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 sternness. Similarly, peptides and mimetics of the PPxY motif would be able to inhibit sternness. Disclosed are compounds that affect the Yap1:Oct4 interaction.

The present disclosure relates to compounds of formulas (A) and (I), pharmaceutically acceptable salts thereof, and solvates of any of the foregoing, pharmaceutical compositions comprising the same, methods of preparing the same, intermediate compounds useful for preparing the same, and methods for treating or prophylaxis of diseases, in particular cancer, such as colorectal cancer, using the same.

##STR00001##

The present disclosure relates to compounds of formulas (A) and (I), pharmaceutically acceptable salts thereof, and solvates of any of the foregoing, pharmaceutical compositions comprising the same, methods of preparing the same, intermediate compounds useful for preparing the same, and methods for treating or prophylaxis of diseases, in particular cancer, such as colorectal cancer, using the same.

##STR00001##

Provided herein are compounds of Formula (I), their pharmaceutically acceptable salts, and their pharmaceutical compositions:

##STR00001##

wherein R.sup.1, R.sup.2, R.sup.3a, R.sup.3b, R.sup.4, R.sup.5, and A are defined in the present disclosure. The compounds are potent inhibitors of the main protease (M.sup.pro) of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), and they are useful in treating or preventing COVID-19 in a subject.

Compounds and methods for use in detecting pregabalin in a sample suspected of containing pregabalin are disclosed. Pregabalin derivatives are described for producing pregabalin conjugates. A pregabalin-immunogenic carrier conjugate may be used as an immunogen for the preparation of an anti-pregabalin antibody. A pregabalin-detectable label conjugate may be used in a signal producing system in pregabalin assays.

Compounds and methods for use in detecting pregabalin in a sample suspected of containing pregabalin are disclosed. Pregabalin derivatives are described for producing pregabalin conjugates. A pregabalin-immunogenic carrier conjugate may be used as an immunogen for the preparation of an anti-pregabalin antibody. A pregabalin-detectable label conjugate may be used in a signal producing system in pregabalin assays.

There are provided bivalent compounds and conjugates thereof, the conjugates comprising a bivalent compound, a targeting moiety, and a bioactive agent, as well as pharmaceutical compositions and methods of use of the conjugate for the treatment, inhibition, or prevention of diseases and disorders which are therapeutic targets of the bioactive agent.

##STR00001##

The invention provides compounds for use as medicaments, which act by inhibiting CYP17A1 and CYP19A1 enzymes. The compounds have particular application in the treatment of cancer especially prostate cancer and breast cancer. The compounds have the formula: [Chem. 1] wherein: R is independently selected from the group consisting of optionally substituted arylamide; optionally substituted alkylarylamide; optionally substituted aryl carboxamide; optionally substituted cyanopiperidine; optionally substituted oxopiperidine; optionally substituted N-(pyridin-3-yl); optionally substituted pyridin-3-yl; optionally substituted pyrazole-4-carboxamide; optionally substituted pyrimidin-4-ylcarboxamide; optionally substituted pyrimidin-4-ylcarboxamide; optionally substituted 1H-pyrrol-2-ylcarboxamide; optionally substituted morpholin carboxamide; optionally substituted 1H-indazol-3-ylcarboxamide; optionally substituted 5-cyanopiperidin-3-ylcarboxamide; optionally substituted quinolin-7-yl; optionally substituted pyrazin-2-ylcarboxamide; optionally substituted 1H-1,3-benzodiazole-6-carboxamide; and optionally substituted 3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-ylcarboxamide; Each R1, R2, R3, R4, R5 is independently selected from the group consisting of H; OH; a halogen atom; OCH.sub.3; and NH.sub.2; and X is independently selected from the group consisting of O, H and OH. Some of the compounds are claimed per se and the invention also encompasses pharmaceutically acceptable salts, solvates, hydrates, primary metabolites and prodrugs thereof.

The invention provides compounds for use as medicaments, which act by inhibiting CYP17A1 and CYP19A1 enzymes. The compounds have particular application in the treatment of cancer especially prostate cancer and breast cancer. The compounds have the formula: [Chem. 1] wherein: R is independently selected from the group consisting of optionally substituted arylamide; optionally substituted alkylarylamide; optionally substituted aryl carboxamide; optionally substituted cyanopiperidine; optionally substituted oxopiperidine; optionally substituted N-(pyridin-3-yl); optionally substituted pyridin-3-yl; optionally substituted pyrazole-4-carboxamide; optionally substituted pyrimidin-4-ylcarboxamide; optionally substituted pyrimidin-4-ylcarboxamide; optionally substituted 1H-pyrrol-2-ylcarboxamide; optionally substituted morpholin carboxamide; optionally substituted 1H-indazol-3-ylcarboxamide; optionally substituted 5-cyanopiperidin-3-ylcarboxamide; optionally substituted quinolin-7-yl; optionally substituted pyrazin-2-ylcarboxamide; optionally substituted 1H-1,3-benzodiazole-6-carboxamide; and optionally substituted 3-oxo-3,4-dihydro-2H-1,4-benzoxazin-7-ylcarboxamide; Each R1, R2, R3, R4, R5 is independently selected from the group consisting of H; OH; a halogen atom; OCH.sub.3; and NH.sub.2; and X is independently selected from the group consisting of O, H and OH. Some of the compounds are claimed per se and the invention also encompasses pharmaceutically acceptable salts, solvates, hydrates, primary metabolites and prodrugs thereof.

The invention concerns lipid assemblies, liposomes having an outer surface comprising a mixture of anionic and cationic moieties; wherein at least a portion of the cationic moieties are imino moieties that are essentially charged under physiological conditions, and their use for serum resistant transfection of cells.