The present disclosure relates to novel compounds, methods, and compositions capable of binding to PCSK9, thereby modulating PCSK9 proprotein convertase enzyme activity. The compounds of the disclosure include compounds Formula (I).

Described herein is the development of an arenophile-mediated, nickel-catalyzed dearomative trans-1,2-carboamination protocol. A range of readily available aromatic compounds was converted to the corresponding dienes using Grignard reagents as nucleophiles. This strategy provided products with exclusive trans-selectivity and high enantioselectivity was observed in case of benzene and naphthalene. The utility of this methodology was showcased by controlled and stereoselective preparation of small, functionalized molecules.

A concise synthesis of (+)-pancratistatin and (+)-7-deoxypancratistatin from benzene using an enantioselective, dearomative carboamination strategy has been achieved. This approach, in combination with the judicious choice of subsequent olefin-type difunctionalization reactions, permits rapid and controlled access to a hexasubstituted core. Finally, minimal use of intermediary steps as well as direct, late stage C-7 hydroxylation provides both natural products in six and seven operations.

Described herein is the development of an arenophile-mediated, nickel-catalyzed dearomative trans-1,2-carboamination protocol. A range of readily available aromatic compounds was converted to the corresponding dienes using Grignard reagents as nucleophiles. This strategy provided products with exclusive trans-selectivity and high enantioselectivity was observed in case of benzene and naphthalene. The utility of this methodology was showcased by controlled and stereoselective preparation of small, functionalized molecules.

A concise synthesis of (+)-pancratistatin and (+)-7-deoxypancratistatin from benzene using an enantioselective, dearomative carboamination strategy has been achieved. This approach, in combination with the judicious choice of subsequent olefin-type difunctionalization reactions, permits rapid and controlled access to a hexasubstituted core. Finally, minimal use of intermediary steps as well as direct, late stage C-7 hydroxylation provides both natural products in six and seven operations.

The present invention provides novel 4-methylsulphone-substituted piperidine urea compounds that are useful for the treatment of dilated cardiomyopathy (DCM) and conditions associated with left and/or right ventricular systolic dysfunction or systolic reserve. The synthesis and characterization of the compounds is described, as well as methods for treating DCM and other forms of heart disease.

The present invention provides novel 4-methylsulphone-substituted piperidine urea compounds that are useful for the treatment of dilated cardiomyopathy (DCM) and conditions associated with left and/or right ventricular systolic dysfunction or systolic reserve. The synthesis and characterization of the compounds is described, as well as methods for treating DCM and other forms of heart disease.

A liquid crystal compound satisfies at least one of physical properties such as a high stability to heat, light and so forth, a high clearing point, a low minimum temperature of a liquid crystal phase, a small viscosity, a suitable optical anisotropy, a large negative dielectric anisotropy, a suitable elastic constant and an excellent compatibility with other liquid crystal compounds. The compound is represented by formula (1). ##STR00001## In the formula, for example, R.sup.1 and R.sup.2 are alkyl having 1 to 15 carbons; ring A.sup.1 and ring A.sup.2 are 1,4-cyclohexylene or 1,4-phenylene, Z.sup.1 and Z.sup.2 are a single bond, (CH.sub.2).sub.2, CHCH, CC, COO, OCO, CH.sub.2O, OCH.sub.2, CF.sub.2O, OCF.sub.2 or CFCF, a and b are 0, 1 or 2, and a sum of a and b is 1 or 2.

A liquid crystal compound satisfies at least one of physical properties such as a high stability to heat, light and so forth, a high clearing point, a low minimum temperature of a liquid crystal phase, a small viscosity, a suitable optical anisotropy, a large negative dielectric anisotropy, a suitable elastic constant and an excellent compatibility with other liquid crystal compounds. The compound is represented by formula (1). ##STR00001## In the formula, for example, R.sup.1 and R.sup.2 are alkyl having 1 to 15 carbons; ring A.sup.1 and ring A.sup.2 are 1,4-cyclohexylene or 1,4-phenylene, Z.sup.1 and Z.sup.2 are a single bond, (CH.sub.2).sub.2, CHCH, CC, COO, OCO, CH.sub.2O, OCH.sub.2, CF.sub.2O, OCF.sub.2 or CFCF, a and b are 0, 1 or 2, and a sum of a and b is 1 or 2.

Novel heterocyclo compounds represented by Formula I wherein X, R1, R2, R3, R4, R5, R6 and n are as described herein are provided. The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of cancer conditions in mammals including humans, including prostate, colon, bladder, melanoma, liver, breast, cervical, ovarian, esophagi, glialblastoma, pancreatic and lung cancer.

Provided are siglec ligands and siglec conjugates. Also provided are methods of use of such conjugates, as well as pharmaceutical compositions thereof.

Provided are siglec ligands and siglec conjugates. Also provided are methods of use of such conjugates, as well as pharmaceutical compositions thereof.