Patent classifications
C07D309/08
NOVEL HEADGROUP LIPID COMPOUNDS AND COMPOSITIONS FOR INTRACELLULAR DELIVERY OF THERAPEUTIC AGENTS
The disclosure features novel lipids and compositions involving the same. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) include a novel lipid as well as additional lipids such as phospholipids, structural lipids, and PEG lipids. Lipid nanoparticles (e.g., empty LNPs or loaded LNPs) further including therapeutic and/or prophylactics such as RNA are useful in the delivery of therapeutic and/or prophylactics to mammalian cells or organs to, for example, regulate polypeptide, protein, or gene expression.
ARYLAMIDE DERIVATIVE HAVING ANTITUMOR ACTIVITY
The present disclosure provides, for example, a compound represented by general formula (6) below or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of the compound or salt:
##STR00001##
wherein X.sub.1, X.sub.2, X.sub.3 and X.sub.4 are each independently —CR.sub.2═ or —N═, R.sub.2 is, for example, a halogen atom, R.sub.1 is, for example, —S(═O).sub.2—NH—R.sub.8, R.sub.8 is, for example, a C1-6 alkyl group, R.sub.3 is, for example, a hydrogen atom, R.sub.5 is, for example, a halogen atom, R.sub.6 is, for example, a hydrogen atom, and R.sub.4 is, for example, a cyclopropyl group. The compounds, salts or solvates provided by the present disclosure exhibit high RAF/MEK complex-stabilizing activity and can be used for the treatment or prevention of cell proliferative disorders, particularly cancers.
ARYLAMIDE DERIVATIVE HAVING ANTITUMOR ACTIVITY
The present disclosure provides, for example, a compound represented by general formula (6) below or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of the compound or salt:
##STR00001##
wherein X.sub.1, X.sub.2, X.sub.3 and X.sub.4 are each independently —CR.sub.2═ or —N═, R.sub.2 is, for example, a halogen atom, R.sub.1 is, for example, —S(═O).sub.2—NH—R.sub.8, R.sub.8 is, for example, a C1-6 alkyl group, R.sub.3 is, for example, a hydrogen atom, R.sub.5 is, for example, a halogen atom, R.sub.6 is, for example, a hydrogen atom, and R.sub.4 is, for example, a cyclopropyl group. The compounds, salts or solvates provided by the present disclosure exhibit high RAF/MEK complex-stabilizing activity and can be used for the treatment or prevention of cell proliferative disorders, particularly cancers.
PROSTAGLANDIN E2 (PGE2) EP4 RECEPTOR ANTAGONISTS
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##
PROSTAGLANDIN E2 (PGE2) EP4 RECEPTOR ANTAGONISTS
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##
SMALL MOLECULES THAT SENSITIZE HIV-1 INFECTED CELLS TO ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY
Compounds and methods of treating HIV-1 in a human infected with HIV-1 or preventing HIV-1 infection in a human susceptible to infection with HIV-1 are provided. The compounds are of formula (I), (II), and (IA), wherein R.sup.1-R.sup.7, X, X′, Y, Y′, Z, and n are defined herein, and the methods comprises administering therapeutically effective amounts of these compounds to the human.
##STR00001##
SMALL MOLECULES THAT SENSITIZE HIV-1 INFECTED CELLS TO ANTIBODY DEPENDENT CELLULAR CYTOTOXICITY
Compounds and methods of treating HIV-1 in a human infected with HIV-1 or preventing HIV-1 infection in a human susceptible to infection with HIV-1 are provided. The compounds are of formula (I), (II), and (IA), wherein R.sup.1-R.sup.7, X, X′, Y, Y′, Z, and n are defined herein, and the methods comprises administering therapeutically effective amounts of these compounds to the human.
##STR00001##
TRIARYL COMPOUNDS FOR TREATMENT OF PD-L1 DISEASES
Compounds are provided that are useful as immunomodulators. The compounds have the Formula (I)
##STR00001##
including stereoisomers and pharmaceutically acceptable salts thereof, wherein R.sup.1a, R.sup.1b, R.sup.1c, R.sup.1d, R.sup.2a, R.sup.2b, R.sup.3, R.sup.3a, R.sup.4, R.sup.6, R.sup.7, R.sup.8, A, Z, X.sup.1 and n are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.
Inhibitors of histone deacetylase
The present invention relates to compounds of formula (I): ##STR00001##
or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein U, J, V, X, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.5 and t are as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. These compounds are useful for promoting cognitive function and enhancing learning and memory formation. In addition, these compounds are useful for treating, alleviating, and/or preventing various conditions, including for example, neurological disorders, memory and cognitive function disorders/impairments, extinction learning disorders, fungal diseases and infections, inflammatory diseases, hematological diseases, and neoplastic diseases in humans and animals.
Inhibitors of histone deacetylase
The present invention relates to compounds of formula (I): ##STR00001##
or a pharmaceutically acceptable salt, hydrate, solvate, or prodrug thereof, wherein U, J, V, X, R.sup.2a, R.sup.2b, R.sup.2c, R.sup.5 and t are as described herein. The present invention relates generally to inhibitors of histone deacetylase and to methods of making and using them. These compounds are useful for promoting cognitive function and enhancing learning and memory formation. In addition, these compounds are useful for treating, alleviating, and/or preventing various conditions, including for example, neurological disorders, memory and cognitive function disorders/impairments, extinction learning disorders, fungal diseases and infections, inflammatory diseases, hematological diseases, and neoplastic diseases in humans and animals.