Abstract: The present disclosure relates to N-demethylation of a compound containing a tertiary N-methylamine, including for example a morphinan alkaloid, in a continuous flow system. In particular, the present disclosure relates to N-demethylation of oxymorphone-3,14-diacetate or 14-hydroxymorphinone-3,14-diacetate using highly active catalytic palladium (0) in a continuous flow system under elevated temperature and pressure condition. The methodology can be utilized towards the synthesis of noroxymorphone via aerobic palladium-catalyzed continuous flow N-demethylation.

Abstract: The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted heterocyclic derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of lysine specific demethylase-1. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.

Abstract: The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted heterocyclic derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of lysine specific demethylase-1. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.

Abstract: The present invention is directed to compounds of formula (I) which are inhibitors of the BACE1 enzyme. Separate aspects of the invention are directed to pharmaceutical compositions comprising said compounds and uses of the compounds to treat disorders for which the reduction of A? deposits is beneficial such as Alzheimer's disease.

Abstract: The present invention relates to compounds of formula hetaryl is a five membered heteroaryl group, containing 1 to 3 heteroatoms, selected from O, S or N; R1 is hydrogen, halogen, lower alkyl, lower alkoxy, lower alkyl substituted by halogen, S-lower alkyl substituted by halogen or lower alkoxy substituted by halogen, or two neighboring carbon atoms may form on phenyl an additional ring containing —O—CH2—O—; n is 1 to 5; R2 is hydrogen or lower alkyl substituted by halogen; R3 is hydrogen or lower alkyl substituted by halogen; or to pharmaceutically active acid addition salts thereof, to racemic mixtures or to its corresponding enantiomers or optical isomers or stereoisomers thereof. The compounds may be used for the treatment of Alzheimer's disease, cerebral amyloid angiopathy, hereditary cerebral hemorrhage with amyloidosis, Dutch-type (HCHWA-D), multi-infarct dementia, dementia pugilistica or Down syndrome.

Abstract: The invention provides organic complexes of Zn2+ that are useful for treating cancer, as well as compositions and kits comprising such complexes, and intermediate monomer compounds that are useful for the preparation of such complexes.

Abstract: A curable composition contains a compound represented by General Formula (1):

Abstract: The present invention provides, inter alia, a compound having the structure: Also provided are compositions containing a pharmaceutically acceptable carrier and a compound according to the present invention. Further provided are methods for treating or ameliorating the effects of an excitotoxic disorder in a subject, methods of modulating ferroptosis in a subject, methods of reducing reactive oxygen species (ROS) in a cell, and methods for treating or ameliorating the effects of a neurodegenerative disease.

Abstract: A substance of Formula (I) for use as a medicament for the treatment of cardiovascular diseases, wherein R is nitrogen or carbon; R1 is selected from the group consisting of a hydrogen, a trifluoromethyl, a methyloxyphenyl, a phenyl, a C1-C3 phenylalkyl, a halogenated phenyl, a halogenated C1-C3 phenylalkyl, a trifluoromethyloxy, a trifluoromethyl oxyphenyl, and a C1-C3 pyridinylalkyl; R2 is selected from the group consisting of a C1-C3 alkyl alcohol optionally substituted with a C1-C3 alkoxyphenyl, a C1-C3 N-alkylmethanamine, a C1-C3 alkoxymethyl, a C1-C3 phenylalkoxymethyl, a C1-C3 cyclopropylalkoxymethyl, and a methoxyethoxymethyl; and R3 is a phenyl or a methoxypyridinyl; and R4 is selected from the group consisting of a hydrogen, a cyano, a C1-C3 sulfonyl, a nitro, and a trifluoromethyl.

Abstract: The present disclosure generally relates to compounds of formula (I), wherein R2 is a phenyl or pyridinyl moiety, useful as immunomodulators. Provided herein are compounds, compositions comprising such compounds, and methods of their use. The disclosure further pertains to pharmaceutical compositions comprising at least one compound according to the disclosure that are useful for the treatment of various diseases, including cancer and infectious diseases.

Abstract: A pyridine based ionic liquid with a fluoride counter anion which catalyzes Fischer indole reaction and click chemistry. Methods of preparing the ionic liquid, and methods of utilizing the ionic liquid as a catalyst to synthesize indoles/indolenines and tetrazoles are also provided.

Abstract: A method for preparing an intermediate for avibactam, and specifically relates to a method for preparing ({[(2S,5R)-2-carbamoyl-7-oxo-1,6-diazabicyclo[3.2.1]oct-6-yl]oxy}sulfonyl)tetrabutylammonium salt (II). With 5R-[(benzyloxy) amino] piperidine-2S-carboxylate oxalate (III) as the raw material is reacted with the amide of Formula IV via amidation to prepare the compound of Formula V; the resulting compound of Formula V is reacted with the carbonylation reagent via urea cyclization to obtain the compound of Formula VI; the benzyl or the substituted benzyl in the compound of Formula VI is removed by catalytic hydrogeneration, then the resulting compound is sulfatated by sulfur trioxide complex and is salinized into tetrabutylammonium to obtain the final product (II).

Abstract: Improved methods of synthesizing 6-aryl-4-aminopicolinates, such as arylalkyl and alkyl 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2-carboxylates and arylalkyl and alkyl 4-amino-3-chloro-5-fluoro-6-(4-chloro-2-fluoro-3-methoxyphenyl)pyridine-2-carboxylates, are described herein. The improved methods include a direct Suzuki coupling step, which eliminates the protection/de-protection steps in the current chemical process, and therefore eliminates or reduces various raw materials, equipment and cycle time as well as modification of other process conditions including use of crude AP, use of ABA-diMe, and varying pH, catalyst concentration, solvent composition, and/or workup procedures. This includes synthesis of 2-aryl-6-aminopyrimidine-4-carboxylates.

Abstract: This invention relates to compounds of general formula (I) in which R1, R2, R3, R4, L, X and Z are as defined herein, and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.

Abstract: The present invention relates to a compound represented by the general formula (I) (wherein the definition of each group has the same meaning as described in the specification). The compound is useful as preventive and/or therapeutic agent for KCNQ2-5 channel-related diseases.

Abstract: This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels.

Abstract: The present invention provides a production method of heterocyclic compound having an excellent CH24H inhibitory action, which is suitable for industrial production. In the present invention, a 2-halogenonicotinic acid or a reactive derivative thereof or a salt thereof is reacted with 4-benzyl-4-hydroxypiperidine acid addition salt to give a (4-benzyl-4-hydroxypiperidin-1-yl) (2-halogenopyridin-3-yl)methanone or a salt thereof, and then the obtained compound is reacted with pyridine-4-boronic acid or a reactive derivative thereof or a salt thereof in the presence of a metal catalyst and a base to give (4-benzyl-4-hydroxypiperidin-1-yl) (2,4?-bipyridin-3-yl)methanone or a salt thereof.

Abstract: An electro-polarizable compound has the following general formula: Core1 is an aromatic polycyclic conjugated molecule having two-dimensional flat form and that self-assembles to form supramolecular structures. R1 are electron donor groups connected to Core1 and R1? are electron acceptor groups connected to Corel, m is number of acceptor groups R1, m? is a number of donor groups R?. The numbers m and m? are equal to 0, 1, 2, 3, 4, 5 or 6, but both m and m? are not both equal to 0. R2 is a substituent comprising one or more ionic groups connected to Core1 directly or via a connecting group; a number p of ionic groups R2 is 0, 1, 2, 3 or 4. The fragment marked NLE has a nonlinear effect of polarization. Core2 is a self-assembling electro-conductive oligomer, a number n of the such oligomers is 0, 2, or 4. R3 is a substituent comprising one or more ionic groups connected to Core2; a number s of the ionic groups R3 is 0, 1, 2, 3 or 4.

Abstract: The present invention relates to substituted heterocyclic derivative compounds, compositions comprising said compounds, and the use of said compounds and compositions for epigenetic regulation by inhibition of bromodomain-mediated recognition of acetyl lysine regions of proteins, such as histones. Said compositions and methods are useful for the treatment of cancer and neoplastic disease.

Abstract: The present invention is directed towards new chemical entities which primarily inhibit the human T-type calcium channels and differentially modulate other key ion channels to control cell excitability, and abnormal neuronal activity particularly involved in the development and maintenance of persistent or chronic pain, and/or neurological disorders. These novel compounds are useful in the treatment and prevention of neurological and psychiatric disorders and diseases in which these ion channels are involved. The invention is also directed towards pharmaceutical formulations comprising these compounds and the uses of these compounds.