- Process for preparing O-ethoxybenzoic acid chloride (by machine translation)
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The method comprises the following steps of (1) ethylation reaction, (2) alkali hydrolysis reaction and (3) acyl chlorination reaction, and is simple in reaction step, strong in operability, mild in reaction conditions, simple in process, easy to control, convenient to use and capable of easily controlling the byproduct HCl and CO. 2 The method is simple in process, convenient to operate, low in raw material cost, high in yield, good in quality and convenient for industrial production. (by machine translation)
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- Hofmann Rearrangement of Carboxamides Mediated by N-Bromoacetamide
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An efficient, one-pot procedure for the Hofmann rearrangement of aromatic and aliphatic amides has been developed. Methyl and benzyl carbamates are produced with N-bromoacetamide in the presence of lithium hydroxide or lithium methoxide, in high yields. β-Phenylamino amides gave five-membered cyclic ureas stereospecifically. Side products of aryl or benzyl bromination were minimized. This procedure offers an easy access to various protected amines or diamines, which represent important synthetic precursors.
- Jevti?, Ivana I.,Do?en-Mi?ovi?, Ljiljana,Ivanovi?, Evica R.,Ivanovi?, Milovan D.
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p. 1550 - 1560
(2016/06/01)
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- Sedinafine derivatives of the microwave-assisted method for preparing
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The invention discloses a microwave-assisted synthesis method of sildenafil derivatives, which mainly comprises the following steps: by using 2-alkoxybenzoic acid and 4-amino-1-methyl-3-n-propyl-1H-pyrazolyl-5-formamide as initial raw materials, carrying out amidation, cyclization, mononitration, nitro reduction, guanidylation and the like to obtain the sildenafil derivatives. The method greatly shortens the reaction time, enhances the reaction efficiency, has the advantages of high yield and high purity, is simple to operate and easy to control, and is beneficial to industrial production of sildenafil analogs.
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Paragraph 0061
(2016/12/07)
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- METHOD FOR PRODUCING OXAZOLE COMPOUND
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An object of the present invention is to provide a novel method for producing an oxazole compound. The invention relates to a method for producing a compound represented by formula (1): wherein R1 is lower alkyl group or halogen substituted lower alkyl group, R2 is lower alkyl group, R5 is lower alkyl group, R11 is lower alkyl group, halogen substituted lower alkyl group or a group represented by formula: -CY2COOR12, wherein Y is a halogen atom, R12 is an alkali metal atom or lower alkyl group, Ar1 is phenyl group substituted with lower alkyl group, etc., or pyridyl group substituted with lower alkyl group, etc., X2, X3 and X9 are the same or different and are halogen atoms, X4 is a leaving group, and M is an alkali metal atom.
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Page/Page column 73-74
(2014/03/25)
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- Small-Molecule Choline Kinase Inhibitors as Anti-Cancer Therapeutics
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Small molecule choline kinase inhibitors having the following formula: are provided herein. Also provided herein are pharmaceutical compositions containing Formula I compounds, together with methods of treating cancer, methods of inhibiting choline kinase enzymatic activity, and methods of treating tumors by administering an effective amount of a Formula I compound.
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Page/Page column 19; 27-28
(2011/10/31)
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- Synthesis of new series of pyrazolo[4,3-d]pyrimidin-7-ones and pyrido[2,3-d]pyrimidin-4-ones for their bacterial and cyclin-dependent kinases (CDKs) inhibitory activities
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Two series of pyrazolo[4,3-d]pyrimidin-7-ones and pyrido[2,3-d]pyrimidin-4- ones were designed, synthesised, and evaluated for their antibacterial activities and CDKs inhibitory activities. The pyridazine derivative: 6-phenyl-5-phenylhydrazono-2,3,4,5-tetrahydropyridazine- 3,4-dione (3a) revealed activity against Staphylococcus aureus as Gram-positive bacteria while compound 2-(2- Ethoxyphenyl-5-Phenylpiperazinosulfonamido)-3H-pyrido [2,3-d]pyrimidin-4-one (13c) was showing moderate antifungal activity against Candida albicans.
- Geffken, Detlef,Soliman, Raafat,Soliman, Farid S.D.,Abdel-Khalek, Magdi M.,Issa, Doaa A.E.
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experimental part
p. 408 - 420
(2012/04/04)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS AND USES THEREOF
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The present invention relates to compounds of formula (I), or pharmaceutical salts, prodrugs, salts of prodrugs, or combinations thereof, formula (I). wherein R1, R2, R3, R4, and L1 are defined in the specfication, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions. The present invention also relates to compounds of formula (II), or pharmaceutical salts, prodrugs, salts of prodrugs, or combinations thereof, formula (II). wherein R1a, R2a, Rx, and n are as defined in the specification, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.
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Page/Page column 52
(2009/06/27)
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- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS AND USES THEREOF
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The present invention relates to compounds of formula (I), or pharmaceutical salts, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, and L1 are defined in the specfication, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions. The present invention also relates to compounds of formula (II), or pharmaceutical salts, prodrugs, salts of prodrugs, or combinations thereof, wherein R1a, R2a and (Rx)n are as defined in the specification, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.
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Page/Page column 16
(2008/06/13)
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- Structural modifications of benzanilide derivatives, effective potassium channel openers. X.
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Large-conductance calcium-activated potassium (BK) channels are involved in many fundamental cell functions. Consistently, the ability to activate BK channels by exogenous compounds is considered as a promising pharmacodynamic pattern for the potential treatment of several pathologies. In this perspective, the development of new and selective BK-openers can be considered as an actual field of research. This paper reports the synthesis and pharmacological evaluation of new benzanilides, useful for deepening the comprehension of the structure-activity relationships, emerged in previous studies on this class of BK-activators. From a structural point of view, these benzanilides belong to a general class of BK-activators, showing a common pharmacophoric model, consisting of two aryl groups linked through an appropriate "spacer" and the almost obligatory presence of a phenolic hydroxyl. In particular, a new series of benzanilides, in which the phenyl rings have been widely changed both on the acidic portion and the basic one of the amide spacer, were synthesised. Their vasorelaxing effects, induced through the activation of BK channels, were also evaluated. Although many compounds exhibited effects which could not be attributed to the activation of BK channels, two derivatives showed a clear profile of BK-activators with vasodilator activity comparable to or slightly lower than that recorded for the reference benzimidazolone NS1619. A further molecular modelling approach allowed us to obtain a molecular electrostatic potential feature which suggests a suitable interaction with the receptor site of the BK channel, from a tri-dimensional point of view. This approach seems to represent a further contribution for the development of new BK-activators, designed on the basis of the pharmacophoric model above-mentioned.
- Calderone, Vincenzo,Coi, Alessio,Fiamingo, Francesca Lidia,Giorgi, Irene,Leonardi, Michele,Livi, Oreste,Martelli, Alma,Martinotti, Enrica
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p. 1421 - 1429
(2007/10/03)
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- 2-SUBSTITUTED PHENYL-5,7-DIALKYL-3,7-DIHYDROPYRROLE[2,3-D]PYRIMIDINE-4-ONE DERIVATIVES, THE PREPARATION AND THE PHARMACEUTICAL USE THEREOF
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The invention relates to the compounds of formula I, their preparation and the pharmaceutical compositions containing the compounds. The invention also relates to the use of the compounds of formula I in preparing medicines, which can treat sexual dysfunction of animals including human (male and female), especially erectile dysfunction of male and the diseases in which the function of phospholipase 5 (cGMP PDE5) is involved.
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Page/Page column 12-13
(2008/06/13)
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- Modulators (inhibitors/ activators) of histone acetyltransferases
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Disclosed are compounds of the formulae: and method of using the compounds to treat cancer, AIDS, HIV infection, and asthma.
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Page/Page column 4
(2008/06/13)
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- Synthesis and characterization of novel 6-fluoro-4-piperidinyl-1,2- benzisoxazole amides and 6-fluoro-chroman-2-carboxamides: Antimicrobial studies
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Novel derivatives of 6-fluoro-4-piperidinyl-1,2-benzisoxazole amides 4(I-VI) were obtained by the condensation of different acid chlorides with 6-fluoro-3-piperidin-4yl-benzo[d]isoxazole. Also, 6-fluoro-chroman-2- carboxamides 6(I-III) were synthesized by using nebulic acid chloride with different amines in presence of triethylamine as acid scavenger and dichloroethane as solvent. The synthesized compounds were characterized by IR, 1H NMR, and CHN analysis. These molecules were evaluated for their efficacy as antimicrobials in vitro by disc diffusion and microdilution method against pathogenic strains such as Bacillus substilis, Escherichia coli, Pseudomonas fluorescens, Xanthomonas campestris pvs, X. oryzae, Aspergillus niger, A. flavus, Fusarium oxysporum, Trichoderma species, F. monaliforme, and Penicillum species. Compounds 4I, 4IV, 4V, 6I, 6II and 6III showed better inhibitory activity than compared to standard drugs. Among these compounds, 4IV and 6III showed potent inhibitory activity against all the strains and found to be nonstrain dependent. The title compounds represent a novel class of potent antimicrobial agents.
- Priya,Basappa,Swamy, S. Nanjunda,Rangappa, Kanchugarakoppal S.
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p. 2623 - 2628
(2007/10/03)
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- Phase transfer catalyzed synthesis of thiosemicarbazide and bis-thiosemicarbazide derivatives of 2-ethoxybenzoic acid
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Reaction of aryloxyacetic acid hydrazide or arenedioxydiacetic acid hydrazide with 2-ethoxybenzoy chloride and ammonium thiocyanate under the condition of solid-liquid phase transfer catalysis using polyethylene glycol-400 (PEG-400) as the catalyst yielded the corresponding thiosemicarbazide or bisthiosemicarbazide derivatives of 2-ethoxybenzoic acid in good-to-excellent yield.
- Wei, Tai-Bao,Zhang, You-Ming,Wang, Hai,Gao, Li-Ming
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p. 1539 - 1544
(2007/10/03)
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- Preparation of non-peptide, highly potent and selective antagonists of arginine vasopressin V1a receptor by introduction of alkoxy groups
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A series of compounds structurally related to 4′-[(4,4-difluoro-5- methylidene-2,3,4,5-tetrahydro-1H-1-benzoazepin-1-yl)carbonyl]benzanilide were synthesized and evaluated for arginine vasopressin (AVP) antagonistic activity. Compounds with alkoxy groups (especially ethoxy group) at the 2′-position of benzanilide possessed potent affinity and selectivity for the V1A receptor versus V2 receptor. Further study has shown that the introduction of 4,4-dimethylaminopiperidino and morpholino groups at carbonylmethylene exhibited more potent affinity and selectivity for V 1A receptors. Consequently, we found that the (Z)-4′-({4,4- Difluoro-5-[(4-dimethylaminopiperidino) carbonylmethylene]-2,3,4,5-tetrahydro- 1H-1-benzoazepin-1-yl}carbonyl)-2-ethoxybenzanilide monohydrochloride (8d) and the (Z)-4′-[(4,4-Difluoro-5-morpholinocarbamoylethylene-2,3,4,5- tetrahydro-1H-1-benzoazepin-1-yl)carbonyl]-2-ethoxybenzanilide (8q) exhibited potent and selective V1A receptor antagonist activity. The synthesis and pharmacological properties of these compounds are detailed in this paper.
- Shimada, Yoshiaki,Taniguchi, Nobuaki,Matsuhisa, Akira,Yatsu, Takeyuki,Tahara, Atsuo,Tanaka, Akihiro
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p. 1075 - 1080
(2007/10/03)
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- Synthesis and structure-activity relationship of dehydroxymethylepoxyquinomicin analogues as inhibitors of NF-κB functions
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We previously found dehydroxymethylepoxyquinomicin (DHMEQ) inhibited NF-κB activation and showed anti-inflammatory activity in vivo. Here we designed and synthesized analogues of DHMEQ and tested their biological activity as NF-κB inhibitors in human T cell leukemia Jurkat cells. The hydroxyl group at the 2-position of the benzamide moiety was found to be essential for the inhibitory activity. But etherification of this group did not diminish the activity completely. Thus, for further mechanistic studies the hydroxyl group at the 2-position may be useful for extension with a linker and biotin moiety.
- Chaicharoenpong, Chanya,Kato, Kuniki,Umezawa, Kazuo
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p. 3933 - 3939
(2007/10/03)
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- Nonpeptide arginine vasopressin antagonists for both V(1A) and V2 receptors: Synthesis and pharmacological properties of 4'-(1,4,5,6- tetrahydroimidazo[4,5-d][1]benzoazepine-6-carbonyl)benzanilide derivatives and 4'-(5,6-dihydro-4H-thiazolo[5,4-d] [1]benzoazepine-6-carbonyl)benzanilide derivatives
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Arginine vasopressin (AVP) has a dual action mainly in the periphery, i.e., vasoconstriction and water reabsorption via V(1A) and V2 receptors; it may play a role in a number of diseases, including congestive heart failure (CHF), hypertension, renal disease, edema, and hyponatremia. We have attempted to develop a new series of orally active AVP antagonists for both V(1A) and V2 receptors based on the hypothesis that the blockade of both V(1A) and V2 receptors might be beneficial to CHF patients. In this report, a series of compounds structurally related to 4'-(1,4,5,6- tetrahydroimidazo[4,5-d][1]benzoazepine-6-carbonyl)benzanilide and 4'-(5,6- dihydro-4H-thiazolo[5,4-d][1]benzoazepine-6-carbonyl)benzanilide were synthesized and examined for AVP antagonist activity for both V(1A) and V2 receptors. As a result, it was found that the 4'-(1,4,5,6- tetrahydroimidazo[4,5-d][1]benzoazepine-6-carbonyl)-2-phenylbenzanilide derivatives showed potent binding affinity for both V(1A) and V2 receptors. Especially, 4'-(2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzoazepine-6- carbonyl)-2-phenylbenzanilide monohydrochloride (18, YM087=conivaptan hydrochloride) exhibited potent binding affinity and AVP antagonist activity, after intravenous administration, for both V(1A) and V2 receptors. Furthermore, YM087 exhibited the most potent oral activity for the V2 receptor. Details of the synthesis and pharmacological properties of this series are presented.
- Matsuhisa, Akira,Taniguchi, Nobuaki,Koshio, Hiroyuki,Yatsu, Takeyuki,Tanaka, Akihiro
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- Asymmetric catalysis, 131([≠]) - Naproxen derivatives by enantioselective decarboxylation
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A new catalytic method to synthesize the important anti-inflammatory agent naproxen [(S)-1] which has to be used as the (S) enantiomer, involves the enantioselective decarboxylation of the 6-methoxynaphth-2-yl derivative 2 of 2-cyanopropionic acid. Compound 2 was stirred in THF at 15 °C with catalytic amounts of chiral bases, which abstracted the carboxyl proton. After decarboxylation, reprotonation of the anion of 6 afforded the enantiomerically enriched naproxen nitrile 6, which may be hydrolyzed to naproxen. A variety of bases were screened, and cinchona alkaloids were found to give the best enantioselectivities. Thus, with quinidine 10, up to 34% ee was obtained for (S)-6. The enantiomeric excess could be increased by turning to amides of 9-amino-9-deoxyepicinchona alkaloids. The most successful 2- ethoxybenzantide 31a of 9-amino-9-deoxyepicinchonine 11 gave up to 71.9% ee (S)-6. Cyclic ethers like THF were suitable solvents, and at a temperature of 15 °C, conversion was quantitative within 24 h in most cases. For high enantioselectivities, 5-10 mol-% of chiral base was sufficient, and the catalyst could be fully recycled after decarboxylation. The model compound 2- cyano-2-phenylpropionic acid (40) was decarboxylated with base 31a to the (S) enantiomer of the corresponding nitrile 41 with 60% ee.
- Brunner, Henri,Schmidt, Peter
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p. 2119 - 2133
(2007/10/03)
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- Chemoselectivity and stereoselectivity of cyclisation of α-diazocarbonyls leading to oxygen and sulfur heterocycles catalysed by chiral rhodium copper catalysts
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Good levels of enantioselectivity have been achieved in intramiolecular C-H insertion reactions of α-diazocarbonyl compounds leading to six-membered oxygen heterocycles (chromanones) through the use of chiral rhodium(II) carboxylates as catalysts.Competition between C-H insertion and sigmatropic rearrangement, the latter leading to five-membered oxygen heterocycles (furanones), was observed with precursors containing a proximal O-allyl side chain.Whereas rhodium carboxylates produced C-H insertion products predominantly, a copper catalyst produced sigmatropic rearrangement products exclusively.A precursor with S-allyl side chain exhibited cyclisation via sigmatropic rearrangement with both copper and rhodium catalyst.
- Ye, Tao,Garcia, Concepcion Fernandez,McKervey, M. Anthony
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p. 1373 - 1380
(2007/10/02)
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- Synthesis, gastrointestinal prokinetic activity and structure-activity relationships of novel N-[[2-(dialkylamino)ethoxy]benzyl]benzamide derivatives
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Novel N-[[2-(dialkylamino)ethoxy]benzyl]benzamide derivatives (II-1-51), derived from the structural modification of metoclopramide (1), were synthesized and examined for their pharmacological activities. Among them, N-[4-[2-(dimethylamino)ethoxy]benzyl]-3,4-dimethoxybenzamide (II-34) which exhibited well balanced gastrointestinal prokinetic and antiemetic activities was selected as a new type of gastrointestinal prokinetic agent.
- Sakaguchi,Nishino,Ogawa,Iwanaga,Yasuda,Kato,Ito
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p. 202 - 211
(2007/10/02)
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