74654-05-0

The invention provides novel neuroactive steroids and pharmaceutical compositions thereof, as well as methods of their preparation and use, in therapy of various diseases and conditions, for example, various neurological or brain diseases.

The present invention relates to solid dispersion of Naloxegol oxalate. Further, the present invention relates to an improved process for Naloxegol oxalate and intermediates thereof.

The invention relates to 1,4-diaminoanthraquinones and an electrolyte, and their use in batteries.

The present invention provides triazolotriazine derivatives of formula (1) as A2A receptor antagonists. Compounds of formula (1) and pharmaceutical compositions including the compounds can be used for the treatment of disorders related to A2A receptor hyperfunctioning, such as certain types cancers. Compounds of formula (1) and methods of preparing the compounds are disclosed in the invention.

The disclosure discloses a dendritic polyethylene glycol derivative and a preparation method and an application thereof. The dendritic polyethylene glycol derivative has a structure of formula (I), has multiple end functional groups, has a stronger water solubility in comparison with linear-chain polyethylene glycol, and can solve a problem of insufficient water solubility due to the increase of load when modifying an insoluble drug by the polyethylene glycol. The preparation method of the dendritic polyethylene glycol derivative provided by the disclosure has mild reaction conditions, is green and environmentally friendly, is low in cost, and is easy to implement industrialization.

The present invention relates to novel triterpene derivatives of formula (I); and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, and ring are as defined herein. The invention also relates to novel triterpene derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.

A novel strategy for the recognition of anions in water using charge-neutral σ-hole halogen and chalcogen bonding acyclic hosts is demonstrated for the first time. Exploiting the intrinsic hydrophobicity of halogen and chalcogen bond donor atoms integrated into a foldamer structural molecular framework containing hydrophilic functionalities, a series of water-soluble receptors was constructed for an anion recognition investigation. Isothermal titration calorimetry (ITC) binding studies with a range of anions revealed the receptors to display very strong and selective binding of large, weakly hydrated anions such as I- and ReO4-. This is achieved through the formation of 2:1 host-guest stoichiometric complex assemblies, resulting in an encapsulated anion stabilized by cooperative, multidentate, convergent σ-hole donors, as shown by molecular dynamics simulations carried out in water. Importantly, the combination of multiple σ-hole-anion interactions and hydrophobic collapse results in I- affinities in water that exceed all known σ-hole receptors, including cationic systems (β2 up to 1.68 × 1011 M-2). Furthermore, the anion binding affinities and selectivity trends of the first example of an all-chalcogen bonding anion receptor in pure water are compared with halogen bonding and hydrogen bonding receptor analogues. These results further advance and establish halogen and chalcogen bond donor functions as new tools for overcoming the challenging goal of anion recognition in pure water.

We describe self-assembled monolayers of novel halogen-bonding and hydrogen-bonding foldamer receptors capable of selectively recruiting perrhenate, iodide and thiocyanate in water. Unprecedented anion sensing via impedance-derived capacitance spectroscopy enables subsequent sensitive and selective anion detection without the need for a redox probe. Importantly, the sensing of any anion should be possible using this novel electrochemical approach.

The present invention relates to an improved process for the preparation of (5α, 6α)-17-allyl-6-(2, 5, 8, 11, 14, 17, 20- heptaoxadocosan-22-yloxy)-4, 5-epoxymorphinan-3, 14-diol which is represented by the following structural formula-1 or its pharmaceut

The present invention relates to solid dispersion of Naloxegol oxalate. Further, the present invention relates to an improved process for Naloxegol oxalate and intermediates thereof.

Carboxylic acids 1a and 1b bearing three poly(ethylene glycol) (PEG) chains and carboxylic acid 1c bearing one PEG chain were designed and synthesized. The carboxylic acids 1a - c were fully characterized by NMR and ESI-HRMS analyses. In a Pd-catalyzed ae

The present invention discloses a Y-type discrete polyethylene glycol derivative and a preparation method thereof, which has the advantages of determined molecular weights and the number of chain segments, and can avoid the defect of heterogeneity of a PEG derivative, meanwhile the preparation method has simple steps, mild conditions, without need for strictly anhydrous environment or performing protection and deprotection steps. In addition, the Y-type discrete polyethylene glycol derivative of the present invention may increase the water solubility of the discrete polyethylene glycol, and solve the problem of insufficient water solubility of the discrete polyethylene glycol-modified insoluble drug caused by an increase of the loading capacity.

The present invention relates to a silicon phthalocyanine complex, the preparation method and the medicinal application thereof. The present invention particularly relates to a silicon phthalocyanine complex of formula (I), the preparation method thereof and a pharmaceutical composition comprising the same, as well as the use thereof as a photosensitizer, in particular the use in the treatment of cancers, wherein each substituent in formula (I) is the same as defined in the description.

With the advent of reversible covalent chemistry the study of the interplay between covalent bond formation and noncovalent interactions has become increasingly relevant. Here we report that the interplay between reversible disulfide chemistry and self-assembly can give rise either to molecular diversity, i.e., the emergence of a unprecedentedly large range of macrocycles or to molecular specificity, i.e., the autocatalytic emergence of a single species. The two phenomena are the result of two different modes of self-assembly, demonstrating that control over self-assembly pathways can enable control over covalent bond formation.

The invention discloses a Y-shaped polyethylene glycol derivative shown as a general formula (I). The Y-shaped polyethylene glycol derivative has the advantage of determined molecular weight and chain segment number; the defects that a polyethylene glycol derivative is a mixture and the molecular weight is not uniform can be avoided; the Y-shaped polyethylene glycol derivative disclosed by the invention has the advantages that the drug loading amount is increased and the problems that the loading amount is improved so that the water solubility is not enough when polyethylene glycol is used for modifying insoluble medicines can be solved. (The general formula (I) is shown in the description) .

Polyacrylamide pseudo crown ethers with large in-chain rings (15–24 membered) were synthesized by hydrogen bond-mediated cyclopolymerization of bisacrylamides comprising poly(ethylene oxide) spacers (PEGnDAAm, ethylene oxide units: n = 3–6). The monomers undergo the intramolecular hydrogen bonding of the bisacrylamide units in halogenated solvents to dynamically place the two olefins adjacently. As a result, the bisacrylamides homogeneously allowed controlled radical cyclopolymerization without any macroscopic gelation in 1,2-dichloroethane, even at relatively high concentration of monomers (200 mM), to directly provide precision cyclopolyacrylamides and the related copolymers with high cyclization efficiency (84–98%). Owing to the in-chain ring pendants, a cyclopolyacrylamide had glass transition temperature higher than a corresponding polyacrylamide with linear pendants.

The invention relates to ether-based bis-imidazole ionic liquid used for absorbing SO2. The ether-based bis-imidazole ionic liquid has the advantages of high absorption capacity, good stability and recyclable performance, no secondary pollution is generated during a desulphurization process, usage of the ether-based bis-imidazole ionic liquid for desulphurization is a technical method having industrial application potential for high-efficiency removal of SO2. According to a preparation method, process is simple, stability of the preparation process is high, and repeatability is good.

The mixture of triterpenoids from birch bark and amphiphilic meso-arylprophyrins was used to develop spherical amorphous nanoparticles. The nanoparticles were studied with the methods of electron microscopy, dynamic light scattering, UV spectroscopy, and

Novel synthesized amino acids of glutamine and lysine that are directly PEGylated with small, monodisperse PEGs, and a novel process for creating novel amino acid monomers using PEGylation. These amino acids are readily incorporated into peptides for a range of different applications.

Ether-functionalized imidazolium-based ionic liquids (EFIILs) exhibit extremely high SO2 solubility. In this paper, a series of EFIILs were prepared, and their structures were confirmed by 1H NMR. The thermodynamic properties of EFIILs, such as density, viscosity and surface tension, were measured from (298.15 to 343.15) K at atmospheric pressure. The molecular volume, coefficient of thermal expansion, standard entropy, surface entropy, and surface enthalpy were calculated from the experimental data. The results indicate that density, viscosity and surface tension of the specific EFIILs show linear decline as temperature rises, and decrease with the increase of ether chain length of the cation at the same temperature. The surface properties of EFIILs were also discussed systematically.

A series of amphiphilic porphyrins appended with pyridinium cation and/or polyethylene glycol have been synthesized and fully characterized by 1H NMR, IR and MALDI-TOF-MS. Their photophysical properties were determined and the singlet oxygen (

(Figure Presented) Reversible formation and dissolution of gold nanoparticles through turning on and off UV light was reported. Gold ions (Au3+) were reduced to monodispersed gold nanoparticles by UV irradiation from a mixture of comb-like poly(oxyethylene)s and a gold salt. The prepared gold nanoparticles dissolved to yield gold ions (Au3+) when the UV light was switched off. Such formation and dissolutioncould be repeated persistently by turning the UV light on and off repea tedly.

A homologous series of polyethylene glycol (PEG) monomethyl ethers were conjugated with three ligand series for nicotinic acetylcholine receptors. Conjugates of acetylaminocholine, the cyclic analog 1-acetyl-4,4-dimethylpiperazinium, and pyridyl ether A-84543 were prepared. Each series was found to retain significant affinity at nicotinic receptors in rat cerebral cortex with tethers of up to six PEG units. Such compounds are hydrophilic ligands which may serve as models for fluorescent/affinity probes and multivalent ligands for nAChR.

An efficient synthetic method for preparing bifurcated amphiphiles has been developed such that the functionality for attachment is located at the interface between the lipophilic and hydrophilic side chains. Attachment of the amphiphile to the repeat uni

The invention provides antihistamine drugs that are chemically modified by covalent attachment of a water-soluble oligomer. A conjugate of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from the characteristics of the antihistamine drug not attached to the water-soluble oligomer.

Starting from a simple chalcone template, structure-activity relationship (SAR) studies led to a series of carboxylated, heteroaryl-substituted chalcone derivatives as novel, potent inhibitors of vascular cell adhesion molecule-1 (VCAM-1) expression. Corr

An aspect of the invention includes a nanoparticle including a substantially monodisperse inorganic core with a surface and a coating substantially covering the surface of the substantially monodisperse inorganic core, wherein the coating includes of at l

An efficient transition metal catalyzed procedure for the reductive alkylation of proteins has been developed. Imines formed from the condensation of aldehydes (1 mM) with lysine residues and the N-terminus can be reduced efficiently by a [Cp*Ir(4,4′-dime

We previously reported a new synthetic methodology termed 'synthesis based on affinity separation' (SAS) in which the desired tagged compound was separated from the reaction mixture by solid-phase extraction using specific molecular recognition of the tag. The interaction between a crown ether tag and polymer-supported ammonium ion was initially employed for SAS. In the present study, a new SAS method using a podand-type tag, a pseudo-benzo-31-crown-10 structure, was elaborated for oligosaccharide synthesis. The podand tag was much easier to synthesize than the corresponding crown ether. The podand moiety was attached to the monosaccharide residue via appropriate linkers. After glycosylation of the tagged monosaccharide with a glycosyl donor, the reaction mixture was subjected to the affinity separation. The desired compounds possessing the podand tag were effectively separated by the affinity between the podand and the ammonium ion. Continuous flow synthesis by integration of a microreactor and the present SAS system was applied for high throughput oligosaccharide synthesis. Georg Thieme Verlag Stuttgart.

This invention is a novel methods of manufacturing chalcones that includes reacting a carbon-linked heteroaryl or heterocyclic substituted benzaldehyde with an acetophenone in a solvent or mixture of solvents in the presence of LiOMe. Also provided are new chalcones for the treatment of medical conditions.

Calcitonin drug-oligomer conjugates that include a calcitonin drug coupled to an oligomer including a single polyalkylene glycol moiety consisting of between 4 and 10 polyalkylene glycol subunits are disclosed. Pharmaceutical compositions including such conjugates and methods of treating bone disorders by administering such conjugates are also disclosed.

A mixture of conjugates in which each conjugate in the mixture comprises a growth hormone drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed.

A mixture of conjugates in which each conjugate in the mixture comprises an insulin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may exhibit higher in vivo activity than a polydispersed mixture of similar conjugates. The mixture may also be more effective at surviving an in vitro model of intestinal digestion than polydispersed mixtures of similar conjugates. The mixture may also result in less inter-subject variability than polydispersed mixtures of similar conjugates.

A mixture of conjugates in which each conjugate in the mixture comprises a calcitonin drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may lower serum calcium levels in a subject by 10, 15 or even 20 percent or more. Moreover, the mixture may be more effective at surviving an in vitro model of intestinal digestion than non-conjugated calcitonin. Furthermore, the mixture may exhibit a higher bioavailability than non-conjugated calcitonin.

A non-polydispersed mixture of conjugates in which each conjugate in the mixture comprises a drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may exhibit higher in vivo activity than a polydispersed mixture of similar conjugates. The mixture may be more effective at surviving an in vitro model of intestinal digestion than polydispersed mixtures of similar conjugates. The mixture may result in less inter-subject variability than polydispersed mixtures of similar conjugates.

Methods for synthesizing proinsulin polypeptides are described that include contacting a proinsulin polypeptide including an insulin polypeptide coupled to one or more peptides by peptide bond(s) capable of being cleaved to yield the insulin polypeptide with an oligomer under conditions sufficient to couple the oligomer to the insulin polypeptide portion of the proinsulin polypeptide and provide a proinsulin polypeptide-oligomer conjugate, and cleaving the one or more peptides from the proinsulin polypeptide-oligomer conjugate to provide the insulin polypeptide-oligomer conjugate. Methods of synthesizing proinsulin polypeptide-oligomer conjugates are also provided as are proinsulin polypeptide-oligomer conjugates. Methods of synthesizing C-peptide polypeptide-oligomer conjugates and other pro-polypeptide-oligomer conjugates are also provided.

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The nitrogen- and oxygen-substituted chiral diols 1 are prepared from tartaric or malic acid.For the introduction of the amino groups, tartaric acid derived electrophiles of increasing reactivity are used: The diester (-> 3), the ditosylate 4 (-> 5), the diepoxide 6 ( -> 1a, e, g, h), and the acyl chloride 7a.The alkylating reagents 9a and 10c, obtained from malic acid, are employed for the synthesis of 1i. - The diols 1 react with lithium aluminium hydride to give complexes, for which a cyclic structure 2 is assumed, and which reduce ketones with prochiral carbonyl C-atoms to optically active alcohols (Table 1 and 2).From the effect of substitution and from the sense of chirality of the predominantly formed enantiomers, several models 11 - 16 are discussed as possible mechanisms of this asymmetric synthesis.