- Method for continuous preparation of nitriles by amides (by machine translation)
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The method comprises the following steps: preparing a lead salt supported by a molecular sieve by a lead salt and a molecular sieve through an impregnation method; and filling a molecular sieve-loaded lead catalyst into a fixed bed reactor. The amide or amide solution is sent into a fixed bed reactor from the top of the fixed bed to be subjected to catalytic dehydration, and the obtained reaction product is led out from the bottom of the fixed bed. The reaction product is separated to obtain the crude product of the nitrile corresponding to the amide. A fixed bed continuous production process is adopted, the reaction process is simple, the production efficiency is high, the product post-treatment is simple, and industrial production is easy to realize. (by machine translation)
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Paragraph 0033-0054; 0061-0065
(2020/12/15)
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- Xanthine derivatives, their preparation and use
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The present invention relates to a xanthine derivative, a pharmaceutically acceptable salt thereof, a solvate of the derivative, a solvate of the pharmaceutically acceptable salt, a chemically protected form or prodrug thereof and a preparation method and a use thereof; and also relates to an intermediate compound used for preparing the xanthine derivative and a preparation method of the intermediate compound. The xanthine derivative and a pharmaceutical composition thereof effectively inhibit the activity of DPP-IV, and can be used for preparing a drug for diseases associated with dipeptidyl peptidase (DPP-IV).
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- Malignant and non-malignant disease treatment with Ras antagonists
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The present disclosure describes new inhibitors or antagonists of Ras useful for the treatment of conditions resulting from Ras-induced or mediated cellular processes, including cellular proliferation, differentiation, apoptosis, senescence, and survival.
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Page/Page column 14; 15
(2016/05/09)
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- HCV PROTEASE INHIBITORS
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The present invention discloses a compound of general formula (I); A is O, S, CH, NH or NR', when O links with Z3, Z1 is N or CRZ1, Z2 is CRZ2, when Z1 links with O, Z2 is CH, Z3 is C-Ar; Ra, Rb, Rc and Rd independently is H, OH, halogen or -Y1-Rm; A1 is NH or CH2; R1' is alkyl, aryl, cycloalkyl, heterocycloalkyl or heteroaryl; A2 is N, O or linking bond; R1 is hydrogen, or, R1 linking covalently with R3 forms C5-C9 saturated or unsaturated hydrocarbon chain substituted by O or N; R3 is alkyl, cycloalkyl, heterocycloalkyl, alkyl substituted by cycloalky etc; R4 is alkoxy-CO, alkyl-NHCO, (alkyl)2NCO, or formyl substituted by aryl, cycloalkyl, heterocycloalkyl.
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Paragraph 0033; 0034
(2014/06/24)
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- HCV Protease Inhibitors
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A compound of general formula (I); A is O, S, CH, NH or NR′, when O links with Z3, Z1 is N or CRZ1, Z2 is CRZ2, when Z1 links with O, Z2 is CH, Z3 is C—Ar; Ra, Rb, Rc and Rd independently is H, OH, halogen or —Y1—Rm; A1 is NH or CH2; R1′ is alkyl, aryl, cycloalkyl, heterocycloalkyl or heteroaryl; A2 is N, O or linking bond; R1 is hydrogen, or, R1 linking covalently with R3 forms C5-C9 saturated or unsaturated hydrocarbon chain substituted by O or N; R3 is alkyl, cycloalkyl, heterocycloalkyl, alkyl substituted by cycloalkyl etc; R4 is alkoxy-CO, alkyl-NHCO, (alkyl)2NCO, or formyl substituted by aryl, cycloalkyl, heterocycloalkyl.
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Paragraph 0090-0092
(2014/06/24)
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- MALIGNANT AND NON-MALIGNANT DISEASE TREATMENT WITH RAS ANTAGONISTS
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The present disclosure describes new inhibitors or antagonists of Ras useful for the treatment of conditions resulting from Ras-induced or mediated cellular processes, including cellular proliferation, differentiation, apoptosis, senescence, and survival.
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- About the reaction of aryl fluorides with sodium sulfide: Investigation into the selectivity of substitution of fluorobenzonitriles to yield mercaptobenzonitriles via SNAr displacement of fluorine
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In this report we describe a simple synthesis of mercaptobenzonitriles from the reaction of fluorobenzonitriles with Na2S in DMF at room temperature and following direct treatment with Zn/HCl. Significantly, 2- and 4-fluorobenzonitriles substituted with chlorine or bromine, but not iodine, undergo selective substitution of fluorine at room temperature to yield synthetically useful halo-substituted mercaptobenzonitriles.
- Taldone, Tony,Patel, Pallav D.,Patel, Hardik J.,Chiosis, Gabriela
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supporting information; experimental part
p. 2548 - 2551
(2012/06/15)
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- Synthesis and biological evaluation of 2-(3′,4′,5′- trimethoxybenzoyl)-3-aryl/arylaminobenzo[b]thiophene derivatives as a novel class of antiproliferative agents
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The biological importance of microtubules in mitosis, as well as in interphase, makes them an interesting target for the development of anticancer agents. Small molecules such as benzo[b]thiophenes are attractive as inhibitors of tubulin polymerization. T
- Romagnoli, Romeo,Baraldi, Pier Giovanni,Cara, Carlota Lopez,Hamel, Ernest,Basso, Giuseppe,Bortolozzi, Roberta,Viola, Giampietro
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scheme or table
p. 5781 - 5791
(2011/02/22)
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- Synthesis and biological evaluation of 2- and 3-aminobenzo[b]thiophene derivatives as antimitotic agents and inhibitors of tubulin polymerization
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Two new series of inhibitors of tubulin polymerization based on the 2-amino-3-(3,4,5-trimethoxybenzoyl)-benzo[b]thiophene molecular skeleton and its 3-amino positional isomer were synthesized and evaluated for antiproliferative activity, inhibition of tub
- Romagnoli, Romeo,Baraldi, Pier Giovanni,Carrion, Maria Dora,Cara, Carlota Lopez,Preti, Delia,Fruttarolo, Francesca,Pavani, Maria Giovanna,Tabrizi, Mojgan Aghazadeh,Tolomeo, Manlio,Grimaudo, Stefania,Di Cristina, Antonella,Balzarini, Jan,Hadfield, John A.,Brancale, Andrea,Hamel, Ernest
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p. 2273 - 2277
(2008/02/02)
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- Structure-activity relationships in the binding of chemically derivatized CD4 to gp120 from human immunodeficiency virus
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The first step in HIV infection is the binding of the envelope glycoprotein gp120 to the host cell receptor CD4. An interfacial "Phe43 cavity" in gp120, adjacent to residue Phe43 of gp120-bound CD4, has been suggested as a potential target for therapeutic intervention. We designed a CD4 mutant (D1D2F43C) for site-specific coupling of compounds for screening against the cavity. Altogether, 81 cysteine-reactive compounds were designed, synthesized, and tested. Eight derivatives exceeded the affinity of native D1D2 for gp120. Structure-activity relationships (SAR) for derivatized CD4 binding to gp120 revealed significant plasticity of the Phe43 cavity and a narrow entrance. The primary contacts for compound recognition inside the cavity were found to be van der Waals interactions, whereas hydrophilic interactions were detected in the entrance. This first SAR on ligand binding to an interior cavity of gp120 may provide a starting point for structure-based assembly of small molecules targeting gp120-CD4 interaction.
- Xie, Hui,Ng, Danny,Savinov, Sergey N.,Dey, Barna,Kwong, Peter D.,Wyatt, Richard,Smith III, Amos B.,Hendrickson, Wayne A.
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p. 4898 - 4908
(2008/03/11)
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- Synthesis and preliminary biological evaluation of new anti-tubulin agents containing different benzoheterocycles
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A new series of compounds, in which the 2-amino-4-methoxyphenyl ring of phenstatin analogue 5 was replaced with 2- or 3-amino-benzoheterocycles, was synthesized and evaluated for antiproliferative activity and inhibition of colchicine binding. The lack of
- Romagnoli, Romeo,Baraldi, Pier Giovanni,Jung, M. Katherine,Iaconinoto, Maria Antonietta,Carrion, Maria Dora,Remusat, Vincent,Preti, Delia,Tabrizi, Mojgan Aghazadeh,Francesca, Fruttarolo,De Clercq, Erik,Balzarini, Jan,Hamel, Ernest
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p. 4048 - 4052
(2007/10/03)
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- Synthesis and analgesic activity of some 1-benzofurans, 1-benzothiophenes and indoles
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3-Unsubstituted 1-benzofurans 1e and 1f, 3-methyl-1-benzofurans 1a-1d, and 3-amino-1-benzofurans 2a-21, as well as 3-amino-1-benzothiophenes 3a, 3b and 3-aminoindoles 4a-4f, 11a, and 11b were prepared and tested as analgesics. The 3-amino-1-benzofurans 2 were prepared from the corresponding 2-hydroxybenzonitriles 5 and phenacyl bromides 6 via intermediates 7. Similar treatment of 2-sulfanylbenzonitrile (8) provided 3-amino-1-benzothiophenes 3. Appropriately substituted 2-aminobenzonitriles 9 then provided N-substituted 3-aminoindoles 4. 1-(Ethoxycarbonyl)indoles 4e and 4f were successfully deprotected giving indoles 11a and 11b, respectively.
- Radl, Stanislav,Hezky, Petr,Urbankova, Jitka,Vachal, Petr,Krejci, Ivan
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p. 280 - 296
(2007/10/03)
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- New disulfide route to 3-(1-piperazinyl)-1,2-benzisothiazole. Nucleus for atypical antipsychotic drugs
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A new, one-step commercial process for the preparation of 3-(1-piperazinyl)-l,2-benzisothiazole hydrochloride, a key intermediate for the syntheses of some new, "atypical antipsychotic" drugs, was developed. Reaction of bis(2-cyanophenyl) disulfide with excess piperazine at 120-140 °C for 3-24 h in the presence of small amounts of DMSO and 2-propanol formed 3-(l-piperazinyl)-l,2-benzisothiazole in 75-80% yields. The DMSO oxidized the liberated 2-mercaptobenzonitrile to regenerate bis(2-cyanophenyl) disulfide, thereby enabling the utilization of both halves of the symmetrical disulfide to generate product. The reaction mechanism for the conversion of the bis(2-cyanophenyl) disulfide to 3-amino-1,2-benzisothiazole involves the formation of ring-opened sulfenamide and benzamidine intermediates and then their subsequent ring closure to regenerate the 1,2-benzisothiazole nucleus. A safe, efficient, and robust process to prepare 3-(l-piperazinyl)-1,2-benzisothiazole under very concentrated reaction conditions was developed and successfully scaled up in the pilot plant to support the development of ziprasidone.
- Walinsky, Stanley W.,Fox, Darrell E.,Lambert, John F.,Sinay, Terry G.
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p. 126 - 130
(2013/09/08)
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- The Stereochemistry of Organometallic Compounds. XLIV* Rhodium-Catalysed Hydroformylation of Some Alkenylthio Aromatic Compounds
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Rhodium-catalysed reactions of o-[(allyl and butenyl)thio] benzonitriles and benzamides with H2/CO give quantitative yields of aldehydes whereas the corresponding benzylamines give only polymeric material. The results are compared with reactions of the analogous alkenylamines and alkenyloxy compounds.
- Campi, Eva M.,Roy Jackson,Trnacek, Andrew E.
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p. 807 - 812
(2007/10/03)
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- β-D-phenylthioxylosides, their method of preparation and their use as therapeutic agents
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The present invention relates, by way of novel industrial products, to the β-D-phenylthioxyloside compounds of the formula STR1 in which: X represents a sulfur atom or an oxygen atom; R1, R2 and R3, which are identical or different, each represent a hydrogen atom, a nitro group, a cyano group, a group --CO--R (in which R represents a C1 -C4 alkyl group or a trifluoromethyl group), an amino group, an acetamido group (NHCOCH3), a C1 -C4 alkoxy group, a trifluoromethyl group or a phenyl group substituted by one or more cyano, nitro or trifluoromethyl groups, it being possible for R1 and R2, taken together, to form, with the phenyl group to which they are bonded, a β-naphthalenyl group which is unsubstituted or substituted by one or more cyano, nitro or trifluoromethyl groups; and Y represents the hydrogen atom or an aliphatic acyl group. These compounds are useful as therapeutic agents, especially as venous antithrombotics.
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- Bromonitromethane. A Versatile Electrophile
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Pathways in reactions of bromonitromethane with a variety of nucleophiles have been investigated.With thiolates, the electrophilic centre is bromine and the initial products are disulphides.When the thiolate ion itself carries an electrophilic centre such as carbonyl or cyano β-to sulphur, the product is a nitrothiophene derived from subsequent reaction of the first-formed disulphide with nitronate ion displaced in the initial process.This provides a generalisation of earlier nitrothiophene synthesis by this route.In reactions with arenesulphinate ion, the electrophilic centre is also bromine and equilibration between the initial reactants and the initial products, sulphonyl bromide and nitronate ion, is established.The components of the equilibrium subsequently react either with each other or with the solvent.Reactions with sulphides are slow and distal substituents such as hydroxy- or cyano- so much reduce reactivity that no reaction is observed.Dimethyl sulfide attacks bromonitromethane at the carbon atom,and subsequent attack on the nitromethyl sulphonium salt initially formed gives methylthionitromethane and trimethylsulphonium bromide.Iodide ion attacks at bromine to give iodine, presumably via iodine bromide, but with tervalent phosphorus nucleophiles, attack is at oxygen giving the corresponding oxides and HCN in a double deoxygenation sequence.For hydroxide, methoxide and hydride ions (from sodium borohydride), nucleophilic attack is at hydrogen and the nitronate ion produced is inert to further attack.There is no evidence of carbene formation by α-elimination.When the anion of bromonitromethane is allowed to react with tributylboron, the anionic migration-displacement which follows boron-carbon bond formation, yields 1-nitropentane.The anion of bromonitromethane is unreactive towards aldehydes and electrophilic alkenes.
- Fishwick, Brian R.,Rowles, David K.,Stirling, Charles J. M.
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p. 1171 - 1180
(2007/10/02)
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- ETUDE DES REACTIONS DE SRN1-PARTIE 10 ACTION DE SULFANIONS SUR LES HALOGENURES D'ARYLE FONCTIONNALISES. SYNTHESE DIRECTE DE BENZOTHIOPHENES ET THIENOPYRIDINES
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Functionalized aromatic halides Ar1XY (Ar1=C6H4, Y=OCH3,CONH2,CN,COCH3,CHO,COC6H5) undergo SRN1 reactions with sulphur anions -SR, either simple (R=C2H5,CH2C6H5) or functionalized (R=(CH2)2OH,(CH2)2CO2Et,CH2CO2Et).Products Ar1YS- formed from the fragmentation of the radical anion Ar1YSR- are related to the redox potential of the aryl moiety Ar1Y and with the energy of the bond S-R.In the heterocyclic series (Ar2=pyridine, Ar3=quinoline) a similar relationship appears but a competitive SN(AR) reaction occurs for pyridine substrates bearing an electron withdrawing group.A direct synthesis of benzothiophen via SRN1 reaction and an improved synthesis of thienopyridines based on the SN(Ar) reaction are reported.
- Beugelmans, Rene,Bois-Choussy, Michele,Boudet, Bernard
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p. 4153 - 4162
(2007/10/02)
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