Abstract: The present invention provides improved processes for the preparation of elagolix and intermediates thereof. The intermediate of formula VII is achieved by a coupling reaction of a compound of formula V and a N-benzylidene protected compound of formula IV: The present invention is suitable for a large-scale production, avoiding the use of potential genotoxic substances and can be performed under mild conditions.

Abstract: This invention provides compositions and methods for treatment of mild, moderate and severe stages of SARS-CoV-2 infection, particularly COVID-19 disease caused by wild type and mutant strains of SARS-CoV-2 using 5-amino-1-(4-(4-chlorobenzyl)-1, 2, 3-triazole-4-carboxamide orotate. Carboxyamidotriazole orotate (CTO) alone or in combination with other therapeutics in standard of clinical care are useful for directing antiviral effects and host-directed antiviral effects against wild type and mutant strains of SARS-CoV-2 throughout the viral life cycle.

Abstract: Small molecule regulators of steroid receptor coactivator (SRC) family proteins are provided, as well as methods for their use in treating or preventing SRC-related diseases. The SRC-related diseases can include cancer, metabolic disorders, human immunodeficiency virus, neurodegenerative disorders, and/or inflammatory diseases. Also provided are methods for regulating SRC family proteins in a cell.

Abstract: The present invention relates to compounds and pharmaceutically acceptable salts of Formulas A and B: wherein A, B, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are as defined above. The invention further relates to pharmaceutical compositions comprising the compounds and pharmaceutically acceptable salts and to methods of treating diabetes mellitus and its complications, cancer, ischemia, inflammation, central nervous system disorders, cardiovascular disease, Alzheimer's disease and dermatological disease pression, virus diseases, inflammatory disorders, or diseases in which the liver is a target organ.

Abstract: This invention is benzothiophene-based estrogen receptor downregulators and their compositions and uses to treat estrogen-related medical disorders.

Abstract: Novel cinchona alkaloid compounds have been synthesized and discovered to have potent cytotoxic activity against cancer cells both in vitro and in vivo. Cinchona alkaloids, including trimeric cinchona alkaloids as well as their polymers can be used as catalysts of complex chemical reactions in organic chemistry, for example for the enantioselective desymmetrization of cyclic anhydrides, asymmetric synthesis of amino acids (Ayyanar Siva, Eagambaram Murugan. Synthesis 2005; 17:2927-2933; Hyeung-geun Park et al. Tetrahedron Letters, Volume 42, Issue 28, 2001, Pages 4645-4648; Shohei Takata et al., RSC Adv., 2016, 6, 72300-72305; Masud Parvez et al., Macromolecules 2014, 47, 6, 1922-1928; Marcelli, T. 2007, UvA-DARE (Digital Academic Repository). https://pure.uva.nl/ws/files/4416997/52576_marcelli_thesis.

Abstract: The present invention provides a process for the manufacture of a compound of formula VIIIa and salts forms of VIIIa where Rc is an aryl sulfonic acid

Abstract: A subject of the present invention is a compound having the general formula (I): a pharmaceutically acceptable salt thereof or a tautomeric form thereof, wherein A, B3, B4, B5, Y, X, B1 and B2 are as defined in any one of claims 1 to 10. Another subject of the invention is the compound as defined above for use as a medicament, in particular for preventing and/or treating inflammation and inflammatory diseases, immune and auto-immune diseases, pain related diseases, genetic diseases and/or cancer.

Abstract: Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.

Abstract: The present invention relates to novel HSP27 inhibitors, in particular thymine derivatives according to general formula (VI), (VII) or (VII) and phenothiazine derivatives according to formula (V), and to their use as drugs for the selective inhibition of the heat shock protein HSP27 (HSPB1), in particular for use in the treatment of carcinomas or cystic fibrosis, said inhibitors having a particularly advantageous activity in the lower micromolar or sub-micromolar active ingredient concentration range with respect to HSP27.

Abstract: The present invention relates to 4-methyldihydropyrimidinone compounds, or pharmaceutically acceptable salts thereof, having ROR? antagonist activity, pharmaceutical compositions comprising the same, and pharmaceutical use thereof. A compound of Formula (1) or (2) or a pharmaceutically acceptable salt thereof, a pharmaceutical composition comprising the same, and pharmaceutical use thereof are provided.

Abstract: This invention provides for flow and batch synthesis processes for the production of Lamivudine and Emtricitabine, including flow and batch synthesis processes wherein at least of the synthesis steps are conducted in a solvent free environment.

Abstract: Provided herein are compounds, compositions including them, and methods of modulating GPR120 activity and treating diseases mediated by GPR120 by administering such compounds and compositions.

Abstract: Compositions for prevention or treatment of non-inflammatory neuronal damage from brain trauma and strokes are provided, and the compositions contain a therapeutically effective amount of a compound selected from the group consisting of Menthol, Linalool, Icilin and combinations thereof. Methods for treatment or prevention of non-inflammatory neuronal damage from brain trauma and strokes are also provided, and the methods include administering such compositions.

Abstract: The present disclosure provides compositions comprising a lyn kinase activator and TRPM8 agonist, and to methods of: reducing blood glucose levels, weight gain, or fat depot levels; treating metabolic syndrome, Syndrome X, obesity, prediabetes, type II diabetes, type I diabetes; treating hypercholesterolemia, hypertension, coronary heart disease, diabetic neuropathy, lipodystrophy, diabetic retinopathy, erectile dysfunction, kidney disease, dyslipidemia, dyslipoproteinemia, a peroxisome proliferator activated receptor-associated disorder, septicemia, a thrombotic disorder, or pancreatitis; inducing the beiging of adipocytes; and preventing pancreatic beta cell degeneration.

Abstract: A compound represented by Formula (I): wherein or the like Y1 is O or the like; Z1 is C(R4) or N; Z2a is C(R5a) or the like; Z3a is C(R6) or the like; R4, R5a and R6 are each independently a hydrogen atom or the like; R1 is substituted or unsubstituted aromatic carbocyclyl or the like; R2a, R2b, R2c and R2d are each independently a hydrogen atom or the like; X is N(R7a) or the like; R7a is a hydrogen atom or the like; R3 is or the like Ring B is a 6-membered aromatic carbocycle or the like; R9a and R10a are each independently halogen or the like; n is an integer from 1 to 5; m is an integer from 0 to 4; and p1 is an integer from 0 to 3, or a pharmaceutically acceptable salt thereof.

Abstract: The present invention relates to pharmaceutical dosage forms for oral administration comprising the drug substance 4-[(5R)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl]-3-fluorobenzonitrile or any pharmaceutically acceptable salt thereof and to processes of making said solid pharmaceutical dosage forms.

Abstract: Bifunctional barbiturate-derivative compounds that increase uric acid excretion and reduce uric acid production, and monofunctional barbiturate-derivative compounds that either increase uric acid excretion or reduce uric acid production are provided. Methods of using these compounds for reducing uric acid levels in blood or serum, for treating disorders associated with excess uric acid, and for maintaining normal uric acid levels in blood or serum, or the whole body, are also provided. Pharmaceutical compositions comprising the bifunctional and monofunctional compounds are also provided.

Abstract: The present invention relates to an improved process for the preparation of macitentan and pharmaceutical acceptable salts thereof. Further present invention also relates to methylene chloride solvate of macitentan and their use in the preparation of pure macitentan.

Abstract: The present invention relates to the use in therapy of 6-((4-(2,3-dimethylphenoxy)piperidin-1-yl)methyl)pyrimidine-2,4(1H,3H)-dione or a pharmaceutically acceptable salt thereof, to pharmaceutically acceptable salts of 6-((4-(2,3-dimethylphenoxy)piperidin-1-yl)methyl)pyrimidine-2,4(1H,3H)-dione and to pharmaceutical formulations comprising 6-((4-(2,3-dimethylphenoxy)piperidin-1-yl)methyl)pyrimidine-2,4(1H,3H)-dione or a pharmaceutically acceptable salt thereof.

Abstract: Described herein are oxime compounds capable of inactivating a nerve agent, blood brain barrier (BBB)-penetration, and/or reactivation of nerve agent-inhibited acetylcholinesterase (AChE) and related methods, systems and compositions for inactivation of one or more nerve agents, therapeutic and/or prophylactic treatment of an individual, and/or decomposition of nerve agent for decontamination.

Abstract: Compounds of Formula I or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof are provided, which are useful for the treatment of hyperproliferative, pain and inflammatory diseases. Methods of using compounds of Formula I or a stereoisomer, tautomer, prodrug or pharmaceutically acceptable salt thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

Abstract: The invention is a pharmaceutical composition for the treatment of HIV infection; containing at least one HIV protease inhibitor as an active ingredient, as well as pharmaceutically acceptable excipients with a specific quantitative component ratio. Additionally, the invention belongs to the process of its production and to a treatment method. The inventive pharmaceutical composition has increased bioavailability and improved technological properties, such as durability, plasticity, disintegration, compared to the prototype drug.

Abstract: The invention relates to a medicament containing a compound of general formula (I), where R1=independently, a straight or branched, saturated, singly- or multiply-unsaturated, optionally substituted C11-C21 alkyl, alkylene or alkinyl group, preferably a C11-C15 alkyl, alkylene or alkinyl group, particularly a C11-C13 alkyl, alkylene or alkinyl group, most preferably a C13 alkyl group, R2=independently, a straight or branched C1-C8 alkyl, alkylene or alkinyl group, preferably a C1-C6 alkyl, alkylene or alkinyl group, in particular a C2-C4 alkyl, alkylene or alkinyl group, most preferably a C3 alkyl group, a —[CH2—(CH2)m-O]nH group with n=1 to 10, preferably n=1 to 5, to m=1 to 5, preferably m=1 to 3, a —CH2—[CH—(OH)]p[CH2—R3]— group, where R3=independently H or OH, p=1 to 7, preferably p=1 to 4, a pentose group or a hexose group, as therapeutically active agent, alone or in combination with one or several further pharmaceutical agents as a combination preparation for the treatment of viral skin diseases and/or

Abstract: A fungicidal composition containing a fungicidally effective amount of the compound of Formula I: 5-fluoro-4-imino-3-methyl-1-tosyl-3,4-dihydropyrimidin-2(1H)-one, and at least one fungicide to provide synergistic control of selected fungi, wherein the at least one fungicide is a succinate dehydrogenase-inhibitor.

Abstract: A fungicidal composition containing a fungicidally effective amount of the compound of Formula I: 5-fluoro-4-imino-3-methyl-1-tosyl-3,4-dihydropyrimidin-2(1H)-one, and at least one fungicide to provide synergistic control of selected fungi wherein the at least one fungicide is a multi-site inhibitor or a strobilurin inhibitor.

Abstract: A fungicidal composition containing a fungicidally effective amount of the compound of Formula I: 5-fluoro-4-imino-3-methyl-1-tosyl-3,4-dihydropyrimidin-2(1H)-one, and at least one fungicide to provide synergistic control of selected fungi wherein the at least one fungicide is a fungicidal sterol biosynthesis-inhibitor.

Abstract: The present invention relates to the treatment of solid tumors in humans such as cancer, especially colorectal cancer (CRC), which involves administering multiple boluses of the diastereomerically pure folate adjuvant [6R]-5,10-methylenetetrahydrofolate in 5-fluorouracil (5-FU) based chemotherapy.

Abstract: The present invention provides methods for increasing plasma dUrd levels comprising the administration of 6R-MTHF. The methods of increasing plasma dUrd increase dUrd levels compared to equimolar concentrations of LV. The present invention also provides methods for increasing TS inhibition comprising the administration of 6R-MTHF. The present invention also provides methods for increasing TS inhibition comprising the administration of 6R-MTHF.

Abstract: Nucleosides and nucleotides (nucleos(t)ides) have been in clinical use for almost 50 years and have become cornerstones of treatment for patients with viral infections or cancer. The approval of several additional drugs over the past decade demonstrates that this family still possesses strong potential. Therefore nucleos(t)ide are of great interest as promising chemotherapeutic agents, including: 2?-deoxy-L-uridine (CAS 31501-19-6), 2?-deoxy-D-uridine (CAS 951-78-0), telbivudine (CAS 3424-98-4), zidovudine (AZT, CAS 30516-87-1), trifluridine (CAS 70-00-8), clevudine (CAS 163252-36-6), PSI-6206 (CAS 863329-66-2), 2?-(S)-2?-chloro-2?-deoxy-2?-fluorouridine (CAS 1673560-41-2), ND06954 (CAS 114248-23-6), stavudine (CAS 3056-17-5), 5-ethynyltavudine (Festinavir, CAS 634907-30-5), torcitabine (CAS 40093-94-5), (?)-beta-D-(2R,4R)-dioxolane-thymine (DOT, 1-((2R,4R)-2-(hydroxymethyl)-1,3-dioxolan-4-yl)-5-methyl-2,4(1H,3H)-pyrimidinedione, CAS No.

Abstract: The present invention provides a crystal that has preferable oral absorption and can be obtained with particularly preferable reproducibility. Provided is a crystal of (R)—N-(1-(3-(cyclopentyloxy)phenyl)ethyl)-3-((2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methoxy)propane-1-sulfonamide.

Abstract: Disclosed herein are compositions comprising lopinavir alone or in combination with ritonavir for use as a medicament in the treatment of cancer or benign proliferative disorders (warts) or in the prevention of the development of cancer. Pharmaceutical compositions formulated for topical application comprising a therapeutically effective amount of lopinavir or a therapeutically effective amount lopinavir and ritonavir in a pharmaceutically acceptable vehicle are also provided. Also disclosed are methods of treating a patient having an HPV related dysplasia of the cervix comprising administering to said patient a therapeutically effective dose of the disclosed pharmaceutical compositions.

Abstract: A fungicidal composition containing a fungicidally effective amount of (a) the compound of Formula I, (3S,6S,7R,8R)-8-benzyl-3-(3-((isobutyryloxy)methoxy)-4-methoxypicolinamido)-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl isobutyrate, and (b) fluxapyroxad, provides synergistic control of selected fungi.

Abstract: The present invention relates to pharmaceutical dosage forms for oral administration comprising the drug substance 4-[(5R)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl]-3-fluorobenzonitrile or any pharmaceutically acceptable salt thereof and to processes of making said solid pharmaceutical dosage forms.

Abstract: This invention is benzothiophene-based estrogen receptor downregulators and their compositions and uses to treat estrogen-related medical disorders.

Abstract: The disclosure describes methods of synthesis of phosphonate ester compounds. The methods according to the disclosure allow for large-scale preparation of phosphonate ester compounds having high purity and stability. Also disclosed are morphic forms of phosphonate ester compounds.

Abstract: The present disclosure relates to solid dosage forms comprising antiviral compounds and methods of using such dosage forms to treat antiviral infection.

Abstract: The invention provides a compound of formula (Ia), and pharmaceutically acceptable salts thereof. The invention also provides use of the compounds or salts as modulators of Kv3.1 and/or Kv3.2, and in the treatment of diseases or disorders where a modulator of Kv3.1 and/or Kv3.2 is required, such as depression and mood disorders, hearing disorders, schizopherenea, substance abuse disorders, sleep disorders or epilepsy.

Abstract: A fungicidal composition containing a fungicidally effective amount of the compound of Formula I: 5-fluoro-4-imino-3-methyl-1-tosyl-3,4-dihydropyrimidin-2(1H)-one, and at least one fungicide to provide synergistic control of selected fungi wherein the at least one fungicide is a multi-site inhibitor or a strobilurin inhibitor.

Abstract: A fungicidal composition containing a fungicidally effective amount of the compound of Formula I: 5-fluoro-4-imino-3-methyl-1-tosyl-3,4-dihydropyrimidin-2(1H)-one, and at least one fungicide to provide synergistic control of selected fungi, wherein the at least one fungicide is a succinate dehydrogenase-inhibitor.

Abstract: A fungicidal composition containing a fungicidally effective amount of the compound of Formula I: 5-fluoro-4-imino-3-methyl-1-tosyl-3,4-dihydropyrimidin-2(1H)-one, and at least one fungicide to provide synergistic control of selected fungi wherein the at least one fungicide is a fungicidal sterol biosynthesis-inhibitor.

Abstract: Disclosed herein are novel GRK2 inhibitors and methods for their use in treating or preventing heart disease, such as cardiac failure, cardiac hypertrophy, and hypertension. In particular, disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salt thereof: wherein the substituents are as described.

Abstract: The present invention provides a fungicidal composition useful as an agricultural and horticultural fungicide having remarkably improved controlling effects against plant diseases, and a method for controlling plant diseases using the composition. A fungicidal composition comprising, as active ingredients, (a) 3-(2,3,4-trimethoxy-6-methylbenzoyl)-5-chloro-2-methoxy-4-methylpyridine (pyriofenone) or its salt and (b) at least one fungicide selected from the group consisting of bixafen, fluxapyroxad, penflufen, isopyrazam, fluopyram, ametoctradin, fenpyrazamine and sedaxane, and a method for controlling plant diseases, which comprises applying the fungicidal composition to plants.

Abstract: The present invention relates to a compound which is an antagonist of the GluK2/GluK5 receptor or an inhibitor of the GluK2/GluK5 receptor expression for use in the treatment or the prevention of epilepsy.

Abstract: A method of classifying a patient for eligibility for cancer therapy based on the presence or absence of splicing variants in a sample of the patient's cancer tissue. Also, a method of screening cancer therapies for efficacy against splicing variants. More specifically, the methods relate to novel splicing variants of genes associated with cancer risk and survival, particularly splicing variants of PIK3CD, FGFR3, TSC2, RASGRP2, ITGA4, MET, NF1 and BAK1. Also more specifically, the methods relate to classifying a patient for eligibility for cancer therapy involving the use of GS-1101.

Abstract: Provided herein are, inter alia, methods and compositions for treating or preventing diseases using SIRT1 inhibitors. The methods provided herein are particularly useful for treating or preventing age-related hematological diseases as well as cancerous hematological diseases. Further provided herein are hematopoietic cells useful for treating or preventing hematological diseases.

Abstract: The invention provides therapeutic compositions and methods for the inhibition of metastasis and for treatment of cancers in human and non-human mammals that are directed to the coformulation and/or coadministration of a dehydropyrimidine dehydrogenase inhibitor such as gimeracil and a pyrrolopyrimidine compound.

Abstract: Provided herein are 5-fluoro-4-imino-3-(alkyl/substituted alkyl)-1-(arylsulfonyl)-3,4-dihydropyrimidin-2(1H)-one and processes for their preparation which may include the use of an alkali carbonate and an alkylating agent

Abstract: The invention relates to fluorinated compounds and their use as integrin receptor antagonists. Novel fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives and pharmaceutically acceptable salts or solvates thereof and their use are described.

Abstract: The present invention provides an agent for alleviating side effects caused by use of an anti-tumor agent, which contains 5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H-pyrimidi nedione (1) represented by formula (1): or a pharmaceutically acceptable salt thereof. The 5-chloro-6-(2-iminopyrrolidin-1-yl)methyl-2,4(1H,3H)-pyrimidinedione or a pharmaceutically acceptable salt thereof exhibit an inflammatory-suppressing action in the digestive tract and advantageously alleviate diarrhea and loss of body weight concomitant with administration of a chemical for treating cancer without suppressing the anti-tumor effect. Thus, the compounds of the present invention are of great value as agents for alleviating side effects caused by use of an anti-tumor agent, which enable not only the chemotherapy to be continuedly carried out, but also the body exhaustion to be effectively prevented.