Amide compounds are disclosed. Also disclosed are pharmaceutical compositions comprising the compounds as well as methods of treating neurodegenerative diseases that involve administering the compounds or pharmaceutical compositions to a subject.

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.

Compounds and compositions including stereoisomers of 6-phenylhexanamide derivative small molecule mitofusin activators are described. In particular, mitofusin activators comprising derivatives of (trans-4-hydroxycyclohexyl)-6-phenylhexanamide, which are useful for treating diseases or disorders associated with a mitochondria-associated disease, disorder, or condition such as diseases or disorders associated with mitofusin-1 (MFN1) and/or mitofusin-2 (MFN2), or mitochondrial dysfunction, are described. Methods of treatment and pharmaceutical formulations are also described.

Compounds and compositions including stereoisomers of 6-phenylhexanamide derivative small molecule mitofusin activators are described. In particular, mitofusin activators comprising derivatives of (trans-4-hydroxycyclohexyl)-6-phenylhexanamide, which are useful for treating diseases or disorders associated with a mitochondria-associated disease, disorder, or condition such as diseases or disorders associated with mitofusin-1 (MFN1) and/or mitofusin-2 (MFN2), or mitochondrial dysfunction, are described. Methods of treatment and pharmaceutical formulations are also described.

Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases, disorders and conditions.

Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases, disorders and conditions.

Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases; disorders and conditions.

Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases; disorders and conditions.

The invention is directed to substituted bridged cycloalkane derivatives. Specifically, the invention is directed to compounds according to Formula I:

##STR00001##

wherein X, a, b, C, D, L.sup.2, L.sup.3, Y.sup.1, Y.sup.2, R.sup.2, R.sup.4, R.sup.5, R.sup.6, z.sup.2, z.sup.4, z.sup.5, and z.sup.6 are as defined herein, and salts thereof.

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 bridged cycloalkane derivatives. Specifically, the invention is directed to compounds according to Formula I:

##STR00001##

wherein X, a, b, C, D, L.sup.2, L.sup.3, Y.sup.1, Y.sup.2, R.sup.2, R.sup.4, R.sup.5, R.sup.6, z.sup.2, z.sup.4, z.sup.5, and z.sup.6 are as defined herein, and salts thereof.

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.