The present specification discloses tripartite androgen receptor eliminators (AREs), pharmaceutical compositions and medicaments comprising such AREs, methods and uses for such AREs and compositions and medicaments, and methods and uses for AREs and compositions and medicaments for treating an androgen receptor signaling-mediated condition, disease or disorder.

The invention provides heterocyclic compounds with quaternary centers and methods of preparing compounds. Methods include the method for the preparation of a compound of Formula (II): ##STR00001##
comprising treating a compound of Formula (I): ##STR00002##
with a transition metal catalyst and under alkylation conditions as valence and stability permit.

The invention provides heterocyclic compounds with quaternary centers and methods of preparing compounds. Methods include the method for the preparation of a compound of Formula (II): ##STR00001##
comprising treating a compound of Formula (I): ##STR00002##
with a transition metal catalyst and under alkylation conditions as valence and stability permit.

The present invention relates to processes and intermediates for preparing compounds of formula (IA), wherein R.sup.1, R.sup.4, R.sup.5, R.sup.6, and L.sup.1 are as defined herein. Compounds of formula (IA) have been found useful as EP.sub.4 receptor agonists useful in the treatment of glaucoma, osteoporosis, neuropathic pain, and related disorders. ##STR00001##

The present invention relates to processes and intermediates for preparing compounds of formula (IA), wherein R.sup.1, R.sup.4, R.sup.5, R.sup.6, and L.sup.1 are as defined herein. Compounds of formula (IA) have been found useful as EP.sub.4 receptor agonists useful in the treatment of glaucoma, osteoporosis, neuropathic pain, and related disorders. ##STR00001##

The invention relates to a novel process for preparing Spiro derivatives, in particular 7-methyl-2-[4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one, and to novel intermediates for use in said process along with processes for preparing said intermediates.

This disclosure provides methods for intermolecular enantioselective C-acylation of lactams with quaternary stereogenic centers by applying a chiral Ni catalyst. The methods comprise treating a lactam of formula (IIa): ##STR00001##
with a chiral Ni catalyst, an aryl nitrile, and an aryl halide to provide compounds of formula (Ia): ##STR00002##

This disclosure provides methods for intermolecular enantioselective C-acylation of lactams with quaternary stereogenic centers by applying a chiral Ni catalyst. The methods comprise treating a lactam of formula (IIa): ##STR00001##
with a chiral Ni catalyst, an aryl nitrile, and an aryl halide to provide compounds of formula (Ia): ##STR00002##

The invention is directed to substituted carbon-linked bicycloalkane derivatives. Specifically, the invention is directed to compounds according to Formula (X):

##STR00001## wherein C′, D′, L.sup.2′, L.sup.3′, R.sup.2′, R.sup.3′, R.sup.4′, R.sup.5′, R.sup.6′, R.sup.7′, R.sup.8′, z.sup.2′, z.sup.3′, z.sup.4′, z.sup.5′, z.sup.6′, X.sup.1, and X.sup.2 are as defined herein; or a salt thereof including a pharmaceutically acceptable salt 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, neurological disorders, pain, 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 carbon-linked bicycloalkane derivatives. Specifically, the invention is directed to compounds according to Formula (X):

##STR00001## wherein C′, D′, L.sup.2′, L.sup.3′, R.sup.2′, R.sup.3′, R.sup.4′, R.sup.5′, R.sup.6′, R.sup.7′, R.sup.8′, z.sup.2′, z.sup.3′, z.sup.4′, z.sup.5′, z.sup.6′, X.sup.1, and X.sup.2 are as defined herein; or a salt thereof including a pharmaceutically acceptable salt 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, neurological disorders, pain, 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.