- Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited
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Recent findings from solid state NMR (ssNMR) studies suggested that the (R)-enantiomer of rimantadine binds to the full M2 protein with higher affinity than the (S)-enantiomer. Intrigued by these findings, we applied functional assays, such as antiviral assay and electrophysiology (EP), to evaluate the binding affinity of rimantadine enantiomers to the M2 protein channel. Unexpectedly, no significant difference was found between the two enantiomers. Our experimental data based on the full M2 protein function were further supported by alchemical free energy calculations and isothermal titration calorimetry (ITC) allowing an evaluation of the binding affinity of rimantadine enantiomers to the M2TM pore. Both enantiomers have similar channel blockage, affinity, and antiviral potency.
- Drakopoulos, Antonios,Tzitzoglaki, Christina,Ma, Chulong,Freudenberger, Kathrin,Hoffmann, Anja,Hu, Yanmei,Gauglitz, Günter,Schmidtke, Michaela,Wang, Jun,Kolocouris, Antonios
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Read Online
- Pentadienyl chemistry of the heavy alkaline-earth metals revisited
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Open-metallocenes of the heavy alkaline-earth metals [(η5- Pdl′)2M(thf)n] (M = Ca (1), Sr (2), n = 1; M = Ba (3), n = 2; Pdl′ = 2,4-tBu2C5H5) are readily prepared by salt-metathesis between MI2 and KPdl′ and characterized by NMR spectroscopy and X-ray diffraction studies. This journal is the Partner Organisations 2014.
- Reiners, Matthias,Fecker, Ann Christin,Freytag, Matthias,Jones, Peter G.,Walter, Marc D.
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Read Online
- Method for preparing 1, 1 and 1 -trifluoro -2 -methyl -2 - propanol
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The invention discloses a method for preparing 1, 1 and 1 -trifluoro -2 -methyl -2 - propanol. To the method, methyl magnesium halide Grignard reagent is prepared from halogenated methane as a raw material in ether solvents, 1, 1 and 1 - trifluoroacetone are reacted in the presence of a catalyst to obtain 1, 1, 1 -trifluoro -2 -methyl -2 -propanol. The method has the advantages of easily available raw materials, convenience in post-treatment and purification, simplicity in operation, relatively low cost, high yield and the like.
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Paragraph 0038
(2021/12/07)
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- Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides
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Magnesium organometallic reagents occupy a central position in organic synthesis. The freshness of these compounds is the key for achieving a high conversion and reproducible results. Common methods for the synthesis of Grignard reagents from metallic magnesium present safety issues and exhibit a batch-to-batch variability. Tubular reactors of solid reagents combined with solution-phase reagents enable the continuous-flow preparation of organomagnesium reagents. The use of stratified packed-bed columns of magnesium metal and lithium chloride for the synthesis of highly concentrated turbo Grignards is reported. A low-cost pod-style synthesizer prototype, which incorporates single-use prepacked perfluorinated cartridges and bags of reagents for the automated on-demand lab-scale synthesis of carbon, nitrogen, and oxygen turbo magnesium bases is presented. This concept will provide access to fresh organomagnesium reagents on a discovery scale and will do so independent from the operator’s experience in flow and/or organometallic chemistry.
- Adamo, Andrea,Berton, Mateo,McQuade, D. Tyler,Sheehan, Kevin
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supporting information
p. 1343 - 1356
(2020/07/10)
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- Identification of the Active Catalyst for Nickel-Catalyzed Stereospecific Kumada Coupling Reactions of Ethers
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A series of nickel complexes in varying oxidation states were evaluated as precatalysts for the stereospecific cross-coupling of benzylic ethers. These results demonstrate rapid redox reactions of precatalysts, such that the oxidative state of the precatalyst does not dictate the oxidation state of the active catalyst in solution. These data provide the first experimental evidence for a Ni0–NiII catalytic cycle for a stereospecific alkyl–alkyl cross-coupling reaction, including spectroscopic analysis of the catalyst resting state.
- Borovik, Andy S.,Dawson, David D.,Jarvo, Elizabeth R.,Oswald, Victoria F.
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supporting information
(2020/03/04)
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- Nickel-Catalyzed Alkyl-Alkyl Cross-Electrophile Coupling Reaction of 1,3-Dimesylates for the Synthesis of Alkylcyclopropanes
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Cross-electrophile coupling reactions of two Csp3-X bonds remain challenging. Herein we report an intramolecular nickel-catalyzed cross-electrophile coupling reaction of 1,3-diol derivatives. Notably, this transformation is utilized to synthesize a range of mono- and 1,2-disubstituted alkylcyclopropanes, including those derived from terpenes, steroids, and aldol products. Additionally, enantioenriched cyclopropanes are synthesized from the products of proline-catalyzed and Evans aldol reactions. A procedure for direct transformation of 1,3-diols to cyclopropanes is also described. Calculations and experimental data are consistent with a nickel-catalyzed mechanism that begins with stereoablative oxidative addition at the secondary center.
- Chen, Pan-Pan,Hong, Xin,Jarvo, Elizabeth R.,McGinnis, Tristan M.,Sanford, Amberly B.,Thane, Taylor A.
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supporting information
(2020/03/23)
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- Compounds of the menthane series. Synthesis of unsaturated primary alcohols with the o- and p-menthane skeletons
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Precursors to terpene alcohols of the o- and p-menthane series (o-cimen-7-ol and o- and p-cimen-9-ols) were synthesized, and their reduction with lithium in ethylenediamine was studied. The reduction of o- and p-cimen-9-ols in the presence of isopropyl alcohol selectively afforded the corresponding 1,4-dihydro derivatives. Under analogous conditions, o-cimen-7-ol was converted into a mixture of unsaturated hydrocarbons. The reduction with lithium in ethylenediamine in the absence of isopropyl alcohol in all cases gave mixtures of menthene alcohols.
- Fedorov,Fedorova,Sheverdov,Pavlov,Eremkin
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p. 806 - 812
(2016/07/30)
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- Nickel-Catalyzed Cross-Electrophile Coupling of Alkyl Fluorides: Stereospecific Synthesis of Vinylcyclopropanes
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The stereospecific reductive cross-electrophile coupling reaction of 2-vinyl-4-halotetrahydropyrans for vinylcyclopropane synthesis is reported. The nickel-catalyzed reaction occurs with both alkyl fluorides and alkyl chlorides. To the best of our knowledge, this is the first reported cross-electrophile coupling reaction of an alkyl fluoride. Ring contraction proceeds with high stereospecificity, providing selective synthesis of either diastereomer of di- and trisubstituted cyclopropanes. The utility of this methodology is demonstrated by several synthetic applications including the synthesis of the natural product dictyopterene A. 2-Vinyl-4-fluorotetrahydrofurans also undergo stereospecific ring contractions, providing access to synthetically useful hydroxymethyl cyclopropanes.
- Erickson, Lucas W.,Lucas, Erika L.,Tollefson, Emily J.,Jarvo, Elizabeth R.
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supporting information
p. 14006 - 14011
(2016/11/06)
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- Efficient C(sp3)-H bond functionalization of isochroman by azadol catalysis
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A novel organocatalytic C(sp3)-H bond functionalization of isochroman under practical conditions has been developed. In the presence of 5.0 mol % of AZADOL, the catalysis proceeded successfully with a broad range of substrates and nucleophiles in excellent yields.
- Muramatsu, Wataru,Nakano, Kimihiro
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supporting information
p. 1549 - 1552
(2015/03/30)
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- Locking out ants - Synthesis and biological evaluation of some fluorinated repellents
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We synthesized a series of fluorinated compounds and tested them in an easy assay for their repellent activity against the ant Myrmica rubra. Depending on their chain length and pattern of fluorination these molecules are efficient repellents for this ant. Fluorinated compounds are stronger repellents than their unfluorinated analogs. 1,1,1-Trifluorotridecan-2-one (4) is an even better repellent against M. rubra than "gold standard" N,N-diethyl-m- toluamide (DEET).
- Csuk, Rene,Tamba, Maria Gabriela,Kluge, Ralph
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experimental part
p. 1069 - 1075
(2011/12/13)
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- Quaternary carbon stereogenic centers through copper-catalyzed enantioselective allylic substitutions with readily accessible aryl- or heteroaryllithium reagents and aluminum chlorides
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The case of the notorious aryls is solved: The first efficient catalytic and enantioselective method for allylic substitutions that furnish quaternary carbon stereogenic centers by additions of aryl- or heteroarylmetals is reported (see scheme). Highly site- and enantioselective processes begin with readily available organolithium reagents.
- Gao, Fang,Lee, Yunmi,Mandai, Kyoko,Hoveyda, Amir H.
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supporting information; body text
p. 8370 - 8374
(2010/12/25)
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- 4- [HETEROCYCLYL-METHYL] -8-FLUORO-QUINOLIN-2-ONES USEFUL AS NITRIC OXIDE SYNTHASE INHIBITORS
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Novel compounds of formulae (II, III) and pharmaceutical compositions have been found to inhibit inducible NOS synthase wherein: R4, R5, R6 and R7 are independently selected from the group consisting of hydrogen, lower alkyl, and halogen; and, R8 has the structure whrein X1, X2, X3, X4, X5, X6, R9, R13, R14 and n are as described herein.
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Page/Page column 61
(2009/04/25)
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- NOVEL CANNABINOID RECEPTOR LIGANDS, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM, AND PROCESS FOR THEIR PREPARATION
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The present invention relates to compounds of f formula (I) as cannabinoid receptor modulators, in particular cannabinoid 1 (CB1) or cannabinoid 2 (CB2 ) receptor modulators, and uses thereof f or treating diseases, conditions and/or disorders modulated by a cannabinoid receptor ( such as pain, neurodegenrative disorders, eating disorders, weight loss or control, and obesity).
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Page/Page column 52
(2009/05/30)
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- Enantioselective total synthesis of brevetoxin A: Unified strategy for the B, E, G, and J subunits
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Brevetoxin A is a decacyclic ladder toxin that possesses 5-, 6-, 7-, 8-, and 9-membered oxacycles, as well as 22 tetrahedral stereocenters. Herein, we describe a unified approach to the B, E, G, and J rings based upon a ring-closing metathesis strategy from the corresponding dienes. The enolate technologies developed in our laboratory allowed access to the precursor acyclic dienes for the B, E, and G medium-ring ethers. The strategies developed for the syntheses of these four monocycles ultimately provided multigram quantities of each of the rings, supporting our efforts toward the completion of a convergent synthesis of brevetoxin A.
- Crimmins, Michael T.,Ellis, J. Michael,Emmitte, Kyle A.,Haile, Pamela A.,McDougall, Patrick J.,Parrish, Jonathan D.,Zuccarello, J. Lucas
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supporting information; experimental part
p. 9223 - 9234
(2010/04/25)
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- Methods for producing trialkyl gallium
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The present invention provides method 1 for producing a trialkyl gallium comprising the steps of reacting gallium, magnesium, and an alkyl halide in an ether, and diluting during the reaction the reaction system with an ether; method 2 for producing a trialkyl gallium comprising the steps of heating in a vacuum a mixture of magnesium and molten gallium, and reacting the mixture with an alkyl halide in a solvent; and method 3 for producing a trialkyl gallium comprising the step of reacting an alkyl metal with an alkylgallium halide compound represented by the formula ???????? Ga2RmX6-m wherein R is a methyl or ethyl group, X is a halogen atom, and m is an integer from 1 to 5.
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- AN IMPROVED PROCESS FOR THE PREPARATION OF TERBINAFINE INTERMEDIATE
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This application discloses an improved process for the preparation of N-methyl-N-(1-naphthylmethyl)-6,6-dimethyl-2-hydroxyheptan-4-ynyl-1-amine, a key intermediate used in the synthesis of terbinafine ((E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine). Process is involving converting tertiary-butylacetylene to its Grignard derivative via transmetallation using lower alkylmagnesium halides and treating it with 1-[N-methyl-N-(1-naphtylmethyl)amino]-2,3-epoxypropane at -10°C to -20°C, slowly heating the reaction mass to reflux temperature and quenching of reaction mass with ammonium chloride to give the compound of the formula-I as crystalline solid.
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Page/Page column 8-9
(2010/02/12)
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- BENZIMIDAZOLE DERIVATIVES
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A compound of formula (I) or a pharmaceutically acceptable salt or prodrug ester thereof; wherein R1-R7 are as disclosed in the specification and pharmaceutical uses thereof.
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Page/Page column 72
(2008/06/13)
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- Butadiene derivatives and process for preparing thereof
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A novel butadiene derivative of the formula: wherein Ring A is heterocycle, or benzene being optionally substituted by lower alkyl, alkoxy, nitro, hydroxy, substituted or unsubstituted amino or halogen, Ring B is heterocycle, or benzene being optionally substituted by lower alkoxy, lower alkylenedioxy or di-lower alkylamino, R1and R2are each H or lower alkyl, one of —COR32and —COR42is carboxyl, and the other is carboxyl being optionally esterified, or the corresponding amide or pyrrolidine derivatives, or a pharmaceutically acceptable salt thereof. Said compounds show excellent PAI-1 inhibitory activity and are useful in the prophylaxis or treatment of various thromboses such as myocardial infarction, intra-atrial thrombus in atrial fibrillation, cerebral infarction, angina pectoris, stroke, pulmonary infarction, deep venous thrombus (DVT), disseminated intravascular coagulation syndrome (DIC), diabetic complications, restenosis after percutaneous transluminal coronary angioplasty (PTCA), etc.
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- Substituted 4-arylmethylene-2-imino-2,3-dihydrothiazoles and derivatives and their pharmaceutical use
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Compounds of Formula I including pharmaceutically acceptable salts thereof in the form of individual enantiomers, racemates, or other mixtures of enantiomers, in which Ar is phenyl, naphthyl or benzo[b]thiophenyl, each of which may be optionally substituted; R1and R2, which may be the same or different, independently are a) H, b) an alkyl group containing 1 to 6 carbon atoms, c) an alkenyl group containing 3 to 6 carbon atoms, d) a cycloalkyl group containing 3 to 7 carbon atoms, e) a cycloalkylmethyl group in which the ring contains 3 to 7 carbon atoms, f) an aryl or heteroaryl group optionally substituted g) an arylalkyl or heteroarylalkyl group each optionally substituted; or R1and R2form an alkylene chain optionally substituted by one or more alkyl groups each containing 1 to 3 carbon atoms, such that, together with the atoms to which they are attached, they form a 5 or 6 membered ring; R3is a) H, b) an aryl or heteroaryl group each optionally substituted c) an optionally substituted arylmethyl group; or d) an alkoxyalkyl group containing 3 to 6 carbon atoms; and R4and R5, which may be the same or different, independently are an alkyl group containing 1 to 3 carbon atoms, or R4and R5together with the atom to which they are attached form a cycloalkyl ring containing 3 to 6 carbon atoms; processes to prepare such compounds; compositions containing such compounds and their use in the treatment of depression, anxiety, Parkinson's disease, obesity, cognitive disorders, seizures, neurological disorders and as neuroprotective agents; are described.
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- Tritioacetylating reagents and processes for preparation thereof
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Novel acetylating and tritioacetylating reagents suitable for preparation of nonlabelled and radiolabelled organic compounds. N-acetoxynaphthalimide, N-tritioacetoxyphthalimide, N-tritioacetoxysuccinimide, N-tritioacetoxynaphthalimide and processes of their preparation. The invention also concerns synthesis of nonlabelled acetylated and tritioacetylated organic compounds from precursors containing a free --NH2, --SH or --OH group.
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- Process for the preparation of lamotrigine
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The invention provides a process for producing lamotrigine of formula (I): STR1 which process comprises subjecting a compound of formula (II): STR2 wherein R is CN or CONH2, in an organic solvent, to ultra violet or visible radiation and, when R is CN, to heat.
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- Process for the preparation of lamotrigine
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Lamotrigine, 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine, may be prepared by treating 6-(2,3-dichlorophenyl)-5-chloro-3-thiomethyl-1,2,4-triazine of formula (II) STR1 with ammonia. Precursors to the compound of formula (II), and their preparation, are also described.
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- Therapeutic agents
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Compounds of formula I STR1 and pharmaceutically acceptable salts thereof in which m is 0, 1 or 2; n is 2, 3, 4 or 5; X is carbonyl or a group of formula II STR2 in which R5 is H or alkyl; Y is an alkylene chain optionally substituted by one or more alkyl groups; Z is an alkylene chain containing 2 to 5 carbon atoms optionally substituted by one or more alkyl groups; R is phenyl optionally substituted by one or more halo substituents or R is naphthyl; and R1 and R2, which are the same or different, are H, alkyl, or arylalkyl, provided that when R1 is benzyl, R2 is H or methyl; have utility in the treatment of depression, anxiety, Parkinson's disease, obesity, cognitive disorders, seizures, neurological disorders such as epilepsy, and as neuroprotective agents to protect against conditions such as stroke.
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- Use of certain imidazol carbazols in treating stress-related manic-depressive disorders
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Use of a mono or bicyclic carbocyclic, or heterocyclic carboxylic, acid ester or amide or an imidazolyl carbazol in the manufaccure of a medicament suitable for the treatment of stress-related psychiatric disorders, for increasing vigilance, for the treatment of rhinitis or serotonin-induced disorders and/or coadministration with another active agent to increase the bioavailability thereof, or for nasal administration.
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- 4-benzyl-1H-indoles and anti-arrthymic use thereof
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Novel 4-benzyl-1H-indoles of the formula STR1 in all diastereoisomeric forms and mixtures thereof having antiarhythmic activity.
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- Process for the preparation of pterin derivatives
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A process of preparing l-biopterin is disclosed which comprises the steps of: Subjecting to selective Grignard reaction D-ribose having the hydroxyl groups in the 2- and 3-positions protected by an acetal group to give 6-deoxy-3,4-O-alkylidene allitol; subjecting the 1- and 2-positions of said allitol to oxidative cleavage to form 5-deoxy-2,3-O-alkylidene-L-ribose followed by deacetalization to give 5-deoxy-L-ribose; reacting 5-deoxy-L-ribose with a hydrazine compound to form a 5-deoxy-L-ribose hydrazone compound; and subjecting said hydrazone compound to condensation reaction with an acid addition salt of 4-hydroxy-2,5,6-triaminopyrimidine followed by oxidation.
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- Therapeutic agents
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This invention relates to compounds of formula I wherein R1 represents hydrogen or together with R2 represents a bond; R2 together with either one of R1 and R3 represents a bond; R3 together with either one of R2 and R4 represents a bond; R4 represents hydrogen or together with R3 represents a bond; R5 represents hydrogen or methyl; R6 represents hydrogen, halo, a C2 6 alkanoyl group, a C2 6 alkoxycarbonyl group, a C1 6 alkylthio group, a C1 6 alkylsulphinyl group, a C1 6 alkylsulphonyl group, carbamoyl, carboxy, or R5 and R6 together with the carbon atom to which they are attached represent a cyclopropyl group; R7 represents hydrogen, halo, trifluoromethyl, methoxy, a C1 6 alkyl group, a C1 6 alkylthio group or a C1 6 alkylsulphinyl group; R8 represents hydrogen, halo or trifluoromethyl; R9 and R10, which may be the same or different, each represent halo; or R9 represents hydrogen and R10 represents hydrogen, halo, trifluoromethyl, hydroxy, nitro, a C2 6 alkanoyloxy group, a C1 6 alkyl group or a C1 6 alkoxy group, which have immunomodulatory activity. Compositions containing these compounds and processes to make them are also disclosed.
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- Synthesis of 2-hydroxy-3,6,10-trimethylbenzocyclooct-5-ene (isoparvifolin), a sesquiterpenic benzocyclooctene
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The synthesis of 2-hydroxy-3,6,10-trimethylbenzocyclooct-5-ene (2) (isoparvifolin), a double bond isomer of the naturally occuring phenolic sesquiterpene (1) (parvifolin) is described.The key intermediate, 6-(3-methoxy-4-methylphenyl)heptanoic acid (3), required for the synthesis of 2 has been made from the keto ester (4) in two ways (4 -> 5 -> 6 -> 7 -> -> 3; 4-> -> 8 -> -> 3).The methoxyaryl heptanoic acid (3) is cyclodehydrated to the benzocyclooctanone (9).Vilsmeier reaction on the corresponding benzocyclooctanol, obtained by NaBH4 reduction of 9 gives the unsaturated aldehyde (10).Two functional group transformations on 10 (CHO -> CH3 and OCH3 -> OH) by standard procedures finally yield isoparvifolin (2).
- Sudalai, A.,Rao, G.S.Krishna
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p. 219 - 222
(2007/10/02)
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- Polymeric polymethine dyes and optical data storage media containing same
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A polymeric tetra-aryl polymethine dye of the general formula in which:, A comprises a conjugated chain of carbon atoms having an equal number of double and single bonds,each R independently represents an alkyl group of 1 to 4 carbon atoms, R1 represents -NR2 or and, X represents an anion. The dyes are suitable for use as recording media in optical recording elements in which information may be recorded and read directly afterwards by means of laser light.
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- Naphtho-[1,2-b]-quinolizium derivatives as antidiarrheal agents
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There are disclosed certain naphtho-[1,2-b]-quinolizium compounds which have antidiarrheal activity. The compounds reduce fluid accumulation caused by enterotoxins produced by bacteria such as Vibrio cholerae or Escherichia coli.
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- Aminoindazole derivatives
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A compound of the formula (I): STR1 wherein W1 and W2 each independently is a hydrogen atom or a STR2 group wherein Y is a n-C1-6 alkylene group or a n-C1-6 alkylene group having a C1-6 alkyl group substituent; and R1 and R2 each independently is a hydrogen atom or a C1-6 alkyl group, and STR3 group in STR4 group may form a saturated heterocyclic ring selected from the group consisting of morpholino, pyrrolidino, piperidino, homopiperidino and piperazino groups, and the saturated heterocyclic ring except the morpholino group may have at least one C1-4 alkyl group, hydroxyl group or halogen atom as a substituent; Z1 is a hydrogen atom, a chlorine atom, a bromine atom, an iodine atom, a hydroxyl group, an amino group, a C1-3 alkyl group or a methoxy group; Z2 is a hydrogen atom or an amino group; when W1 and W2 are both hydrogen atoms, Z1 is a hydroxyl group or an iodine atom and Z2 is hydrogen atom, or Z1 and Z2 are both amino groups; when Z1 and Z2 are both hydrogen atoms, the STR5 group in either W1 or W2 is a morpholino group; when Z1 is a chlorine atom, a hydroxyl group, an iodine atom, a methyl group or a methoxy group, Z2 is a hydrogen atom; when Z1 is an amino group, Z2 is a hydrogen atom or an amino group; when Z1 is a methyl group, a methoxy group or an amino group, Z1 is in the 5-position; when Z1 is an iodine atom, Z1 is in the 5- or 7-position; and when Z1 and Z2 are both amino groups, Z1 and Z2 are in the 5- and 7-positions; and the physiologically acceptable acid addition salt thereof which compounds have pharmaceutical utility, e.g.: treating inflammation.
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- Carboxylic acid ester and an insecticidal and/or acaricidal composition containing the same
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This invention relates to a novel carboxylic acid ester represented by the following general formula (I) and an insecticidal and/or acaricidal composition containing the same as an active ingredient: STR1 wherein X is represented by the formula, STR2 and further also relates to a carboxylic acid or a reactive derivative thereof represented by the general formula, STR3 wherein R16 is hydroxy group, chlorine or bromine atom, or a C1-2 alkoxy group, W is oxygen atom or --CH2 -- group, k is an integer of 0 or 1, E is hydrogen, chlorine, fluorine or bromine atom, and n is an integer of 1 to 4.
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- Analgesic 9,9-dimethylbenzomorphanes
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9,9-Dimethyl-6,7-benzomorphan derivatives having an oxygen-containing substituent on the nitrogen atom, optionally an alkyl or phenyl 5-substituent and optionally a hydroxy, alkoxy or acyloxy 2'-substituent have analgetic and/or morphine-antagonist properties.
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- Anti-hypertensive benzodioxan derivatives
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This invention relates to benzodioxanylalkylpiperidines, to processes for producing them and to the pharmaceutical compositions containing such compounds as active ingredient. This invention also relates to a method for treating hypertension in hypertensive mammals.
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- 3-Aminoindazole derivatives
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A compound of the formula (I): STR1 wherein W1 is a hydrogen atom or a STR2 group wherein Y is a C1-6 alkylene group or a C1-6 alkylene group having a C1-6 alkyl group substituent; and R1 and R2 each independently is a hydrogen atom or a C1-6 alkyl group and R1 and R2 may form a C4-6 heterocyclic ring or a nitrogen-containing C4-6 heterocyclic ring together with the adjacent nitrogen atom and the C4-6 heterocyclic rings may have at least one C1-6 alkyl group, hydroxyl group or halogen atom; W2 is a hydrogen atom or a STR3 group wherein Z is a C1-6 alkylene group or a C1-6 alkylene group having a C1-6 alkyl group substituent; and R3 and R4 each independently is a hydrogen atom or a C1-6 alkyl group and R3 and R4 may form a C4-6 heterocyclic ring or a nitrogen-containing C4-6 heterocyclic ring together with the adjacent nitrogen atom and the C4-6 heterocyclic rings may have at least one C1-6 alkyl group, hydroxyl group or halogen atom; when W1 is a hydrogen atom, W2 is the STR4 group; and when W2 is a hydrogen atom, W1 is the STR5 group; and the pharmaceutically acceptable acid addition salt thereof having antiinflammatory, analgesic and digestive tract ulcer suppressing activity.
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- Tetrahydrothiopyrano[2,3-b]indole derivatives
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Tetrahydrothiopyrano[2,3-b]indole derivative represented by the formula I: STR1 wherein R1 is hydrogen, alkyl, hydroxyalkyl, alkenyl, aralkyl, aryl, --COR5 (wherein R5 is alkyl, alkenyl, aryl or alkoxy) or STR2 (wherein Y is alkylene, oxoalkylene, hydroxyalkylene and R6 and R7 are each hydrogen or alkyl): R2 is hydrogen or alkyl; R3 is hydrogen, alkyl, hydroxyalkyl, alkenyl, aralkyl, aryl or dialkylaminoalkyl or STR3 is pyrrolidino, piperidino, piperazino, 4-alkylpiperazino, 4-arylpiperazino or morpholino; R4 is hydrogen or alkyl; A is methylene, alkylmethylene, ethylene, alkylethylene; X is hydrogen or one or two groups selected from the group consisting of halogen, alkyl, alkoxy, hydroxy and halogenoalkyl; and n is an integer of 0 to 2 and its pharmaceutically acceptacle salts; synthesized from 2-propargylthioindole or 2-(4-hydroxy-2-butynylthio)-indole; useful as analgesic and anti-inflammatory agent.
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- Amides
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Glycinamides of formula (1): wherein E has seven to nine carbon atoms and is branched alkyl, alkylcycloalkyl or cycloalkylalkyl or their acid addition salts, methods of preparing them, pharmaceutical compositions containing them and their use in medicine as anti-depressants.
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- Substituted pyrazolo (1,5-a)pyrimidines and their use as anxiolytic agents
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This disclosure describes substituted pyrazolo[1,5-a]pyrimidines which possess anxiolytic activity.
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- THE MONOMETHYL AND DIMETHYL DERIVATIVES OF BENZOPYRENE
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Convenient syntheses of the previously unknown complete set of six isomeric monomethyl derivatives of benzopyrene, 1-, 2-, 3-, 4-, 9- and 10-methylbenzopyrene, are described.Syntheses of 1-, 2- and 3-methylbenzopyrene were accomplished through reaction of 7H-benzanthrene (or its 1-Me derivative as appropriate) with 1,3-bis(dimethylamino)trimethinium perchlorate (or its 1-Me derivative) followed by thermal electrocyclic ring closure accompanied by elimination and aromatization.The earlier claim that the analogous isomeric benzopyrene derivatives are principal products of reactions of this type is disproven.Synthesis of 3,6- and 4,5-dimethylbenzopyrene are also described.The structural assignments of all mono- and dimethylbenzopyrene products are supported by high resolution 270 MHz proton NMR spectra; the chemical shifts and coupling constants of all aromatic protons are fully assigned.
- Lee, Hongmee,Shyamasundar, N.,Harvey, Ronald G.
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p. 2563 - 2568
(2007/10/02)
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- Infrared Matrix Isolation Study of Magnesium Metal Atom Reactions. Spectra of an Unsolvated Grignard Species
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Reactions of magnesium atoms with methyl halides in argon matrices have given rise to four product bands which can be assigned to a new chemical species, at 543, 1305, 2800, and 2892 cm-1.All four are hydrogenic in nature, and are assigned to the four vibrations of a C3v methyl group in the reaction product.Evidence is presented for insertion of the magnesium atom into the carbon-halogen bond of the methyl halide to form a species H3CMgX, for X = Cl, Br, I.Similar reactions were observed with calcium and strontium atoms, while zinc atoms did not react with methylhalides under these conditions.No evidence was detected for a strong polar covalent carbon-magnesium bond, suggesting that the unsolvated Grignard reagent formed here has a structure other than that of the solvated solution species.
- Ault, Bruce S.
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p. 3480 - 3484
(2007/10/02)
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- Pyrazolo[1,5-a]pyrimidines and imidazo-[1,5-a]pyrimidines
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This disclosure describes substituted pyrazolo[1,5-a]pyrimidines and imidazo[1,5-a]pyrimidines which possess anxiolytic activity.
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- 2-(4H-1-Benzopyran-6-yl)propionic acids
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There are described compounds of formula I, STR1 in which Ra is hydrogen, alkyl, alkenyl or phenyl, R3, R5, R7 and R8, which may be the same or different, are each hydrogen, alkyl, alkoxy, halogen, hydroxy, alkenyl or phenyl, Rx is hydrogen or alkyl, Ry and Rz are both hydrogen, or together represent a carbonyl oxygen atom, Rb and Rc are both hydrogen or together represent a carbon-carbon bond, Provided that when Rx is hydrogen, Ry and Rz together represent a carbonyl oxygen atom and R5, R7 and R8 are all hydrogen then Ra is other than methyl or phenyl, And pharmaceutically acceptable derivatives thereof. There are also described methods for making the compounds and pharmaceutical, e.g. anti-inflammatory, compositions containing the compounds.
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- Novel indan derivatives
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Novel indan compounds of the formula STR1 wherein A and X are each ethylene or vinylene; B is C2-4 alkylene; R and R2 are each hydrogen or C1-4 alkyl; R1 is C1-8 alkyl; C = Z is C = O, or STR2 and its non-toxic salts, which are useful as antiulcers, gastric secretion inhibitors, and hypotensors.
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- N-tricyclic derivatives of azetidine and pharmaceutical compositions and methods containing them
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Novel N-tricyclic derivatives of azetidine are disclosed of the general formula: STR1 WHERE A is a --CH2 --S-- or --S--CH2 -- group, the remaining substituents being defined in the specification. Illustrative is the compound 1-[11-(6,11-dihydro-dibenzo [b,e] thiopinyl)]-3-methylamino-azetidine. The compounds are useful for their anti-depressant, anti-convulsant and anxiolytic activities.
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- Process for the preparation of androstane-3,17-dione derivatives
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A process for the preparation of androstane-3,17-dione compounds of the formula STR1 wherein X is 1,2-methylene or 1- or 2-methyl, comprises fermenting a sterol of the formula STR2 wherein X is as above and R1 is the hydrocarbon residue of 8-10 carbon atoms, of a sterol, with a microorganism culture capable of effecting the side chain degradation of sterols.
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- Process for the preparation of 4-androstene-3,17-dione derivatives
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A process for the preparation of 4-androstene-3,17-dione derivatives of the formula STR1 wherein X is 6,7-methylene or fluoro, chloro, or methyl in the 6- or 7-position, comprises fermenting a sterol of the formula STR2 wherein X is as above and R1 is a hydrocarbon residue of 8-10 carbon atoms with a microorganism culture capable of degrading the side chain of a sterol.
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- 3-Piperidine-methanols
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1,2,3,4,4a,5,10,10a-octahydro-5-(Y3)-5-(Y4)-benzo[g]quinolines and 1,2,3,4,4a,9b-hexahydro-5-(Y3)-5-(Y4)-5H-indeno[1,2,b]pyridines wherein Y3 and Y4 are hydrogen, alkyl or phenyl, which are useful as antagonists of strong analgesics, are obtained by cyclizing derivatives of 2-(phenyl or benzyl)-α-(Y3)-α-(Y4)-3-piperidinemethanols. The latter are obtained from corresponding 3-piperidinecarboxylic acids.
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- 2,4-Diamino-5-benzylpyrimidines
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2,4-Diamino-5-benzylpyrimidines characterized by the formula SPC1 Wherein R1, R2, A1, Z and n are as hereinafter set forth, are described. The 2,4-diamino-5-benzylpyrimidines of the invention have useful antibacterial activity. More particularly, they block bacterial dihydrofolate reductase and potentiate the antibacterial activity of sulfonamides.
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