Abstract: MCF7-fibroblast co-cultures are a valuable model of resistance to apoptosis induced by hormonal therapies, such as Tamoxifen and Fulvestrant. These mixed co-cultures demonstrate the induction of mito-sternness and ribo-stemness features. Molecular therapeutic targets were identified through label-free proteomics of MCF7-fibroblast co-cultures, and independently validated using a bioinformatics approach. The resulting Mito-Signature is prognostic of endocrine treatment failure, tumor recurrence, and distant metastasis, and may be used to identify patients at risk of treatment failure. Such patients may be treated with a mitochondrial biogenesis inhibitor to reduce the risk of treatment failure, and/or to increase the effectiveness of the hormone therapy.

Abstract: The disclosure provides TNIK and/or MAP4K4 kinases inhibitors for the treatment of disease. In one aspect, disclosed herein are kinase inhibitors having a structure of Formula (A), (A*), (I), (IIA), or (IIB). Further described herein are pharmaceutical composition comprising these compounds and methods of using these compounds. In one aspect, disclosed herein are methods of treating a disease or condition by administering the kinases inhibitors described herein.

Abstract: The disclosure provides TNIK and/or MAP4K4 kinases inhibitors for the treatment of disease. In one aspect, disclosed herein are kinase inhibitors having a structure of Formula (A), (A*), (I), (IIA), or (IIB). Further described herein are pharmaceutical composition comprising these compounds and methods of using these compounds. In one aspect, disclosed herein are methods of treating a disease or condition by administering the kinases inhibitors described herein.

Abstract: The present invention relates to potent antibacterial activity of novel bisbenzimidazoles (SP12a and SP12b) against both Gram positive and Gram negative bacteria and a synergistic composition comprising Bisbenzimidazole (HN12b) in combination with Efflux pump inhibitors against most of the pathogenic bacterial strains.

Abstract: This invention provides a method for enantioselective synthesis of cis-imidazolines and related structures through chiral resolution. A chiral acid is used to separate enantiomeric precursors of the cis-imidazolines from a racemic mixture by selective crystallization. Both enantiomers can be cyclized into the desired cis-imidazoline by complementary pathways. Compounds can be synthesized according to the invention with an enantiomeric excess as high as 99%. Cis-imidazolines such as Nutlin-3a prepared according to this invention may be used for treating cancer, killing senescent cells, or treating senescence-associated conditions.

Abstract: This invention provides a method for enantioselective synthesis of cis-imidazolines and related structures through chiral resolution. A chiral acid is used to separate enantiomeric precursors of the cis-imidazolines from a racemic mixture by selective crystallization. Both enantiomers can be cyclized into the desired cis-imidazoline by complementary pathways. Compounds can be synthesized according to the invention with an enantiomeric excess as high as 99%. Cis-imidazolines such as Nutlin-3a prepared according to this invention may be used for treating cancer, killing senescent cells, or treating senescence-associated conditions.

Abstract: An inverter producing an alternating current from a direct current source has a primary stage coupled to the direct current source having a step-up transformer, a first switching circuit coupling the direct current to the transformer primary and a rectifier coupled to a secondary of the transformer for producing a DC voltage; a controller for the first switching circuit providing pulse drive signals to control switches of the first switching circuit to cause current to flow in the transformer primary and induce an alternating current in the transformer secondary; a secondary stage receiving the DC voltage having a second switching circuit and a controller for the second switching circuit for generating control signals to cause current through the second switching circuit to flow in alternate directions thorough the load.

Abstract: The present invention is directed to solvates and various polymorphic forms of (E)-1-[[[5-(4-chlorophenyl)-2-furanyl]methylene]amino]-3-[4-(4-methyl-1-piperazinyl)butyl]-2,4-imidazolidinedione dihydrochloride and pharmaceutical compositions thereof.

Abstract: Disclosed herein is at least one cyclopropyl amide derivative, at least one pharmaceutical composition comprising at least one cyclopropyl amide derivative disclosed herein, and at least one method of using at least one cyclopropyl amide derivative disclosed herein for treating at least one histamine H3 receptor associated condition therewith.

Abstract: The present invention relates to new crystalline salt forms of flibanserine which have valuable pharmacological properties, to a process for their manufacture, to pharmaceutical formulations containing them and to their use as medicament.

Abstract: The present invention relates to novel triazole Hsp90 inhibitors that possess significant inhibitory activity against Hsp90, which are suitable for the treatment of hyperproliferative diseases such as cancer, infections, immune disorders, inflammation, and CNS related disorders. Furthermore, pharmaceutical compositions, including combination products, are also provided in the present application. Further provided are methods of using the pharmaceutical compositions and/or combination products.

Abstract: The disclosure is directed to a monohydrate crystalline form of 3-(5-(4-(3-fluoropropyl)piperazin-1-yl)benzimidazol-2-yl)-1-azaazulen-2-one, possessing diffraction peaks of about 12.9°, 15.9°, 17.9°, 21.2°, 22.9°, 23.5° and 24.5°. Its preparation method and pharmaceutical composition thereof are also provided.

Abstract: The invention relates to novel compounds, processes for their preparation and their use in protecting biological materials from radiation damage (radioprotection).

Abstract: The invention relates to a DGAT inhibitor of formula including any stereochemically isomeric form thereof, wherein A represents CH or N; the dotted line represents an optional bond in case A represents a carbon atom; X represents —O—C(?O)—; —C(?O)—C(?O)—; —NRx—C(?O)—; —Z—C(?O)—; —Z—NRx—C(?O)—; —C(?O)—Z—; —NRx—C(?O)—Z—; —C(?S)—; —NRx—C(?S)—; —Z—C(?S)—; —Z—NRx—C(?S)—; —C(?S)—Z—; —NRx—C(?S)—Z—; Z represents a bivalent radical selected from C1-6alkanediyl, C2-6alkenediyl or C2-6alkynediyl; wherein each of said C1-6alkanediyl, C2-6alkenediyl or C2-6alkynediyl may optionally be substituted; and wherein two hydrogen atoms attached to the same carbon atom in C1-6alkanediyl may optionally be replaced by C1-6alkanediyl; Y represents —C(?O)—NRx— or —NRx—C(?O)—; R1 represents adamantanyl, C3-6cycloalkyl; aryl1 or Het1; R2 represents C3-6cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl, 2,3-dihydrobenzofuranyl or a 6-membered aromatic heterocycle containing 1 or 2 N atoms, wherein said

Abstract: The present invention provides compounds which are useful as inhibitors of lysine-specific demethylase 1 (“LSD1”). The present invention also relates to pharmaceutical compositions containing these compounds. The present invention also relates to a method for preparing these compounds. The present invention also relates to a method of treating a mammalian disorder in which LSD1 levels are elevated by administering these compounds and compositions to a patient in need thereof. The present invention also relates to a method for decreasing histone demethylase activity in a mammal comprising administering to the mammal an effective amount of these compounds and compositions.

Abstract: Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: wherein Y, Z, R1, and s are defined herein.

Abstract: The present invention provides a compound represented by the following formula (I): wherein: Ring A represents an optionally substituted piperazine ring, an optionally substituted morpholine ring, or an optionally substituted bromopiperazine ring; R1 and R2 are the same or different from each other, and represent a hydrogen atom or optionally substituted lower alkyl; R3 and R4 are the same or different from each other, and represent a hydrogen atom or halogenated or non-halogenated lower alkyl; R3 to R7 are the same or different from each other, and represent a hydrogen atom, hydroxy, optionally substituted lower alkyl, optionally substituted lower alkenyl, optionally substituted lower alkoxy, optionally substituted cycloalkyl, optionally substituted aryl, an optionally substituted aromatic heterocyclic ring, optionally substituted amino, or acyl; and represents a single bond or double bond, wherein R2 and R3 do not exist when carbon atoms respectively adjacent to R2: and R3 form a double bond, and there is n

Abstract: The present invention relates to anti-HCV compounds, compositions comprising the same and methods of using the same to treat HCV infection.

Abstract: The invention relates to a group of 1H-imidazole derivatives which are modulators of cannabinoid CB2 receptors, to methods for the preparation of these compounds, to novel intermediates useful for the synthesis of said imidazole derivatives, to methods for the preparation of these intermediates, to pharmaceutical compositions containing one or more of these 1H-imidazole derivatives as active ingredient, as well as to the use of these pharmaceutical compositions for the treatment of disorders in which cannabinoid CB2 receptors are involved. The compounds have the general formula (I) wherein R1-R4 have the meanings given in the specification.

Abstract: A compound of formula (I), wherein R3, R4, G, B, M, and Z are as defined in the claims, and pharmaceutically acceptable salts thereof are disclosed. The compounds of formula (I) possess utility as FGFR inhibitors and are useful in the treatment of a condition, where FGFR kinase inhibition is desired, such as cancer.

Abstract: The present invention pertains to a compound of formula (I) wherein R1, R2, R3, and R4 are each hydrogen or sulfate monoester with the proviso that R1, R2, R3, and R4 cannot simultaneously be hydrogen, processess for their preparation and their use as pharmaceuticals in the treatment of CNS disorders.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention. The present invention relates to novel antiviral compounds represented herein above, pharmaceutical compositions comprising such compounds, and methods for the treatment or prophylaxis of viral (particularly HCV) infection in a subject in need of such therapy with the compounds.

Abstract: The present application relates to novel 1-phenyl-1H-imidazo[1,2-b]pyrazole derivatives, to processes for their preparation, to their use for the treatment and/or prevention of diseases and to their use for preparing medicaments for the treatment and/or prevention of diseases, in particular angiogenic disorders and hyperproliferative disorders, where neovascularization plays a role, such as, for example, neoplastic disorders and tumour disorders. Such treatments can be carried out as monotherapy or else in combination with other medicaments or further therapeutic measures.

Abstract: The invention is directed to compounds of Formula I: wherein Z, X, J, R2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase. Methods of treating autoimmune diseases; and diseases with an inflammatory component; treating metastasis from ovarian cancer, uterine cancer, breast cancer, prostate cancer, lung cancer, colon cancer, stomach cancer, hairy cell leukemia; and treating pain, including skeletal pain caused by tumor metastasis or osteoarthritis, or visceral, inflammatory, and neurogenic pain; as well as osteoporosis, Paget's disease, and other diseases in which bone resorption mediates morbidity including rheumatoid arthritis, and other forms of inflammatory arthritis, osteoarthritis, prosthesis failure, osteolytic sarcoma, myeloma, and tumor metastasis to bone with the compounds of Formula I, are also provided.

Abstract: The invention provides conjugate-based antifungal or antibacterial prodrugs formed by coupling at least one anti-fungal agent or antibacterial agent with at least one linker and/or carrier. The prodrugs are of formula: (i) (AFA)m-X-(L)n; (ii) [(AFA)m?-X]p-L; (iii) AFA-[X-(L)n?]q; or (iv) (AFA)m?-X, wherein: AFA is an antifungal agent or an antibacterial agent; L is a carrier; X is a linker; m ranges from 1 to 10; n ranges from 2 to 10; m? is 1 to 10; p is 1 to 10; n? is 1 to 10; and q is 1 to 10, provided that q? and n are not both 1; and m? is 1 to 10. The invention also provides nanoparticles comprising the conjugate-based prodrugs. Additionally, the invention also provides non-conjugated antifungal and antibacterial agents in the form of nanoparticles.

Abstract: The present invention relates to compounds useful as Chemokine Receptor antagonists. Compounds of general formula I are provided: or pharmaceutically acceptable salts thereof. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compounds and compositions for the inhibition of Chemokine Receptors and also for the treatment of various diseases, conditions, or disorders, including acute or chronic inflammatory disease, cancer or osteolytic bone disorders.

Abstract: The benzo[d]imidazole derivatives of piperidine and piperazine are 5-piperazinyl and 5-piperadinyl-1H-benzo[d]imidazol-2(3H)-ones that exhibit D2 and 5-HT1A receptor binding affinities, making them suitable for use as the active ingredient of pharmaceuticals for the treatment of schizophrenia. The derivatives have the general formula: where X is carbon or nitrogen and R is a selected biaryl group, or a pharmaceutically acceptable salt thereof. The piperidinyl compounds are prepared by removal of the Boc group from tert-Butyl-4-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)piperidine-1-carboxylate. Subsequent reductive amination with a selected biarylaldehyde completes the synthesis of the 5-piperazinyl-1H-benzo[d]imidazol-2(3H)-ones. The piperazinyl compounds are prepared by preparation of the intermediate tert-Butyl 4-(3,4-diaminophenyl)piperazine-1-carboxylate.

Abstract: The invention further relates to a DGAT inhibitor of formula including any stereochemically isomeric form thereof, wherein A represents CH or N; the dotted line represents an optional bond in case A represents a carbon atom; X represents —NRx—C(?O)—; —Z—C(?O)—; —Z—NRx—C(?O)—; —S(?O)p-; —C(?S)—; —NRx—C(?S)—; —Z—C(?S)—; —Z—NRx—C(?S)—; —O—C(?O)—; —C(?O)—C(?O)—; R1 represents a 5-membered monocyclic heterocycle containing at least 2 heteroatoms; a 6-membered aromatic monocyclic heterocycle; or a 5-membered heterocycle containing at least 2 heteroatoms fused with phenyl, cyclohexyl or a 5- or 6-membered heterocycle; wherein each of said heterocycles may optionally be substituted; R2 represents R3; R3 represents C3-6cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl, 2,3-dihydrobenzofuranyl or a 6-membered aromatic heterocycle containing 1 or 2 N atoms, wherein said C3-6cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxolyl, 2,3-dihydrobenzofuranyl or 6-

Abstract: The present invention relates to anti-HCV compounds, compositions comprising the same and methods of using the same to treat HCV infection.

Abstract: The invention provides crystalline solid forms of (((S)-1-{(S)-2-[4-(4?-{[6-((2R,5S)-2,5-dimethyl-4-methylcarbamoyl-piperazin-1-yl)-pyridine-3-carbonyl]-amino}-2?-trifluoromethoxy-biphenyl-4-yl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester. The invention also provides pharmaceutical compositions comprising such crystalline solid forms, methods of using such crystalline solid forms to treat hepatitis C virus infection, and processes useful for preparing such crystalline solid forms.

Abstract: The present invention relates to uses, methods and compositions for the treatment of pulmonary hypertension.

Abstract: This invention comprises the novel compounds of formula (I) wherein n, m, t, R1, R2, R3, R4, L, Q, X, Y, Z and have defined meanings, having histone deacetylase inhibiting enzymatic activity; their preparation, compositions containing them and their use as a medicine.

Abstract: The present invention relates to known and novel compounds of formula (I) as herein described and pharmaceutical compositions thereof. The compounds of formula (I) have inhibitory effect on the Wnt pathway and are therefore useful in the preparation of a medicament, in particular for the treatment of cancer.

Abstract: The present invention is directed to benzoimidazole compounds of the formula: and enantiomers, diastereomers, racemates, and pharmaceutically acceptable salts thereof. Compounds of the present invention are useful in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions modulated by prolyl hydroxylase activity.

Abstract: The invention further relates to a DGAT inhibitor of formula (I), including any stereochemically isomeric form thereof, wherein A represents CH or N; the dotted line represents an optional bond in case A represents a carbon atom; X represents —NRx—C(?O)—; —Z—C(?O)—; —Z—NRx—C(?O)—; —S(?O)p—; C(?S)—; —NRx—C(?S)—; —Z—C(?S)—; —Z—NRx—C(?S)—; —O—C(?O)—; —C(?O)—C(?O)—; R1 represents a 5-membered monocyclic heterocycle containing at least 2 heteroatoms; a 6-membered aromatic monocyclic heterocycle; or a 5-membered heterocycle containing at least 2 heteroatoms fused with phenyl, cyclohexyl or a 5-or 6-membered heterocycle; wherein each of said heterocycles may optionally be substituted; R2 represents R3; R3 represents C3-6cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzodioxinyl, 1,3-benzodioxlyl, 2,3-dihydrobenzofuranyl or a 6-membered aromatic heterocycle containing 1 or 2 N atoms, wherein said C3-6cycloalkyl, phenyl, naphtalenyl, 2,3-dihydro-1,4-benzo-dioxinyl, 1,3-benzodioxolyl, 2,3-dihydrobenzofuranyl or 6-m

Abstract: Heterocyclic compounds that modulate the hedgehog signaling pathway, pharmaceutical composition thereof and their therapeutic applications.

Abstract: A novel arylpiperazine-containing imidazole 4-carboxamide derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising the same as an active ingredient for preventing or treating a depressive disorder are provided.

Abstract: A compound represented by formula (I) or a pharmacologically acceptable salt thereof, which can inhibit a fibroblast growth factor receptor (FGFR) family kinase in cancer tissues. (In the formula, A represents a 5- to 10-membered heteroaryl group, or a C6-10 aryl group; R1 and R2 independently represent H, OH, X, CN, NO2, a C1-4 haloalkyl group, a C1-6 alkyl group, or the like <R1 and R2 together form a (substituted) 3- to 10-membered heterocyclyl group or a (substituted) 5- to 10-membered heteroaryl group>; R3 represents H, a C1-5 alkyl group, a C6-10 aryl group, a C1-5 alkyl group, or a C1-4 haloalkyl group; and R4 represents H, X, a C1-3 alkyl group, a C1-4 haloalkyl group, OH, CN, NO2, or the like.

Abstract: Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula (I) as follows: wherein Y, Z, R1, and s are defined herein.

Abstract: The invention is directed to compounds of Formula I: wherein Z, X, J, R2 and W are set forth in the specification, as well as solvates, hydrates, tautomers and pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase. Methods of treating autoimmune diseases; and diseases with an inflammatory component; treating metastasis from ovarian cancer, uterine cancer, breast cancer, prostate cancer, lung cancer, colon cancer, stomach cancer, hairy cell leukemia; and treating pain, including skeletal pain caused by tumor metastasis or osteoarthritis, or visceral, inflammatory, and neurogenic pain; as well as osteoporosis, Paget's disease, and other diseases in which bone resorption mediates morbidity including rheumatoid arthritis, and other forms of inflammatory arthritis, osteoarthritis, prosthesis failure, osteolytic sarcoma, myeloma, and tumor metastasis to bone with the compounds of Formula I, are also provided.

Abstract: The present invention relates to particular esters of bendamustine and related compounds, and medical uses thereof.

Abstract: This invention relates to novel heteroaryl substituted pyrazole compounds, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for treating hyper-proliferative and/or angiogenesis disorders, as a sole agent or in combination with other active ingredients or therapeutic measures.

Abstract: The invention relates to radioprotectors of formula (I), processes for their preparation and their use in protecting biological materials from radiation damage. In diagnostic and therapeutic radiology, particularly in cancer radiotherapy, the radioprotectors of the present invention may be used to protect certain normal tissues or structures from radiation damage. The radioprotectors of formula (I) may also have uses in decreasing the effects of irradiation in non-medical scenarios, both civil and military.

Abstract: The present invention relates to the treatment of oncological, chronic inflammatory and similar diseases with the aid of new families of chemical compounds having improved efficiency with regard to the inhibition of Abl kinase and mutant forms thereof, as well as other therapeutically significant kinases. It describes protein kinase inhibitors in the form of compounds of general formula (I) and compounds of general formula (II), or a tautomer, an individual isomer, a mixture of isomers, a pharmaceutically acceptable salt, a solvate or a hydrate thereof.

Abstract: The invention relates to a substituted phenylpiperazine aryl alkanol derivative represented by the following general formula and its salt and hydrate, wherein C1 and C2 represent chiral carbon atoms, and the compound is one of the six isomers: (1RS, 2SR), (1RS, 2RS), (1R, 2S), (1S, 2S), (1R, 2R) or (1S, 2R); and R, R1, R2, R3 and Ar are as defined in the specification. The derivative is non-opioid analgesic, has good analgesic effect and relatively small side effects. The invention also relates to a composition comprising the derivative and its use.

Abstract: The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Abstract: The disclosure relates to piperazine derivatives, compositions, and methods related thereto. In certain embodiments, the disclosure relates to inhibitors of NADPH-oxidase.

Abstract: Disclosed are compounds which inhibit the activity of anti-apoptotic protein family members, compositions containing the compounds and uses of the compounds for preparing medicaments for treating diseases during which occurs expression one or more than one of an anti-apoptotic protein family member.

Abstract: Compounds represented by formula I: or pharmaceutically acceptable salts and solvates thereof, wherein A, B, B?, X, Y, R1, R1?, R2, R2?, R3, R3?, R5, R5?, R6, m, n, or p are as defined herein, are useful for treating flaviviridae viral infections.

Abstract: The disclosure is directed to a monohydrate crystalline form of 3-(5-(4-(3-fluoropropyl)piperazin-1-yl)benzimidazol-2-yl)-1-azaazulen-2-one, possessing diffraction peaks of about 12.9°, 15.9°, 17.9°, 21.2°, 22.9°, 23.5° and 24.5°. Its preparation method and pharmaceutical composition thereof are also provided.