This disclosure provides compounds with Bcl inhibitory activity based on a new chemical scaffold. The phospholidine compounds can include a P-phenyl phospholidine moiety which is substituted with an N-aryl or N-heteroaryl group. The P-phenyl phospholidine moiety can be optionally substituted at phosphorus with thio (S) instead of oxo (O). A second heteroatom attached to phosphorus can be cyclically linked to the N-substituted nitrogen atom of the phospholidine that is attached to the phosphorus to provide, together with the phosphorus atom through which they are connected, a heterocyclic ring. By incorporating such a cyclic constraint between two phosphorus substituents of the core linking moiety a favorable binding conformation can be promoted in the compounds. Selected compounds promote apoptosis in senescent cells, and can be developed for treating senescent-related conditions, such as osteoarthritis, ophthalmic disease, pulmonary disease, and atherosclerosis. Selected compounds promote apoptosis in cancer cells, and can be developed as chemotherapeutic agents.

In the field of organic phosphorus chemistry, especially the chemistry of bulky organophosphorus compounds, a process for the synthesis of compound of formula (I). This process is especially useful to obtain chiral bulky phosphorus compounds. The present invention also relates to compounds of formula (VII), (VIII), (IX) and (X) and their processes of manufacturing starting from a compound of formula (I).

##STR00001##

The invention relates to oligomerization of olefins, such as ethylene, to higher olefins, such as a mixture of 1-hexene and 1-octene, using a catalyst system that comprises a) a source of chromium b) one or more activators and c) a phosphacycle-containing ligating compound. Additionally, the invention relates to a phosphacycle-containing ligating compound and a process for making said compound.

This disclosure provides compounds with Bcl inhibitory activity based on a new chemical scaffold, as shown in Formula (I). ##STR00001##
The phospholidine compounds can include a P-phenyl phospholidine moiety which is substituted with an N-aryl or N-heteroaryl group. The P-phenyl phospholidine moiety can be optionally substituted at phosphorus with thio (S) instead of oxo (O). A second heteroatom attached to phosphorus can be cyclically linked to the N-substituted nitrogen atom of the phospholidine that is attached to the phosphorus to provide, together with the phosphorus atom through which they are connected, a heterocyclic ring. By incorporating such a cyclic constraint between two phosphorus substituents of the core linking moiety a favorable binding conformation can be promoted in the compounds. Selected compounds promote apoptosis in senescent cells, and can be developed for treating senescent-related conditions, such as osteoarthritis, ophthalmic disease, pulmonary disease, and atherosclerosis. Selected compounds promote apoptosis in cancer cells, and can be developed as chemotherapeutic agents.

This disclosure provides compounds with Bcl inhibitory activity based on a new chemical scaffold. Acyl phosphonamidate compounds may include a P-phenyl phosphonamidate moiety which is N-acylated with an aroyl or heteroaroyl group. The P-phenyl phosphonamidate moiety can be optionally substituted at phosphorus with thio (S) instead of oxo (O), and/or with a thioxy group or a second amino group instead of an oxy group. One of the heteroatoms attached to phosphorus can be cyclically linked to a carbon atom of the adjacent phenyl ring attached to the phosphorus to provide, together with the phosphorus atom through which they are connected, a heterocyclic ring. By incorporating such a cyclic constraint between two phosphorus substituents of the core linking moiety a favorable binding conformation can be promoted in the compounds. Selected compounds promote apoptosis in senescent cells, and can be developed for treating senescent-related conditions, such as osteoarthritis, ophthalmic disease, pulmonary disease, and atherosclerosis. Selected compounds promote apoptosis in cancer cells, and can be developed as chemotherapeutic agents.

The invention relates to oligomerization of olefins, such as ethylene, to higher olefins, such as a mixture of 1-hexene and 1-octene, using a catalyst system that comprises a) a source of chromium b) one or more activators and c) a phosphacycle-containing ligating compound. Additionally, the invention relates to a phosphacycle-containing ligating compound and a process for making said compound.

Compounds having the following structure (I) or a stereoisomer, tautomer or pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2 and R.sup.3 are as defined herein, and wherein at least one of R.sup.1, R.sup.2 and R.sup.3 is not H, are provided. Pharmaceutical compositions comprising the compounds and methods for use of the compounds for treating diseases associated with overexpression of a cyclin-dependent kinase (CDK) are also provided.

##STR00001##

The invention relates to oligomerization of olefins, such as ethylene, to higher olefins, such as a mixture of 1-hexene and 1-octene, using a catalyst system that comprises a) a source of chromium b) one or more activators and c) a phosphacycle-containing ligating compound. Additionally, the invention relates to a phosphacycle-containing ligating compound and a process for making said compound.

An organic compound denoted by formula [1],

##STR00001##

where each of X.sub.1 and X.sub.2 is independently selected from an alkyl group optionally having a substituent, an aryl group optionally having a substituent, and an aralkyl group optionally having a substituent, each of R.sub.11 to R.sub.20 is independently selected from a hydrogen atom and a substituent, Y represents an alkyl group optionally having a substituent or an aryl group optionally having a substituent, and each of A.sub.1.sup. and A.sub.2.sup. independently represents a monovalent anion.

Provided herein are prodrug compounds, their preparation and their uses, such as treating liver diseases or nonliver diseases via intervening in molecular pathways in the liver.