The present invention provides a compound of Formula (I) and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are PRMT5 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat cancer, sickle cell, and hereditary persistence of foetal hemoglobin (HPFH) mutations.
Compounds of Formula I: and their pharmaceutically acceptable salts are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines.
A61K 31/685 - Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
C07F 9/6561 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
Compounds of Formula (I): and their pharmaceutically acceptable salts are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines.
C07F 9/6561 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
A61K 31/675 - Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
The present invention relates to Compounds of Formula (I) or Formula (II) or a pharmaceutically acceptable salt, solvate or enantiomer thereof, wherein A, B, R1, R2, R3, R4, Q and V are as defined herein. The present invention also relates to pharmaceutical compositions comprising a Compound of Formula (I) or Formula (II) and to their use in therapy.
A61K 31/7064 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
Compounds of Formula (I): (Formula (I)) and their pharmaceutically acceptable salts are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines.
Compounds of Formula I: and pharmaceutically acceptable salts and co-crystals thereof are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines.
C07F 9/6561 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
7.
CYCLIC PHOSPHATE SUBSTITUTED NUCLEOSIDE COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
The present invention relates to Cyclic Phosphate Substituted Nucleoside Compounds of Formula (I), and pharmaceutically acceptable salts thereof, wherein A, B, R1, R2, R3, Q and V are as defined herein. The present invention also relates to compositions comprising a Cyclic Phosphate Substituted Nucleoside Compound, and methods of using the Cyclic Phosphate Substituted Nucleoside Compounds for treating or preventing HCV infection in a patient.
A61K 31/7056 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
The present invention relates to Cyclic Phosphate Substituted Nucleoside Derivatives of Formula (I), and pharmaceutically acceptable salts thereof, wherein A, B, Q, V, R1, R2 and R3 are as defined herein. The present invention also relates to compositions comprising a Cyclic Phosphate Substituted Nucleoside Derivative, and methods of using the Cyclic Phosphate Substituted Nucleoside Derivatives for treating or preventing HCV infection in a patient.
A61K 31/7056 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
The present invention relates to methods of treating or preventing a viral infection using Compounds of Formula (I); or a pharmaceutically acceptable salt thereof, wherein A, B, R1, R2, R3, Q and V are as defined herein. The present invention also relates to compositions comprising a Compound of Formula (I).
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
Compounds of Formula I and pharmaceutically acceptable salts and co-crystals thereof are useful for the inhibition of HIV reverse transcriptase. The compounds may also be useful for the prophylaxis or treatment of infection by HIV and in the prophylaxis, delay in the onset or progression, and treatment of AIDS. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antiviral agents, immunomodulators, antibiotics or vaccines.
The present invention relates to novel nucleoside derivatives of formula (I) as defined in claim 1, pharmaceutical compositions comprising the compounds, processes of preparation thereof, and methods of use thereof for treating cancer.
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 19/11 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids containing cyclic phosphate
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
The present application relates to novel nucleoside derivatives of formula (I) as claimed in claim 1, pharmaceutical compositions comprising the compounds, processes of preparation thereof, and methods of use thereof for treating cancer.
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 19/11 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids containing cyclic phosphate
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
Provided herein are compounds, compositions, and methods for the treatment of cancer, including leukemia. In one embodiment, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-cancer agents.
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 19/11 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids containing cyclic phosphate
C07H 19/20 - Purine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 19/213 - Purine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids containing cyclic phosphate
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
A61K 31/7076 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
A61P 35/02 - Antineoplastic agents specific for leukemia
14.
3'-SUBSTITUTED METHYL OR ALKYNYL NUCLEOSIDES FOR THE TREATMENT OF HCV
Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 3'-substituted methyl or alkynyl nucleosides of Formula I: (I); or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein Base, PD, RA, RB1, RB2, RC and Z are as defined herein.
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 19/11 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids containing cyclic phosphate
C07H 19/20 - Purine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
A61K 31/7072 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
A61K 31/708 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
Provided herein are crystalline and salt forms of methyl N-{(1R)-2-[(2S)-2-{5-[4-(6- {2- [(2S)- 1 - {(2S)-2- [(methoxycarbonyl)amino] -3 -methylbutanoyl} pyrro lidin-2-yl]-3H- benzimidazol-5-y1}thieno[3,2-b]thiophen-3-y1)phenyl]-1H-imidazol-2-yl}pyrrolidin-1-y1]-2- oxo-1-phenylethyl} carbamate, a Flaviviridae, including hepatitis C, virus inhibitor, pharmaceutical compositions comprising the compound, and processes of preparation thereof. Also provided are methods of its use for the treatment of a Flaviviridae, including HCV, infection in a subject in need thereof.
C07D 409/04 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring- member bond
A61K 31/4178 - 1,3-Diazoles not condensed and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
PHARMACEUTICAL COMPOSITIONS COMPRISING A 5,5-FUSED HETEROARYLENE FLAVIVIRIDAE INHIBITOR AND THEIR USE FOR TREATING OR PREVENTING FLAVIVIRIDAE INFECTION
Provided herein are spray-dried particles comprising a 5,5-fused heteroarylene hepatitis C virus inhibitor compound and methods of their preparation. Also provided herein are pharmaceutical compositions comprising a 5,5-fused heteroarylene hepatitis C virus inhibitor compound, method of their preparation, and their use for treating or preventing hepatitis C virus infection.
Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are solid forms of Compound I: (Compound I)
A61K 9/48 - Preparations in capsules, e.g. of gelatin, of chocolate
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
A61K 31/4184 - 1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
A61K 31/7072 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
Provided herein are methods for the production of cyclic phosphate, cyclic phosphoramidate, cyclic thiophosphate, and cyclic phosphonate nucleoside compounds. Also provided herein are compounds useful in the production of cyclic phosphate, cyclic phosphoramidate, cyclic thiophosphate, and cyclic phosphonate nucleoside compounds. In certain embodiments, the cyclic phosphate, cyclic phosphoramidate, cyclic thiophosphate, and cyclic phosphonate nucleoside compounds are of Formula (I): wherein: Base, RA, RB, X, R1 and R2 are as defined herein. The cyclic phosphate, cyclic phosphoramidate, cyclic thiophosphate, and cyclic phosphonate nucleoside compounds are useful in the treatment of viral infections, including hepatitis C virus infections in hosts in need thereof.
Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 4'-OR nucleosides of Formula I: (I); or a pharmaceutically acceptable salt thereof, wherein Base, PD, R, Z1, Z2, Z3, and Z4 are as defined herein.
Provided herein are compounds, compositions and methods for the treatment of liver cancer such as hepatocellular carcinoma, cholangiocarcinoma, or biliary tract cancer. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-cancer agents. In certain embodiments, the compounds are nucleoside analogs of Formula I: (I); or a pharmaceutically acceptable salt thereof, wherein Base, Z1, Z2, Z3, Z4, V, W, X, Ar, R1 and R2 are as described herein.
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 19/20 - Purine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
A61K 31/7076 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
A61K 31/708 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
21.
2'-DICHLORO AND 2'-FLUORO-2'-CHLORO NUCLEOSIDE ANALOGUES FOR HCV INFECTION
Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are 2'-dichloro or 2'-fluoro-2'-chloro nucleoside analogue compounds which display remarkable efficacy and bioavailability for the treatment of, for example, HCV infection in a human. In certain embodiments, the compounds are of Formula (I):or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof; wherein each of RA and RB is independently Cl or F, wherein at least one of RA and RB is C1; and Base, PD and Z are as described herein.
C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
C07D 473/40 - Heterocyclic compounds containing purine ring systems with halogen atoms or perhalogeno-alkyl radicals directly attached in position 2 or 6
C07D 405/04 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring- member bond
C07F 9/6561 - Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
C07H 5/02 - Compounds containing saccharide radicals in which the hetero bonds to oxygen have been replaced by the same number of hetero bonds to halogen, nitrogen, sulfur, selenium, or tellurium to halogen
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
C07H 19/11 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids containing cyclic phosphate
A61K 31/513 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
A61K 31/7064 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are nucleoside analogs of Formula I: or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof, wherein Base, Z1 Z2, Z3, Z4, V, W, X, Y, Ar, R1and R2 are as described herein.
C07D 239/47 - One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
C07D 239/54 - Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
C07D 239/553 - Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with halogen atoms or nitro radicals directly attached to ring carbon atoms, e.g. fluorouracil
C07D 473/16 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 two nitrogen atoms
C07D 473/18 - Heterocyclic compounds containing purine ring systems with oxygen, sulfur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
Provided herein are compounds, compositions and methods for the treatment of Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are D-alanine phosphoramidate pronucleotides of 2'-methyl 2'-fluoro guanosine nucleoside which display remarkable efficacy and bioavailability for the treatment of, for example, HCV infection in a human. In certain embodiments, the compounds are of Formula I or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form or polymorphic form thereof; where W and R are as described herein.
C07H 19/207 - Purine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids the phosphoric or polyphosphoric acids being esterified by a further hydroxylic compound, e.g. flavine-adenine dinucleotide or nicotinamide-adenine dinucleotide
A61K 31/7076 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
A61K 31/708 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid having oxo groups directly attached to the purine ring system, e.g. guanosine, guanylic acid
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE (France)
UNIVERSITE DE MONTPELLIER (France)
Inventor
Mayes, Benjamin Alexander
Moussa, Adel M.
Dousson, Cyril B.
Gosselin, Gilles
Pierra, Claire
Dukhan, David
Abstract
Provided herein are compounds, compositions, and methods for the treatment of viral infections, for example, Flaviviridae infections, including HCV infections. In certain embodiments, compounds and compositions of nucleoside derivatives are disclosed, which can be administered either alone or in combination with other anti-viral agents. In certain embodiments, the compounds are D-amino acid phosphoramidate halogeno pyrimidine nucleoside analog compounds which display remarkable efficacy and bioavailability for the treatment of, for example, HCV infection in a human. In certain embodiments, the compounds are of Formula (I); or a pharmaceutically acceptable salt, solvate, stereoisomeric form, tautomeric form, or polymorphic form thereof, wherein: PD, X, R1, R2, RA, and RB are as described herein.
C07H 19/10 - Pyrimidine radicals with the saccharide radical being esterified by phosphoric or polyphosphoric acids
A61K 31/7068 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
A61K 31/7072 - Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
patents
