- Density functional theory calculations, vibration spectral analysis and molecular docking of the antimicrobial agent 6-(1,3-benzodioxol-5-ylmethyl)-5-ethyl-2-{[2-(morpholin-4-yl)ethyl] sulfanyl}pyrimidin-4(3H)-one
-
Vibrational spectral analysis and quantum chemical computations based on density functional theory have been performed on the antimicrobial agent 6-(1,3-benzodioxol-5-ylmethyl)-5-ethyl-2-{[2-(morpholin-4-yl)ethyl]sulfanyl}pyrimidin-4-(3H)-one. The equilibrium structural geometry, various bonding features and harmonic vibrational wavenumbers of the title compound have been investigated using DFT-B3LYP function at 6-311++G(d,p) basis set. The detailed interpretations of the vibrational spectra have been carried out with the aid of VEDA 4 program. The various intramolecular interactions of the title compound have been exposed by natural bond orbital analysis. The FT-IR and FT-Raman spectra of the title molecule have been recorded and analyzed. Blue-shifting of the C-H wavenumber along with a decrease in the C-H bond length attribute for the formation of the C-H...O hydrogen bonding provide an evidence for a charge transfer interaction. Also, the distribution of natural atomic charges reflects the presence of intramolecular hydrogen bonding. The analysis of the electron density of HOMO and LUMO gives an idea of the delocalization and the low value of energy gap indicates electron transfer within the molecule. Moreover, molecular docking studies revealed the possible binding of the title molecule to different antimicrobial target proteins.
- Almutairi, Maha S.,Soumya,Al-Wabli, Reem I.,Hubert Joe,Attia, Mohamed I.
-
-
Read Online
- Total Synthesis of [14C]-Labelled Homoharringtonine
-
A total synthesis of enantiomerically pure [14C]-labelled (-)-homoharringtonine in 17 steps is reported. This synthetic process enabled the production of Good Manufacturing Practice (GMP) compliant (-)-[14C]homoharringtonine that was used in a human mass balance study that was a post-approval commitment to the U.S. Food and Drug Administration. (-)-Homoharringtonine, also called omacetaxine mepesuccinate, is approved to treat adult patients with chronic myeloid leukemia (CML), a blood and bone marrow disease. In November 2012, the product was commercialised as Synribo in the U.S., marketed by Teva Pharmaceuticals. The total synthesis of (-)-[14C]homoharringtonine, for use in clinical studies, was achieved 17-steps, starting from 14C-labelled potassium cyanide.
- Marguerit, Melanie,Little, Gill,Wang, Yi,He, Linli,Allwein, Shawn,Reif, James,Rossi, Jason,Roemmele, Renee,Bakale, Roger
-
-
Read Online
- Studies on Pyrrolidones. An Improved Synthesis of N-Arylmethyl Pyroglutamic Acids
-
Low solubility of the aromatic aldehyde in a water/ethanol medium can prevent the sodium borohydride reductive alkylation of the sodium salt of glutamic acid. In that case, the reductive alkylation can be realized in methanol by using a triethylammonium salt. The uses of 2 molar equivalent of triethylammonium salt of glutamic acid for one molar equivalent of aldehyde strongly raise the yields. Cyclization of the N-substituted glutamic acids obtained gives then N-arylmethyl pyroglutamic acids in good yields.
- Bourry, Anne,Akue-Gedu, Rufine,Rigo, Benoit,Henichart, Jean-Pierre,Sanz, Gerard,Couturier, Daniel
-
-
Read Online
- Method for synthesizing piperonyl chloride through continuous flow reaction
-
The invention provides a method for synthesizing piperonyl chloride through continuous flow reaction, which comprises the following steps: enabling 1,3-Benzodioxole and a chloromethylation reagent to pass through a continuous flow reactor through a metering pump, preheating, mixing, reacting, and carrying out after-treatment to obtain the piperonyl chloride. The method for synthesizing piperonyl chloride through continuous flow reaction is stable and feasible in process, capable of accurately controlling conditions, high in yield, high in reaction rate, good in selectivity, simple and convenient to operate, safe and environment-friendly, has an enlarged production prospect, and has a huge practical value in the aspect of improving the production efficiency.
- -
-
Paragraph 0035-0076
(2021/05/01)
-
- Synthesis of 1,2,3-triazole derivatives of hydnocarpic acid isolated from carpotroche brasiliensis seed oil and evaluation of antiproliferative activity
-
Carpotroche brasiliensis is a tree native to Brazil, belonging to the family Flacurtiaceae, whose seeds contain a group of cyclopentenyl fatty acids: Gorlic (12%), chaulmugric (27%), and hydnocarpic (48.7%). These compounds are considered the main therapeutic agents in the treatment of leprosy. In the present study, a series of novel triazole compounds were obtained by conjugation between hydnocarpic acid and functionalized azides via copper(I)-catalyzed azidealkyne cycloaddition reaction (CuAAC). Hydnocarpic acid and its derivatives were tested against estrogen-positive breast carcinoma (MCF-7), hepatocellular carcinoma (HepG2), and non-small cell lung cancer (A549) cell lines. The (R)-(1-(pyridin-2-ylmethyl)-1H-1,2,3-triazol-4-yl)methyl-11-(cyclopent-2-en-1-yl)undecanoate (8) displayed promising antiproliferative activity against A549 cells. We demonstrated that this compound selectively inhibited the viability of A549 cell cultures. Furthermore, compound 8 inhibited the clonogenic capacity of A549 cells, and this effect was associated to its ability to inhibit cell cycle progression at G1 phase. These findings indicate that 8 is a promising antitumor agent on A549 cells and support further studies to evaluate the molecular mechanisms underlying its antiproliferative activity. In addition, hydnocarpic acid should be considered as a promising chemical prototype to obtain novel antineoplastic agents.
- De Sousa, Bianca L.,Demuner, Antonio J.,Dos Santos, Marcelo H.,Ferraz, Guilherme O.,Ferreira-Silva, Guilherme A.,Ionta, Marisa,Osorio, Liseth S.,Pilau, Eduardo J.,Silva, Evandro,Vareja?, Eduardo V. V.
-
p. 2500 - 2510
(2020/11/18)
-
- AN EFFICIENT AND ENVIRONMENT FRIENDLY PROCESS FOR CHLOROMETHYLATION OF SUBSTITUTED BENZENES
-
Disclosed herein is an efficient, environment friendly and commercially viable process for preparation of chloromethylated compound of formula I in substantially pure form and high yield, from the compound of formula II. The process includes contacting the compound of formula II with a chloromethylating agent generated in-situ by reaction of a formaldehyde precursor and hydrogen chloride, in a suitable solvent/contacting medium and in the presence of a catalytic amount of a short chain/low molecular weight carboxylic acid of formula III. I II III wherein, R1, R2, R3 and R4 are as defined in the description.
- -
-
Paragraph 0064-0074; 0080
(2020/12/30)
-
- 2-Amino-purine derivative compound, preparing method and use thereof
-
According to one aspect, provided are a purine compound, a stereoisomer, a derivative, a solvate, or a pharmaceutically acceptable salt thereof, a manufacturing method thereof and uses thereof. According to the same, the compound, and the stereoisomer, derivative, solvate, or pharmaceutically acceptable salt thereof have low cytotoxicity, and exhibit high selective inhibitory activity against HSP90, and antiproliferative effect of cancer cells, thereby being useful for preventing or treating cancer.(AA) Density(BB) Compound(CC) andbeta;- tubulinCOPYRIGHT KIPO 2018
- -
-
Paragraph 0310-0315
(2018/05/29)
-
- Preparation method of piribedil
-
The invention provides a preparation method of piribedil. The preparation method comprises the following steps of: preparing piperonyl chloride; preparing piperazinyl pyrimidine; and preparing piribedil. The preparation method of piribedil is simple, low in production cost, high in integral yield of reaction and convenient for industrial production, and has huge promotional meaning.
- -
-
Paragraph 0020; 0023; 0026
(2017/10/13)
-
- Synthetic method of piribedil
-
The invention relates to a synthetic method of piribedil. The synthetic method is a brand new process comprising the steps of synthesizing piperonyl piperazine in one step under the effects of pentamethyleneamine, piperazine pyrimidine and paraformaldehyde, and reacting by virtue of piperonyl piperazine and dichloropyrimidine so as to synthesize piribedil. Piperonyl piperazine has not been synthesized by virtue of the synthetic method before. Compared with a traditional synthetic method of piribedil, the synthetic method has the advantages that synthetic steps are simplified, the three wastes are reduced, the utilization ratio of pentamethyleneamine is remarkably increased, and the after-treatment is relatively environment-friendly.
- -
-
Paragraph 0010; 0017
(2017/04/03)
-
- A heliotropin synthetic method
-
The invention relates to the technical field of the medical intermediate fine chemical industry and in particular relates to a synthetic method of piperonal. The synthetic method comprises the following steps: 1 uniformly mixing benzodioxole, formaldehyde with concentration of 40% and a primary catalyst dodecyl trimethyl ammonium bromide with a solvent, then adding hydrochloric acid with concentration of 35-37% and standing for layering after reaction, thus obtaining a piperonyl chloride solution, wherein the solvent is trichloromethane, tetrachloromethane or methylbenzene; 2 preparing a sodium bicarbonate or sodium carbonate water solution with concentration less than or equal to that of a saturated solution, adding the sodium bicarbonate or sodium carbonate water solution to the piperonyl chloride solution and reacting to obtain a piperonyl alcohol solution; 3 introducing air into the piperonyl alcohol solution to oxidize the piperonyl alcohol solution to generate a piperonal solution by using both ferric nitrate and 4-hydroxy-2,2,4,4-methylpiperidine nitroxyl free radical as final catalysts. The synthetic method provided by the invention has the advantages of accessible raw materials, mild reaction conditions, stable and high yield, few byproducts and low cost.
- -
-
Paragraph 0092; 0093; 0094; 0095; 0096; 0097; 0098
(2017/06/02)
-
- Preparation method of high-quality piribedil
-
The invention provides a preparation method of high-quality piribedil. The preparation method of the high-quality piribedil comprises preparation of piperonyl chloride, preparation of piperazinyl pyrimidine and preparation of piribedil. The method is simple and brief, the production cost is low, the reaction overall yield is high, industrialized production is facilitated, and great popularization significance is achieved.
- -
-
Paragraph 0020; 0023; 0026
(2018/01/09)
-
- Novel pyrrolo pyrimidine derivatives and composition for preventing or treating cancer comprising the same
-
The present invention relates to a novel pyrrolo pyrimidine compound represented by chemical formula 1, pharmaceutically acceptable salt or hydrate thereof, a manufacturing method thereof, and a pharmaceutical composition comprising the compound for preventing or treating cancer. In chemical formula 1, R^1, R^2, R^3, R^4, R^5, and X are the same as defined in the specification.COPYRIGHT KIPO 2016
- -
-
Paragraph 0287; 0288; 0289; 0290
(2016/11/24)
-
- Endothelin antagonists benzene oxygen benzene acetic acids and its preparation method and application
-
The invention provides a phenoxy phenylacetic acid endothelin antagonist shown in a formula (I) or a pharmaceutically acceptable salt thereof, and also provides a preparation method of the benzene oxygen phenylacetic acid endothelin antagonist or the pharmaceutically acceptable salt thereof, and an application thereof in preparation of a medicament for treating cardiovascular and cerebrovascular diseases, tumors, diabetes mellitus, nephrosis, asthma or hyperthyroidism.
- -
-
Paragraph 0075-0076
(2016/11/02)
-
- AN EFFICIENT PROCESS FOR THE SYNTHESIS OF ALKOXY SUBSTITUTED BENZALDEHYDES
-
The present invention relates to the synthesis of alkoxy substituted benzaldehydes obtained from the corresponding alkoxy substituted benzenes. Alkoxy substituted benzaldehydes are products of broad commercial interest and are used as end products and intermediates in flavor and fragrance applications and pharmaceutical ingredients. For example, 3,4-methylendioxybenzaldehyde (also known as heliotropin or piperonal) is used widely both as a end product and intermediate for the above mentioned applications. Other examples include 3,4-dimethoxybenzaldehyde, 3,4,5- trimethoxybenzaldehyde and 3,4-ethylenedioxybenzene which are intermediates in the synthesis of active pharmaceutical intermediates.
- -
-
Page/Page column 20
(2016/07/27)
-
- Discovery of phenoxybutanoic acid derivatives as potent endothelin antagonists with antihypertensive activity
-
A series of phenoxybutanoic acid derivatives were synthesized and tested for their antagonistic activity on the contraction of the rat thoracic aortic ring induced by endothelin-1. Preliminary screening results showed that 6e and 6g with benzoheterocycles demonstrated significant antagonistic activities when compared to the reference compound BQ123. The results from additional assays for the binding affinity and selectivity for endothelin receptors showed that 6e was a selective ETA antagonist with a nanomolar IC50. Moreover, 6e was effective in relieving hypoxia-induced pulmonary arterial hypertension and right ventricular weight ratio. Therefore, 6e may have potential for further development as a therapeutic agent for the treatment of cardiovascular diseases.
- Cai, Jin,Liu, Ligang,Hong, Kwon Ho,Wang, Peng,Li, Lushen,Cao, Meng,Sun, Chunlong,Wu, Xiaoqing,Zong, Xi,Chen, Junqing,Ji, Min
-
p. 657 - 667
(2015/02/19)
-
- Ethyl cinnamate derivatives as promising high-efficient acaricides against Psoroptes cuniculi: Synthesis, bioactivity and structure-activity relationship
-
This paper reported the synthesis, structure-activity relationship (SAR) and acaricidal activity in vitro against Psoroptes cuniculi, a mange mite, of 25 ethyl cinnamate derivatives. All target compounds were synthesized and elucidated by means of MS, 1H- and 13C-NMR analysis. The results showed that 24 out of 25 tested compounds at 1.0 mg/mL demonstrated acaricidal activity in varying degrees. Among them, 6, 15, 26, 27 and 30 showed significant activity with median lethal concentration values (LC50) of 89.3, 119.0, 39.2, 29.8 and 41.2 μg/mL, respectively, which were 2.1- to 8.3-fold the activity of ivermectin (LC50=247.4 μg/mL), a standard drug in the treatment of Psoroptes cuniculi. Compared with ivermectin, with a median lethal time value (LT50) of 8.9 h, 27 and 30 showed smaller LTM50 values of 7.9 and 1.3 h, respectively, whereas 6, 15 and 26 showed slightly larger LT50 values of 10.6, 11.0 and 10.4 h at 4.5 μmol/mL. SARs showed that the presence of o-NO2 or m-NO2 on the benzene ring significantly improved the activity, whereas the introduction of a hydroxy, methoxy, acetoxy, methylenedioxy, bromo or chloro group reduced the activity. (E)-Cinnamates were more effective than their (Z)-isomer. Nevertheless, the carbon-carbon double bond in the acrylic ester moiety was proven not to be essential to improve the activity of cinnamic acid esters. Thus, the results strongly indicate that cinnamate derivatives, especially their dihydro derivatives, should be promising candidates or lead compounds for the development of novel acaricides for the effective control of animal or human acariasis.
- Zhang, Bingyu,Lv, Chao,Li, Weibo,Cui, Zhiming,Chen, Dongdong,Cao, Fangjun,Miao, Fang,Zhou, Le
-
p. 255 - 262
(2015/04/22)
-
- Copper-catalyzed nucleophilic trifluoromethylation of benzylic chlorides
-
Reactions of primary and secondary benzylic chlorides with trifluoromethyltrimethylsilane in the presence of a catalytic amount of copper(i) thiophene-2-carboxylate (CuTC) have been found to give the corresponding benzylic trifluoromethylated products in good to high yields. the Partner Organisations 2014.
- Miyake, Yoshihiro,Ota, Shin-Ichi,Shibata, Masashi,Nakajima, Kazunari,Nishibayashi, Yoshiaki
-
supporting information
p. 5594 - 5596
(2014/07/22)
-
- Cu-Catalyzed Suzuki-Miyaura reactions of primary and secondary benzyl halides with arylboronates
-
A copper-catalyzed Suzuki-Miyaura coupling of benzyl halides with arylboronates is described. Varieties of primary benzyl halides as well as more challenging secondary benzyl halides with β hydrogens or steric hindrance could be successfully converted into the corresponding products. Thus it provides access to diarylmethanes, diarylethanes and triarylmethanes. This journal is the Partner Organisations 2014.
- Sun, Yan-Yan,Yi, Jun,Lu, Xi,Zhang, Zhen-Qi,Xiao, Bin,Fu, Yao
-
supporting information
p. 11060 - 11062
(2014/09/30)
-
- ACC INHIBITORS AND USES THEREOF
-
The present invention provides compounds useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.
- -
-
Paragraph 1299;
(2013/05/22)
-
- DMSO-catalyzed chlorination of alcohols using N-phenylbenzimidoyl chloride
-
N-phenylbenzimidoyl chloride has been demonstrated as an efficient chlorination reagent catalyzed by dimethyl sulfoxide (DMSO) in conversion of alcohols to corresponding chlorides. The reaction conditions were mild, and most of the substrates gave satisfactory yields. The configuration inversion of the chlorination was proved using optically active phenyl alcohols. The amount of DMSO can be as low as 0.001 eq without reducing the efficiency of the chlorination. A plausible mechanism for the reaction was proposed and proved by experiments. The reaction is stereoselective and potentially chemoselective among primary benzyl alcohols, secondary benzyl alcohols, and unactivated aliphatic alcohols.
- Wang, Qiang,Xu, Jian,Xu, Zhou-Qing,Yan, Ji-Dan
-
p. 2071 - 2076
(2013/06/05)
-
- Enantioselective synthesis of amaryllidaceae alkaloids (+)-vittatine, (+)-epi-vittatine, and (+)-buphanisine
-
Cat. on a hot tin roof: Enantioselective catalytic Michael addition of α-cyanoketones to acrylates under bifunctional organocatalysis was used to construct the unique arylic all-carbon quaternary stereocenter, which is synthetically crucial in the chemical synthesis of optically pure cis-aryl hydroindole alkaloids. The protocol offers an asymmetric route to (+)-vittatine, (+)-epi-vittatine, and (+)-buphanisine. Copyright
- Wei, Meng-Xue,Wang, Cheng-Tao,Du, Ji-Yuan,Qu, Hu,Yin, Pei-Rong,Bao, Xu,Ma, Xiao-Yan,Zhao, Xian-He,Zhang, Guo-Biao,Fan, Chun-An
-
supporting information
p. 1966 - 1971
(2013/09/23)
-
- METHOD FOR PRODUCING A HIGH-PURITY AROMATIC METHYL ALCOHOL AND HIGH-PURITY AROMATIC METHYL ALCOHOL COMPOSITION HAVING EXCELLENT PRESERVATION STABILITY
-
An object of the present invention is to provide a high-purity aromatic methyl alcohol compound having reduced a bis(arylmethyl)ether compound as a side product mixed thereinto and a high-purity aromatic methyl alcohol composition having excellent preservation stability and methods for producing them. The object of the present invention is achieved by a method for producing a high-purity aromatic methyl alcohol compound, which comprises obtaining a high-purity aromatic methyl alcohol compound in high yield from an aromatic methyl alcohol-containing crude product by subjecting the crude product to distillation in the presence of an anti-decomposition agent. Further, the object for the preservation stability is achieved by producing a high-purity aromatic methyl alcohol composition using the obtained high-purity aromatic methyl alcohol compound.
- -
-
Page/Page column 14-15
(2013/02/27)
-
- A highly chemoselective and rapid chlorination of benzyl alcohols under neutral conditions
-
A rapid and highly selective chlorination method has been developed using 2,4,6-trichloro-1,3,5-triazine (TCT) catalyzed by dimethyl sulfoxide. The reactions take 10 to 40 minutes, and the yields are almost quantitative. The neutral reaction conditions are compatible with substrates bearing acid-labile functional groups. Both competitive intramolecular and intermolecular reactions for benzyl alcohols in the presence of aliphatic alcohols indicate high selectivity. The procedure has been successfully used in the selective chlorination of gastrodin, a clinically used neuromedicine. This procedure represents a useful new tool in organic and medicinal chemistry. Georg Thieme Verlag Stuttgart.
- Sun, Lili,Peng, Guisheng,Niu, Hongmei,Wang, Qiang,Li, Chunbao
-
experimental part
p. 3919 - 3924
(2009/05/26)
-
- Arylethenylbenzofuroxan derivatives as drugs for chagas disease: Multigram batch synthesis ysubg a wuttug#bideb process
-
In the present work, we developed robust processes for the preparation of new antitrypanosomal benzofuroxans, E and Z isomers of 5-arylethenylbenzo[1,2-c] 1,2,5-oxadiazole p1N-oxide 1-6, in muhigram batch through Wittig-Boden conditions as the key synthetic step. In these conditions, the generation of the benzofurazans, as secondary byproduct, was minimized.
- Porcal, Williams,Merlino, Alicia,Boiani, Mariana,Gerpe, Alejandra,Gonzalez, Mercedes,Cerecetto, Hugo
-
p. 156 - 162
(2013/01/03)
-
- A mild and efficient desilylation of O-tert-butyldimethylsilyl ethers mediated by chlorotrimethylsilane and potassium fluoride dihydrate in acetonitrile
-
Desilylation of O-tert-butyldimethylsilyl ethers was achieved by a reagent system consisting of chlorotrimethylsilane and potassium fluoride dihydrate in acetonitrile. This alternative desilylation procedure is chemoselective, generally effective and operationally simple, and should find practical applications in organic synthesis. Georg Thieme Verlag Stuttgart.
- Peng, Yu,Li, Wei-Dong Z.
-
p. 1165 - 1168
(2007/10/03)
-
- INDENE DERIVATIVES AND PROCESS FOR THE PREPARATION THEREOF
-
The inventive indene derivatives of formula (I) are capable of selectively modulating the activities of peroxisome proliferator activated receptors (PPARs), causing no adverse side effects, and thus, they are useful for the treatment and prevention of disorders modulated by PPARs, i.e., metabolic syndromes such as diabetes, obesity, arteriosclerosis, hyperlipidemia, hyperinsulinism and hypertension, inflammatory diseases such as osteoporosis, liver cirrhosis and asthma, and cancer.
- -
-
Page/Page column 42
(2010/02/14)
-
- 1,3-BENZODIOXOL-5-YLMETHYL METHYL SULFONE AND ITS DERIVATIVES, PREPARATION METHOD THEREOF AND WHITENING COMPOSITION CONTAINING THE SAME
-
The present invention relates to novel compounds, 1,3-benzodioxol-5-ylmethyl methyl sulfone and its derivatives and to preparation method thereof. In detail, 1,3-benzodioxol-5-ylmethyl methyl sulfone and its derivatives have strong tyrosinase inhibitory activity and thereby can inhibit melanin biosynthesis and exhibit skin-whitening effect. Further, the present invention relates to skin-whitening compositions containing 1,3-benzodioxol-5-ylmethyl methyl sulfone and its derivatives as an active ingredient.
- -
-
Page/Page column 6; 8-9
(2010/02/13)
-
- PROCESS FOR SYNTHESISING HELIOTROPINE AND ITS DERIVATIVES
-
A new high-yield, easily industrialized process for synthesising compounds of formula (IV), in which X1 and X2, the same or different, are linear or branched C1-C8 alkyls, n and m are 0,1 or 2, with the proviso that n and m are not simultaneously 0; or (OX1)n and (OX2)m taken together form an O-T-O group where T is chosen from -CH2-, -CH2CH2-, -CH2CH2CH2-, -C(CH3)2-. The process comprises treating a chloromethyl derivative (I) with an alkaline acetate to form the intermediate acetylderivative (II); the intermediate (II) is to hydrolysed to form the alcohol (III); the alcohol (III) is then oxidised in the presence of air and catalysts to obtain the desired derivative (IV). The process runs its course within a short period of time, with high yields and high selectivity; in addition, the process does not require purification and separation of the intermediates and can therefore be favourably conducted in a single batch.
- -
-
Page/Page column 8-9
(2008/06/13)
-
- Methods for synthesis of alpha-d-gal (1~>3) gal-containing oligosaccharides
-
This invention relates to reagents and methods for synthesis of biologically active di- and tri-saccharides comprising α-D-Gal(1→3)-D-Gal. In particular the invention provides novel reagents, intermediates and processes for the solution or solid phase synthesis of α-D-galactopyranosyl-(1→3)-D-galactose, and derivatives thereof. In one preferred embodiments the invention provides a protected monosaccharide building block of general formula (II): in which R3 is methoxy or methyl; R1 is H, benzoyl, pivaloyl, 4-chlorobenzoyl, acetyl, chloroacetyl, levulinoyl, 4-methylbenzoyl, benzyl, 3,4-methylenedioxybenzyl, 4-methoxybenzyl, 4-chlorobenzyl, 4-acetamidobenzyl, or 4-azidobenzyl; and R2 is H, Fmoc, benzoyl, pivaloyl, 4-chlorobenzoyl, acetyl, chloroacetyl, levulinoyl, 4-methylbenzoyl, benzyl, 3,4-methylenedioxybenzyl, 4-methoxybenzyl, 4-chlorobenzyl, 4-acetamidobenzyl, or 4-azidobenzyl.
- -
-
-
- Design, synthesis and antiproliferative activity of tripentones: A new series of antitubulin agents
-
Structure-activity relationship studies of a new series of tripentones (thieno[2,3-b]pyrrolizin-8-ones), led us to prepare several derivatives with antiproliferative activities. The most promising 3-(3-hydroxy-4-methoxyphenyl)thieno[2,3-b]pyrrolizin-8-one 20 (leukemia L1210, IC50 = 15 nM) was shown to be a potent inhibitor of tubulin polymerization.
- Lisowski, Vincent,Enguehard, Cecile,Lancelot, Jean-Charles,Caignard, Daniel-Henri,Lambel, Stephanie,Leonce, Stephane,Pierre, Alain,Atassi, Ghanem,Renard, Pierre,Rault, Sylvain
-
p. 2205 - 2208
(2007/10/03)
-
- Benzamide analogs useful as PARP (ADP-ribosyltransferase, ADPRT) DNA repair enzyme inhibitors
-
A range of 3-oxybenzamide compounds and related quinazolinone compounds are disclosed which can act as potent inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase or PARP enzyme (EC 2.4.2.30), and which thereby can provide useful therapeutic compounds for use in conjunction with DNA-damaging cytotoxic drugs or radiotherapy to potentiate the effects of the latter. The compounds disclosed include 3-benzyloxybenzamides, 3-oxybenzamides in which a chain of 5 or more methylene groups terminate in a halogen atom or in a purin-9-yl moiety, certain benzoxazole-4-carboxamide compounds and certain quinazolinone compounds. In formula X and Y together may form a bride -X-Y- that represents the grouping (a), (b) or (c )wherein R5 is H, alkyl, aryl or aralkyl.
- -
-
-
- ANTIVIRAL ETHERS OF ASPARTATE PROTEASE SUBSTRATE ISOSTERES
-
Antiretroviral compounds (which are effective, for example, against HIV) of the formula I STR1 in which R 1 is an acyl radical lower-alkoxyl-lower-alkanoyl whose lower alkoxy radical is unsubstituted or is substituted by halogen, phenyl, lower alkoxy or a heterocyclic radical selected from piperidinyl, pyrrolidinyl, tetrahydropyranyl, tetrahydrofuranyl, thiazolidinyl, thiazolyl, indolyl or 4H-1-benzopyranyl which is unsubstituted or substituted by oxo, hydroxyl, amine, lower alkyl, lower-alkoxycarbonyl and/or phenyl-lower-alkoxycarbonyl; lower alkanoyl which is unsubstituted or is substituted by one of the said unsubstituted or substituted heterocyclic radicals; arylcarbonyl or heterocyclylcarbonyl which are substituted by heterocyclyl or heterocyclyl-lower-alkyl; phenyl-lower-alkanoyl which is substituted by hydroxyl and lower alkyl; or arylsulfonyl;or the residue of an amino acid which is defined in accordance with the description (and which may be acylated on the amino nitrogen by one of the abovementioned acyl radicals);R 2 and R 3 are in each case cyclohexyl, cyclohexenyl, phenyl, naphthyl or tetrahydronaphthyl which are unsubstituted or substituted by lower alkyl, phenyl, cyanophenyl, phenyl-lower-alkyl, halogen, halo-lower-alkyl, cyano, hydroxyl, lower alkoxy, phenyl-lower-alkoxyl, pyridyl-lower-alkoxy, lower-alkoxy-lower-alkoxy, lower-alkoxycarbonyl-lower-alkoxy, carboxyl-lower-alkoxy, hydroxyl-lower-alkoxy, carbamoyl-lower-alkoxy, cyano-lower-alkoxy, and phenyl-lower-alkanesulfonyl which is unsubstituted or substituted by halogen;R 4 is lower alkyl, cyclohexyl or phenyl; and R 5 is lower alkyl; and n is 1 or 2, or salts thereof, are novel.
- -
-
-
- Synthesis of potent and orally active HIV-protease inhibitors
-
A series of potent HIV-protease inhibitors has been prepared. Several of the newly synthesized compounds showed high plasma levels after oral administration to animals. Based on the overall biological profile, CGP 61755 was chosen for further preclinical evaluation. For this compound, a 10 step synthesis potentially suitable for large scale production was developed.
- Capraro, Hans-Georg,Bold, Guido,Faessler, Alexander,Cozens, Robert,Klimkait, Thomas,Lazdins, Janis,Mestan, Juergen,Poncioni, Bernard,Roesel, Johannes L.,Stover, David,Lang, Marc
-
p. 273 - 278
(2007/10/03)
-
- SYNTHESES BASED ON β-PHENYLETHYLAMINES. I. PREPARATION OF SUBSTITUTED β-PHENYLETHYLAMINES
-
A comparative study has been made of methods of synthesizing substituted β-phenylethylamines via the corresponding nitriles and via nitrostyrenes, and a superiority of the latter method has been established.The possibility has been shown for the first time of reducing nitrostyrenes to saturated amines with diisobutylaluminum hydride (DIBAH).The use of DIBAH as reducing agent enables amines to be obtained in high yields.
- Vinogradova, V. I.,Yunusov, M. S.,Kuchin, A. V.,Tolstikov, G. A.,Sagandykov, R. T.,et al.
-
-
- A SHORT VERSATILE SYNTHESIS OF ARYLTETRALIN LIGNANS INCLUDING DEOXYISOPODOPHYLLOTOXIN AND EPI-ISOPODOPHYLLOTOXIN
-
Cyclisation of tandem conjugate addition products (10), (15), and (20), prepared by reaction of anions derived from benzyl phenyl and benzyl t-butyl sulphides with but-2-en-4-olide, affords a series of aryltetralin lignans belonging to either the 'normal' or the 'retro' lactone series.Desulphurisation of compound (15) followed by cyclisation, or desulphurisation of the cyclised product (22b), affords deoxyisopodophyllotoxin (5), while treatment of compound (22b) with mercury(II) trifluoroacetate yields epi-isopodophyllotoxin (6).
- Pelter, Andrew,Ward, Robert S.,Pritchard, Martyn C.,Kay, I. Trevor
-
p. 1615 - 1624
(2007/10/02)
-
- HIGHLY STEREOSELECTIVE SYNTHESIS OF (2E,4E)-DIENAMIDES AND (2E,4E)-DIENOATES VIA A DOUBLE ELIMINATION REACTION
-
Highly stereoselective synthesis of (2E,4E)-dienamides and (2E,4E)-dienoates was achieved through a double elimination reaction of β-acetoxy sulfones.
- Mandai, Tadakatsu,Moriyama, Tadashi,Tsujimoto, Koichiro,Kawada, Mikio,Otera, Junzo
-
p. 603 - 606
(2007/10/02)
-
- Electrochemical Stability of Catechols with a Pyrene Side Chain Strongly Adsorbed on Graphite Electrodes for Catalytic Oxidation of Dihydronicotinamide Adenine Dinucleotide
-
The electrochemical stability and reactivity of 4-catechol (PSCH2) and 4-catechol (PECH2) strongly adsorbed on graphite electrodes were investigated as a function of the applied potential at pH 7.0.The surface coverage of these compounds ranged from 0.1 x 10-9 to 2.7 x 10-9 mol/cm2.The ''modified'' electrodes exhibited deactivation which could be explained by second-order reactions between the catechols and the electrochemically produced quinones coupled with a second-order reaction between the quinones.The ethano compound showed a much larger decay rate, probably because of free rotation around the saturated bond connecting the pyrene part and the catechol group.The deactivation was apparently not associated with decomposition of the compounds.The catechols in the oxidized form could catalytically oxidize NADH.The overpotential for NADH oxidation was thus decreased from 410 to 150 mV vs.SCE at pH 7.0.However, the catalytic current was found to decrease exponentially with increasing number of scans.The rate of this deactivation of the catalytic electrode was found to be inversely proportional to the coverage of immobilized mediator.The deactivation could be explained by a chemical coupling reaction between the mediator and NADH, forming a complex which gradually blocked off the surface of the electrode.The probable nature of the complex makes it unlikely that ''capping'' of active sites, e.g., the 2, 5, and 6 positions, on the catechol ring would effectively prevent the blocking and, hence, deactivation of the catalytic electrodes.
- Jaegfeldt, Hans,Kuwanw, Theodore,Johansson, Gillis
-
p. 1805 - 1814
(2007/10/02)
-
- Piperonylamine derivatives
-
N-propargyl-piperonylamine of the structural formula: STR1 and its addition salts are useful in reducing appetite, fatigue, and aggression.
- -
-
-