7489 results about "Pyrimidine" patented technology

Modified oligonucleotides are provided containing bases selected from unsubstituted and 3-substituted pyrazolo[3,4-d]pyrimidines and 5-substituted pyrimidines, and optionally have attached minor groove binders and reporter groups.

The present invention provides a polynucleotide that not only has a high RNA interference effect on its target gene, but also has a very small risk of causing RNA interference against a gene unrelated to the target gene. A sequence segment conforming to the following rules (a) to (d) is searched from the base sequences of a target gene for RNA interference and, based on the search results, a polynucleotide capable of causing RNAi is designed, synthesized, etc.:(a) The 3′ end base is adenine, thymine, or uracil,(b) The 5′ end base is guanine or cytosine,(c) A 7-base sequence from the 3′ end is rich in one or more types of bases selected from the group consisting of adenine, thymine, and uracil, and(d) The number of bases is within a range that allows RNA interference to occur without causing cytotoxicity.

The present invention provides heteroaryl substituted pyrrolo[2,3-b]pyridines and heteroaryl substituted pyrrolo[2,3-b]pyrimidines that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.

The present invention relates to nucleoside derivatives for the treatment of Hepatitis C viral infections including compounds of formula I, pharmaceutical compositions comprising these compounds and methods for treatment or prophylaxis of Hepatitis C Virus mediated diseases employing said compounds in monotherapy or in combination therapy. The present invention further provides a process for preparing 1′,3′,4′-triacyl pyrimidine nucleoside from a N, 1′,3′,4′-tetraacylpyrimidine nucleoside

4-Amino-1-((2R,3S,4S,5R)-5-azido-3,4-dihydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-1H-pyrimidin-2-one (I:R1=R2=R3=R4=H) and prodrugs thereof are hepatitis C(HCV) polymerase inhibitors. Also disclosed are compositions and methods for inhibiting HCV and treating HCV-mediated diseases, processes for making the compounds and synthetic intermediates employed in the process.

The present invention provides a compound of formula I and the use thereof for the therapeutic treatment, prevention or amelioration of a disease or disorder characterized by elevated β-amyloid deposits or β-amyloid levels in a patient.

Modified oligonucleotides are provided containing bases selected from unsubstituted and 3-substituted pyrazolo[3,4-d]pyrimidines and 5-substituted pyrimidines, and optionally have attached minor groove binders and reporter groups.

The present invention relates to novel compounds, in particular novel thieno-pyridine and thieno-pyrimidine derivatives according to Formula (I), wherein all radicals are defined in the application. The compounds according to the invention are positive allosteric modulators of metabotropic receptors-subtype 2 ("mGluR2") which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved.

A compound of the formula (1):wherein R1 and R2 are the same or different and represent a hydrogen atom, a hydroxyl protecting group, a phosphate group, or —P(R3)R4, wherein R3 and R4 are the same or different and represent a hydroxyl group, an amino group, an alkoxy group having from 1 to 4 carbon atoms, a cyanoalkoxy group having from 1 to 5 carbon atoms or an amino group substituted by an alkyl group having from 1 to 4 carbon atoms; A represents an alkylene group having from 1 to 4 carbon atoms and B represents a purin-9-yl group, a 2-oxo-pyrimidin-1-yl group, a substituted purin-9-yl group or a substituted 2-oxo-pyrimidin-1-yl group having a substituent α selected from the group consisting of a hydroxyl group which may be protected, an alkoxy group having from 1 to 4 carbon atoms, a mercapto group which may be protected, an alkylthio group having from 1 to 4 carbon atoms, an alkoxy group having from 1 to 4 carbon atoms, an amino group which may be protected, a mono- or di-alkylamino group which may be substituted by an alkyl group having from 1 to 4 carbon atoms, an alkyl group having from 1 to 4 carbon atoms and a halogen atom; or a salt thereof.

The present invention relates to a compound represented by Formula (I): (wherein Ar1 represents an imidazolyl group which may be substituted with 1 to 3 substituents; Ar2 represents a pyridinyl group, a pyrimidinyl group, or a phenyl group which may be substituted with 1 to 3 substituents; X1 represents (1) —C≡C— or (2) a double bond etc. which may be substituted; R1 and R2 represent, for example, a C1-6 alkyl group or C3-8 cycloalkyl group which may be substituted) or a pharmacologically acceptable salt thereof and to the use thereof as pharmaceutical agents. The object of the present invention is to find a therapeutic or preventive agent for diseases caused by Aβ. According to the present invention, a therapeutic or preventive agents for diseases caused by Aβ can be provided.

The present invention provides heteroaryl substituted pyrrolo[2,3-b]pyridines and heteroaryl substituted pyrrolo[2,3-b]pyrimidines that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.

A class of 2′-fluoro-nucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer. The compounds have the general formulae: wherein[0001]Base is a purine or pyrimidine base;[0002]R1 is OH, H, OR3, N3, CN, halogen, including F, or CF3, lower alkyl, amino, loweralkylamino, di(lower)alkylamino, or alkoxy, and base refers to a purine or pyrimidine base;[0003]R2 is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug; acyl, or other pharmaceutically acceptable leaving group which when administered in vivo, is capable of providing a compound wherein R2 is H or phosphate; sulfonate ester including alkyl or arylalkyl sulfonyl including methanesulfonyl, benzyl, wherein the phenyl group is optionally substituted with one or more substituents as described in the definition of aryl given above, a lipid, an amino acid, peptide, or cholesterol; and[0004]R3 is acyl, alkyl, phosphate, or other pharmaceutically acceptable leaving group which when administered in vivo, is capable of being cleaved to the parent compound, or a pharmaceutically acceptable salt thereof.

The present invention relates to novel pyrimidine, pyrrolo-pyrimidine, pyrrolo-pyridine, pyridine, purine and triazine compounds which are able to modulate epidermal growth factor receptor (EGFR), including Her-kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.

Provided are compounds represented by: X is O, S or NR6, R1 is H or (CH2)mR5, R2, R2', R3 and R3' are independently NO2, N3 or (CH2)mR5, OH R4 is H, OR6, SR6, NR6R6a, CN, C(O)OR6, C(O)NR6R6a, R6, OR7 or (CH2)nR7, R5 is H, halo, OR6, SR6, NR6R6a, CN, C(O)OR6, C(O)NR6R6a, R6, OR7 or (CH2)mR7, R6 and R6a are individually H, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl or substituted aryl, R7 is: R8 is H, F, SR9 or OR9, R9 is H, alkyl, alkenyl, alkynyl, aryl or hydroxyprotecting group, Y is H, CH3 or (CH2)mR5, Z is O or S W is CH2, CF2, CHF or O, m is 0-4, B is adenine, guanine, cytosine, uracil, thymine, modified purines and pyrimidines substituted pyridines, five membered heterocycles substituted by at least one of amines, substituted amines, amides, substituted amides, esters, halogens, alkyls, ethers; and pharmaceutically acceptable salts thereof and prodrugs thereof. These ring systems may be substituted.

An herbicidal composition containing (a) a pyridine or pyrimidine carboxylic acid component and (b) a second cereal or rice herbicide component provides synergistic control of selected weeds.

An efficient synthetic route to antiviral 2′,3′-dideoxy-2′,3′-didehydro-nucleosides, such as 2′,3′-dideoxy and 2′- or 3′-deoxyribo-nucleoside analogs, from available precursors is disclosed, with the option of introducing functionality as needed. In one embodiment, a method for the preparation of β-D and β-L-2′,3′-dideoxy-2′,3′-didehydro-nucleosides is described that includes: activating a compound of structure (1) wherein B is a pyrimidine or purine base and Y is O, S or CH2 with an acyl halide of the formula X—C(═O)R1, X—C(═O)C(R1)2OC(═O)R1 or X—C(═O)OR1 (wherein X is a halogen, and each R1 is independently hydrogen, lower alkyl, alkyl, aryl or phenyl); reducing the resulting compound with a reducing agent to form a 2′,3′-dideoxy-2′,3′-didehydro-nucleoside; and optionally deprotecting the nucleoside. The haloacylation of the first step can form the 2′-acyl-3′-halonucleoside, the 3′-acyl-2′-halonucleoside, or a mixture thereof.

A novel crystalline form of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide, pharmaceutical compositions containing said crystalline form and the use of said crystalline form in the treatment of pain, cancer, inflammation, neurodegenerative disease or Trypanosoma cruzi infection are disclosed. In some embodiments, the novel crystalline form comprises a stable polymorph of (S)—N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate. The present invention is further directed to a process for the preparation of the novel crystalline form.

The present invention is directed to imidazo[1,2-b][1,2,4]triazines and imidazo[1,2-a]pyrimidines, and pharmaceutical compositions thereof, which are inhibitors of kinases such as c-Met and are useful in the treatment of cancer and other diseases related to the dysregulation of kinase pathways.

The present invention relates to urotensin II receptor antagonists, pharmaceutical compositions containing them and their use.

The present invention provides a novel pyrimidine compound having an excellent adenosine receptor (A1, A2A, A2B receptor) antagonistic action. More specifically, it provides a compound represented by the following formula, a salt thereof or a solvate of them. In the formula, R1 and R2 are the same as or different from each other and each represents a hydrogen atom, an alkyl group having one to six carbon atoms which may be substituted, an alkenyl group having two to six carbon atoms which may be substituted, an alkynyl group having two to six carbon atoms which may be substituted, a cycloalkyl group having three to eight carbon atoms which may be substituted, a cycloalkenyl group having three to eight carbon atoms which may be substituted, a 5 to 14-membered non-aromatic heterocyclic group which may be substituted, an aromatic hydrocarbon cyclic group having six to fourteen carbon atoms which may be substituted, a 5 to 14-membered aromatic heterocyclic group which may be substituted, an acyl group having one to six carbon atoms which may be substituted or an alkylsulfonyl group having one to six carbon atoms which may be substituted; R3 represents a hydrogen atom, a halogen atom, a cyano group, an alkyl group having one to six carbon atoms which may be substituted, an alkenyl group having two to six carbon atoms which may be substituted, an alkynyl group having two to six carbon atoms which may be substituted, an aromatic hydrocarbon cyclic group having six to fourteen carbon atoms which may be substituted, a 5 to 14-membered aromatic heterocyclic group which may be substituted, a nitrogen atom which may be substituted, an oxygen atom which may be substituted or a sulfur atom which may be substituted; R4 represents an aromatic hydrocarbon cyclic group having six to fourteen carbon atoms which may be substituted, a 5 to 14-membered aromatic heterocyclic group which may be substituted or a 5 to 14-membered non-aromatic heterocyclic group having at least one or more unsaturated bonds which may be substituted; and R5 represents an aromatic hydrocarbon cyclic group having six to fourteen carbon atoms which may be substituted or a 5 to 14-membered aromatic heterocyclic group which may be substituted.

The present invention relates to diaryl pyrimidine-2,4-diamines, pharmaceutical compositions thereof, and the use of the compounds and compositions for the inhibition of kinases. The compounds, analogs, and pharmaceutically acceptable salts thereof, and pharmaceutical compositions can be used in the treatment and prevention of cancer.

A class of 2′-fluoro-nucleoside compounds are disclosed which are useful in the treatment of hepatitis B infection, hepatitis C infection, HIV and abnormal cellular proliferation, including tumors and cancer. The compounds have the general formulae:whereinBase is a purine or pyrimidine base;R1 is OH, H, OR3, N3, CN, halogen, including F, or CF3, lower alkyl, amino, loweralkylamino, di(lower)alkylamino, or alkoxy, and base refers to a purine or pyrimidine base;R2 is H, phosphate, including monophosphate, diphosphate, triphosphate, or a stabilized phosphate prodrug; acyl, or other pharmaceutically acceptable leaving group which when administered in vivo, is capable of providing a compound wherein R2 is H or phosphate; sulfonate ester including alkyl or arylalkyl sulfonyl including methanesulfonyl, benzyl, wherein the phenyl group is optionally substituted with one or more substituents as described in the definition of aryl given above, a lipid, an amino acid, peptide, or cholesterol; andR3 is acyl, alkyl, phosphate, or other pharmaceutically acceptable leaving group which when administered in vivo, is capable of being cleaved to the parent compound, or a pharmaceutically acceptable salt thereof.

The present invention provides (i) processes for preparing a 2′-deoxy-2′-fluoro-2′-methyl-D-ribonolactone derivatives, (ii) conversion of intermediate lactones to nucleosides with potent anti-HCV activity, and their analogues, and (iii) methods to prepare the anti-HCV nucleosides containing the 2′-deoxy-2′-fluoro-2′-C-methyl-β-D-ribofuranosyl nucleosides from a preformed, preferably naturally-occurring, nucleoside.

An oligo- or polynucleotide analogue having one or more structures of the general formulawhere B is a pyrimidine or purine nucleic acid base, or an analogue thereof,is disclosed. The use of this analogue provides an oligonucleotide analogue antisense molecule, which is minimally hydrolyzable with an enzyme in vivo, has a high sense strand binding ability, and is easily synthesized.

Pyrrolopyrimidines and related analogs are described and demonstrated to have utility as Heat Shock Protein 90 (HSP90) inhibiting agents used in the treatment and prevention of various HSP90 mediated disorders, e.g., proliferative disorders. Methods of synthesis and use of such compounds are also described and claimed.

4-amido-pyrimidine compounds, derivatives and compositions thereof, and synthetic methods described herein are useful for modulating ATP-Binding Cassette (“ABC”) transporters or fragments thereof, including Cystic Fibrosis Transmembrane Conductance Regulator (“CFTR”). The present invention also relates to methods of treating ABC transporter mediated diseases using such modulators.

One aspect of the present invention relates to a double-stranded oligonucleotide comprising at least one ligand. In certain embodiments, a ligand is bound to only one of the two oligonucleotide strands comprising the double-stranded oligonucleotide. In certain embodiments, both of the oligonucleotide strands of the double-stranded oligonucleotide independently comprise a bound ligand. In certain embodiments, the oligonucleotide strands comprise at least one modified sugar moiety. In certain embodiments, a phosphate linkage in one or both of the strands of the oligonucleotide has been replaced with a phosphorothioate or phosphorodithioate linkage. In a preferred embodiment, the ligand is cholesterol or 5β-cholanic acid. Another aspect of the present invention relates to a single-stranded oligonucleotide comprising at least one ligand. In certain embodiments, the oligonucleotide comprises at least one modified sugar moiety. In certain embodiments, a phosphate linkage of the oligonucleotide has been replaced with a phosphorothioate or phosphorodithioate linkage. In a preferred embodiment, the ligand is cholesterol or 5β-cholanic acid. The ligand improves the pharmacokinetic properties of the oligonucleotide.