Disclosed is a process for the preparation of anthraquinodimethane derivatives and anthrone derivatives useful as electron transporting molecules which comprises the condensation reaction of anthraquinones with active methylene compounds in the presence of a Lewis acid and a base.A process for the preparation of anthraquinodimethane derivative and anthrone derivatives which consists essentially of the reaction of an anthraquinone with an active methylene compound selected from the group consisting of malononitrile, malonate, dinitromethane, and betadiketone in the presence of an organic solvent, a base, and a Lewis acid, which reaction is affected at a temperature of from about 0° C. to about 30° C.

This invention is generally directed to processes for the preparation of electron transporting compounds, and more specifically the present invention is directed to specific processes for obtaining anthraquinodimethane derivatives and related anthrone derivatives. Therefore, in one embodiment of the present invention there are prepared anthraquinone and anthrone Pharmaceutical Intermediates  derivatives by the reaction of an anthraquinodimethane with active methylene compounds, inclusive of malononitrile, in a suitable organic solvent, which reaction is accomplished in the presence of a base and a Lewis acid. The resulting anthraquinodimethane derivatives and related anthrone derivatives are useful as electron transporting compounds in imaging members containing therein a photogenerating layer. These imaging members are the claimed subject matter of a copending application U.S. Ser. No. 709,867 entitled Photoresponsive Imaging Members With Electron Transporting Layers, the disclosure of this copending application being totally incorporated herein by reference.

There is also disclosed in U.S. Pat. No. 4,474,865 imaging members with electron transporting layers of fluorenylidene derivatives. These electron transporting compounds differ from those of the present invention in that they are based on the fluorenone structure with a 5-member central ring; while the transporting compounds of the present invention are based on anthrone manufacturer and anthraquinone structures which contain a 6-member central ring. In addition, while the fluorenylidene derivatives are relatively planar in structure, the anthrone and anthraquinone derivatives of the present invention are buckled and assume a butterfly-like conformation.

While the above-described photoresponsive imaging members are suitable for their intended purposes there continues to be a need for improved imaging members, particularly layered imaging members, which not only generate acceptable images but which can be repeatedly used in a number of imaging cycles without deterioration thereof from the machine environment or surrounding conditions. Additionally, there continues to be a need for improved layered photoconductive imaging members wherein the materials selected are substantially inert to users of these members. Also, there continues to be a need for positively charged imaging members with electron transporting compounds. Additionally, there continues to be a need for improved photoresponsive imaging members which can be prepared with a minimum number of processing steps, and wherein the layers are sufficiently adhered to one another to allow the continuous use of these members in imaging and printing processes.

Also, there is a need for electron transport compounds which are compatible with common matrix polymers, inclusive of polycarbonates, and polyesters enabling the dispersion of these compounds to be maintained for the useful life of the layered imaging members. Moreover, there continues to be a need for a simple synthetic process for the preparation of anthrone products , and anthraquinodimethane electron transporting compounds.

A further specific object of the present invention is the provision of an improved photoresponsive imaging member containing a photogenerating layer, and in contact therewith an electron transporting layer of anthrone derivatives prepared by the processes illustrated herein.

Another specific object of the present invention is the provision of an improved photoresponsive imaging member containing a photogenerating layer, and in contact therewith an electron transporting layer of anthraquinodimethane derivatives prepared by the processes illustrated herein.

The primary object of the present invention and other related objects are accomplished by the provision of processes for the preparation of anthraquinodimethane derivatives and anthrone supplier derivatives useful as electron transporting molecules which comprises the condensation reaction of anthraquinones with active methylene compounds in the presence of a Lewis acid and a base. The aforementioned electron transporting compounds prepared in accordance with the process of the present invention are useful for incorporation into the layered photoresponsive imaging members are disclosed in the referenced copending application entitled Photoresponsive Imaging Members With Electron Transporting Layers.

A process according to claim 9, wherein the 2-acylamino-2'-carboxy-diphenylmethane is 2-acetylamino-2'-carboxy-diphenylmethane whereby the 4-acylamino-anthrone is 4-acetamino-anthrone and the oxidation product is 1-acetamino-anthraquinone.
The present invention relates to a process for the preparation of 4-acylamino- anthrones from 2-acylamino-2'-carboxy-diphenylmethanes and their further processing to acylaminoanthraquinones.

Formyl- and acetyl-amino- anthrone are known from German Pat. No. 594,168. They are prepared by reacting 4-aminoanthrone with formic acid or, respectively, acetic anhydride.

It has now been found that 4-acylamino- anthrones are obtained quite generally in a technically advantageous manner when 2-acylamino-2'-carboxy-diphenylmethanes are treated with an acid condensing agent.

This was surprising insofar as it was to be seen from German Pat. No. 594,168 that the treatment of 2-formylamino-2'-benzylbenzoic acid with phosphorus oxychloride leads to a pyrrolanthrone.

Anthrone products derivatives having hydroxy, ether or hydrocarbyl groups in 10-position, for example 10,10-dimethoxyanthrone, are excellent photoinitiators for the UV-curing of unsaturated systems. Preferable systems are monomeric or oligomeric acrylates and their mixtures.

The systems may be used in thin layers as for instance for coatings or printing inks.
The invention relates to the use of anthrone derivatives as initiators for the photopolymerisation of unsaturated compounds and to photopolymerisable systems containing such anthrone manufacturer derivatives. The proposed anthrone derivatives are derivatives of 10-mono- or -di-hydroxyanthrone.

Photochemical polymerisation processes have achieved considerable importance industrially, above all in those cases where thin layers have to be cured within a short time, such as, for example, when curing lacquer coatings or when drying printing inks. Compared with conventional curing processes, UV irradiation in the presence of photoinitiators has a number of advantages, the most important of which is probably the high rate of photo-curing. The rate is highly dependent on the photoinitiator used and there has been no lack of attempts to replace the conventional initiators by ever better and more effective compounds. The most effective photoinitiators include derivatives of benzoin, above all benzoin ethers such as are described, for example, in British Pat. Nos. 1,254,231 and 1,156,460 or in Swiss Pat. No. 511,902.

The 4-acylamino- anthrones obtained according to the invention are intermediates for the advantageous preparation of 1-acyl-aminoanthraquinones.

The procedure for this can be that the particular 4-acylaminoanthrone is dissolved or suspended in water, sulfuric acid, water/sulfuric acid, a solvent or a water/solvent mixture, and oxidized. Thus, the compounds of the formula I in which R 2  represents an ether radical and R 1  is hydrogen or is identical to R 2  can be manufactured from anthrone by monohalogenation or dihalogenation in the 10-position and subsequent reaction with the corresponding hydroxy compound R 2 OH, or an alkali metal compound thereof, as is described for the case of the monomethoxy compound in J. Chem. Soc. 1931, 3340 and for the case of the dimethoxy compound in Liebigs Ann. 396 (1913), 180.

Compounds of the formula I in which R 1 is hydroxyl and R 2 is a hydrocarbon radical can be manufactured from anthraquinone by a Grignard reaction and can optionally be converted into the compounds in which R 2 represents an ether group and R 1 represents a hydrocarbon radical by an etherification by customary methods, as is described for the corresponding methyl compounds in Bull. Soc. Chim. France 1974, 288.

134.5 g of 2-acetylamino-2'-carboxy-diphenylmethane (0.5 mole) are introduced into 340 ml of 100% strength sulfuric acid and, by means of cooling, the temperature is not allowed to rise above 40° C. The mixture is then warmed to 40° C for 3 hours, a dark green solution being obtained. For isolation, the mixture is discharged at 20° onto a mixture of 770 g of ice and water. After stirring briefly, the mixture is filtered. The sulfuric acid content in the filtrate is 43-44%. In order to remove the mother liquor, the residue is washed several times with small amounts of water until neutral. After drying, 123 g of 4-acetamino- anthrone are obtained.

134.5 g of 2-acetylamino-2'-carboxyl-diphenylmethane (0.5 mole) are introduced into 260 ml of 100% strength sulfuric acid and, by means of cooling, the temperature is not allowed to rise above 30° C. The mixture is then warmed to 30° C for 6 hours, a dark green solution being formed. For isolation, the mixture is discharged at 20° C onto a mixture of 570 g of ice and water. After stirring briefly, the mixture is filtered. The sulfuric acid content of the filtrate is 43%. In order to remove the bulk of the sulfuric acid, the residue is washed several times with small amounts of water. The paste is then introduced into 500 ml of water, while stirring, and the pH value of the mixture is adjusted to 8 with 10% strength sodium carbonate solution. The mixture is again filtered and the residue is washed once with water. After drying, 113 g of 4-acetamino- anthrone supplier are obtained.

Bianthrone compounds including those having halogen, lower alkyl and hydrogen substituents in the ring structure, are used to sensitize organic photoconductive systems so that they will respond to electromagnetic radiation in the visible portion of the spectrum. Typical of the sensitizers that can be used are 2,2'-dibromobianthrone and bianthrone.

This invention relates generally to sensitizers for organic photoconductive members, and in particular, relates to the addition of bianthrone-type compounds for the purpose of increasing the sensitivity range to electromagnetic radiation in the visible portion of the spectrum.

In the photoelectrostatic copying art, a recording member is prepared by applying a photoconductive layer to a conductive support. A large number of organic compounds are known to have utility in electrophotographic systems such as aromatic compounds which may include naphthalene, biphenyl, fluorene, anthracene, phenanthrene, acenaphthene, chrysene, diphenylamine, and carbazole; polymeric organic photoconductors which include polystyrenes, polyvinylxylenes, polyvinylcarbazoles, poly-α-vinylnaphthalene, polyindene and polycarbonates. In this art it is conventional to use polymeric-type organic photoconductors as well as monomeric materials with the former polymerizing to form a continuous film and the latter being dispersed in film forming binders. In their unsensitized condition, the organic photoconductive materials in most instances are known to have a rather slow response to electromagnetic radiation in the visible range, being more sensitive to radiation in the ultraviolet region of the spectrum.

In systems where the photoconductive material is in monomeric form and is dispersed into a resin binder solution, the bianthrone derivatives may be added directly up to 100 percent based on the weight of the organic photoconductive material.

Chlorobenzene has been found to be a suitable solvent for the bianthrones and its derivatives permitting concentration of sensitizer up to 10 percent by weight of the organic photoconductor.

The preferred sensitizers are the halogen and hydrogen substituted bianthrone compounds. However, excellent sensitizing effects are obtained using the alkyl and fluoro derivatives.

The combination of ingredients is thoroughly mixed so that in the case of the polymeric photoconductive systems complete and uniform solution occurs. In the case of dispersion the materials are ball milled for a period of approximately 24 hours to obtain uniform blending of all ingredients. The mixture is then applied to a suitable substrate having the proper conductivity by such known techniques as a meniscus coater or trailing-blade coater, applying a thin film of the coating solution or dispersion to the surface. The solvent is then evaporated by forced air drying by passing the coating web through a heated oven. It has been found that best results are obtained by applying the coating formulations at a rate such that the sheet on a dry basis has a photoconductive layer in the range of 0.1-1.0 mil thick, the preferred thickness being in the range of 0.2-0.5 mil thick.

Emodin anthrone, emodin bianthrone manufacturer , protohypericin, and hypericin may be synthesized from emodin according to the procedure identified in FIG. 1. Emodin anthrone is formed by reducing emodin with hydroiodic acid (HI) in glacial acetic acid, as described in Jacobson, R. A. and Adams, R., J. Amer. Chem. Soc., vol. 46, pp. 1312-16 (1924), which is incorporated herein by specific reference.

Emodin anthrone is dimerized to give the 10,10'-coupled bianthrones by reacting emodin anthrone with ferric chloride (FeCl 3 ) in ethanol, as described in Kinget, R., Planta. Med., vol. 15, pp. 233-39 (1967), which is also incorporated herein by specific reference. This reaction results in two diastereomers, the meso and the dl-pair. These compounds are readily separated on reverse phase high pressure liquid chromatography ("HPLC"). Subsequent oxidation of the bianthrones with oxygen in methanol containing triethylamine produces protohypericin, which is converted into hypericin upon exposure to sunlight. Alternatively air oxidation of the bianthrones in hot ammonium hydroxide and exposure to sunlight give rise to hypericin. The resulting compounds are characterized by HPLC, thin layer chromatography ("TLC"), and ultraviolet/visual spectrometry.

Initial screening of hypericin, protohypericin, emodin anthrone, and emodin bianthrones against HCMV in vitro demonstrate that hypericin, protohypericin, and the emodin bianthrones are active, but the emodin anthrone is not active. In addition, the compounds quinalizarin, rhein, alizarin, physcione, aloin, anthraquinone, chrysophanol, aloe-emodin, 1,8-dihydroxyanthraquinone, quinizarin, anthraflavic acid, purpurin, anthrarufin, and sennosides A & B have also been tested against HCMV. The chemical structures of these compounds are illustrated in FIG. 2. Emodin, emodin anthrone (active against DHPG resistant HCMV strain), emodin bianthrone (mixed, d,l, and meso), protohypericin, hypericin, rhein, alizarin, quinalizarin, quinizarin, and 1,8-dihydroxyanthraquinone show activity against HCMV.

Anthrone is produced by an intramolecular condensation of hydroanthraquinone such as tetrahydroanthraquinone or dihydroanthrahydroquinone by heating it in the absence of oxygen with or without an inert solvent.
A process for producing anthrone which consists essentially of intramolecularly condensing a hydroanthraquinone by heating said hydroanthraquione in vacuo or in the presence of an inert gas, and in the absence of oxygen, wherein said hydroanthraquinone is 1,4,4a,9a-tetrahydroaquinone or 1,4-dihydroanthrahydroquinone and wherein when said hydroanthraquinone is tetrahydroanthraquinone the reaction is effected at a temperature of higher than 200° C and when said hydroanthraquinone is dihydroanthrahydroquinone, the reaction is effected at a temperature of higher than 150° C.

1. Field of the Invention

The present invention relates to a novel process for producing anthrone which is useful as intermediates for dyes, photosensitizers, analytical reagents and other organic compounds. The anthrone is especially useful as intermediates for benzanthrone derivatives as dyes.

2. Description of the Prior Arts
 Anthrone has been produced by reducing anthraquinone with a mineral acid and a metal such as copper, aluminum, iron, zinc or tin. For example, it has been known that anthrone is produced by reducing anthraquinone with tin and hydrochloric acid in about 7 times of acetic acid in "Organic Syntheses Vol. 1 pages 60 to 61." It has been also known that anthrone is produced by reducing anthraquinone with copper or iron and sulfuric acid and anthrone is converted to benzanthrone.

These conventional processes for producing anthrone have industrial disadvantages that expensive anthraquinone is used as a raw material and a large amount of powdery metal and a mineral acid which are expensive and not easily post-treated should be used and 7 to 10 times of a solvent to the raw material should be used.

The inventors have studied to produce anthrones without such disadvantages.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide a process for producing anthrone without using expensive raw materials. It is another object of the present invention to provide a process for producing anthrone without a pollution of waste water caused by using powdery metal and a mineral acid as a reducing agent. The foregoing and other objects of the present invention have been attained by an intramolecular condensation of hydroanthraquinone especially tetrahydroanthraquinone or its isomer of dihydroanthrahydroquinone by heating it in the absence of oxygen with or without an inert solvent.

 Anthrone reaction is resulted by an intramolecular condensation of hydroanthraquinone such as 1,4,4a,9a-tetrahydroanthraquinone and 1,4-dihydroanthrahydroquinone under a dehydration by heating it in the absence of oxygen.

The hydroanthraquinones used as the starting material include tetrahydroanthraquinones (hereinafter referring to as THAQ) such as 1,4,4a,9a-THAQ and 1,2,3,4-THAQ and dihydroanthrahydroquinones (hereinafter referring to as DHAHQ) such as 1,4-DHAHQ and a mixture thereof and a mixture of 1,4,4a,5,8,8a,9a,10a-octahydroanthraquinone and dihydroanthraquinone and quinhydrone compounds.

It is preferable to use 1,4,4a,9a-tetrahydroanthraquinone (1,4,4a,9a-THAQ) or its isomer of 1,4-dihydroanthrahydroquinone (1,4-DHAHQ).

The 1,4,4a,9a-THAQ can be easily produced by Diels-Alder reaction of 1,4-naphthoquinone with butadiene. The 1,4-DHAHQ can be easily produced by an enolization of 1,4,4a,9a-THAQ with an acid or a base.

The reaction mechanism of the intramolecular condensation as anthronizing reaction is not clear though the general reactions are as follows.
It is preferable to use 1,4-DHAHQ in the absence of a solvent, a base, because the reaction velocity is high. However, the reaction velocity is enough high in the presence of a solvent with or without a base even though THAQ is used, because THAQ is converted to DHAHQ by the enolization.

The process of the present invention is carried out in the absence of a solvent. The starting material of DHAHQ or THAQ is charged in a reactor which can be uniformly and rapidly heated and which may equip with a stirrer. Air in the reactor is purged in vacuum or by substituting with an inert gas of nitrogen. The content is heated at suitable temperature for suitable time to attain the intramolecular condensation. After the reaction, the reaction mixture in the reactor contains anthrone and by-products of anthraquinone, anthracene and the unreacted materials of DHAHQ or THAQ and polymers thereof.

When the content of anthrone manufacturer   in the crude product is high, the crude product can be used as the raw material for the next reaction step such as the step of producing benzoanthrone. Anthrone can be separated by extracting with a solvent which does not dissolve the byproducts but dissolves anthrone such as an aromatic hydrocarbon e.g. benzene. Anthrone can be purified by a recrystallization.

In general, when the reaction temperature is higher, the reaction velocity for producing anthrone is increased but anthrone is further converted to the by-products. Accordingly, the reaction time should be short.

Oxygen should be removed from the reaction system because the starting materials are easily oxidized to form anthraquinone and the selectivity of anthrone product is decreased. When the oxygen content is quite small in the reaction system, it is considered to be absence of oxygen. The oxygen containing gas such as air in the reactor is removed by purging with an inert gas which is inert to the starting material and anthrone or by sucking in vacuum. The inert gas can be nitrogen, rare gas, carbon dioxide gas etc. and it is preferably nitrogen having high purity because of economical.

 

 

from:freepatentsonline

 The field of medicine as an important fine chemical industry has become over the past decade the focus of development and competitiveness, with the progress of science and technology, many Chinese medicine has been continuously developed for the benefit of humanity, these Chinese medicine relies on new synthesis of high-quality the production of pharmaceutical intermediates , new drugs are patent-protected, and not compatible with the existence of intermediate problems, so the new pharmaceutical intermediates and application of domestic and foreign markets are very optimistic about the prospects. Many new varieties of pharmaceutical intermediates, can not be fully introduced, this paper began to study in Taiwan in recent years, great concern a new type of pharmaceutical intermediates and pharmaceutical intermediates for a number of important new technology.

1 - (6 - methoxy -2 - naphthyl) ethanol

Non-steroidal anti-inflammatory drug naproxen a variety of synthesis methods, including carbonylation of highly selective synthetic route, environmental friendliness, the carbonylation synthesis of non-steroidal anti-inflammatory drugs is superior to the traditional route. Carbonylation naproxen is the key intermediate 1 - (6 - methoxy -2 - naphthyl) ethanol.

4 - C S-o-phenylenediamine
O-p-nitroaniline as the raw material, and sodium thiocyanate in the presence of methanol, after sulfur cyanide, n-propyl bromide has been replaced by 4 - S-C -2 - p-nitroaniline, and then reduction of 4 - C o-S diamine, as a result of 4 - S-C -2 - nitroaniline structure of S-containing C, so the reduced 4 - C S-o-phenylenediamine is one of the key to study abroad, nickel or platinum group metal-catalyzed hydrogenation technology as a catalyst poisoning or C S-easy to easy to damage and difficult to industrialization; and hydrazine hydrate easily restore explosion; therefore the most suitable for industrial production to synthesis of sodium reduction, although the salt water would produce a certain, but the technology can be *. The research was also reported reduction of carbon monoxide catalyst, but there are distance from the industrialization.

α-methylene ketones

4,4 ‘- dimethoxy-N-methyl acetate

4,4 ‘- dimethoxy-N-methyl acetate is an important cardiovascular and cerebrovascular diseases Nimodipine treatment of the intermediate cutting Niger, Nigeria cutting horizon is the development of Japan’s Fujisawa Pharmaceutical Company, listed in 1989 the second generation of calcium antagonist, is currently the international market dominated by cardiovascular and cerebrovascular disease treatment, there is no domestic production. To glyoxylic acid as raw materials and trimethyl orthoformate in the presence of concentrated sulfuric acid has been synthesized dimethoxy methyl acetate, the latter with methyl acetate, methanol reaction of sodium 4,4 ‘- dimethoxy-N - methyl acetate.

C3-chloro-cephalosporin acid

C3-chloro-cephalosporin acid is an pharmaceutical intermediates cephalosporin cefaclor, cefaclor by the United States developed by Eli Lilly and efficient second-generation oral cephalosporins, because of its apparent efficacy and advantages of oral , in the United States in 2001 sales 8000 million yuan, ranking the second antibiotic. C3-chloro-cephalosporin acid synthesis, there are two routes, 1) is a salt of penicillin G after oxidation, esterification, ring expansion, reduction, oxidation, reduction, oxidation, to acetyl-, hydrolysis and other multi-step synthesis, too many steps , the yield is low; 2) is 7 - amino-cephalosporin acid (7-ACA) as raw materials ,7-ACA in 3 - position of the nuclear transformation of the mother, due to its 7 - bit amino and 4 - carboxy-bit activity high, it is first necessary to protect, 4 - carboxy-protection methods used to produce tert-butyl, diphenylmethyl ester and nitro-benzyl ester; 7 - amino-phenoxy protection may be methyl, benzyl, as well as the top three silyl chloride, such as silylated reagents protection. Followed by nucleophilic substitution and redox reactions, first of all, through the sulfur nucleophiles, such as ethyl xanthate, thiourea or thiol acid of cephalosporin for nucleophilic substitution of ethoxy groups, re-use of nickel as a catalyst for hydrogenation restore the generation of 3 - Central District acid methylene cephalosporins; double bond outside the ring and then proceed to the oxidation and reduction, the general choice of oxidant ozone, the key to control the depth of oxidation, reducing agent are used bisulfite, dimethyl sulfide Sulfur dioxide and trimethyl phosphate, etc.; The third step is chlorinated, from the protection of the base and the hydrolysis reaction, the use of chlorination agent SOCl2, PCl3, POCl3, COCl3 or solid phosgene, etc., can be chlorinated, from acid hydrolysis step has been completed C3l chlorophthalic acid cephalosporin nucleus.

 2 - one tetralin
2 - one tetralin LCD mainly for medicine and industry, strong demand at home and abroad in recent years, the conventional synthetic route is to replace the acid as raw materials with thionyl chloride to form chloride, allyl chloride and to acid cyclization reaction and the synthesis of 2 - keto tetralin, which is not the existence of economic and shortcomings, such as solvent recovery is not easy; recently developed a new type of domestic one-pot acylation using trifluoro acetic anhydride / phosphoric acid catalyst system, by to replace the acid to react with ethylene, the reaction process may be trifluoroacetic acid trifluoro acetic anhydride into direct recycling, and less corrosion of equipment, very prospect.

N-benzyl–N-methyl diethanolamine

N-benzyl–N-methyl-ethanolamine is an important pharmaceutical intermediates , anti-asthma and can be synthesized antiallergic, anti-hypertension drug nicardipine and some new drug treatment of cardiovascular diseases; synthetic pesticides can also herbicides, plant disinfection agents and preservatives, such as metal. N-benzyl–N-methyl-ethanolamine synthesis of three routes, 1) is N-benzyl–N-methyl-amine and ethylene oxide reaction; 2) is N-benzyl–N-methyl amine and chlorine low-temperature reaction of ethanol; 3) 2 - benzyl ethanol amine and poly-formaldehyde, formic acid mixture, heating reaction, and then to deal with excess sodium hydroxide, ether isomers and benzene used for extraction.

 

 

from:chemz

Flu refers to illnesses caused by a number of different influenza viruses. Flu can cause a range of symptoms and effects, from mild to lethal.
Two strains of flu, seasonal flu and the H1N1 (Swine) flu, are currently circulating in the United States. A third, highly lethal H5N1 (Bird) flu is being closely tracked overseas.
Most healthy people recover from the flu without problems, but certain people are at high risk for serious complications.

Extensive efforts are underway to track and monitor the spread of all flu viruses. In the U.S., epidemiologists at the Centers for Disease Control (CDC) are working with states to collect, compile and analyze reports of flu outbreaks. More on the current situation.
Flu symptoms may include fever, coughing, sore throat, runny or stuffy nose, headaches, body aches, chills and fatigue. In H1N1 flu infection, vomiting and diarrhea may also occur.
Annual outbreaks of the seasonal flu usually occur during the late fall through early spring. Most people have natural immunity, and a seasonal flu vaccine is available. In a typical year, approximately 5 to 20 percent of the population gets the seasonal flu and approximately 36,000 flu-related deaths are reported.

 

 

 

 

 

This year, the H1N1 flu virus(Pharmaceutical Intermediates ) may cause a more dangerous flu season with a lot more people getting sick, being hospitalized and dying than during a regular flu season. H1N1 is a new virus first seen in the United States. It is contagious and spreads from person to person. Like seasonal flu, illness in people with H1N1 can vary from mild to severe.

A flu pandemic occurs when a new influenza A virus emerges for which there is little or no immunity in the human population; the virus causes serious illness and spreads easily from person-to-person worldwide. On June 11, 2009, the World Health Organization  (WHO) declared that a global pandemic of H1N1 flu is underway.

H5N1 (Bird) flu is an influenza A virus subtype that is highly contagious among birds. Rare human infections with the H5N1 (Bird) flu virus have occurred. The majority of confirmed cases have occurred in Asia, Africa, the Pacific, Europe and the Near East. Currently, the United States has no confirmed human H5N1 (Bird) flu infections, but H5N1 (Bird) flu remains a serious concern with the potential to cause a deadly pandemic.

 

 

from:timepharm

Zidovudine or azidothymidine (AZT) is Pharmaceutical Intermediates , the first approved for treatment of HIV. Zidovudine was the first drug approved for the treatment of AIDS and HIV infection. Like other reverse transcriptase inhibitors, AZT works by inhibiting the action of reverse transcriptase, the enzyme that HIV uses to make a DNA copy of its RNA. The viral double-stranded DNA is subsequently spliced into the DNA of a target cell, where it is called a provirus. Jerome Horwitz of Barbara Ann Karmanos Cancer Institute and Wayne State University School of Medicine first synthesized AZT in 1964, under a US National Institutes of Health (NIH) grant.

It was originally intended to anti-live cancer , but failed to show efficacy and had an unacceptably high side effect profile. In 1985, when Samuel Broder, Hiroaki Mitsuya, and Robert Yarchoan, three scientists in the National Cancer Institute (NCI), collaborating with Janet Rideout and several other scientists at Burroughs Wellcome (now GlaxoSmithKline), started working on it as an AIDS drug . After showing that this drug was an effective agent against HIV in vitro, the team conducted the initial clinical trial that provided evidence that it could increase CD4 counts in AIDS patients.

AZT does not destroy the HIV infection, but only delays the progression of the disease and the replication of virus, even at very high doses. During prolonged AZT treatment HIV has the ability to gain an increased resistance to AZT by mutation of the reverse transcriptase. A study showed that AZT could not impede the resumption of virus production, and eventually cells treated with AZT produced viruses as much as the untreated cells. So as to slow the development of resistance, it is generally recommended that AZT be given in combination with another reverse transcriptase inhibitor and an antiretroviral from another group, such as a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor.

AZT may be used in combination with other antiretroviral medications to substantially reduce the risk of HIV infection following a significant exposure to the virus (such as a needle-stick injury involving blood or body fluids from an individual known to be infected with HIV). AZT is also recommended as part of a regimen to prevent mother-to-child transmission of HIV during pregnancy, labor and delivery. With no treatment, approximately 25% of infants whose mothers are infected with HIV will become infected.

AZT has been shown to reduce this risk to approximately 8% when given in a three-part regimen during pregnancy, delivery and to the infant for 6 weeks after birth. Use of appropriate combinations of antiretroviral medications and cesarean section when necessary can further reduce mother-child transmission of HIV to 1-2%. Common side effects of AZT include nausea, headache, changes in body fat, and discoloration of fingernails and toenails. More severe side effects include anaemia and bone marrow suppression. These unwanted side effects might be caused by the sensitivity of the γ-DNA polymerase in the cell mitochondria. AZT has been shown to work additively or synergistically with many anti-HIV agents; however, acyclovir and ribavirin decrease the antiviral effect of AZT.
Formal Chemical Name (IUPAC)
1-((2R,4S,5S)-4-azido-5-(hydroxymethyl)tetrahydrofuran-2-yl)-5-methylpyrimidine-2,4(1H,3H)-dione

 

 

from:timepharm

An enzyme that normally helps break down stored fats becomes highly active in some cancer cells and makes them more likely to spread, researchers have found.

When the enzyme, called monoacylglycerol lipase (MAGL), goes into overdrive in cancer cells, it breaks down stored fats to produce large amounts of free fatty acids, which are the building blocks of cell membranes and of fatty molecules that serve as signals between cells. These free fatty acids then produce other smaller molecules that promote cancer growth and progression, the study authors noted.
The finding that stored fats in cancer cells can cause them to become more aggressive offers a possible explanation for the reported link between obesity and cancer, according to the researchers at the Scripps Research Institute in California. They also said MAGL may offer a new target for treating aggressive forms of cancer or for preventing cancer progression.

“Historically, research has focused on the mechanisms leading to cancer formation, and therapies have focused on taking out cancer cells. But here we were looking for pathways that lead to cancer aggressiveness,” corresponding author Benjamin Cravatt, chair of the Scripps Research Department of Chemical Physiology, said in a news release.

He noted that people who eat high-fat foods are constantly introducing free fatty acids into their bodies.
“We have shown that cancer cells have their own pathways to produce free fatty acids, which will enable them to become more aggressive. Less malignant cancer cells do not appear to have adopted an autonomous pathway to increase their own pools of free fatty acids. Thus, taking free fatty acids from the diet could assist these cells in developing a more malignant phenotype,” Cravatt said.
The study was published in the Jan. 8 issue of the journal Cell.

 

N-Acetyl-D-glactosamine      CAS: 1811-31-0

 

 

from:timepharm|anti cancer

 

The human immunodeficiency virus (HIV) attacks the body's immune system. A healthy immune system is what keeps you from getting sick.
Because HIV damages your immune system, you are more likely to get sick from bacteria and viruses. It is also harder for your body to fight off these infections when you do get them, so you may have trouble getter better. HIV is the condition that causes acquired immunodeficiency syndrome (AIDS ).

HIV can only be passed from person to person through body fluids, such blood, semen and vaginal fluid. Children born to infected mothers can also become infected during pregnancy. The most common ways HIV is passed are:
1.By having unprotected anal, vaginal or oral sex with an infected person.
2.By sharing needles and syringes for injecting drugs with an infected person.

What happens after a person gets HIV?
After being infected with HIV, your body works hard to attack the virus. With your body fighting, the virus can't make as many copies of itself. Even though you still have HIV, you'll begin to look well and feel well again. The usual blood tests will be normal.

However, during this time, the virus is still attacking your lymph nodes. Lymph nodes are the centers of your body's immune system. The virus may also attack your brain tissue and slowly cause damage there.
Over 10 to 15 years, HIV kills so many CD4 cells that your body can no longer fight off infections. When your CD4 cell count is 200 or less per mL, you have AIDS (a normal count is 600 to 1000). Once you have AIDS (which stands for acquired immunodeficiency syndrome), you can easily catch many serious infections.

Now, Here will introduce  4-Nitrophenyl Chloroformate (CAS:7693-46-1 ) to you.

 

This is used as a pharmaceutical Intermediates of anti-HIV. If you are interested in this pharmaceutical Intermediates, you can have more information at www.timepharm.com .

 

from:News|timepharm

A novel beta-cyclodextrin dimer, 1,10-phenanthroline-2,9-dimethyl-bridged-bis(6-monoammonio-beta-cyclodextrin) (phenBisCD, L), was synthesized. Its zinc complex (ZnL) has been prepared, characterized, and applied as a new catalyst for diester hydrolysis. The formation constant (logK(ML)=9.56+/-0.01) of the complex and deprotonation constant (pK(a)=8.18+/-0.04) of the coordinated water molecule were determined by a potentiometric pH titration at (298+/-0.1) K. Hydrolytic kinetics of carboxylic acid esters were performed with Bis(4-nitrophenyl) carbonate HPLC 99%   (BNPC) and 4-nitrophenyl acetate (NA) as substrates. The obtained hydrolysis rate constants showed that ZnL has a very high rate of catalysis for BNPC hydrolysis, giving a 3.89x10(4)-fold rate enhancement over uncatalyzed hydrolysis at pH 7.01, relative to only a 42-fold rate enhancement for NA hydrolysis. Moreover, the hydrolysis second-order rate constants of both BNPC and NA greatly increases with pH. Hydrolytic kinetics of a phosphate diester catalyzed by ZnL was also investigated by using bis(4-nitrophenyl) phosphate (BNPP) as the substrate. The pH dependence of the BNPP cleavage in aqueous buffer shows a sigmoidal curve with an inflection point around pH 8.11, which was nearly identical to the pK(a) value from the potentiometric titration. The k(cat) of BNPP hydrolysis promoted by ZnL was found to be 9.9x10(-4) M(-1) s(-1), which is comparatively higher than most other reported Zn(II)-based systems. The possible intermediate for the hydrolysis of BNPP, Bis(4-nitrophenyl) carbonate HPLC 99%, and NA catalyzed by ZnL is proposed on the basis of kinetic and thermodynamic analysis.

Description: Bis(4-Nitrophenyl) Carbonate
Synonym: Bis(p-Nitrophenyl) Carbonate; p,p'-Dinitrodiphenylcarbonate
CAS: 5070-13-3
Assay: ≥99% (HPLC)
Appearance: white to off-white solid
Molecular: C13H8N2O7
Application: Anti-HIV as Pharmaceutical Intermediates

 

Organocatalysis uses small organic molecules predominantly composed of C, H, O, N, S and P to accelerate chemical reactions. The advantages of organocatalysts include their lack of sensitivity to moisture and oxygen, their ready availability, low cost, and low toxicity, which confers a huge direct benefit in the production of pharmaceutical intermediates when compared with (transition) metal catalysts.

In the example of the N-BOC-4-Hydroxypiperidine,it is believed that piperidine forms a reactive iminium ion intermediate with the carbonyl compound:

Description: N-BOC-4-Hydroxypiperidine
Synonym: N-(Tert-Butoxycarbonyl)-4-Hydroxypiperidine
CAS: 109384-19-2
Assay: ≥98% (GC)
Appearance: white or off-white  powder
Molecular:  C10H19NO3
Application: Pharmaceutical Intermediates