Compounds are provided having the structure of Formula (I): ##STR00001##
or a pharmaceutically acceptable isomer, racemate, hydrate, solvate, isotope, or salt thereof, wherein A, B, L, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.8, m and n are as defined herein. Such compounds modulate the opioid receptor, particulare the mu-opioid receptor (MOR) and/or the kappa-opioid receptor (KOR), and/or the delta-opioid receptor (DOR). Products containing such compounds, as well as methods for their use and preparation, are also provided.

The invention generally relates to methods of making substituted arenes via direct C—H, C—O, C—S, or C—N bond conversion and methods of synthesizing isotopically-labeled substituted arenes via direct carbon-halogen bond conversion. The invention also relates to anaerobic catalyst systems comprising an acridinium photocatalyst and a nucleophile selected from a halide, a cyanide, and an isotopically-labeled amine. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

The invention generally relates to methods of making substituted arenes via direct C—H, C—O, C—S, or C—N bond conversion and methods of synthesizing isotopically-labeled substituted arenes via direct carbon-halogen bond conversion. The invention also relates to anaerobic catalyst systems comprising an acridinium photocatalyst and a nucleophile selected from a halide, a cyanide, and an isotopically-labeled amine. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

A solidification or crystallization method is disclosed, which includes providing at least a first organic compound and at least one volatile co-former organic compound. A mixture of at least the first organic compound and the co-former organic compound is formed, wherein either the first organic compound or the volatile co-former organic compound includes a hydrogen acceptor moiety and the other includes a hydrogen donor moiety, thereby allowing the formation of hydrogen bonds between the first organic compound and the volatile co-former organic compound. The mixture is allowed to stand for sufficient time for the mixture to liquify at a temperature below that of the melting points of the components, thereby forming a liquid mixture. The volatile co-former organic compound is allowed to evaporate, thereby resulting in crystallization of at least the first organic compound. The method can be a co-crystallization method if there are two organic compounds.

A solidification or crystallization method is disclosed, which includes providing at least a first organic compound and at least one volatile co-former organic compound. A mixture of at least the first organic compound and the co-former organic compound is formed, wherein either the first organic compound or the volatile co-former organic compound includes a hydrogen acceptor moiety and the other includes a hydrogen donor moiety, thereby allowing the formation of hydrogen bonds between the first organic compound and the volatile co-former organic compound. The mixture is allowed to stand for sufficient time for the mixture to liquify at a temperature below that of the melting points of the components, thereby forming a liquid mixture. The volatile co-former organic compound is allowed to evaporate, thereby resulting in crystallization of at least the first organic compound. The method can be a co-crystallization method if there are two organic compounds.

Phenyl rings provide a robust scaffold for molecular design, given the limited number of ring carbon atoms and the fixed geometry in between. However, it can be difficult to form highly substituted phenyl rings suitable for covalent attachment of multiple moieties thereto. Moreover, binding phenyl rings to a surface in a fixed geometry may be difficult. Hexasubstituted benzenes having certain structural features may alleviate the foregoing difficulties by providing versatile groups for further functionalization and surface attachment. Such hexasubstituted benzenes may have a structure of

##STR00001##

in which each X is independently Cl, Br or N.sub.3, and each Z is independently —CH(Br)CH.sub.3, —CH(N.sub.3)CH.sub.3, —CH═CH.sub.2, —CH.sub.2CH.sub.3, —CH.sub.2CH.sub.2SiR′.sub.3 (R′=hydrocarbyl), or

##STR00002##

Alternating groups in the hexasubstituted benzenes may be directed toward opposite faces of the phenyl ring, such that orthogonal reactive groups are directed toward the opposite faces. Certain groups may facilitate surface attachment of the hexasubstituted benzenes.

Phenyl rings provide a robust scaffold for molecular design, given the limited number of ring carbon atoms and the fixed geometry in between. However, it can be difficult to form highly substituted phenyl rings suitable for covalent attachment of multiple moieties thereto. Moreover, binding phenyl rings to a surface in a fixed geometry may be difficult. Hexasubstituted benzenes having certain structural features may alleviate the foregoing difficulties by providing versatile groups for further functionalization and surface attachment. Such hexasubstituted benzenes may have a structure of

##STR00001##

in which each X is independently Cl, Br or N.sub.3, and each Z is independently —CH(Br)CH.sub.3, —CH(N.sub.3)CH.sub.3, —CH═CH.sub.2, —CH.sub.2CH.sub.3, —CH.sub.2CH.sub.2SiR′.sub.3 (R′=hydrocarbyl), or

##STR00002##

Alternating groups in the hexasubstituted benzenes may be directed toward opposite faces of the phenyl ring, such that orthogonal reactive groups are directed toward the opposite faces. Certain groups may facilitate surface attachment of the hexasubstituted benzenes.

Compounds and compositions comprising compounds that modulate histone acyl transferase (HAT). The invention further provides methods for treating neurodegenerative disorders, conditions associated with accumulated amyloid-beta peptide deposits, Tau protein levels, and/or accumulations of alpha-synuclein as well as cancer by administering a compound that modulates HAT to a subject.

The invention provides for compounds that are HAT activators or inhibitors. The invention further provides a method for treating neurodegenerative diseases, cancer and other malignant conditions, or to increase memory in a subject not suffering from a neurodegenerative disease by administering HAT activators or inhibitors to a subject in need thereof. The method further comprises co-administration of HD AC inhibitors with HAT activators or HD AC activators with HAT inhibitors.

The present invention relates to novel, optionally substituted, N-benzyl-2-phenoxybenzamide derivatives of formula (I), as modulators of EP4 and/or EP2 receptors of prostaglandin E2 (PGE2), to processes for their preparation, to pharmaceutical compositions comprising said compounds and to said compound for use in the treatment of pathological conditions, disorders or diseases that can improve by modulation of EP4 and/or EP2 receptors of prostaglandin E2 (PGE2) such as cancer disease, pain, inflammation, neurodegenerative diseases and kidney diseases.

##STR00001##