a method for production and use thereof for production of a medicament.
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Page/Page column 24
(2010/11/08)
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- An improved method for preparation of cefpodoxime proxetil
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Cefpodoxime proxetil, a third-generation cephalosporin for oral administration, was synthesized by a method based on the following sequence of reactions: acylation of 7-aminocephalosporanic acid (7-ACA) with S-benzothiazol-2-yl(2-amino-4-thiazolyl)(methoxyimino)thioacetate (MAEM), chloroacetylation of the cefotaxime formed with chloroacetyl chloride, esterification of the acid function with 1-iodoethyl isopropyl carbonate and final cleavage of chloroacetamide protective group by treatment with thiourea in N,N-dimethylacetamide. The developed procedure allows us to obtain better yields of cefpodoxime proxetil and to eliminate the final purification step by column chromatography, necessary during the synthesis of this antibiotic by the previously reported methods.
- Rodriguez, Juan C.,Hernandez, Ricardo,Gonzalez, Maritza,Rodriguez, Zalua,Tolon, Blanca,Velez, Herman,Valdes, Barbara,Lopez, Miguel A.,Fini, Adamo
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p. 363 - 369
(2007/10/03)
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- Improved synthesis of dialkylaminopyrrolines
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The literature synthesis of 5-dialkylamino-3,4-dihydro-2H-pyrroles from 5-methoxy-3,4-dihydro-2H-pyrrole has been much improved. In initial assays, the pyrrolinium salts obtained on alkylation of the dibutylaminoamidine are excellent "naked halide" catalysts.
- Flosser, David A.,Olofson, Roy A.
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p. 2045 - 2052
(2007/10/03)
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- Aryloxymethylcarbonochloridate ester intermediates for use in synthesizing pro drugs and their use therefor
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The present invention relates to hitherto unknown intermediate of formula, in which R1 stands for hydrogen or a straight or branched aliphatic C1 -C20 carbon chain or an aryl or aralkyl group, aryl and "ar" meaning an aromatic or heterocyclic, 5- or 6-membered ring substituent containing 1 or 2 hetero atoms selected among O, S and N, R1 optionally being further substituted, and its chain being interrupted by hetero atoms like oxygen, or by carbonyl group(s); and R3 stands for hydrogen or C1 -C3 alkyl. The present intermediates can be used in a one step method for producing prodrugs of formula, where D-H =drug itself.
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- PRODRUGS OF IMIDAZOLE CARBOXYLIC ACIDS AS ANGIOTENSIN II RECEPTOR ANTAGONISTS
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Prodrugs of imidazole carboxylic acids which are AII antagonists useful in treating hypertension, pharmaceutical compositions thereof and a method of treating hypertension using such prodrugs are disclosed.
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- COMPETITION BETWEEN n,?- AND n,?-ORBITAL INTERACTIONS IN CHLORINATED ETHERS R-O-CHClR1
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Using the AM-1 method, we have studied CH2=CH-O-CHClR1 molecules (R1 = H, Me).We have shown that the sc conformation with respect to the Csp3-O bond is preferred.We have systematized the 35Cl NOR data on the degree of manifestation of the generalized anomeric effect in R-OCHClR1 2C(=O)> molecules.We have established that enhancement of n,? conjugation in the R-O fragment leads to weakening of the n,? interaction in the O-C-Cl triad.
- Bredikhin, A. A.,Kirillovich, V. A.,Safin, I. A.,Vereshchagin, A. N.
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p. 2185 - 2189
(2007/10/02)
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- 1'-(substituted)ethyl-7β-[2-(2-aminothiazol-4-yl)acetamido]-3-[[[1-(2-dimethylaminoethyl)-1H-tetrazol-5-yl]thio]methyl]ceph-3-em-4-carboxylate derivatives having antibacterial utility
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A compound of the formula: STR1 wherein R is 2-methylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, n-pentyl, an alkyl group of 6 or 7 carbon atoms, or an alkenyl group of 2 to 7 carbon atoms, or a pharmaceutically acceptable salt thereof and processes for preparing the same are provided. The compound can orally be applied as antibiotics having improved absorbability.
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- Phenothiazine and derivatives and analogs and use as leukotriene biosynthesis inhibitors
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Phenothiazine derivatives and analogs thereof having the Formula I are useful as inhibitors of the biosynthesis of mammalian leukotrienes. As such, these compounds are useful therapeutic agents for treating allergic conditions, asthma, cardiovascular disorders and inflammation, and are useful as cytoprotective agents. STR1
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- Process for the preparation of α-chlorinated chloroformates
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Process for the preparation of α-chlorinated chloroformates with the formula STR1 where R is H, an aliphatic or aromatic hydrocarbon radical or heterocyclic radical, substituted or non-substituted and n an integer. The process consists of reacting ClCOOCCl3 or Cl3 COCOOCCl3 with an aldehyde with formula R--(CHO)n in the presence of a compound, which in the medium releases a pair of ions, the anion of which being a halide which can attack the aldehyde function, because of the weak attractive power of the cation of this compound.
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- Process for the synthesis of α-chlorinated chloroformates
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Process for the synthesis of α-chlorinated chloroformates, and new α-chlorinated chloroformates. The invention relates to a new process for the manufacture of α-chlorinated chloroformates and, to new α-chlorinated chloroformates as new industrial products. The process according to the invention consists of a synthesis, by catalytic phosgenation, of α-chlorinated chloroformates of the formula: STR1 in which: R represents a substituted or unsubstituted hydrocarbon radical and m represents an integer superior or equal to one, this synthesis consisting in reacting phosgene with the aldehyde R--CHO)m, in the presence of a catalyst which is an organic or inorganic substance which is capable in a medium containing an aldehyde of the formula R--CHO)m, phosgene and, possibly, a solvent, of generating a pair of ions one of which is an halogenide anion and the other is a cation which is sufficiently separated from said halogenide anion so as to give to the latter a nucleophilic power enabling it to react with the function(s) aldehyde of the molecule R--CHO)m.
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- Benzo[A]phenothiazines and hydro-derivatives
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Pharmaceutical compositions containing a compound of Formula I: STR1 wherein X is O, S, SO or SO2 and R2, R3, R4 and R5 may be positioned anywhere on the structure, or a pharmaceutically-acceptable salt thereof and certain novel benzo[a]phenothiazines, which compositions and compounds are useful in treating allergic conditions, asthma, cardiovascular disorders, inflammation and pain and are useful as cytoprotective agents.
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- A New Reagent for the Selective, High-Yield N-Dealkylation of Tertiary Amines: Improved Syntheses of Naltrexone and Nalbuphine
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Secondary amine hydrochlorides are obtained in high yield by reaction of tertiary amines with α-chloroethyl chloroformate followed by warming the intermediate carbamate in methanol.
- Olofson, R. A.,Martz, Jonathan T.,Senet, Jean-Pierre,Piteau, Marc,Malfroot, Thierry
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p. 2081 - 2082
(2007/10/02)
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