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.

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.

The present invention relates to novel compounds of formula (I) and pharmaceutical compositions containing these compounds. The compounds provided herein can act as prostaglandin E2 (PGE2) EP4 receptor antagonists, which renders them highly advantageous for use in therapy, particularly in the treatment or prevention of cancer, a neovascular eye disease, inflammatory pain, or an inflammatory disease, such as, e.g., multiple sclerosis, rheumatoid arthritis or endometriosis.

##STR00001##

The present invention relates to novel compounds of formula (I) and pharmaceutical compositions containing these compounds. The compounds provided herein can act as prostaglandin E2 (PGE2) EP4 receptor antagonists, which renders them highly advantageous for use in therapy, particularly in the treatment or prevention of cancer, a neovascular eye disease, inflammatory pain, or an inflammatory disease, such as, e.g., multiple sclerosis, rheumatoid arthritis or endometriosis.

##STR00001##

Provided herein piperazine and piperidine derivatives, their synthesis and use thereof in inhibiting VDAC oligomerization, apoptosis and mitochondria dysfunction. Also provided methods of treatment of diseases associated with said processes, e.g. Alzheimer's and Parkinson's diseases.

Provided herein piperazine and piperidine derivatives, their synthesis and use thereof in inhibiting VDAC oligomerization, apoptosis and mitochondria dysfunction. Also provided methods of treatment of diseases associated with said processes, e.g. Alzheimer's and Parkinson's diseases.

The present invention provides a compound represented by formula (I) or a pharmaceutically acceptable salt thereof which has the effect of antagonizing the LPA1 receptor.

This disclosure describes fentanyl haptens, a fentanyl hapten-carrier conjugate, methods of making the fentanyl hapten-carrier conjugate, and methods of using the fentanyl hapten-carrier conjugate including, for example, as a prophylactic vaccine to counteract toxicity from exposure to fentanyl, fentanyl derivatives, and fentanyl analogs. In some embodiments, the fentanyl hapten-carrier conjugate or a composition including the fentanyl hapten-carrier conjugate may be used in an anti-opioid vaccine.

Provided herein piperazine and piperidine derivatives, their synthesis and use thereof in inhibiting VDAC oligomerization, apoptosis and mitochondria dysfunction. Also provided methods of treatment of diseases associated with said processes, e.g. Alzheimer's and Parkinson's diseases.

Provided herein piperazine and piperidine derivatives, their synthesis and use thereof in inhibiting VDAC oligomerization, apoptosis and mitochondria dysfunction. Also provided methods of treatment of diseases associated with said processes, e.g. Alzheimer's and Parkinson's diseases.