249 results about "Phosphodiester alpha" patented technology

The invention provides methods and compositions for improving the fidelity of a sequencing-by-synthesis reaction by using a nucleotide derivative that forms a hydrogen bond with a complementary nucleotide on a template, but fails to form a phosphodiester bond with the 3′ hydroxyl group of a primer under conditions otherwise suitable for a polymerization reaction; thereby blocking incorporation of a mismatched nucleotide.

The present invention provides highly phosphorylated lysosomal hydrolases, methods of modifying lysosomal hydrolases with the lysosomal targeting pathway enzymes GlcNAc-phosphotransferase and / or phosphodiester alpha-GlcNAcase.

The present invention is directed to the use of a PDE4 inhibitor and a glucocorticoid to treat peripheral B-cell neoplasms. In particular, the present invention provides a method of treating individuals (e.g. patients) diagnosed with peripheral B-cell leukemias by administering pharmaceutical compositions comprising Type 4 cyclic adenosine monophosphate phosphodiesterase inhibitors and a glucocorticoid. Preferably, the combination of the PDE4 inhibitor and the glucocorticoid has a synergistic effect on apoptosis such that the level of apoptosis induced is greater than the level that would be expected by simply adding a PDE4 inhibitor to a glucocorticoid.

The invention provides methods for synthesizing oligonucleotides using nucleoside monomers having carbonate protected hydroxyl groups that are deprotected with α-effect nucleophiles. The α-effect nucleophile irreversibly cleave the carbonate protecting groups while simultaneously oxidizing the internucleotide phosphite triester linkage to a phosphodiester linkage. The procedure may be carried out in aqueous solution at neutral to mildly basic pH. The method eliminates the need for separate deprotection and oxidation steps, and, since the use of acid to remove protecting groups is unnecessary, acid-induced depurination is avoided. Fluorescent or other readily detectable carbonate protecting groups can be used, enabling monitoring of individual reaction steps during oligonucleotide synthesis. The invention is particularly useful in the highly parallel, microscale synthesis of oligonucleotides.

Methods of modulating type-I interferon production in a cell are provided. Aspects of the methods include modulating cytosolic cyclic di-adenosine monophosphate (c-di-AMP) activity in the cell in a manner sufficient to modulate type-I interferon production in the cell. Additional aspects of the invention include c-di-AMP activity modulatory compositions, e.g., c-di-AMP, mutant Listeria bacteria, cyclase and / or phosphodiesterase nucleic acid or protein compositions, etc. The subject methods and compositions find use in a variety of applications, including therapeutic applications.

Provided are sequencing-by-binding methods of detecting cognate nucleotides using a crippled DNA polymerizing enzyme that possesses the ability to bind the next correct nucleotide downstream of a primer in a template-dependent fashion, but does not possess the activity needed to promote phosphodiester bond formation. Use of the crippled DNA polymerase permits interrogation of one nucleotide at a time, without incorporation of any nucleotide. Labeled nucleotides, such as fluorescently labeled nucleotides, can be used in conjunction with the crippled DNA polymerase to establish cognate nucleotide identity in a rapid manner.

The present invention relates to a new use for compounds that inhibit phosphodiesterase 1 (PDE1), e.g., that inhibit PDE1-mediated suppression of the dopamine D1 receptor and / or progesterone signaling pathways, including, e.g., methods of treatment or prophylaxis for conditions which may be ameliorated by enhancing the progesterone signaling response, particularly female sexual dysfunction.

Compounds of general structural formula (I) wherein A represents a 5- or 6-membered heteroaryl group containing at least one heteroatom selected from the group consisting of oxygen, nitrogen, and sulfur, and use of the compounds, and salts and solvates thereof, as therapeutic agents, are disclosed.

The invention belongs to the technical field of medicines and particularly relates to a phosphodiesterase-4 inhibitor as shown in a general formula (I) and a pharmaceutically acceptable salt, a stereoisomer or a solvent compound thereof. In the formula, R1, R2, R3, R4, R5, R6, R7, R8, R9, R7', R8', R9', L and a ring A are as defined in the specification. The invention further relates to a preparation method for the compound, a pharmaceutical composition with the compound, and an application of the compound and the pharmaceutical composition to preparation of drugs for treating and / or preventing inflammatory diseases, disease symptoms and disease conditions characterized by or related with undesired inflammatory immune reaction and all diseases induced by or related with TNF-alpha (tumor necrosis factor-alpha) and PDE-4 (phosphodiesterase-4) hypersecretion.

Recombinant fission yeast cells and methods of using them are described, which provide for identification of chemical and biological inhibitors or activators of a target exogenous phosphodiesterase (PDE). The invention provides, in some aspects, compounds that inhibit cAMP PDE activity and compositions that include such compounds. The invention, in part, also includes methods of using cAMP PDE-inhibiting compounds in the treatment of cAMP PDE-associated diseases and / or disorders.

The present invention provides compounds having the formula: wherein A is a nitrogen-, oxygen-, or sulfur-linked aryl, alkyl, cyclic, or heterocyclic group, the group being further substituted with an electron contributing moiety; B is hydrogen, or a halogen, amino, or thiol group; C is hydrogen, or a halogen, amino, or thiol group; and D is a primary alcohol, a hydrogen, or an oxygen, nitrogen, carbon, or sulfur linked to phosphate, a phosphoryl group, a pyrophosphoryl group, or adenosine monophosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted phosphodiester bridge, or to adenosine diphosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted pyrophosphodiester bridge. The present invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds. Also provided are methods for inhibiting an ADP-ribosyl transferase, ADP-ribosyl cyclase, ADP-ribosyl hydrolase, or NAD-dependent deacetylase enzyme, and methods for treating a disease or condition associated with an ADP-ribosyl transferase, ADP-ribosyl cyclase, ADP-ribosyl hydrolase, or NAD-dependent deacetylase enzyme in a subject in need of treatment thereof.

The present invention relates to novel compounds of the formula I which are inhibitors of phosphodiesterase type 10A and to their use for the manufacture of a medicament and which thus are suitable for treating or controlling of medical disorders selected from neurological disorders and psychiatric disorders, for ameliorating the symptoms associated with such disorders and for reducing the risk of such disorders.whereinQ is O or S, X1 is N or CH, X2 is N or C—R7; X3 is O, S—X4═C(R8)—, where C(R8) is bound to the carbon atom which carries R2, or —X5═C(R9)—, where X5 is bound to the carbon atom which carries R2; X4 is N or C—R9; X5 is N;Het is selected from optionally substituted phenyl, monocyclic hetaryl and fused bicyclic hetaryl;R1 is selected inter alia from hydrogen, halogen, OH, C1-C4-alkyl, trimethylsilyl, C1-C4-alkylsulfanyl, C1-C4-alkoxy-C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkoxy-C1-C4-alkoxy, the moiety Y1-Cyc1;R2 is selected inter alia from hydrogen, halogen, OH, C1-C4-alkyl, trimethylsilyl, C1-C4-alkoxy-C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkoxy-C1-C4-alkoxy, C2-C4-alkenyloxy, etc;A represents one of the following groups A1, A2, A3, A4 or A5:where * indicates the points of attachment to Het and to the nitrogen atom, respectively;and where R3 to R9, R3e, R3f, A′, Y1 and Cyc1 are defined in the claims.

Sequence-specific oligonucleotides are provided having substantially pure chiral Sp phosphorothioate, chiral Rp phosphorothioate, chiral Sp alkylphosphonate, chiral Rp alkylphosphonate, chiral Sp phosphoamidate, chiral Rp phosphoamidate, chiral Sp phosphotriester, and chiral Rp phosphotriester linkages. The novel oligonucleotides are prepared via a stereospecific SN2 nucleophilic attack of a phosphodiester, phosphorothioate, phosphoramidate, phosphotriester or alkylphosphonate anion on the 3' position of a xylonucleotide. The reaction proceeds via inversion at the 3' position of the xylo reactant species, resulting in the incorporation of phosphodiester, phosphorothioate, phosphoramidate, phosphotriester or alkylphosphonate linked ribofuranosyl sugar moieties into the oligonucleotide.

The present invention is directed to 7-aza-quinazoline compounds of general structural formula Iwhich are useful as therapeutic agents for the treatment of central nervous system disorders associated with phosphodiesterase 10 (PDE10).

The invention relates to the combined administration of a PDE4 inhibitor and a PDE5 inhibitor for the treatment of a disease in which phosphodiesterase 4 (PDE4) and / or phosphodiesterase 5 (PDE5) is detrimental.

The invention relates to a method for producing mushroom, which comprises that breaking mushroom and adding water, adding common salt to dissolve for 2-20h, adding some prolease to process enzymolysis, disinfecting enzyme and separating the filter solution; adding 5'-phosphodiesterase into filter solution to process the enzymolysis, disinfecting the enzyme and separating to obtain the filter solution; concentrating the filter solution into paste or atomizing and drying into powder. The invention processes two times of enzymolysis, while the product is abundant in amino acid, polypeptide, polysaccharide, or the like. And the invention has high solubility and stability in neutral or weak-alkali water solution, and some solubility in weak-acid water solution.

The invention relates to inhibitors of the phosphodiesterase 4 (PDE4) enzyme. More particularly, the invention relates to compounds that are derivatives of 1-phenyl-2-pyridinyl alkyl alcohols, methods of preparing such compounds, compositions containing them and therapeutic use thereof.

The invention relates to compounds of general formula (I); 1a, 1 b, 1 c and 1 d. The invention also relates to a method for the production thereof, pharmaceutical preparations containing said compounds and / or physiologically compatible salts thereof which can be produced therefrom and / or solvates thereof, and to the pharmaceutical use of said compounds, salts or solvates thereof as inhibitors of phosphodiesterase 4. The compounds comprise active ingredients for the treatment of diseases which can have a positive influence by inhibiting the activity of phosphodiesterase 4 and / or TNFα-release, for example, in lymphocytes, eosinophile and basophile granulocytes, macrophages and mastocytes.

Methods and compositions are disclosed for the treatment of taste and smell disorders. The compositions comprise phosphodiesterase inhibitors and are formulated for intranasal administration.

Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols are useful as inhibitors of the phosphodiesterase 4 (PDE4) enzyme and the treatment of certain conditions such as COPD.

The invention is based upon the discovery that red blood cells contain phosphodiesterase 3B (PDE3B), and that inhibition of that phosphodiesterase allows for an enhanced accumulation of cAMP and subsequent release of ATP. It was further discovered that RBCs treated with insulin accumulate significantly less cAMP and release significantly less ATP than normal RBCs. Likewise, RBCs of patients suffering from type 2 diabetes (hyperinsulinemia) accumulate significantly less cAMP and release significantly less ATP than normal RBCs. It was further discovered that prostaglandin analogues synergistically work with phosphodiesterase 3B inhibitors to improve or increase cAMP accumulation and ATP release by RBCs. Thus the invention is directed to compositions and methods for improving ATP release by RBCs, via administering PDE3B inhibitor or a combination of PDE3B inhibitor and prostaglandin analogue.

The present invention generally relates to the transdermal delivery of sildenafil and other phosphodiesterase type 5 inhibitors. While transdermal transport of sildenafil in creams and other topical formulations have been previously described, propylene glycol has not previously been recognized as a transdermal enhancer. However, in some aspects of the present invention, certain concentrations of propylene glycol can have a surprising effect on the transdermal delivery of sildenafil and other phosphodiesterase type 5 inhibitors, e.g., doubling the amount of transdermal delivery in some cases.

Derivatives of 1-phenyl-2-pyridinyl alkyl alcohols according to formula (I) are useful as inhibitors of the phosphodiesterase 4 (PDE4) enzyme.

The invention relates to the combined administration of a pulmonary surfactant and a PDE5 inhibitor for the treatment of a disease in which pulmonary surfactant malfunction and / or phosphodiesterase 5 (PDE5) activity is detrimental.

The invention belongs to the field of preparation of chemical raw medicaments, and more in particular relates to an improved preparation method for a phosphodiesterase 5 inhibitor tadalafil. A specific synthesis route is shown in the specification. The method comprises the following steps of performing Pictet-Spengler cyclization reaction and chloroacetyl chloride acylation on starting reactants (D-tryptophan methyl ester hydrochloride and piperonal) to obtain an intermediate product, directly performing subsequent reaction on the intermediate product without purification, preparing an intermediate 1-(1,3-benzodioxol-5-yl)-2-(chloracetyl)-2,3,4,9-tetrahydro-1H-pyridino-[3,4,-B]indol-3-thiophenate methyl by using a one-pot reaction method, performing column chromatography purification to obtain a single cis-isomer, and finally reacting the single cis-isomer with methylamine hydrochloride in the presence of an inorganic base to obtain the tadalafil.

The present invention relates, e.g., to a minimal set of protein-coding genes which provides the information required for replication of a free-living organism in a rich bacterial culture medium, wherein (1) the gene set does not comprise the 101 genes listed in Table 2; and / or wherein (2) the gene set comprises the 381 protein-coding genes listed in Table 3 and, optionally, one of more of: a set of three genes encoding ABC transporters for phosphate import (genes MG410, MG411 and MG412; or genes MG289, MG290 and MG291); the lipoprotein-encoding gene MG185 or MG260; and / or the glycerophosphoryl diester phosphodiesterase gene MG293 or MG385.

A method for treatment of multiple sclerosis and related disease states. A histamine H2 mimicking agent is administered in an amount which is effective to stimulate production of a cyclic AMP in the body. A phosphodiesterase inhibitor is administered in conjunction with the histamine H2 mimicking agent to conserve the cyclic AMP which is thus produced. It is believed that the increased cyclic AMP levels serve to maintain the patient's myelin against self degeneration. The histamine H2 mimicking agent may be histamine phosphate and the phosphodiesterase inhibitor may be caffeine. The histamine H2 mimicking agent and the phosphodiesterase inhibitor may be mixed in a gel and administered using a transdermal patch.

1-Phenyl-2-pyridinyl alkyl alcohol compounds are effective as inhibitors of the phosphodiesterase 4 (PDE4) enzyme and may be used to prevent and / or treat certain diseases or conditions.