Provided herein are processes for preparing an oligomer (e.g., a morpholino oligomer). The synthetic processes described herein may be advantageous to scaling up oligomer synthesis while maintaining overall yield and purity of a synthesized oligomer.

Provided herein are processes for preparing an oligomer (e.g., a morpholino oligomer). The synthetic processes described herein may be advantageous to scaling up oligomer synthesis while maintaining overall yield and purity of a synthesized oligomer.

The present invention discloses a compound with the following formula (I), or a tautomer, mesomer, racemate, enantiomer, and diastereoisomer thereof, or a mixture form thereof, or a pharmaceutically acceptable salt thereof, or a prodrug molecule thereof, wherein D is selected from:

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The invention further discloses the use of the compound in the preparation of drugs for preventing and/or treating cancers, and the use of the compound in the preparation of drugs for inhibiting cancer metastasis. The compound of the present invention can effectively inhibit the proliferation and metastasis of cancer cells by adjusting the acidity of a tumor microenvironment to achieve a better effect in clinical cancer treatment, and has broad application prospects.

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This disclosure provides compounds with Bcl inhibitory activity based on a new chemical scaffold. Phosphonamidate compounds typically include a P-phenyl phosphonamidate moiety which is substituted with an N-aryl or N-heteroaryl group. The P-phenyl phosphonamidate moiety may 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 may be cyclically linked to the N-substituted nitrogen atom that is attached to the phosphorus to provide a heterocyclic ring. By incorporating such a cyclic constraint between two phosphorus substituents of the core linking moiety, a favorable binding conformation may 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. Phosphonamidate compounds typically include a P-phenyl phosphonamidate moiety which is substituted with an N-aryl or N-heteroaryl group. The P-phenyl phosphonamidate moiety may 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 may be cyclically linked to the N-substituted nitrogen atom that is attached to the phosphorus to provide a heterocyclic ring. By incorporating such a cyclic constraint between two phosphorus substituents of the core linking moiety, a favorable binding conformation may 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 invention relates generally to olefin metathesis catalyst compounds, to the preparation of such compounds, compositions comprising such compounds, methods of using such compounds, articles of manufacture comprising such compounds, and the use of such compounds in the metathesis of olefins and olefin compounds. The invention has utility in the fields of catalysts, organic synthesis, polymer chemistry, and industrial and fine chemicals industry.

The invention features compounds of the general formula (I) in which the variable groups are as defined herein, and to their preparation and use.

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The invention features compounds of the general formula (I) in which the variable groups are as defined herein, and to their preparation and use.

##STR00001##

This invention relates generally to olefin metathesis catalyst compounds, to the preparation of such compounds, compositions comprising such compounds, methods of using such compounds, articles of manufacture comprising such compounds, and the use of such compounds in the metathesis of olefins and olefin compounds. The invention has utility in the fields of catalysts, organic synthesis, polymer chemistry, and industrial and fine chemicals industry.

The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a transthyretin (TTR) gene, and methods of using the dsRNA to inhibit expression of TTR.