The invention is directed to substituted piperidine derivatives. Specifically, the invention is directed to compounds according to Formula IIII: ##STR00001##
wherein A, B, X, Y, L.sup.1, L.sup.2, L.sup.3, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.9, z.sup.2, z.sup.4, z.sup.5, and z.sup.6 are as defined herein, and salts thereof. The compounds of the invention are inhibitors of the ATF4 pathway and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, diabetes, Parkinson disease, Huntington's disease, Creutzfeldt-Jakob Disease, and related prion diseases, progressive supranuclear palsy, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, inflammation, fibrosis, chronic and acute diseases of the liver, chronic and acute diseases of the lung, chronic and acute diseases of the kidney, chronic traumatic encephalopathy (CTE), neurodegeneration, dementia, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting the ATF4 pathway and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

A method of treating patients by using a pharmaceutical composition for intra-intestinal administration comprises (i) a dopamine replacement agents, (ii) a dopamine decarboxylase inhibitor (DDI), and (iii) a COMT inhibitor where the composition is continuously administrated.

The present invention relates in part to nucleic acids encoding proteins, nucleic acids containing non-canonical nucleotides, therapeutics comprising nucleic acids, methods, kits, and devices for inducing cells to express proteins, methods, kits, and devices for transfecting, gene editing, and reprogramming cells, and cells, organisms, and therapeutics produced using these methods, kits, and devices. Methods for inducing cells to express proteins and for reprogramming and gene-editing cells using RNA are disclosed. Methods for producing cells from patient samples, cells produced using these methods, and therapeutics comprising cells produced using these methods are also disclosed.

The invention relates to Spirocyclic ether derivatives of pyrazolo[1,5-a]pyrimidine-3-carboxyamide of general formula (I) which are inhibitors of phosphodiesterase 2, useful in treating central nervous system diseases and other diseases. In addition, the invention relates to processes for preparing pharmaceutical compositions as well as processes for manufacture the compounds according to the invention.

The invention discloses a substituted pyrazole compound of formula (I), preparation method therefor, a pharmaceutical composition and a medical use thereof. The said compound features excellent stability, solubility, and low cytotoxicity, which is significantly beneficial for neurological protection, effectively preventing and treating nerve cell injuries. It is an ideal pharmaceutical compound for preventing or treating stroke, cerebral embolism, stroke sequelae, stroke-related motor dysfunction, mitochondrial encephalomyopathy, and amyotrophic lateral sclerosis. ##STR00001##

The present invention relates to novel steroidal compounds of formula (I), process for preparation of the same and composition comprising these compounds. ##STR00001##

The present invention relates to novel steroidal compounds of formula (I), process for preparation of the same and composition comprising these compounds. ##STR00001##

Disclosed herein are compositions and methods for treating a sigma-2 receptor-mediated condition or disorder, including treating one or more symptoms of a sigma-2 receptor-mediated condition or disorder.

There is provided in the present application a pharmaceutical composition comprising a peptide comprising the amino acid sequence of YEKLLDTEI (SEQ ID NO: 1) or a functional variant thereof, a pH adjusting agent, and a filler. The peptide is an active peptide for the treatment of a central nervous system injury. The present application also provides a pharmaceutical composition comprising a chimeric peptide comprising an active peptide and an internalization peptide, a pH adjusting agent, and a filler. The present application also provides medical use of a pharmaceutical composition comprising the active peptide or the chimeric peptide.

Compounds of the present invention and pharmaceutically acceptable compositions thereof, are useful as modulators of 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 compounds of the present invention.