The invention features a series of heterocyclic derivatives that inhibit tumor necrosis factor alpha (TNF-) induced necroptosis. The heterocyclic compounds of the invention are described by Formulas (I)-(VIII) and by Compounds (1)-(7), (13)-(26), (27)-(33), (48)-(57), and (58)-(70). These necrostatins are shown to inhibit TNF- induced necroptosis in FADD-deficient variant of human Jurkat T cells. The invention further features pharmaceutical compositions featuring necrostatins. The compounds and compositions of the invention may also be used to treat disorders where necroptosis is likely to play a substantial role.

The present invention relates to an optically active axially chiral -allenic alcohol, a synthesis method and use thereof. The invention relates to a method of preparing a highly optically active chiral -allenic alcohol by using propargyl alcohol, aldehyde and chiral ,-diphenyl-L-prolinol under the protection of tert-butyldimethylsilyl with an accelerant zinc bromide. The axially chiral -allenic alcohol has the structural formula (I). The method of the present invention has the following advantages: the synthesis route is short, operations are simple, raw materials are readily available, separation and purification are convenient, the substrate has high universality, the total yield is high, and enantioselectivity and diastereoselectivity are high. The highly optically active axially chiral -allenic alcohol synthesized by the method of the present invention can conveniently synthesize 2,5-dihydrofuran compounds having central chirality and complete chirality, and at the same time can further synthesize axially chiral allenic amine and allenic malonic ester compounds having complete chirality. ##STR00001##

The present invention relates to an optically active axially chiral -allenic alcohol, a synthesis method and use thereof. The invention relates to a method of preparing a highly optically active chiral -allenic alcohol by using propargyl alcohol, aldehyde and chiral ,-diphenyl-L-prolinol under the protection of tert-butyldimethylsilyl with an accelerant zinc bromide. The axially chiral -allenic alcohol has the structural formula (I). The method of the present invention has the following advantages: the synthesis route is short, operations are simple, raw materials are readily available, separation and purification are convenient, the substrate has high universality, the total yield is high, and enantioselectivity and diastereoselectivity are high. The highly optically active axially chiral -allenic alcohol synthesized by the method of the present invention can conveniently synthesize 2,5-dihydrofuran compounds having central chirality and complete chirality, and at the same time can further synthesize axially chiral allenic amine and allenic malonic ester compounds having complete chirality. ##STR00001##

An object of the present invention is to provide novel amine-protecting groups useful for the synthesis of special amino acids. Provided is an amine-protecting group.

An object of the present invention is to provide novel amine-protecting groups useful for the synthesis of special amino acids. Provided is an amine-protecting group.

Compounds having the following structure (VI-A): ##STR00001##
or any pharmaceutically acceptable salt or solvate thereof, or any stereoisomer thereof, wherein R.sub.E1, R.sub.E2, R.sub.E3, R.sub.E4, Z.sub.E2 and Z.sub.E3 are as disclosed herein, are provided. Pharmaceutical compositions comprising the compounds, and methods for use of the compounds for treating disorders associated with necrosptosis are also provided.

Compounds having the following structure (VI-A): ##STR00001##
or any pharmaceutically acceptable salt or solvate thereof, or any stereoisomer thereof, wherein R.sub.E1, R.sub.E2, R.sub.E3, R.sub.E4, Z.sub.E2 and Z.sub.E3 are as disclosed herein, are provided. Pharmaceutical compositions comprising the compounds, and methods for use of the compounds for treating disorders associated with necrosptosis are also provided.

A composition for film formation includes a compound represented by formula (1) and a solvent. In the formula (1), R.sup.1, R.sup.2 and R.sup.3 each independently represent a group represented by the formula (a). In the formula (a), R.sup.A represents a hydrogen atom, an aryl group, or an alkyl group unsubstituted or substituted with at least one of a hydroxy group and an aryl group. R.sup.B represents a single bond or an arylene group. A part or all of hydrogen atoms on an aromatic ring of the aryl group and the arylene group may be substituted with a halogen atom, a hydroxy group, an amino group, a sulfanyl group, or a monovalent organic group having 1 to 20 carbon atoms and not including an aromatic ring. ##STR00001##

A composition for film formation includes a compound represented by formula (1) and a solvent. In the formula (1), R.sup.1, R.sup.2 and R.sup.3 each independently represent a group represented by the formula (a). In the formula (a), R.sup.A represents a hydrogen atom, an aryl group, or an alkyl group unsubstituted or substituted with at least one of a hydroxy group and an aryl group. R.sup.B represents a single bond or an arylene group. A part or all of hydrogen atoms on an aromatic ring of the aryl group and the arylene group may be substituted with a halogen atom, a hydroxy group, an amino group, a sulfanyl group, or a monovalent organic group having 1 to 20 carbon atoms and not including an aromatic ring. ##STR00001##

CB-7 exhibits a weak TLR7 inhibiting effect in normal mice. The present invention provides a novel compound with a stronger TLR7 inhibiting effect than CB-7, a pharmaceutically acceptable salt of said compound, or a prodrug of said compound or salt. The present invention also provides a drug for the prevention or treatment of diseases associated with the activation of TLR7, said drug including the aforementioned TLR7 activation inhibitor.