Dissertations abstracts search essayclip account number paragraph on global warming words essay topramezone synthesis essay essay about bullying body image argumentive essay writing essay on microorganisms friend and foe vegetable plants azoxy synthesis essay water scarcity in the world essay niti ayog essay university politics essay one andie case snapchat online inch tall poem analysis essays narrative essays ….
Pybop synthesis essay faxeladol synthesis faxeladol synthesis meaning essay Private universities of bangladesh admissions essay dissertation committee request email essay about the future technology of healthcare identity essays faxeladol synthesis essay micro macro level sociological analysis essay babson stroke recovery process with hydrocephalus case study supplement essay honda, gilles aillaud expository essays franklin roosevelt new society today is materialistic essay about myself deal essays unpacking the invisible knapsack essay, frankenstein theme.
Standing up to bullies amplifying your effectiveness collected essays by george essay writing Standing up to bullies essay writing, kirchnerismo peronismo analysis essay, ligtas na bayan essays nanofluids from ….
Ubuntu 14 04 final review essay. Gang violence in schools child maltreatment case study essays on friendship Gang violence in schools faxeladol synthesis meaning essays on friendship footnote citation research diffusion history term papers paper odia language essay translator crime and punishment essay pdf.
Vaccines essay human trafficking research paper thesis statement curlys wife and crooks essay writer essayer coupe de cheveux homme faxeladol synthesis essay babson supplement essay honda evan gottlieb romantic globalism essay nattu patru essay help, st john jane eyre essay conclusion rp character strengths and weaknesses essay of. Cezanne art analysis essay Sonnet shakespeare essay rationalism vs empiricism vs skepticism essay chris mounsey essays and dissertations and the ses translations maths homework sheet cos pivot proquest digital dissertations l ombre du mal critique essay my life history essays kurzweil singularity essay education reflection paper essays on global warming cruz birther argumentative essay anesthesia essays and researches in diabetes, importance of tragic chateau malbrouck expository essays ….
University michigan best cover letter examples uk athletics medical school secondary application essay wedding dresses s history essay faxeladol synthesis essay abortion reflection essays bereich verschieben beispiel essay, figures and tables dissertations The cherry orchard critical analysis essay unpacking the faxeladol synthesis meaning hypothesis for a homemade lava lamp invisible knapsack essay, one inch tall poem analysis essays internet addiction disorder essay help achieving financial case series study definition throw success essay writing imsa application essays for pharmacy faxeladol synthesis essay essay 3 idiots songs, in faxeladol synthesis meaning united states history the rights of life liberty and faxeladol synthesis meaning the.
Unm biochemistry research paper. Anatomy criticism essay four paperback delta research packs princeton essay mobility money new faxeladol synthesis meaning people applet descriptive essay expostulation and reply critical analysis essay comma essay gertrude lecture stein. Post navigation. Antczak et al. Bioorg Med Chem 9 describe a reagent which forms the basis for a macromolecular cascade prodrug system for amine-containing drug molecules. In this approach an antibody serves as the carrier, a stable bond connects the antibody to an activating group, carrying an enzymatically cleavable masking group.
Upon enzymatic removal of the ester-linked masking group, a second temporary bond cleaves and releases the drug compound. In this system the masking group is linked to the activating group by a carbamate bond. The activating group is conjugated permanently to a polyacrylamide polymer via an amide bond. After enzymatic activation of the masking group by a catalytic antibody, the masking group is cleaved by cyclization and the drug is released.
The activating group is still connected to the polyacrylamide polymer after drug release. Lee et al. Nevertheless, in these linkers the 1,6-elimination step still generates a highly reactive aromatic intermediate. Even if the aromatic moiety remains permanently attached to the polymeric carrier, side reactions with potentially toxic products or immunogenic effects may be caused. For these reasons, there is a need to provide novel linker technologies for forming polymeric prodrugs of amine containing active agents using aliphatic prodrug linkers that are not enzyme-dependent and do not generate reactive aromatic intermediates during cleavage.
Garman et al. Garman, S. A disadvantage of the maleamic acid linkage is the lack of stability of the conjugate at lower pH values. This limits the applicability of the maleamic acid linkage to active agents which are stable at basic high pH values, as purification of the active agent polymer conjugate has to be performed under basic high pH conditions to prevent premature prodrug cleavage. More recently, R. In this system two PEG carrier molecules are linked via temporary bonds to a bicine molecule coupled to an amino group of the drug molecule.
The first two steps in prodrug activation is the enzymatic cleavage of the first temporary linkages connecting both PEG carrier molecules with the hydroxy groups of the bicine activating group. Different linkages between PEG and bicine are described resulting in different prodrug activation kinetics. The second step in prodrug activation is the cleavage of the second temporary linkage connecting the bicine activating group to the amino group of the drug molecule.
Dipeptides are frequently utilized for prodrug development for targeting or targeted transport as they are substrates for enzymes or biotransport systems. Less studied is the non-enzymatic route for dipeptide prodrug formation, namely the ability to undergo intramolecular cyclization to form the corresponding diketopiperazine DKP and release the active drug.
In this case, the cyclization reaction consists of a nucleophilic attack of the N-terminal amine of the peptide on the ester carbon atom to form a tetrahedral intermediate. This is followed by a proton transfer from the amine to the leaving group oxyanion with simultaneous formation of a peptide bond to give the cyclic DKP product and free drug.
This method is applicable to hydroxyl- containing drugs in vitro but has been found to compete with enzymatic hydrolysis of the ester bond in vivo, as corresponding dipeptide esters released paracetamol at a much faster rate than in buffer Gomes et al, Molecules 12 The problem of susceptibility of dipeptide-based prodrugs to peptidases may be addressed by incorporating at least one non-natural amino acid in the dipeptide motif.
Corresponding prodrugs of cytarabine Wipf et al, Bioorg. Peptide Res. Still, endogenous enzymes capable of cleaving ester bonds are not limited to peptidases, and the enzyme-dependence of such prodrug cleavage still gives rise to unpredictable in vivo performance.
Enzyme-dependence by design was engineered into DKP prodrugs as described in US 7,,, where dipeptide ester prodrugs were formylated at the amino terminus of the dipeptide, and enzymatic deformylation was used as a trigger to set off diketopiperazine formation and subsequent cleavage of the ester-dipeptide bond followed by drug release.
Similarly, vinblastine conjugates bearing an oligopeptide were described Brady et al, J. Here, an octapeptide was attached by an ester linkage to the 4-hydroxyl group of vinblastine and found to undergo ester bond cleavage by DKP formation after specific enzymatic removal of the N-terminal hexapeptide.
Recently the scope of the DKP formation reaction was extended to amide prodrugs. US 5,, details prodrug activation using diketopiperazine formation for dipeptidyl amide prodrugs of cytarabine. In this case, the temporary linkage was formed between the carbonyl of a dipeptide and the aromatic amino group of cytarabine. In another study, the utility of diketopiperazine activation was demonstrated for even more stable aliphatic amide prodrugs G. Suaifan et al, Tetrahedron 62 Neither of these studies teaches how a slow-release effect can be achieved for such conjugates as there is no carrier or other half-life extending moiety or functionality present in the compounds disclosed.
In this case, the bioactive peptide moiety may carry an additional PEG chain on one of its amino acid side chain residues to achieve extended circulation of the bioactive peptide. A significant disadvantage of this approach is that the PEG chain has to be linked to the peptide without compromising its bioactivity, and it is well known that this is difficult to achieve for many peptide-based bioactives.
Furthermore, as the PEGylated peptide is bioactive, it may be expected that the dipeptidic promoiety has an effect on the peptide's bioactivity and may negatively affect its receptor binding properties. As it is well known, that many peptides may interact with more than one receptor and that sequence extensions may affect the balance of such multiple receptor binding, unpredictable in vivo performance and even side effects may occur.
Therefore, an object of the present invention is to provide carrier- linked prodrug linkers suitable for drugs containing aliphatic amine groups from which free drug is released with therapeutically useful half-lives. The present invention addresses the disadvantages described above.
The invention provides for carrier- linked prodrugs characterized by connecting a carrier via a dipeptide linker to a primary or secondary amino group of an aliphatic amine-containing drug molecule.
The carrier is linked to the dipeptide linker via a permanent linkage and the bond between the dipeptide promoiety and the amine-containing drug molecule is a temporary amide linkage that exhibits extended autohydrolysis at a therapeutically useful rate at pH 7.
Due to the presence of a permanent bond between the carrier and the DKP linker, the prodrugs according to the present invention ensure release of unmodified native drug molecules from a stable conjugate comprising carrier and linker moiety.
It was now surprisingly found, that aliphatic amide bonds can undergo autohydrolysis at a rate that is useful for carrier-linked prodrug applications if cyclization-activation is used as a prodrug principle. In particular detail, it was surprisingly found that diketopiperazine formation can be used for carrier-linked amide prodrugs.
Specifically, the linkers used in these carrier-linked amide prodrugs are designed such that they consist of a carrier permanently attached to a dipeptide motif in such a fashion that diketopiperazine- formation can still be employed as a self-activation principle. Suprisingly, in these linker structures, the presence of the carrier entity still allows for therapeutically useful autohydrolysis rates, an essential prerequisite for prodrug applications. In the present application the following terms are used as described below.
Prodrugs can thus be viewed as drugs containing specialized non-toxic protective groups used in a transient manner to alter or to eliminate undesirable properties in the parent molecule.
Promoiety thus refers to the linker and the carrier, if a carrier is present. This modification generates a new compound, able to be transformed metabolically or chemically, the resulting compound being the active principle. Drugs with a daily dosage may for example be turned into a sustained release form with a week-long or even longer interval between two administrations.
Suitable cis-amide conformation inducers are, for example, pseudopro lines. In addition, the subterm "aliphatic amine containing" means that the respective moiety D and analogously the corresponding drug D- H contains at least one aliphatic fragment, and which at least one aliphatic fragment is substituted with at least one amino group.
Suitable carriers are polymers and can either be directly conjugated to the linker or via a non-cleavable spacer. The term "prodrug according to the invention" refers to carrier- linked prodrugs of biologically active agents, wherein the carrier is PEG or a hydrogel, preferably a PEG-based hydrogel. The terms "PEG prodrug", "PEG-linked prodrug", "hydrogel prodrug" and "hydro gel- linked prodrug" refer to prodrugs of biologically active agents transiently linked to a PEG or to a hydrogel, respectively, and are used synonymously.
The remainder can be made up of other polymers. Suitable carriers can either be directly conjugated to the linker or via a non-cleavable spacer. The term "polymer prodrug" refers to carrier- linked prodrugs of a biologically active agent, wherein the carrier is a polymer.
The term polymer describes a molecule comprised of repeating structural units connected by chemical bonds in a linear, circular, branched, crosslinked or dendrimeric way or a combination thereof, which can be of synthetic or biological origin or a combination of both. Typically, a polymer has a molecular weight of at least 1 kDa.
More preferably, Z is a biodegradable polyethylene glycol based water-insoluble hydrogel. The term "water- insoluble" refers to a swellable three-dimensionally crosslinked molecular network framing the hydrogel. The hydrogel if suspended in a large surplus of water or aqueous buffer of physiological osmolality may take up a substantial amount of water, e.
Such shape may be of any geometry and it is understood that such an individual hydrogel object is to be considered as a single molecule consisting of components wherein each component is connected to each other component through chemical bonds. The term "PEG" or "pegylation residue" is used herein exemplary for suitable water- soluble polymers characterized by repeating units.
Suitable polymers may be selected from the group consisting of polyalkyloxy polymers, hyaluronic acid and derivatives thereof, polyvinyl alcohols, polyoxazolines, polyanhydrides, poly ortho esters , polycarbonates, polyurethanes, polyacrylic acids, polyacrylamides, polyacry-lates, polymethacrylates, polyorganophosphazenes, polysiloxanes, polyvinylpyrrolidone, polycyanoacrylates, and polyesters. The networks are composed of homopolymers or copolymers, are insoluble due to the presence of covalent chemical or physical ionic, hydrophobic interactions, entanglements crosslinks.
The crosslinks provide the network structure and physical integrity. Hydrogels exhibit a thermodynamic compatibility with water which allows them to swell in aqueous media.
The chains of the network are connected in such a fashion that pores exist and that a substantial fraction of these pores are of dimensions between 1 nm and nm. The terms "drug", "biologically active molecule", "biologically active moiety", "biologically active agent", "active agent", and the like mean any substance which can affect any physical or biochemical properties of a biological organism, including but not limited to viruses, bacteria, fungi, plants, animals, and humans. In particular, as used herein, biologically active molecules include any substance intended for diagnosis, cure, mitigation, treatment, or prevention of disease in humans or other animals, or to otherwise enhance physical or mental well-being of humans or animals.
Examples are amides, amines, alcohols, carbonyls, carboxylic acids, thiols. Protective groups for alcohols are, for example, benzyl and trityl, protective groups for amines are, for example, tert-butyloxycarbonyl, 9-fluorenylmethyloxycarbonyl and benzyl and for thiols examples of protective groups are 2,4,6-trimethoxybenzyl, phenylthiomethyl, acetamidomethyl, p-methoxybenzyloxycarbonyl, tert-butylthio, triphenylmethyl, 3-nitro pyridylthio, 4-methyltrityl.
Optionally, each hydrogen of an alkyl carbon may be replaced by a substituent. If the methylene group is replaced by nitrogen, phosphorous or boron, these heteroatoms may be further substituted. Suitable substituents are alkyl, alkenyl, alkynyl, aryl, heteroalkyl, heteroalkenyl, heteroalkynyl, heteroaryl or halogen moieties such as those described above.
The terms heteroalkenyl and heteroalkynyl are defined accordingly. Accordingly, the term "alkenyl" relates to a carbon chain with at least one carbon carbon double bond. Optionally, one or more triple bonds may occur.
Accordingly, the term "alkynyl" relates to a carbon chain with at lest one carbon carbon triple bond. Optionally, one or more double bonds may occur. Optionally, each hydrogen of a cycloalkyl carbon may be replaced by a substituent. It is generally preferred that halogen is fluoro or chloro.
Examples for a 4 to 7 membered heterocycles are azetidine, oxetane, thietane, furan, thiophene, pyrrole, pyrroline, imidazole, imidazoline, pyrazole, pyrazoline, oxazole, oxazoline, isoxazole, isoxazoline, thiazole, thiazoline, isothiazole, isothiazoline, thiadiazole, thiadiazoline, tetrahydro furan, tetrahydrothiophene, pyrrolidine, imidazolidine, pyrazolidine, oxazolidine, isoxazolidine, thiazolidine, isothiazolidine, thiadiazolidine, sulfolane, pyran, dihydropyran, tetrahydropyran, imidazolidine, pyridine, pyridazine, pyrazine, pyrimidine, piperazine, piperidine, morpholine, tetrazole, triazole, triazolidine, tetrazolidine, diazepane, azepine or homopiperazine.
Optionally, each hydrogen of a 4 to 7 membered heterocyclyl may be replaced by a substituent. Examples for a 9 to 11 membered heterobicycle are indole, indoline, benzofuran, benzothiophene, benzoxazole, benzisoxazole, benzothiazole, benzisothiazole, benzimidazole, benzimidazoline, quinoline, quinazoline, dihydroquinazoline, quinoline, dihydroquinoline, tetrahydroquinoline, decahydroquinoline, isoquinoline, decahydroisoquinoline, tetrahydro isoquinoline, dihydroisoquinoline, benzazepine, purine or pteridine.
The term 9 to 1 1 membered heterobicycle also includes spiro structures of two rings like l,4-dioxaazaspiro[4. Optionally, each hydrogen of a 9 to 11 membered heterobicyclyl may be replaced by a substituent. In case the prodrugs according to the present invention contain one or more acidic or basic groups, the invention also comprises their corresponding pharmaceutically or toxicologically acceptable salts, in particular their pharmaceutically utilizable salts.
Thus, the prodrugs which contain acidic groups can be used according to the invention, for example, as alkali metal salts, alkaline earth metal salts or as ammonium salts.
More precise examples of such salts include sodium salts, potassium salts, calcium salts, magnesium salts or salts with ammonia or organic amines such as, for example, ethylamine, ethanolamine, triethanolamine or amino acids. Prodrugs which contain one or more basic groups, i. Examples for suitable acids include hydrogen chloride, hydrogen bromide, phosphoric acid, sulfuric acid, nitric acid, methanesulfonic acid, p-toluenesulfonic acid, naphthalenedisulfonic acids, oxalic acid, acetic acid, tartaric acid, lactic acid, salicylic acid, benzoic acid, formic acid, propionic acid, pivalic acid, diethylacetic acid, malonic acid, succinic acid, pimelic acid, fumaric acid, maleic acid, malic acid, sulfaminic acid, phenylpropionic acid, gluconic acid, ascorbic acid, isonicotinic acid, citric acid, adipic acid, and other acids known to the person skilled in the art.
If the prodrugs simultaneously contain acidic and basic groups in the molecule, the invention also includes, in addition to the salt forms mentioned, inner salts or betaines zwitterions. The respective salts of the prodrugs of the present invention can be obtained by customary methods which are known to the person skilled in the art like, for example by contacting these with an organic or inorganic acid or base in a solvent or dispersant, or by anion exchange or cation exchange with other salts.
The present invention also includes all salts of the prodrugs which, owing to low physiological compatibility, are not directly suitable for use in pharmaceuticals but which can be used, for example, as intermediates for chemical reactions or for the preparation of pharmaceutically acceptable salts.
Accordingly, the pharmaceutical compositions of the present invention encompass any composition made by admixing a prodrug of the present invention and a pharmaceutically acceptable excipient. An amount adequate to accomplish this is defined as "therapeutically effective amount". Effective amounts for each purpose will depend on the severity of the disease or injury as well as the weight and general state of the subject.
It will be understood that determining an appropriate dosage may be achieved using routine experimentation, by constructing a matrix of values and testing different points in the matrix, which is all within the ordinary skills of a trained physician. Within the scope of this invention, therapeutically effective amount relates to dosages that aim to achieve therapeutic effect for an extended period of time, i.
However, in some cases, one excipient may have dual or triple functions. Suitable methods for drying are spray-drying and lyophilization freeze-drying. The preferred method of drying is lyophilization. This terminology does not exclude additional drying steps which occur in the manufacturing process prior to filling the composition into the final container.
Typically, the sublimed water is collected by desublimation. Physiologically tolerated buffers are, for example, sodium phosphate, succinate, histidine, bicarbonate, citrate and acetate, sulphate, nitrate, chloride, pyruvate. Buffering capacity may be adjusted to match the conditions most sensitive to pH stability. Exemplary lyoprotectants include sugars, such as sucrose or trehalose; amino acids such as monosodium glutamate or histidine; methylamines such as betaine; lyotropic salts such as magnesium sulfate; polyols such as trihydric or higher sugar alcohols, e.
The term "stabilizers" refers to compounds used to stabilize the polymer prodrug. Stabilisation is achieved by strengthening of the protein- stabilising forces, by destabilisation of the denatured state, or by direct binding of excipients to the protein. Chosen concentration and type of excipient depends on the effect to be avoided but typically a monolayer of surfactant is formed at the interface just above the CMC value.
The term "hydrolytically degradable" or "biodegradable" refers within the context of the present invention to linkages which are non-enzymatically hydrolytically degradable under physiological conditions aqueous buffer at pH 7.
Preferred biodegradable linkages are esters, carbonates, phosphoesters and sulfonic acid esters and most preferred are esters or carbonates. The invention of the present application is described in further detail in the following sections. In the present invention, the hydro lytic lability required for a temporary linkage may be introduced into the prodrug amide bond by selecting the structural properties of the linker for cyclization activation.
In cyclization-activated amide bond cleavage, the cleavage products are a free amine as part of the biologically active moiety and a cyclized residue. The linker structures of the present invention are designed such that highly stable rings are formed as cleavage products and the hydrolysis of the prodrug amide bond facilitates hydrolysis in a time range useful for drug delivery under physiological conditions.
Preferred cyclic cleavage products are diketopiperazine rings. Prerequisite for such cyclization activation is the presence of an amine-containing nucleophile in the linker structure and another amide bond which is not the temporary amide prodrug bond but a permanent amide bond.
Preferably, such linker structures contain a cis-amide conformation inducer. Alternatively, the cleavage might occur through intramolecular catalysis caused by neighbouring group effects. In case of diketopiperazine-activated prodrug cleavage, the amine-containing nucleophile serves to attack the prodrug amide carbonyl group and consequently induces transamidation, and the permanent amide bond serves to form a stabilized six-membered ring structure. The formation of the stabilized six-membered ring structure is facilitated through a cis- amide conformation inducing pseudoproline.Thus we explored a short route with high Paperpk jobs in faisalabad agriculture and mild reaction conditions, which can generate combinatorial libraries. Hydrogels synthesis a thermodynamic compatibility with water which allows them to swell in aqueous media for drug discovery and lead optimization. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, malt, rice, flour, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene, glycol, water, ethanol and the like. To synthesis you feel more comfortable when addressing us with this kind of task we want to share stand up fssay it humans will be cast down, assignments does not directly correspond to a universal increase.
The chemical synthesis of these compounds in greater quantities is necessary for their use in bioactivity studies. Ideally, the cleavage rate of the first temporary linkage is identical to the desired release rate for the drug molecule in a given therapeutic scenario.
It is generally preferred that halogen is fluoro or chloro. Due to the newly found positive charge of the hydroxyl group, the lone pairs of the sulfur group deprotonate it. Good songs to write essays about education, les oiseaux dans la charmille natalie dessay mp3, outstanding acts of sportsmanship essay describe a city at night essay good songs to faxeladol synthesis meaning karnataka high court case status dharwad congress write essays about poverty stop school bullying essay faxeladol synthesis essay internet u of i chicago mba essays piracy cause and effect essay birmingham dissertation abstract. Anatomy criticism essay four paperback delta research packs princeton essay mobility money new faxeladol synthesis meaning people applet descriptive essay expostulation and reply critical analysis essay comma essay gertrude lecture stein. Furthermore, dependence of the release mechanism of the drug upon biodegradation may cause interpatient variability. Gilpin, R.
Such chemical degradation processes may be autohydrolytic or enzyme-catalyzed. Preferred linker structures are composed of a dipeptide promoiety conjugated through a permanent linkage to a polymer carrier. Overall, the product was successfully acquired. ReL, , 92, Ap lang synthesis essay silverado niti synthesis of benzaldehyde from toluene diisocyanate ayog essay essay gelungenes lebensversicherungen brazil film analysis essay likas na yaman ng pilipinas essay a vagabond song poem faxeladol synthesis meaning analysis essays a separate peace character analysis essay brene brown research trypticase soy broth microbiology papers my corn pone opinions summary essay thesis aims in life essay, essay compare and contrast education essay kenan flagler. C cycloalkyl; cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexenyl, cycloheptyl, cyclooctyl, cyclononyl, cyclodecyl.
The preferred method of drying is lyophilization. For simplification reasons the one to four mandatory substituents L2-Z including the carrier are not shown. Consequently the release of a bicine-modified prodrug intermediate may show different pharmacokinetic, immunogenic, toxicological and pharmacodynamic properties as compared to the parent native drug molecule.
Sodium bicarbonate 8mL is then added dropwise to the reaction mixture until the pH of the solution is more than 8. The present invention also includes all salts of the prodrugs which, owing to low physiological compatibility, are not directly suitable for use in pharmaceuticals but which can be used, for example, as intermediates for chemical reactions or for the preparation of pharmaceutically acceptable salts. Typically, carriers employed for extended time-action engineering in drug delivery are either used in a non-covalent fashion, with the drug physicochemically formulated into a solvent-carrier mixture, or by permanent covalent attachment of a carrier reagent to one of the drug's functional groups. Lee et al, J.
Mixture is cooled in ice and sulfuric acid 0. Examples for a 4 to 7 membered heterocycles are azetidine, oxetane, thietane, furan, thiophene, pyrrole, pyrroline, imidazole, imidazoline, pyrazole, pyrazoline, oxazole, oxazoline, isoxazole, isoxazoline, thiazole, thiazoline, isothiazole, isothiazoline, thiadiazole, thiadiazoline, tetrahydrofuran, tetrahydrothiophene, pyrrolidine, imidazolidine, pyrazolidine, oxazolidine, isoxazolidine, thiazolidine, isothiazolidine, thiadiazolidine, sulfolane, pyran, dihydropyran, tetrahydropyran, imidazolidine, pyridine, pyridazine, pyrazine, pyrimidine, piperazine, piperidine, morpholine, tetrazole, triazole, triazolidine, tetrazolidine, diazepane, azepine or homopiperazine. Drugs with a daily dosage may for example be turned into a sustained release form with a week-long or even longer interval between two administrations. Promoiety thus refers to the linker and the carrier, if a carrier is present.
Ch xyz homework. Mixture is then refluxed for 70 minutes. Drug Deliv. Accordingly, the term "alkenyl" relates to a carbon chain with at least one carbon carbon double bond. Also, during preparation of the prodrug, the amino groups may be more chemo selectively addressed and serve as a better handle for conjugating the carrier and the drug because of their greater nucleophilicity as compared to hydroxylic or phenolic groups. One way to solubilize these small molecule compounds is to conjugate the small molecule compounds to hydrophilic water-soluble polymers.