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 compounds of the invention as shown by general structure I, as shown below, are effective in treating filovirus infections. ##STR00001## X is selected from the group consisting of O and H; R.sup.1 is selected from (C.sub.6 to C.sub.10) aryl and (C.sub.2 to C.sub.9) heteroaryl, and R.sup.2 is selected from (C.sub.1 to C.sub.10) alkyl, (C.sub.1 to C.sub.10) alkenyl, (C.sub.1 to C.sub.10) alkynyl, (C.sub.3 to C.sub.10) cycloalkyl, and (C.sub.5 to C.sub.10) cycloalkenyl, and NR.sup.3aR.sup.3b is defined in the specification. These compounds are effective in treating filovirii infections including Ebolavirus and Marburg virus.

The compounds of the invention as shown by general structure I, as shown below, are effective in treating filovirus infections. ##STR00001## X is selected from the group consisting of O and H; R.sup.1 is selected from (C.sub.6 to C.sub.10) aryl and (C.sub.2 to C.sub.9) heteroaryl, and R.sup.2 is selected from (C.sub.1 to C.sub.10) alkyl, (C.sub.1 to C.sub.10) alkenyl, (C.sub.1 to C.sub.10) alkynyl, (C.sub.3 to C.sub.10) cycloalkyl, and (C.sub.5 to C.sub.10) cycloalkenyl, and NR.sup.3aR.sup.3b is defined in the specification. These compounds are effective in treating filovirii infections including Ebolavirus and Marburg virus.

A compound of Formula (I), or a pharmaceutically acceptable salt thereof, is described, wherein the substituents are as defined herein. Pharmaceutical compositions comprising the same and method of using the same are also described.

##STR00001##

The disclosure provides ionizable amine lipids and salts thereof (e.g., pharmaceutically acceptable salts thereof) useful for the delivery of biologically active agents, for example delivering biologically active agents to cells to prepare engineered cells. The ionizable amine lipids disclosed herein are useful as ionizable lipids in the formulation of lipid nanoparticle-based compositions.

Binding of the transcriptional co-activator, YAP1, to the transcription factor Oct4, induces Sox2, which is a transcription actor necessary for the self-renewal of stem-like cells from non-small cell lung cancer. The WW domain of YAP1 binds to the PPxY motif of Oct4 to induce Sox2. Delivering a peptide corresponding to the WW domain could prevent the induction of Sox2 and stemness. Similarly, peptides and mimetics of the PPxY motif would be able to inhibit sternness. Disclosed are compounds that affect the Yap1:Oct4 interaction.

Provided herein are methods and compounds for targeted autophagy.

The present invention relates to novel compounds of formula (I) and pharmaceutical compositions containing these compounds. The compounds provided herein can act as prostaglandin E2 (PGE2) EP4 receptor antagonists, which renders them highly advantageous for use in therapy, particularly in the treatment or prevention of cancer, a neovascular eye disease, inflammatory pain, or an inflammatory disease, such as, e.g., multiple sclerosis, rheumatoid arthritis or endometriosis.

##STR00001##

The present invention relates to a heterocyclic sulfoximine compound represented by formula (I), and racemates, enantiomers, pharmaceutically acceptable salts or solvates thereof. Also disclosed herein are an intermediate compound for synthesizing the compound, a preparation method therefor, and a pharmaceutical composition comprising the compound and use thereof. The compound is RET, RET mutant, or RET fusion protein inhibitor, capable of treating diseases caused by abnormal activity of RET, RET mutant, or RET fusion protein, for example, tumors.

A compound is represented by formula I. A stereoisomer, tautomer, solvate, polymorph of the compound or a pharmaceutically acceptable salt of the compound, a pharmaceutical composition containing the compound, a preparation method of the compound, and the medical use of the compound are provided.

##STR00001##