The present invention relates to the discovery that certain non-naturally occurring, non-peptide amide compounds and amide derivatives, such as oxalamides, ureas, and acrylamides, are useful flavor or taste modifiers, such as a flavoring or flavoring agents and flavor or taste enhancer, more particularly, savory (the umami taste of monosodium glutamate) or sweet taste modifiers, savory or sweet flavoring agents and savory or sweet flavor enhancers, for food, beverages, and other comestible or orally administered medicinal products or compositions.

The present invention relates to the discovery that certain non-naturally occurring, non-peptide amide compounds and amide derivatives, such as oxalamides, ureas, and acrylamides, are useful flavor or taste modifiers, such as a flavoring or flavoring agents and flavor or taste enhancer, more particularly, savory (the umami taste of monosodium glutamate) or sweet taste modifiers, savory or sweet flavoring agents and savory or sweet flavor enhancers, for food, beverages, and other comestible or orally administered medicinal products or compositions.

There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds of the invention.

There are disclosed compounds that modulate or inhibit the enzymatic activity of indoleamine 2,3-dioxygenase (IDO), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders, such as cancer, viral infections and/or inflammatory disorders utilizing the compounds 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##

Disclosed is a composition and method for a therapeutic treatment that is able to combat neuroinflammation caused by diseases and disorders such as Alzheimer's disease, Parkinson's disease, and traumatic brain injury. The class of urea compounds acts by blocking at targeted receptors in the brain that contribute to the increase in inflammation. Combinations of receptors, H1 receptor, H2 receptor, dopamine transporter (DAT), and/or 5HT3C receptor, are individually and/or collectively inhibited by the same compositions of the present disclosure, and this ability leads to a decrease in brain edema. The DAT inhibitory effects additionally maintains dopamine levels in a patient.

Disclosed is a composition and method for a therapeutic treatment that is able to combat neuroinflammation caused by diseases and disorders such as Alzheimer's disease, Parkinson's disease, and traumatic brain injury. The class of urea compounds acts by blocking at targeted receptors in the brain that contribute to the increase in inflammation. Combinations of receptors, H1 receptor, H2 receptor, dopamine transporter (DAT), and/or 5HT3C receptor, are individually and/or collectively inhibited by the same compositions of the present disclosure, and this ability leads to a decrease in brain edema. The DAT inhibitory effects additionally maintains dopamine levels in a patient.

The present invention relates to amide derivatives of Formula (XIIIa) and pharmaceutical compositions thereof that modulate the activity of the PGI2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: Pulmonary arterial hypertension (PAH); idiopathic PAH; familial PAH; PAH associated with a collagen vascular disease, a congenital heart disease, portal hypertension, HIV infection, ingestion of a drug or toxin, hereditary hemorrhagic telangiectasia, splenectomy, pulmonary veno-occlusive disease (PVOD) or pulmonary capillary hemangiomatosis (PCH); PAH with significant venous or capillary involvement; platelet aggregation; coronary artery disease; myocardial infarction; transient ischemic attack, angina; stroke; ischemia-reperfusion injury; restenosis; atrial fibrillation; blood clot formation in an angioplasty or coronary bypass surgery individual or in an individual suffering from atrial fibrillation; atherosclerosis; atherothrombosis; asthma or a symptom thereof; a diabetic-related disorder such as diabetic peripheral neuropathy, diabetic nephropathy or diabetic retinopathy; glaucoma or other disease of the eye with abnormal intraocular pressure; hypertension; inflammation; psoriasis; psoriatic arthritis; rheumatoid arthritis; Crohn's disease; transplant rejection; multiple sclerosis; systemic lupus erythematosus (SLE); ulcerative colitis; ischemia-reperfusion injury; restenosis; atherosclerosis; acne; type 1 diabetes; type 2 diabetes; sepsis; and chronic obstructive pulmonary disorder (COPD).

The present invention relates to amide derivatives of Formula (XIIIa) and pharmaceutical compositions thereof that modulate the activity of the PGI2 receptor. Compounds of the present invention and pharmaceutical compositions thereof are directed to methods useful in the treatment of: Pulmonary arterial hypertension (PAH); idiopathic PAH; familial PAH; PAH associated with a collagen vascular disease, a congenital heart disease, portal hypertension, HIV infection, ingestion of a drug or toxin, hereditary hemorrhagic telangiectasia, splenectomy, pulmonary veno-occlusive disease (PVOD) or pulmonary capillary hemangiomatosis (PCH); PAH with significant venous or capillary involvement; platelet aggregation; coronary artery disease; myocardial infarction; transient ischemic attack, angina; stroke; ischemia-reperfusion injury; restenosis; atrial fibrillation; blood clot formation in an angioplasty or coronary bypass surgery individual or in an individual suffering from atrial fibrillation; atherosclerosis; atherothrombosis; asthma or a symptom thereof; a diabetic-related disorder such as diabetic peripheral neuropathy, diabetic nephropathy or diabetic retinopathy; glaucoma or other disease of the eye with abnormal intraocular pressure; hypertension; inflammation; psoriasis; psoriatic arthritis; rheumatoid arthritis; Crohn's disease; transplant rejection; multiple sclerosis; systemic lupus erythematosus (SLE); ulcerative colitis; ischemia-reperfusion injury; restenosis; atherosclerosis; acne; type 1 diabetes; type 2 diabetes; sepsis; and chronic obstructive pulmonary disorder (COPD).

Compounds of Formula (Ia) ##STR00001##
wherein R is a C.sub.6-C.sub.12 substituted or unsubstituted aryl, a C.sub.6-C.sub.12 substituted or unsubstituted heteroaryl, a C.sub.1-C.sub.6 substituted or unsubstituted alkyl or NRR, Q is C(O), O, NR, S, S(O).sub.2, C(O).sub.2 (CH2)p Y is C(O), O, NR, S, S(O).sub.2, C(O).sub.2 (CH2)p Z is H or C.sub.1-C.sub.4 alkyl, R is H, C(O), S(O).sub.2, C(O).sub.2, a C.sub.6-C.sub.12 substituted or unsubstituted aryl, a C.sub.6-C.sub.12 substituted or unsubstituted heteroaryl or a C.sub.1-C.sub.6 substituted or unsubstituted alkyl, when substituted, aryl, heteroaryl and alkyl are substituted with halogen, C.sub.6-C.sub.12 heteroaryl, NRR or COOZ, which have diagnostic and therapeutic properties, such as the treatment and management of prostate cancer and other diseases related to NAALADase inhibition. Radiolabels can be incorporated into the structure through a variety of prosthetic groups attached at the X amino acid side chain via a carbon or hetero atom linkage.