Synthesis of syrbactin proteasome inhibitors

Patent metadata

Field	Value
Publication number	US-9783572-B2
Application number	US-201615171513-A
Country	US
Kind code	B2
Filing date	Jun 2, 2016
Priority date	Dec 3, 2009
Publication date	Oct 10, 2017
Grant date	Oct 10, 2017

Abstract

The disclosure relates generally to methods for the preparation of a family of natural compounds, the syrbactins and their analogs.

First claim

What is claimed is:

1. A method of treating a subject having a cancer selected from the group consisting of lymphoma, acute lymphocytic leukemia, multiple myeloma and Waldenstrom's macroglobulinemia, comprising administering to the subject in need thereof a combination therapy comprising one or more chemotherapeutic drugs and an effective amount of a compound having a structure of:

wherein,
R 3 is an alkyl;
R 8 is

R 9 is either a (C 1 -C 6 )alkyl, or a (C 1 -C 6 )alkenyl;
Z is an unsubstituted (C 11 -C 16 )alkyl; and
X is NH or O.

2. The method of claim 1 , wherein the compound has a structure:

wherein,
R 3 is a (C 1 -C 6 )alkyl;
R 8 is

R 9 is either a (C 1 -C 3 )alkyl, or a (C 1 -C 3 )alkenyl;
Z is an unsubstituted (C 11 -C 16 )alkyl; and
X is NH or O.

3. The method of claim 2 , wherein the compound has a structure:

wherein,
R 3 is either a methyl, ethyl, propyl, or C(CH 3 ) 2 ;
R 8 is

R 9 is either a methyl or an ethyl;
Z is an unsubstituted (C 11 -C 16 ) alkyl; and
X is NH or O.

4. The method of claim 3 , wherein the compound is selected from the group consisting of:

5. The method of claim 4 , wherein the compound has the structure of:

6. The method of claim 1 , wherein the one or more chemotherapeutic drugs are selected from alkylating drugs, antimetabolites, purine antagonists, pyrimidine antagonists, spindle poisons, antitumor antibiotics, platinum-containing anti-cancer drugs, hormone analogs, or any combination of the foregoing.

7. The method of claim 1 , wherein the one or more chemotherapeutic drugs are selected from melphalan, doxorubicin, cylophosphamide, or any combination of the foregoing.

8. A method of treating a subject having lupus erythematosus or rheumatoid arthritis comprising administering to the subject in need thereof an effective amount of a compound having a structure of:

wherein,
R 3 is an alkyl;
R 8 is

R 9 is either a (C 1 -C 6 )alkyl, or a (C 1 -C 6 )alkenyl;
Z is an unsubstituted (C 11 -C 16 )alkyl; and
X is NH or O.

9. The method of claim 8 , wherein the compound has a structure:

wherein,
R 3 is a (C 1 -C 6 )alkyl;
R 8 is

R 9 is either a (C 1 -C 3 )alkyl, or a (C 1 -C 3 )alkenyl;
Z is an unsubstituted (C 11 -C 16 )alkyl; and
X is NH or O.

10. The method of claim 9 , wherein the compound is selected from the group consisting of:

11. The method of claim 10 , wherein the compound has the structure of:

Assignees

• Univ California

Inventors

• Pirrung Michael C

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07D245/02

  not condensed with other rings · CPC title

• C07D285/00 Primary

  Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00 · CPC title

• C07D273/02

  having two nitrogen atoms and only one oxygen atom · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title