There are described compounds of formula (I): (I) and their use as a medicament in the treatment of diseases associated with the abnormal or elevated catabolism of tryptophan, such as, cancer, immunosuppression, viral infection, depression, a neurodegenerative disorder, trauma, age-related cataracts, organ transplant rejection, or an autoimmune disorder in a patient.

##STR00001##

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.

The present disclosure provides a benzene fused heterocyclic derivative of Formula (I): is a single or double bond; n is an integer of 0 or 1; A is —CH.sub.2—, —CH(OH)—, or —C(O)—; G is C or N; X is —CH.sub.2—, O, or —C(O)—; Y is alkyl, aryl, or heterocyclic alkyl optionally substituted with at least one substituent independently selected from a group consisting of: H, halogen, alkyl, alkyl substituted with at least one halogen, aryl, aryl substituted with at least one halogen, —NR.sub.y1R.sub.y2, —OR.sub.y1, —R.sub.y1C(O)R.sub.y3, —C(O)R.sub.y1, —C(O)OR.sub.y2, —C(O)OR.sub.y2Ry3, —NR.sub.y1C(O)R.sub.y2, —NR.sub.y1C(O)NR.sub.y2R.sub.y3, —NR.sub.y1C(O)OR.sub.y2R.sub.y3, —NR.sub.y1C(O)R.sub.y2OR.sub.y3, C(O)NR.sub.y1(R.sub.y2R.sub.y3), —C(O)NR.sub.y1(R.sub.y2OR.sub.y1), —OR.sub.y2R.sub.y3, and —OR.sub.y2OR.sub.y3, wherein each of R.sub.y1 and R.sub.y2 is independently selected from a group consisting of H, oxygen, alkyl, and aryl, and R.sub.y3 is aryl optionally substituted with at least one halogen; Z is —NR.sub.z1R.sub.z2, —NR.sub.z1R.sub.z3, —OR.sub.z1, —OR.sub.z1R.sub.z3, —C(O)R.sub.z1R.sub.z3, —C(O)OR.sub.z1R.sub.z3, —NR.sub.z1C(O)R.sub.z2R.sub.z3, —NR.sub.z1C(O)OR.sub.z2R.sub.z3, —C(O)NR.sub.z1R.sub.z3, or OR.sub.z2OR.sub.z3, wherein each of R.sub.z1 and R.sub.z2 is independently selected from a group consisting of H, oxygen, alkyl and aryl, and R.sub.z3 is aryl optionally substituted with at least one substituent independently selected from a group consisting of halogen, OH, —R.sub.zaCOOR.sub.zb, —OR.sub.zaCOOR.sub.zb, —R.sub.zaSO.sub.2R.sub.zb, —R.sub.zaSO.sub.2NR.sub.zbR.sub.zcR.sub.zd, —R.sub.zaC(O)R.sub.zbR.sub.zc, —R.sub.zaC(O)NR.sub.zbR.sub.zcR.sub.zd, —RZ.sub.aC(O)NR.sub.zbSO.sub.2R.sub.zc, wherein Rza is nil or alkyl, R.sub.zb is H or alkyl, each of R.sub.zb and R.sub.zc is independently selected from a group consisting of H, OH, alkyl, aryl, alkoxyl, or NR.sub.zbR.sub.zc is a nitrogen-containing heterocyclic alkyl ring, R.sub.zd is nil or a sulfonyl alkyl group. ##STR00001##

The present invention provides novel diarylurea derivatives (compounds of formula (I)) and their uses. The compounds of the present invention are demonstrated to be allosteric modulators of the CB1 receptor, and therefore useful for the treatment of diseases and conditions mediated by CB1.

Provided herein are compounds, pharmaceutical compositions, and methods of treatment for various diseases or conditions, such as cancer. In one aspect, the method comprises the treatment of metastatic cancers. Compounds and methods provided herein are also used for the treatment of diseases such as inflammatory disease, cardiovascular disease, autoimmune disease, and dry eye syndrome. Further provided herein are dietary supplement formulations and methods for supporting a healthy lifestyle.

Provided herein are compounds, pharmaceutical compositions, and methods of treatment for various diseases or conditions, such as cancer. In one aspect, the method comprises the treatment of metastatic cancers. Compounds and methods provided herein are also used for the treatment of diseases such as inflammatory disease, cardiovascular disease, autoimmune disease, and dry eye syndrome. Further provided herein are dietary supplement formulations and methods for supporting a healthy lifestyle.

The present invention relates to phenyl urea derivatives useful for the treatment of inflammatory diseases, pharmaceutical compositions containing them and their use as tools or as pharmaceuticals as modulators of the N-formyl peptide receptor (FPR), including FPR1 and FPR2, or as selective agonists of the FPR1 receptor.

##STR00001##

The present invention relates to phenyl urea derivatives useful for the treatment of inflammatory diseases, pharmaceutical compositions containing them and their use as tools or as pharmaceuticals as modulators of the N-formyl peptide receptor (FPR), including FPR1 and FPR2, or as selective agonists of the FPR1 receptor.

##STR00001##

Novel diphenylurea and benzylbenzenesulfonamide compounds are disclosed along with methods of inhibiting the activity of TRPV1 and methods of treating pain associated with transient receptor potential vanilloid type 1 (TRPV1) using such compounds