Disclosed are compounds of Formula (I′), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds inhibit PD-1/PD-L1 interaction and are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.

##STR00001##

Disclosed are compounds of Formula (I′), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds inhibit PD-1/PD-L1 interaction and are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.

##STR00001##

Intermediates and methods are provided for the preparation of selected C5aR antagonist compounds.

Intermediates and methods are provided for the preparation of selected C5aR antagonist compounds.

A compound is shown in formula I and can be in the form of a pharmaceutically acceptable salt, or a stereoisomer, or a solvate, or a prodrug, or a metabolite. The compound takes effect rapidly and has a long-time local anesthetic effect following a single dose, with the sensory nerve blocking time being greater than the motor nerve blocking time, has both a long-acting local anesthetic effect and a selective local anesthetic effect, significantly reduces side effects of the compositions QX314 and QX314 and a quaternary ammonium salt compound with surfactant structural characteristics, and is safer. The compound of formula I of the present invention and a pharmaceutically acceptable salt thereof can be used for preparing drugs that have a long-time local anesthetic effect and a selective local anesthetic effect.

A compound is shown in formula I and can be in the form of a pharmaceutically acceptable salt, or a stereoisomer, or a solvate, or a prodrug, or a metabolite. The compound takes effect rapidly and has a long-time local anesthetic effect following a single dose, with the sensory nerve blocking time being greater than the motor nerve blocking time, has both a long-acting local anesthetic effect and a selective local anesthetic effect, significantly reduces side effects of the compositions QX314 and QX314 and a quaternary ammonium salt compound with surfactant structural characteristics, and is safer. The compound of formula I of the present invention and a pharmaceutically acceptable salt thereof can be used for preparing drugs that have a long-time local anesthetic effect and a selective local anesthetic effect.

This disclosure relates to novel detergents for use in various procedures including, for example, nucleic acid amplification reactions such as polymerase chain reaction (PCR). Methods for preparing the modified detergents are also described.

This disclosure relates to novel detergents for use in various procedures including, for example, nucleic acid amplification reactions such as polymerase chain reaction (PCR). Methods for preparing the modified detergents are also described.

The invention is directed to substituted piperidine derivatives. Specifically, the invention is directed to compounds according to Formula IIII: ##STR00001##
wherein A, B, X, Y, L.sup.1, L.sup.2, L.sup.3, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.9, z.sup.2, z.sup.4, z.sup.5, and z.sup.6 are as defined herein, and salts 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, 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 piperidine derivatives. Specifically, the invention is directed to compounds according to Formula IIII: ##STR00001##
wherein A, B, X, Y, L.sup.1, L.sup.2, L.sup.3, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.9, z.sup.2, z.sup.4, z.sup.5, and z.sup.6 are as defined herein, and salts 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, 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.