Fumagillol heterocyclic compounds and methods of making and using same

Patent metadata

Field	Value
Publication number	US-10023561-B2
Application number	US-201715596512-A
Country	US
Kind code	B2
Filing date	May 16, 2017
Priority date	Aug 11, 2015
Publication date	Jul 17, 2018
Grant date	Jul 17, 2018

Abstract

Disclosed herein, in part, are fumagillol compounds and methods of use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of making fumagillol compounds are provided. The compounds are contemplated to have activity against methionyl aminopeptidase 2.

First claim

What is claimed is:

1. A method of treating type II diabetes in a patient in need thereof, comprising administering a therapeutically effective amount of a compound represented by:

wherein:
p is 2;
B is R i R j N—; wherein R i and R j taken together with the nitrogen to which they are attached form a 4-9 membered monocyclic, bridged bicyclic, fused bicyclic or spirocyclic heterocyclic ring, which may have an additional heteroatom selected from the group consisting of N, O, and S(O) w (wherein w is 0, 1 or 2);

wherein
the 4-9 membered monocyclic, bridged bicyclic, fused bicyclic or spirocyclic heterocyclic ring may be optionally substituted on carbon by one, two, or more substituents selected from the group consisting of halogen, hydroxyl, oxo, cyano, C 1-6 alkyl, C 1-6 alkoxy, and R a R b N-carbonyl-; wherein said C 1-6 alkyl may optionally be substituted by one, two, or more substituents selected from the group consisting of fluorine and hydroxyl;
wherein if said 4-9 membered monocyclic, bridged bicyclic, fused bicyclic or spirocyclic heterocyclic ring contains a —NH moiety, that nitrogen may be optionally substituted by a substituent selected from the group consisting of C 1-6 alkyl and C 1-6 alkyl-S(O) 2 —; wherein C 1-6 alkyl and C 1-6 alkyl-S(O) 2 — may optionally be substituted by one or more fluorines;
R a and R b are independently selected, for each occurrence, from the group consisting of hydrogen and C 1-3 alkyl; wherein C 1-3 alkyl may optionally be substituted by one or more substituents selected from halogen, cyano, oxo and hydroxyl;
or a pharmaceutically acceptable salt or stereoisomer thereof.

2. The method of claim 1 , wherein B is:

3. The method of claim 1 , wherein the compound is represented by:

4. The method of claim 1 , wherein the compound is selected from the group consisting of (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-enyl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl 3-(2-morpholinoethyl)azetidine-1-carboxylate and a pharmaceutically acceptable salt or stereoisomer thereof.

5. The method of claim 1 , wherein the patient is obese.

6. The method of claim 1 , wherein the patient is overweight.

Assignees

• Zafgen Inc

Inventors

• Vath James E
• Zahler Robert

Classifications

• C07D401/14

  containing three or more hetero rings · CPC title

• C07D417/14

  containing three or more hetero rings · CPC title

• C07D405/12 Primary

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K31/403

  condensed with carbocyclic rings, e.g. carbazole · CPC title

• C07D491/08

  Bridged systems · CPC title