Disclosed are compounds, compositions and methods for treating diseases, disorders, or medical conditions that are affected by the modulation of DHODH. Such compounds are represented by Formula (I) as follows:

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wherein R.sup.1a, R.sup.1b, R.sup.2, and R.sup.3, are defined herein.

This document provides compounds that are inhibitors of NF-κB activity, as well as the methods of using such compounds for treating diseases and conditions such as cancer, inflammatory conditions, or autoimmune diseases.

The efficient preparation method of a tedizolid intermediate includes the following steps: 1) subjecting 2-fluoro-4-substituted phenylacetic acid to a reaction with a Vilsmeier reagent, and adding a resulting reaction solution to an MX aqueous solution for quenching to obtain an intermediate shown in formula (II); and 2) subjecting the intermediate shown in formula (II) obtained in step 1) and 1-(2-methyl-2H-tetrazol-5-yl)ethanone to one-pot synthesis in the presence of an alkali and an ammonia source to obtain the intermediate shown in formula (I). In this method, a pyridine ring of the key intermediate shown in formula (I) is obtained through a ring-closing reaction of the 1-(2-methyl-2H-tetrazol-5-yl)ethanone and a Vinamidinium salt, and a key methyltetrazolyl group is introduced into the structure, which successfully avoids the use of highly-toxic sodium cyanide and sodium azide, the use of expensive palladium catalyst, and the use of methylation with low selectivity.

The efficient preparation method of a tedizolid intermediate includes the following steps: 1) subjecting 2-fluoro-4-substituted phenylacetic acid to a reaction with a Vilsmeier reagent, and adding a resulting reaction solution to an MX aqueous solution for quenching to obtain an intermediate shown in formula (II); and 2) subjecting the intermediate shown in formula (II) obtained in step 1) and 1-(2-methyl-2H-tetrazol-5-yl)ethanone to one-pot synthesis in the presence of an alkali and an ammonia source to obtain the intermediate shown in formula (I). In this method, a pyridine ring of the key intermediate shown in formula (I) is obtained through a ring-closing reaction of the 1-(2-methyl-2H-tetrazol-5-yl)ethanone and a Vinamidinium salt, and a key methyltetrazolyl group is introduced into the structure, which successfully avoids the use of highly-toxic sodium cyanide and sodium azide, the use of expensive palladium catalyst, and the use of methylation with low selectivity.

Provided herein are compounds that bind to BF3 of an androgen receptor (AR), which can modulate the AR for the treatment of Kennedy's disease

The present application discloses a synthesis method of chiral nicotine from nicotinate and γ-butyrolactone, including the following steps: Step S1: performing condensation under an alkaline condition, and performing ring opening reaction with hydrochloric acid; Step S2: reacting with (+)-B-diisopinocampheyl chloroborane to produce a chiral hydroxyl group; Step S3: performing a chlorination reaction; and Step S4: performing cyclization under an alkaline condition to obtain the chiral nicotine. In the present application, nicotinate and γ-butyrolactone, both cheap and readily available, are used as raw materials, so as to reduce the production cost of (S)-nicotine. (+)-B-diisopinocampheyl chloroborane is used to reduce a carbonyl group of an intermediate to obtain a target chiral center. The (+)-B-diisopinocampheyl chloroborane induces the production of a chiral hydroxyl group, chlorination and cyclization are performed to form chiral (S)-demethylnicotine, and finally amine methylation is performed to obtain (S)-nicotine with photochemical activity.

The present application discloses a synthesis method of chiral nicotine from nicotinate and γ-butyrolactone, including the following steps: Step S1: performing condensation under an alkaline condition, and performing ring opening reaction with hydrochloric acid; Step S2: reacting with (+)-B-diisopinocampheyl chloroborane to produce a chiral hydroxyl group; Step S3: performing a chlorination reaction; and Step S4: performing cyclization under an alkaline condition to obtain the chiral nicotine. In the present application, nicotinate and γ-butyrolactone, both cheap and readily available, are used as raw materials, so as to reduce the production cost of (S)-nicotine. (+)-B-diisopinocampheyl chloroborane is used to reduce a carbonyl group of an intermediate to obtain a target chiral center. The (+)-B-diisopinocampheyl chloroborane induces the production of a chiral hydroxyl group, chlorination and cyclization are performed to form chiral (S)-demethylnicotine, and finally amine methylation is performed to obtain (S)-nicotine with photochemical activity.

The present disclosure relates to certain amides and heterocyclic compounds and uses of these amides and heterocyclic compounds to inhibit Rho-associated protein kinases and treat diseases including autoimmune disorders, graft versus host disease (GVHD), inflammation, cardiovascular disorders, central nervous system disorders, and neoplastic disorders.

In one aspect, compounds of Formula AA, or a pharmaceutically acceptable salt thereof, are featured or a pharmaceutically acceptable salt thereof, wherein the variables shown in Formula A can be as defined anywhere herein.

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The present invention relates to bispecific compounds, compositions, and methods for treating diseases or conditions mediated by aberrant histone deacety lase 6 (HDAC6) activity.