225 results about "Phosphodiester alpha" patented technology

This application relates to a series of novel compounds that are selective inhibitors of phosphodiesterase type 9 ("PDE9") for the treatment of chronic heart failure. More particularly, the application relates to pyrazolo[3,4-d]pyrimidinone compounds for use in the treatment and prevention of chronic heart failure.

The present invention relates to a pharmaceutical combination comprising a PDE5 inhibitor and l-arginine.

The disclosure provides the administration of inhibitors of phosphodiesterase 1 (PDE1) for the treatment and prophylaxis of diseases or disorders characterized by inflammation, including methods of treatment and pharmaceutical compositions for use therein.

The invention discloses a tricyclic fused heterocyclic PDE3 / 4 dual inhibitor, and a preparation and use therefor. Specifically provided is a compound having structural formula (I) or a pharmaceutically acceptable form thereof, wherein each substituent is as defined in the description, respectively. The compound or the pharmaceutically acceptable form thereof can be used as a phosphodiesterase inhibitor and has high activity.

The invention belongs to the field of medicinal chemistry, and particularly relates to a 3, 8-dyhydroxyl-6H-benzo [c] chromene-6-ketone 8-site hydroxyl etherified derivative of a phosphodiesterase 2 inhibitor and application of the 3, 8-dyhydroxyl-6H-benzo [c] chromene-6-ketone 8-site hydroxyl etherified derivative. The 3, 8-dyhydroxyl-6H-benzo [c] chromene-6-ketone 8-position hydroxyl etherified derivative is shown in the specification. According to the invention, 2-bromo-5-hydroxy-benzoic acid is used as a raw material, and etherification, hydrolysis and cyclization are carried out to obtain a final product. The purposes of reducing the reaction time, improving the product purity and improving the reaction yield are achieved by improving the reaction temperature, adjusting the catalyst concentration and optimizing the purification method. Meanwhile, the compound obtained by the invention has good PDE2 inhibitory activity. # imgabs0 #

The invention provides oligonucleotide and / or oligonucleotide analogue molecules that are antagonists of a microRNA, preferably antagonists of human microRNAs hsa-miR-23b-3p and hsa-miR-218-5p, that comprise a mixture of phosphorothioate and phosphodiester linkages, and that are conjugated to at least one oleic acid molecule. Inhibiting these microRNAs allows to increase the endogenous levels of the corresponding proteins MBNL1 and / or MBNL2. The present invention further provides compositions comprising said oligonucleotides and / or oligonucleotide analogue molecules and their uses for the treatment and prevention of DM in a subject in need thereof.

Disclosed herein are capped RNA transcripts comprising one or more modified nucleotides at position +3 or higher with reference to a 5' terminus of the RNA molecule, and methods of making the same. Also provided are compositions comprising one or more of the capped RNA transcripts provided herein, and methods of using said compositions for therapeutic applications.

The invention provides low-dose formulations of guanylate cyclase-C (“GCC”) agonist peptides and methods for their use. The formulations of the invention can be administered either alone or in combination with one or more additional therapeutic agents, preferably an inhibitor of cGMP-dependent phosphodiesterase or a laxative.

The present invention describes antisense oligonucleotides comprising one or more alpha-L-threofuranosyl (TNA) nucleosides linked to adjacent nucleosides via phosphodiesters (PO) inter-nucleoside linkages and methods of modulating the properties of antisense oligonucleotides by introducing such TNA nucleosides. These are particularly useful for antisense spacer oligonucleotides.

Oligomeric compounds (including those that are antisense agents or portions thereof) are provided that comprise a modified oligonucleotide having at least one modified internucleoside linking group.SOLUTION: By an oligomeric compound comprising a modified oligonucleotide consisting of 12 to 70 linked nucleosides linked via internucleoside linking groups, wherein at least one nucleoside comprises a modified sugar moiety and wherein at least one internucleoside linking group is a phosphodiester or phosphorothioate internucleoside linking group.SELECTED DRAWING: Figure 1

To provide a recombinant polynucleotide for treating a particular disease of ectopic tissue calcification, and to provide a viral vector containing the recombinant polynucleotide.SOLUTION: Provided is a recombinant polynucleotide encoding a precursor polypeptide comprising an Azurocidin signal peptide fused to ectonucleotide pyrophosphatase / phosphodiesterase- 1 (ENPP1) or to ectonucleotide pyrophosphatase / phosphodiesterase-3 (ENPP3), the precursor polypeptide being proteolytically cleaved to produce soluble ENPP1 or soluble ENPP3 which is active to reduce ectopic calcification of soft tissue, upon expression of the polynucleotide in mammalian cells.SELECTED DRAWING: Figure 4

The invention relates in general to the field of CAR-T cells. The invention in particular relates to improved methods for obtaining CAR-T cells, and improved CAR-T cells, as well as uses thereof. The method in further relates to activating or expressing a phosphodiesterase (PDE) in T-cells during CAR-T cell generation.

This invention belongs to the field of medicinal chemistry, specifically relating to benzofuran compounds or their pharmaceutically acceptable salts, their preparation methods, and applications. The benzofuran compounds of this invention can significantly inhibit the activity of phosphodiesterase 4 and can be used to prepare drugs for treating inflammatory diseases, autoimmune diseases, or neuropsychiatric disorders, especially for stroke and ischemic dementia-related diseases.

The present invention is related to a composition comprising a phosphodiesterase 3A modulator compound in synergistic combination with an inhibitor compound selected from the group consisting of: an inhibitor of Bcl-2 family proteins, a mTOR inhibitor, a histone deacetylase (HDAC) inhibitor, a DNA-dependent protein kinase (DNA-PK) inhibitor, an inhibitor of integrin alpha 2 protein, a NEDD8-activating enzyme (NAE) inhibitor and a PAK4 inhibitor for use in the treatment of cancer.

The disclosure relates to the combination of inhibitors of phosphodiesterase 1 (PDE1) useful for the treatment of certain cancers or tumors, such as colon cancer. In another embodiment, the disclosure relates to the use of inhibitors of PDE1 and an optional antitumor agent for the treatment of certain cancers or tumors.

A phosphodiesterase type 5 inhibitor is used in the preparation of a medicament for resisting fibrotic diseases. Experiments in animal models of ischemia-reperfusion (UIRI)-induced renal fibrosis, unilateral ureteral obstruction (UUO)-caused kidney fibrosis and idiopathic pulmonary fibrosis show that a PDE5 inhibitor such as tadalafil, sildenafil and vardenafil can significantly inhibit the expression of multiple fibrosis iconic proteins such as fibronectin, collagen I, renal injury molecule-1, and α-skeletal muscle actin in UIRI and UUO renal fibrosis lesions, improves glomerulopathy, degree of renal tubular distension, renal interstitial collagen fiber deposition and inflammatory cell infiltration, reduces the fibrotic area within the lesion, and significantly inhibits the progression of renal fibrosis; and the PDE5 inhibitor can significantly improve smooth muscle proliferation and inflammatory cell infiltration in bronchioles and pulmonary arterioles of idiopathic pulmonary fibrosis lesion, improve damage condition of alveolar tissue, and significantly inhibit the progression of pulmonary fibrosis.

Disclosed herein are capped RNA transcripts comprising one or more modified nucleotides at position +3 or higher with reference to a 5' terminus of the RNA molecule, and methods of making the same. Also provided are compositions comprising one or more of the capped RNA transcripts provided herein, and methods of using said compositions for therapeutic applications.

This invention discloses a genetically engineered bacterium capable of synthesizing large quantities of natural cyclic diguanylate (c-di-GMP) and its applications. It involves knocking out the major phosphodiesterase gene chr1_233 as described in claim 1 within the sphingobium xenophagum C2 strain. This invention rationally designs and modifies the c-di-GMP synthesis and degradation pathways and the inhibitory site of major diguanylate cyclase activity in heterologous sphingobium-consuming bacteria, constructing a series of genetically engineered bacteria capable of synthesizing large quantities of natural c-di-GMP. This provides the industry with a green, simple, economical, and efficient method for producing natural c-di-GMP, and offers a series of high-quality and inexpensive raw materials for the preparation of STING agonists or immune adjuvants, or for the preparation of drugs for treating diseases related to STING protein function.

To provide a method for producing and using a pharmaceutical composition including a cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 9 inhibitor.SOLUTION: An oral pharmaceutical composition contains: 6-[(3S,4S)-4-methyl-1-pyrimidine-2-ylmethyl)pyrrolidine-3-yl]-3-tetrahydropyran-4-yl-7H-imidazo [1,5-a] pyrazine-8-one(compound 1), or a pharmaceutical acceptable salt thereof, solvate, or polymorph by approximately 100 mg to approximately 300 mg; a filler selected from alpha starch by approximately 4 wt.% to approximately 6 wt.% and / or microcrystalline cellulose by approximately 15 wt.% to approximately 50 wt.%; and processing aid selected from colloidal silicon dioxide approximately 1 wt.% to approximately 2.5 wt.% and / or magnesium stearate approximately 0.5 wt.% to approximately 1.5 wt.%, where the oral pharmaceutical composition is in a form of a solid tablet suitable for administration to a patient.SELECTED DRAWING: Figure 2

The invention relates to a process for the production of a mixed P═O / P═S backbone oligonucleotide comprising a selective oxidation of an intermediary phosphite triester compound of formula I into a phosphodiester compound of formula II according to the scheme with an oxidation solution obtained by mixing iodine, an organic solvent and water, characterized in that the oxidation solution has been aged for a time period that is sufficient to selectively oxidize the phosphite triester compound of formula I into the phosphodiester compound of formula II without oxidizing the phosphorothioate internucleotide linkages.

The present disclosure relates generally to processes for providing compounds that can be used as inhibitors of ectonucleotide pyrophosphatase / phosphodiesterase 1 (ENPP1), which inhibitors can be useful in treating or preventing soft bone diseases, such as hypophosphatasia (HPP).

This application relates to a series of novel compounds that are selective inhibitors of phosphodiesterase type 9 ("PDE9") for the treatment of chronic heart failure. More specifically, this application relates to pyrazolo[3,4-d]pyrimidinone compounds for use in the treatment and prevention of chronic heart failure.

To provide small-molecule modulators of ectonucleotide pyrophosphatase / phosphodiesterase 1 (ENPP1).SOLUTION: Provided is a compound having the structure of Formula (I), or a pharmaceutically acceptable salt or solvate thereof: SELECTED DRAWING: None

The present invention relates to a product for treating, preventing or ameliorating prostate cancer in a subject in need thereof, wherein the product induces the expression of PDE4D7 or promotes the activity of phosphodiesterase 4D7. The product may be a direct or indirect activator of PDE4D7 activity, or a product for expressing or promoting PDE4D7 expression in a subject. The invention also defines kits of the product and in vitro or ex vivo uses of the product.

This specification describes methods for treating cancer using small molecule ectonucleotide pyrophosphatase / phosphodiesterase 1 (ENPP1) inhibitors and additional agents.

The invention discloses an application of a novel phosphodiesterase 4 (PDE4) inhibitor ZL-n-91 in preparation of drugs for treating growth and metastasis of small cell lung cancer. In-vitro cytology experiments and in-vivo zoology experiments show that the phosphodiesterase 4 inhibitor ZL-n-91 can significantly inhibit proliferation and metastasis of small cell lung cancer, and the phosphodiesterase 4 inhibitor ZL-n-91 is expected to treat small cell lung cancer and has good development and application prospects.

Provided herein are methods for treating hypophosphoesterase (HPP), the methods comprising administering a therapeutically effective amount of an inhibitor of exonucleotide pyrophosphatase / phosphodiesterase 1 (ENPP1).