Enzyme compositions, steroid derivatives, enzyme inhibitors, and methods of making same for pharmaceutical applications

Patent metadata

Field	Value
Publication number	US-11214591-B2
Application number	US-201916576406-A
Country	US
Kind code	B2
Filing date	Sep 19, 2019
Priority date	Sep 19, 2018
Publication date	Jan 4, 2022
Grant date	Jan 4, 2022

Abstract

The present disclosure provides for a synthetic strategy to incorporate a C12α-hydroxy group from the methylene (—CH2-) in a steroid backbone, combining synthetic chemistry and enzymology techniques to develop a selective inhibitor for cytochrome P450 8B1, and developing a selective P450 8B1 inhibitor, which can be used as a tool to study P450 8B1 and treat health issues.

First claim

The invention claimed is:

1. A compound having a general formula (I) or a pharmaceutically acceptable salt thereof:

2. A compound having a general formula (II) or a pharmaceutically acceptable salt thereof:

3. The general formula of claim 1 , wherein the general formula is reductively animated to produce at least one derivative.

4. The at least one derivative of claim 3 , wherein the derivative is a 12-dimethylamino derivative.

5. The at least one derivative of claim 3 , wherein the derivative is a substrate of P450 8B1.

6. A pharmaceutical composition comprising the compound of claim 1 .

7. The general formula of claim 2 , wherein the general formula is reductively animated to produce at least one derivative.

8. The at least one derivative of claim 7 , wherein the derivative is a 12-dimethylamino derivative.

9. The at least one derivative of claim 7 , wherein the derivative is a substrate of P450 8B1.

10. A pharmaceutical composition comprising the compound of claim 2 .

Assignees

• Univ Texas

Inventors

• Yoshimoto Francis

Classifications

• C07J9/00

  Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane · CPC title

• C07J43/003

  not condensed · CPC title

• C07J51/00

  Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00 · CPC title

• C07J9/005

  containing a carboxylic function directly attached or attached by a chain containing only carbon atoms to the cyclopenta[a]hydrophenanthrene skeleton · CPC title

• C07J41/0005

  the nitrogen atom being directly linked to the cyclopenta(a)hydro phenanthrene skeleton · CPC title