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

The present invention relates to a new compound of formula (I) wherein the variables have the meaning as indicated in the claims; or an enantiomer or salt thereof. The compounds of formula (I) are useful in the control of parasites, in particular endoparasites, in and on vertebrates.

##STR00001##

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 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.

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

A method for preparing norbornyl (meth)acrylate by reacting norbornene with (meth)acrylic acid in the presence of boron trifluoride as catalyst, wherein a) boron trifluoride is initially charged in (meth)acrylic acid or an organic solvent, b) the initial charge is heated to a temperature of 75 to 110° C., c) norbornene is added or a mixture comprising norbornene and (meth)acrylic acid is added and d) the norbornyl (meth)acrylate obtained is isolated from the reaction mixture.

A method for preparing norbornyl (meth)acrylate by reacting norbornene with (meth)acrylic acid in the presence of boron trifluoride as catalyst, wherein e) boron trifluoride is initially charged in (meth)acrylic acid, f) the initial charge is heated to a temperature of 75 to 110 C., g) norbornene is added and h) the norbornyl (meth)acrylate obtained is isolated from the reaction mixture.

A method for preparing norbornyl (meth)acrylate by reacting norbornene with (meth)acrylic acid in the presence of boron trifluoride as catalyst, wherein e) boron trifluoride is initially charged in an organic solvent, f) the initial charge is heated to a temperature of 75 to 110 C., g) a mixture comprising norbornene and (meth)acrylic acid is added and h) the norbornyl (meth)acrylate obtained is isolated from the reaction mixture.

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

Disclosed is a cyclopropanation process comprising the step of reacting an alkene compound having at least one carbon-carbon double bond with at least one dihaloalkane. The reaction is carried out in the presence of (i) particulate metal Zn, (ii) catalytically effective amount of particulate metal Cu or a salt thereof, (iii) at least one haloalkylsilane, and (iv) at least one solvent.