Fumagillol heterocyclic compounds and methods of making and using same

Patent metadata

Field	Value
Publication number	US-9682965-B2
Application number	US-201615354834-A
Country	US
Kind code	B2
Filing date	Nov 17, 2016
Priority date	Aug 11, 2015
Publication date	Jun 20, 2017
Grant date	Jun 20, 2017

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 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 compound of claim 1 , wherein B is:

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

4. A compound 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. A pharmaceutically acceptable composition comprising a compound of claim 1 , and a pharmaceutically acceptable excipient.

6. A pharmaceutically acceptable composition comprising:
(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 or pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable excipient.

7. The composition of claim 5 , wherein the composition is formulated as a unit dose.

8. The composition of claim 5 , wherein the composition is formulated for subcutaneous administration.

9. The composition of claim 5 , wherein the composition is formulated for intravenous administration.

Assignees

• Zafgen Inc

Inventors

• Vath James E
• Zahler Robert

Classifications

• A61K31/4025

  not condensed and containing further heterocyclic rings, e.g. cromakalim · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• A61K31/5383

  ortho- or peri-condensed with heterocyclic ring systems · CPC title

• C07D405/12 Primary

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

• A61K9/0019

  Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00) · CPC title