In an embodiment of the invention, a composition for treating a cell population comprises a medicant. The medicant moiety can be an illudofulvene analog. In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The affinity moiety can be an antibody, an antibody fragment, a receptor protein, a peptidic growth factor, an anti-angiogenic protein, a specific binding peptide, protease cleavable peptide, a glycopeptide, a peptide, a peptidic toxin, a protein toxin and an oligonucleotide. The affinity moiety can be covalently bound to the medicant via a linker.

A method for producing (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid represented by the formula (10) below:

##STR00001##

the method including removing the protecting group from the hydroxyl group in a compound represented by formula (7) below:

##STR00002##

(wherein P represents a protecting group, R.sup.3 represents an alkyl group containing 1 to 4 carbon atoms, and A represents an alkyl group containing 1 to 10 carbon atoms, an aryl group containing 6 to 12 carbon atoms, an alkyloxy group containing 1 to 4 carbon atoms, or an aralkyloxy group containing 7 to 20 carbon atoms) to synthesize a compound represented by formula (8) below:

##STR00003##

(wherein R.sup.3 represents an alkyl group containing 1 to 4 carbon atoms, and A represents an alkyl group containing 1 to 10 carbon atoms, an aryl group containing 6 to 12 carbon atoms, an alkyloxy group containing 1 to 4 carbon atoms, or an aralkyloxy group containing 7 to 20 carbon atoms).

A method for producing (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid represented by the formula (10) below:

##STR00001##

the method including removing the protecting group from the hydroxyl group in a compound represented by formula (7) below:

##STR00002##

(wherein P represents a protecting group, R.sup.3 represents an alkyl group containing 1 to 4 carbon atoms, and A represents an alkyl group containing 1 to 10 carbon atoms, an aryl group containing 6 to 12 carbon atoms, an alkyloxy group containing 1 to 4 carbon atoms, or an aralkyloxy group containing 7 to 20 carbon atoms) to synthesize a compound represented by formula (8) below:

##STR00003##

(wherein R.sup.3 represents an alkyl group containing 1 to 4 carbon atoms, and A represents an alkyl group containing 1 to 10 carbon atoms, an aryl group containing 6 to 12 carbon atoms, an alkyloxy group containing 1 to 4 carbon atoms, or an aralkyloxy group containing 7 to 20 carbon atoms).

A process for the preparation of a polyunsaturated thiol comprising: (1) reacting a polyunsaturated alcohol in the presence of a compound of formula R.sub.2—SO.sub.2Hal wherein R.sub.2 is a C.sub.1-20 hydrocarbyl group, such an C.sub.1-10 alkyl group, to form a polyunsaturated sulphonyl ester; (2) converting the polyunsaturated sulphonyl ester to a polyunsaturated thioester by reacting with an anion of formula .sup.−SC(═O)R.sub.4 wherein R.sub.4 is a C.sub.1-20 hydrocarbyl group; (3) converting the polyunsaturated thioester to form a polyunsaturated thiol optionally in the presence of an antioxidant, e.g. using a metal carbonate. (4) reacting said polyunsaturated thiol with a compound (LG)R.sup.3COX wherein X is an electron withdrawing group and R.sup.3 is an alkylene group carrying a leaving group (LG), such as LG-CH.sub.2— forming

##STR00001## where X is an electron withdrawing group and LG is a leaving group; optionally in the presence of an antioxidant, so as to form a polyunsaturated ketone compound.

A process for the preparation of a polyunsaturated thiol comprising: (1) reacting a polyunsaturated alcohol in the presence of a compound of formula R.sub.2—SO.sub.2Hal wherein R.sub.2 is a C.sub.1-20 hydrocarbyl group, such an C.sub.1-10 alkyl group, to form a polyunsaturated sulphonyl ester; (2) converting the polyunsaturated sulphonyl ester to a polyunsaturated thioester by reacting with an anion of formula .sup.−SC(═O)R.sub.4 wherein R.sub.4 is a C.sub.1-20 hydrocarbyl group; (3) converting the polyunsaturated thioester to form a polyunsaturated thiol optionally in the presence of an antioxidant, e.g. using a metal carbonate. (4) reacting said polyunsaturated thiol with a compound (LG)R.sup.3COX wherein X is an electron withdrawing group and R.sup.3 is an alkylene group carrying a leaving group (LG), such as LG-CH.sub.2— forming

##STR00001## where X is an electron withdrawing group and LG is a leaving group; optionally in the presence of an antioxidant, so as to form a polyunsaturated ketone compound.

A series of phenelzine analogs comprising a phenelzine scaffold linked to an aromatic moiety and their use as inhibitors of lysine-specific demethylase 1 (LSD1) and/or one or more histone deacetylases (HDACs) is provided. The presently disclosed phenelzine analogs exhibit potency and selectivity for LSD1 versus MAO and LSD2 enzymes and exhibit bulk, as well as, gene specific histone methylation changes, anti-proliferative activity in several cancer cell lines, and neuroprotection in response to oxidative stress. Accordingly, the presently disclosed phenelzine analogs can be used to treat diseases, conditions, or disorders related to LSD1 and/or HDACs, including, but not limited to, cancers and neurodegenerative diseases.

A series of phenelzine analogs comprising a phenelzine scaffold linked to an aromatic moiety and their use as inhibitors of lysine-specific demethylase 1 (LSD1) and/or one or more histone deacetylases (HDACs) is provided. The presently disclosed phenelzine analogs exhibit potency and selectivity for LSD1 versus MAO and LSD2 enzymes and exhibit bulk, as well as, gene specific histone methylation changes, anti-proliferative activity in several cancer cell lines, and neuroprotection in response to oxidative stress. Accordingly, the presently disclosed phenelzine analogs can be used to treat diseases, conditions, or disorders related to LSD1 and/or HDACs, including, but not limited to, cancers and neurodegenerative diseases.

In an embodiment of the invention, a composition for treating a cell population comprises a medicant. The medicant moiety can be an illudofulvene analog. In an embodiment of the invention, a composition for treating a cell population comprises an Affinity Medicant Conjugate (AMC). The affinity moiety can be an antibody, an antibody fragment, a receptor protein, a peptidic growth factor, an anti-angiogenic protein, a specific binding peptide, protease cleavable peptide, a glycopeptide, a peptide, a peptidic toxin, a protein toxin and an oligonucleotide. The affinity moiety can be covalently bound to the medicant via a linker.

The invention relates to a multi-stage process for preparing 2,6-dialkylphenylacetic acids of the general formula (I) by reacting 2,6-dialkylbromobenzenes with (1) magnesium, (2) a formamide, (3) an acid, (4) hydrogenation of the benzaldehyde obtained, (5) activation of the benzyl alcohol obtained, (6) cyanation of the activated benzyl alcohol and (7) hydrolysis of the nitrile obtained.

This disclosure relates to modulators of liver receptor homologue 1 (LRH-1) and methods of managing disease and conditions related thereto. In certain embodiments, modulators are derivatives of hexahydropentalene. In certain embodiments, this disclosure relates to methods of treating or preventing cancer, diabetes, or cardiovascular disease by administering an effective amount of a hexahydropentalene derivative disclosed herein.