- Methylation and Hydroxylation Studies on Aloe-emodin
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The chemistry of aloe-emodin (3) has been explored with a view toward its use as a synthon for the regiospecific synthesis of adriamycin and analogues of it.Routes for satisfactory large-scale monomethyl ether formation at C8 (4) and regiospecific introduction of a phenolic oxygen function at C4 (21) are described.Interesting side reactions were encountered, including an apparent peri O to O acyl wandering reaction during methylation and a reductive debromination reaction during displacement of an aryl bromide by methanolic methoxide.
- Alexander, Jose,Bhatia, Ashok V.,Mitscher, Lester A.,Omoto, Shoji,Suzuki, Toshio
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Read Online
- Impact of N-Alkylamino Substituents on Serotonin Receptor (5-HTR) Affinity and Phosphodiesterase 10A (PDE10A) Inhibition of Isoindole-1,3-dione Derivatives
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In this study, a series of compounds derived from 4-methoxy-1H-isoindole-1,3(2H)-dione, potential ligands of phosphodiesterase 10A and serotonin receptors, were investigated as potential antipsychotics. A library of 4-methoxy-1H-isoindole-1,3(2H)-dione derivatives with various amine moieties was synthesized and examined for their phosphodiesterase 10A (PDE10A)-inhibiting properties and their 5-HT1A and 5-HT7 receptor affinities. Based on in vitro studies, the most potent compound, 18 (2-[4-(1H-benzimidazol-2-yl)butyl]-4-methoxy-1H-isoindole-1,3(2H)-dione), was selected and its safety in vitro was evaluated. In order to explain the binding mode of compound 18 in the active site of the PDE10A enzyme and describe the molecular interactions responsible for its inhibition, computer-aided docking studies were performed. The potential antipsychotic properties of compound 18 in a behavioral model of schizophrenia were also investigated.
- Czopek, Anna,Partyka, Anna,Bucki, Adam,Paw?owski, Maciej,Ko?aczkowski, Marcin,Siwek, Agata,G?uch-Lutwin, Monika,Koczurkiewicz, Paulina,P?kala, El?bieta,Jaromin, Anna,Tyliszczak, Bo?ena,Weso?owska, Anna,Zagórska, Agnieszka
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- Synthetic process of rhein
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The invention relates to a synthetic process of rhein. The synthetic process comprises the steps of: adopting 2,3-dimethyl phenol as a raw material, performing methylation and oxidation to obtain 3-methoxy phthalic acid, performing dehydration by using acetic anhydride to obtain acid anhydride, then performing a Friedel-Crafts reaction between the obtained acid anhydride and excess methyl anisoleunder the action of aluminum trichloride to obtain the product, and then conducting cyclization by using sulfuric acid to obtain an intermediate chrysophanol, performing acetylation on the obtained chrysophanol, performing oxidation to obtain diacerein, and finally carrying out deacetylation to synthesize rhein.
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- Preparation method of 3-hydroxyl phthalic anhydride
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The invention belongs to the technical field of organic synthesis and in particular relates to a preparation method of a key medical intermediate, 3-hydroxyl phthalic anhydride. The method comprises the following steps: with a compound I as a raw material, oxidizing the raw material to obtain 3-methoxyl phthalic acid; performing a reaction on 3-methoxyl phthalic acid to generate 3-hydroxyl phthalic acid; and performing dehydration and condensation on 3-hydroxyl phthalic acid to generate 3-hydroxyl phthalic anhydride. 3-hydroxyl phthalic anhydride prepared by the method provided by the invention is high in yield and good in purity. The method is free of special equipment demands, has mild conditions and is safe and environmental-friendly in an industrial process, and the process technology provided by the invention can be industrially performed.
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Paragraph 0033; 0034
(2017/09/18)
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- Metallo-β-lactamase inhibitory activity of 3-alkyloxy and 3-amino phthalic acid derivatives and their combination effect with carbapenem
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3-Alkyloxy and 3-amino phthalic acid derivatives were found to have metallo-β-lactamase inhibitory activity. Among them, 3-amino phthalic acid derivatives showed both potent activity against metallo-β-lactamase, IMP-1 inhibitory activity and a strong combination effect with biapenem (BIPM), carbapenem antibiotic. In particular, the 4′-hydroxy-piperidine derivative showed strong IMP-1 inhibitory activity and a combination effect with various antibiotics.
- Hiraiwa, Yukiko,Morinaka, Akihiro,Fukushima, Takayoshi,Kudo, Toshiaki
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p. 5841 - 5850
(2013/09/12)
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- Insecticidal Benzenedicarboxamide Derivative
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The present invention relates to a novel benzenedicarboxamide derivative and the use thereof as an insecticide having the formula (I) wherein the chemical groups W1 to W9, and R1 to R3 are as defined here-in.
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Page/Page column 106
(2011/08/06)
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- PHARMACEUTICAL COMPOUNDS
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The invention provides a compound for use in medicine, the compound being a compound of the formula (VI0) or a salt, solvate, tautomer or N-oxide thereof: wherein the bicyclic group: is selected from the structures C1, C5 and C6: wherein n is 0, 1, 2 or 3; R1 is hydrogen, hydroxy, or O—Rz; R2a is hydroxy, methoxy or O—Rz; provided that at least one of R1 and R2a is O—Rz; Rz is Lp-Rp1; SO3H; a glucuronide residue; a mono-, di- or tripeptide residue; or Lp is a bond, C═O, (C═O)O, (C═O)NRp1 or S(O)xNRp1; x is 1 or 2; Rp1 is hydrogen or a an optionally substituted C1-25 hydrocarbyl group containing 0, 1 or 2 carbocyclic rings and 0, 1, 2, 3, 4, 5 or 6 carbon-carbon multiple bonds, provided that Rp1 is not hydrogen when Lp is a bond, C═O or (C═O)O; and provided also that O—Rz does not contain an O—O moiety; and excluding compounds wherein R1 is hydroxy and R2a is methoxy; Rp2 and Rp3 are the same or different and each is a group Rp1; and R3, R4a, R8 and R10 are defined in the claims. The compounds of formula (VI0) are pro-drugs of parent compounds wherein R1 and/or R2a are hydroxy, wherein the parent compounds have Hsp90 inhibiting activity.
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Page/Page column 103
(2010/06/22)
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- PHARMACEUTICAL COMBINATIONS
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The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1- 5 hydrocarbyloxy; R4 is selected from hydrogen; a group -(O)n-R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The combinations have activity as Hsp90 inhibitors.
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Page/Page column 245
(2008/06/13)
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- PHARMACEUTICAL COMBINATIONS
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The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1-5 hydrocarbyloxy; R4 is selected from hydrogen; a group -(O)n-R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The combinations have activity as Hsp90 and/or glycogen synthase kinase-3 and/or cyclin dependent kinase inhibitors.
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Page/Page column 267-268
(2008/06/13)
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- PHARMACEUTICAL COMBINATIONS
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The invention provides combinations comprising (or consisting essentially of) one or more ancillary compound(s) and a compound of the formula (I): or salts, tautomers, solvates and N-oxides thereof; wherein R1 is hydroxy or hydrogen; R2 is hydroxy; methoxy or hydrogen; provided that at least one of R1 and R2 is hydroxy; R3 is selected from hydrogen; halogen; cyano; optionally substituted C1-5 hydrocarbyl and optionally substituted C1-5 hydrocarbyloxy; R4 is selected from hydrogen; a group -(O)n-R7 where n is 0 or 1 and R7 is an optionally substituted acyclic C1-5 hydrocarbyl group or a monocyclic carbocyclic or heterocyclic group having 3 to 7 ring members; halogen; cyano; hydroxy; amino; and optionally substituted mono- or di-C1-5 hydrocarbyl-amino; or R3 and R4 together form a monocyclic carbocyclic or heterocyclic ring of 5 to 7 ring members; and NR5R6 forms an optionally substituted bicyclic heterocyclic group having 8 to 12 ring members of which up to 5 ring members are heteroatoms selected from oxygen, nitrogen and sulphur. The combinations have activity as Hsp90 and/or glycogen synthase kinase-3 and/or cyclin dependent kinase and/or aurora kinase inhibitors.
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Page/Page column 319-320
(2008/06/13)
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- PHARMACEUTICAL COMPOUNDS
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The invention provides the use of a compound for the manufacture of a medicament for the treatment of pain, wherein the compound is a compound of the formula (Vl): or a salt, solvate, tautomer or N-oxide thereof; wherein the bicydic group: is selected from the structures C1, C5 and C6: wherein n, R1, R2a, R3, R4a, R8 and R10 are as defined in the claims. The invention also provides the use of a compound of the formula (Vl) for the manufacture of a medicament for the prophylaxis or treatment of a fungal, protozoal, viral or parasitic disease state or condition (other than a disease state or condition due to Plasmodium falciparum) or for use in the prophylaxis or treatment of Ewing's sarcoma, atherosclerosis or lupus erythematosus
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Page/Page column 163
(2008/06/13)
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- Synthesis of 1,2- and 1,3-dicarboxylic acids via Pd(II)-catalyzed carboxylation of aryl and vinyl C-H bonds
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A Pd(II)-catalyzed reaction protocol for the direct carboxylation of benzoic and phenylacetic acid derivatives to form dicarboxylic acids has been developed. The reaction conditions are also applicable for the carboxylation of vinyl C-H bonds. The first C-H insertion Pd-aryl complex from carboxylic acids has been characterized by X-ray crystallography. Copyright
- Giri, Ramesh,Yu, Jin-Quan
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supporting information; experimental part
p. 14082 - 14083
(2009/03/11)
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- Inhibitors of phenylalanine ammonia-lyase: Substituted derivatives of 2-aminoindane-2-phosphonic acid and 1-aminobenzylphosphonic acid
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Six derivatives of 2-aminoindane-2-phosphonic acid and 1-aminobenzylphosphonic acid were synthesized. The compounds were tested both as inhibitors of buckwheat phenylalanine ammonia-lyase (in vitro) and as inhibitors of anthocyanin biosynthesis (in vivo). (±)-2-Amino-4-bromoindane-2-phosphonic acid was found to be the strongest inhibitor from investigated compounds. The results obtained are a basis for design of phenylalanine ammonia-lyase inhibitors useful in the enzyme structure studies in photo labelling experiments.
- Miziak, Piotr,Zon, Jerzy,Amrhein, Nikolaus,Gancarz, Roman
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p. 407 - 415
(2007/10/03)
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- N-hydroxyphthalimide/cobalt(II) catalyzed low temperature benzylic oxidation using molecular oxygen
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A variety of (substituted) aryl glyoxylates is formed in good to excellent yield under very mild conditions by direct oxidation of the corresponding arylacetic esters or mandelic acid esters with molecular oxygen and N-hydroxyphthalimide/cobalt(II) acetate as catalyst. Heteroaromatic analogs are more difficult to oxidize with this system. The effect of substitution in the aromatic ring of N-hydroxyphthalimide on the oxidation of ethylbenzene has been studied. Electron withdrawing substituents accelerate the oxidation of ethylbenzene and promote the formation of acetophenone. Electron donating substituents lead to decreased rates of oxidation and enhance the selectivity for 1-phenylethanol. (C) 2000 Elsevier Science Ltd.
- Wentzel, Bastienne B,Donners, Maurice P.J,Alsters, Paul L,Feiters, Martinus C,Nolte, Roeland J.M
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p. 7797 - 7803
(2007/10/03)
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- Process for producing rhein and diacerhein
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The following description sets forth a process for producing rhein, diacerhein and other diacyl derivatives thereof, which comprises the following steps: treatment of a diphenylketone STR1 in which R1 is --OR', --NR'R", --SR', where R' and R" are H, an alkyl or aromatic group; R2 is H or a protective group, R3 is --OH or C1 -C4 alkyl, with an acid or superacid to give a 1-aminoanthraquinone derivative, diazotisation, replacement of the --NH2 group by --OH, optional removal of the protective group, and acylation.
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- Process for producing rhein and diacerhein
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The following description sets forth a process for producing rhein, diacerhein and other diacyl derivatives thereof, which comprises the following steps: treatment of a diphenylketone in which R1is -OR', -NR'R'', -SR', where R' and R'' are H, an alkyl or aromatic group; R2is H or a protective group. R3is -OH or C1-C4alkyl, with an acid or superacid to give a 1-aminoanthraquinone derivative, diazotisation, replacement of the -NH2group by -OH, optional removal of the protective group, and acylation.
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- New rhein derivatives and new processes for producing rhein derivatives
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The present description relates to new anthraquinone-derivatives endowed with inhibitory activity of the serine proteinase enzymes, useful for the treatment of rheumatoid arthritis, acute respiratory syndrome of adult, and pulmonary emphysema, and to new processes for the preparation of rhein derivatives.
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- Studies of the New Herbicide KIH-6127. Part I. Novel Synthesis of Methyl 6-Acetylsalicylate as a Key Synthetic Intermediate for the Preparation of 6-Acetyl Pyrimidin-2-yl Salicylates and Analogues
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A novel synthesis of methyl 6-acetylsalicylate as a key synthetic intermediate for methyl 2-[(4,6-dimethoxypyrimidin-2-yl)oxy]-6-[1-(methoxyimino)ethyl]benzoate (KIH-6127) was studied, and directed at 6-substituted pyrimidin-2-yl salicylate herbicides and their analogues. Three synthetic approaches were successful: a modification of the Sandmeyer reaction of 6-acetylanthranilate (Method A), a direct ring-opening reaction of 3-methylphthalide using potassium permanganate, and magnesium nitrate (Method B), and a regioselective ortholithiation of the protected 3-hydroxyacetophenone (Method C). These methods were applicable for the synthesis of various 6-acyl salicylates.
- Tamaru, Masatoshi,Saito, Yoshihiro
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p. 125 - 130
(2007/10/03)
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- Directed ortho metalation of n,n-diethyl benzamides. Methodology and regiospecific synthesis of useful contiguously tri- and tetra-substituted oxygenated aromatics, phthalides and phthalic anhydrides
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Full experimental details for the directed ortho metalation approch to a variety of simple ortho-substituted N,N-diethyl benzamides (Table 1) and contiguously 1,2,3- and 1,2,3,4-substituted benzamides (Tables 2) are given. The efficient conversion of these benzamides (6, 10, 12, 13, 18, 19) into phthalides (9a-b, 16b-c, 17) and phthalic anhydrides (8,16a), compounds previously available by demanding, classical methods, is detailed. A short synthesis of iso-ochracinic acid (27) is described.
- De Silva,Reed,Billedeau,Wang,Norris,Snieckus
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p. 4863 - 4878
(2007/10/02)
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- Facile Interconversion of the Isomeric Acid Chlorides Derived from Half Methyl Esters of 3-Methoxyphthalic Acid
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The isomeric acid chlorides obtained by treating the half methyl esters of 3-methoxyphthalic acid with thionyl chloride interconvert so readily that it is not practical to isolate one acid chloride free of the other.At equilibrium the main isomer is the a
- Gupta, Dahmendra N.,Hodge, Philip,Hurley, Peter N.
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p. 391 - 394
(2007/10/02)
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- An Efficient and Flexible Approach for the Total Synthesis of (+/-)-11-Deoxydaunomycinone and (+/-)-Daunomycinone
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A flexible and regiospecific synthesis of (+/-)-daunomycinone and (+/-)-11-deoxydaunomycinone, the two aglycones of the antitumor anthracycline antibiotics, has been achieved starting from a common synthon, 2-acetyl-8-bromo-5-hydroxy-1,2,3,4-tetrahydronap
- Rao, A. V. Rama,Mehendale, A. R.,Reddy, K. Bal
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p. 1154 - 1164
(2007/10/02)
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- 1,4-dimethoxy-1,3-butadiene as a Donor Diene in Diels-Alder Cycloadditions
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The title compound (DMBU) is a useful diene in cycloadditions.Since DMBU is readily obtained in two steps from 1,4-dihydroxy-2-butyne, it should be regarded as an inexpensive and abundant starting material.Diels Alder products were obtained from DMBU and the dienophiles, dimethyl acetylenedicarboxylate, ethyl propiolate, benzyne, fumaronitrile, tetracyanoethene, maleic anhydride, 1,2-dibenzoylethene, diethyl azodicarboxylate, and four 1,4-quinones.The aromatization of some of these products was studied.As determined by gas chromatography and 1H NMR, DMBU is obtained as three isomers Z,Z/Z,E/E,E = (60 +/-3):(34 +/- 3):(6 +/- 2).While the Z,Z form is less reactive, the Z,E and E,E isomers react with tetracyanoethene at rates similar to that of 1-methoxy-1,3-butadiene.
- Hiranuma Hidetoshi,Miller, Sidney I.
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p. 5083 - 5088
(2007/10/02)
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- A Convenient Preparation of 3-Methoxyphthalic Acid
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Oxidation of 1,2,3,4-tetrahydro-5-methoxynaphthalene by potassium permanganate in the presence of cetyltrimethylammonium bromide affords 3-methoxyphthalic acid in 60-65percent yield
- Rao, M. Vishnumurthi,Bhatt, M. Vivekananda
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p. 344 - 345
(2007/10/02)
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