# US 2019/0169181 A1 · Fumagillol compounds and methods of making and using same

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- Number: US 2019/0169181 A1
- Document ID: US20190169181A1
- Status: Published application
- Kind: A1
- Application number: 16/324,692
- Filed: 2017-08-11
- Published: 2019-06-06
- Earliest claimed: 2016-08-11
- Assignees: Zafgen, Inc.
- Applicants: Zafgen, Inc.
- Inventors: Robert Zahler; James E. Vath
- Web page: https://patentgrep.com/patent/US20190169181A1

## CPC

- C07D 413/14: containing three or more hetero rings
- A61P 3/04: Anorexiants; Antiobesity agents
- C07D 405/14: containing three or more hetero rings
- C07D 407/14: containing three or more hetero rings
- C07D 417/14: containing three or more hetero rings
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## 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.

## Claims

### Claim 1

A compound represented by Formula I:
wherein:
is a single or double bond;
R1 is selected from the group consisting of hydrogen and C1-6alkyl; wherein C1-6alkyl may optionally be substituted by one, two, or more substituents each independently selected from the group consisting of halogen, cyano, hydroxyl, and N(RbRc);
L is selected from the group consisting of a bond and —C(RL1RL2)—;
A is a 5- or 6-membered monocyclic heteroaryl ring having one, two, or three heteroatoms each independently selected from O, S, or N; wherein A may be optionally substituted on an available carbon by a substituent independently selected for each occurrence from the group consisting of halogen, hydroxyl, C1-6alkyl, C1-6alkoxy, C3-6cycloalkyl, phenyl, heterocyclyl, oxo, and —N(Rb)(Rc); wherein C1-6alkyl, C1-6alkoxy, or C3-6cycloalkyl may optionally be substituted by one, two, three or more substituents each independently selected from the group consisting of halogen, cyano, hydroxyl, and —N(Rb)(Rc), and wherein A may be optionally substituted on an available nitrogen by Rh;
RL1 and RL2 are each independently selected from the group consisting of hydrogen, halogen, hydroxyl, C1-6alkyl, C3-6cycloalkyl, and C1-6alkoxy; wherein C1-6alkyl, C3-6cycloalkyl, and C1-6alkoxy may optionally be substituted by one or more halogen atoms or a group selected from cyano or hydroxyl;
Ra, Rb, and Rc are each independently selected, for each occurrence, from the group consisting of hydrogen and C1-6alkyl; wherein C1-6alkyl may optionally be substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, and hydroxyl; or Rb and Rc may form, together with the nitrogen to which they are attached, a 4-6 membered heterocycle;
Rh is independently selected for each occurrence from the group consisting of hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkyl-S(O)2—, and C1-6alkoxycarbonyl-, wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkyl-S(O)2—, and C1-6alkylcarbonyl- may optionally be substituted by one or more substituents selected from RP;
RP is independently selected, for each occurrence, from the group consisting of halogen, hydroxyl, cyano, C1-6alkoxy, and heterocyclyl; wherein heterocyclyl has one, two or three heteroatoms each independently selected from the group consisting of O, NR′ (wherein R′ is H or C1-3alkyl) and S(O)w (wherein w is 0, 1, or 2); wherein heterocyclyl may optionally be substituted by one, two or three substituents each independent selected from the group consisting of halogen, hydroxyl, and C1-6alkyl; wherein C1-6alkyl may optionally be substituted by one, two or three halogens;
or a pharmaceutically acceptable salt, stereoisomer, ester, or prodrug thereof.

### Claim 2 (depends on 1)

The compound of claim 1, wherein A is substituted with C1-2alkyl, oxo, or —N(Rb)(Rc).

### Claim 3 (depends on 1, 2)

The compound of claim 1 or 2, wherein Rh is selected from the group consisting of hydrogen and C1-6alkyl-RP.

### Claim 4 (depends on 1, 2, 3)

The compound of any one of claims 1-3, wherein RP is selected from the group consisting
wherein R55 is selected from the group consisting of hydrogen and C1-2alkyl; wherein C1-2alkyl may optionally be substituted by one or two halogens.

### Claim 5 (depends on 1, 2, 3, 4)

The compound of any one of claims 1-4, wherein Ra is hydrogen or methyl.

### Claim 6 (depends on 1, 2, 3, 4, 5)

The compound of any one of claims 1-5, wherein L is selected from the group consisting of a bond, —CH2—, —CHMe-, and —CMe2-.

### Claim 7 (depends on 1, 2, 3, 4, 5, 6)

The compound of any one of claims 1-6, wherein L is a bond.

### Claim 8 (depends on 1, 2, 3, 4, 5, 6, 7)

The compound of any one of claims 1-7, wherein R1 is selected from the group consisting of hydrogen, methyl, ethyl, isopropyl, and sec-butyl.

### Claim 9 (depends on 1, 2, 3, 4, 5, 6, 7, 8)

The compound of any one of claims 1-8, wherein R1 is isopropyl.

### Claim 10 (depends on 1, 2, 3, 4, 5, 6, 7, 8)

The compound of any one of claims 1-8, wherein R1 is methyl.

### Claim 11 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10)

The compound of any one of claims 1-10, wherein A is selected from the group consisting of:
wherein X2 independently for each occurrence is selected from the group consisting of O and S;
each R66, R77, R88 and R99 is independently selected for each occurrence from the group consisting of hydrogen, halogen, hydroxyl, C1-2alkyl, heterocyclyl, and —NRbRc; wherein C1-2alkyl may optionally be substituted by one, two or three substituents each independently selected from the group consisting of hydroxyl and halogen; and
Rhh is selected from the group consisting of hydrogen, C1-6alkyl, and —C1-3alkyl-heterocyclyl, wherein the heterocyclyl has one, two or three heteroatoms each independently selected from the group consisting of O, NR′ (wherein R′ is hydrogen or C1-3alkyl) and S(O)w (wherein w is 0, 1, or 2); and wherein heterocyclyl may optionally be substituted by a substituent selected from the group consisting of C1-3alkyl (optionally substituted with 1-3 halogens), halogen, and hydroxyl.

### Claim 12 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11)

The compound of any one of claims 1-11 wherein A is selected from the group consisting of:
wherein
Rhh is hydrogen, C1-6alkyl or —C1-3alkyl-heterocyclyl, wherein heterocycyl may optionally be substituted by a substituent selected from the group consisting of C1-3alkyl (optionally substituted by one, two, or three halogens), halogen, and hydroxyl;
and R99 is heterocyclyl.

### Claim 13 (depends on 11, 12)

The compound of claim 11 or 12, wherein Rhh is selected from the group consisting of:
wherein R55 is selected from the group consisting of hydrogen and C1-2alkyl; wherein
C1-2alkyl may optionally be substituted by 1 or 2 halogens.

### Claim 14 (depends on 13)

The compound of claim 13, wherein Rhh is selected from the group consisting of:

### Claim 15 (depends on 12)

The compound of claim 12, wherein R99 is selected from the group consisting of:

### Claim 16

A compound represented by:
wherein:
is a single or double bond;
R1 is selected from the group consisting of hydrogen and C1-6alkyl; wherein C1-6alkyl may optionally be substituted by one, two, or more substituents each independently selected from the group consisting of halogen, cyano, hydroxyl, and N(RbRc);
L is selected from the group consisting of a bond and —C(RL1RL2)—;
A is selected from the group consisting of:
wherein
Rhh is hydrogen, C1-6alkyl or —C1-3alkyl-heterocyclyl, wherein heterocycyl may optionally be substituted by a substituent selected from the group consisting of C1-3alkyl (optionally substituted by one, two, or three halogens), halogen, and hydroxyl;
R99 is heterocyclyl;
RL1 and RL2 are each independently selected from the group consisting of hydrogen, halogen, hydroxyl, C1-6alkyl, C3-6cycloalkyl, and C1-6alkoxy; wherein C1-6alkyl, C3-6cycloalkyl, and C1-6alkoxy may optionally be substituted by one or more halogen atoms or a group selected from cyano or hydroxyl;
Ra, Rb, and Rc are each independently selected, for each occurrence, from the group consisting of hydrogen and C1-6alkyl; wherein C1-6alkyl may optionally be substituted by one or more substituents selected from the group consisting of halogen, cyano, oxo, and hydroxyl; or
Rb and Rc may form, together with the nitrogen to which they are attached, a 4-6 membered heterocycle;
Rh is independently selected for each occurrence from the group consisting of hydrogen, C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkyl-S(O)2—, and C1-6alkoxycarbonyl-, wherein C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C1-6alkyl-S(O)2—, and C1-6alkylcarbonyl-may optionally be substituted by one or more substituents selected from RP;
RP is independently selected, for each occurrence, from the group consisting of halogen, hydroxyl, cyano, C1-6alkoxy, and heterocyclyl; wherein heterocyclyl has one, two or three heteroatoms each independently selected from the group consisting of O, NR′ (wherein R′ is H or C1-3alkyl) and S(O)w (wherein w is 0, 1, or 2); wherein heterocyclyl may optionally be substituted by one, two or three substituents each independent selected from the group consisting of halogen, hydroxyl, and C1-6alkyl; wherein C1-6alkyl may optionally be substituted by one, two or three halogens;
or a pharmaceutically acceptable salt, stereoisomer, ester, or prodrug thereof.

### Claim 17

A compound selected from the group consisting of: (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-1-(5-amino-1,3,4-oxadiazol-2-yl)-2-methylpropyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-2-methyl-1-(5-(methylamino)-1,3,4-oxadiazol-2-yl)propyl)carbamate; (3R,4S,5 S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl ((R)-2-methyl-1-(5-(methylamino)-1,3,4-oxadiazol-2-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-1-(1H-imidazol-2-yl)-2-methylpropyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-2-methyl-1-(1-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-imidazol-2-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-2-methyl-1-(1-(((S)-1-methylpyrrolidin-2-yl)methyl)-1H-imidazol-2-yl)propyl)carbamate; (3R,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl ((R)-2-methyl-1-(5-(methylamino)-1,3,4-thiadiazol-2-yl)propyl)carbamate; (3R,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-2-methyl-1-(5-(methylamino)-1,3,4-thiadiazol-2-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-2-methyl-1-(4H-1,2,4-triazol-3-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-2-methyl-1-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl ((R)-2-methyl-1-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl ((R)-2-methyl-1-(1-(((S)-1-methylpyrrolidin-3-yl)methyl)-1H-imidazol-4-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-2-methyl-1-(1-(((R)-1-methylpyrrolidin-3-yl)methyl)-1H-imidazol-4-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-2-methyl-1-(1-(((S)-1-methylpyrrolidin-2-yl)methyl)-1H-imidazol-4-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-2-methyl-1-(1-(((S)-1-methylpyrrolidin-3-yl)methyl)-1H-imidazol-4-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-2-methyl-1-(1-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-imidazol-4-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-2-methyl-1-(1-(2-morpholinoethyl)-1H-imidazol-4-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-1-(1-(((S)-1-(2,2-difluoroethyl)pyrrolidin-3-yl)methyl)-1H-imidazol-4-yl)-2-methylpropyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-1-(1-(((R)-1-(2,2-difluoroethyl)pyrrolidin-3-yl)methyl)-1H-imidazol-4-yl)-2-methylpropyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-2-methyl-1-(4-oxo-1,4-dihydropyridin-2-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-2-methyl-1-(1H-1,2,3-triazol-4-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-2-methyl-1-(1-(((S)-1-methylpyrrolidin-3-yl)methyl)-1H-pyrazol-4-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-2-methyl-1-(1-(((R)-1-methylpyrrolidin-3-yl)methyl)-1H-pyrazol-4-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl ((S)-2-methyl-1-(2-methyl-1-(((S)-1-methylpyrrolidin-3-yl)methyl)-1H-imidazol-4-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-1-(6-(3,3-difluoroazetidin-1-yl)pyridin-3-yl)-2-methylpropyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-2-methyl-1-(6-morpholinopyridin-3-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-3-methyl-1-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)butan-2-yl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-1-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)propan-2-yl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-1-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)butan-2-yl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl ((R)-3-methyl-1-(5-oxo-2,5-dihydro-1,2,4-oxadiazol-3-yl)butan-2-yl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl ((R)-3-methyl-1-(4H-1,2,4-triazol-3-yl)butan-2-yl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl ((R)-1-(5-amino-1,3,4-oxadiazol-2-yl)-3-methylbutan-2-yl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl ((R)-3-methyl-1-(5-(methylamino)-1,3,4-oxadiazol-2-yl)butan-2-yl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-3-methyl-1-(5-(methylamino)-1,3,4-thiadiazol-2-yl)butan-2-yl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl ((R)-3-methyl-1-(5-(methylamino)-1,3,4-thiadiazol-2-yl)butan-2-yl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl ((R)-1-(5-amino-1,3,4-thiadiazol-2-yl)-3-methylbutan-2-yl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-1-(5-amino-1,3,4-thiadiazol-2-yl)-3-methylbutan-2-yl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl (2-methyl-2-(1-(((R)-1-methylpyrrolidin-2-yl)methyl)-1H-imidazol-4-yl)propyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl (2-methyl-2-(4H-1,2,4-triazol-3-yl)propyl)carbamate; (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 ((S)-1-(1-isobutyl-1H-imidazol-4-yl)-2-methylpropyl)(methyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl ((S)-1-(6-(azetidin-1-yl)pyridin-3-yl)-2-methylpropyl)carbamate; (3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl((S)-1-(1-isobutyl-1H-imidazol-4-yl)-2-methylpropyl)carbamate; and a pharmaceutically acceptable salt or stereoisomer thereof.

### Claim 18 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)

A pharmaceutically acceptable composition comprising a compound of any one of claims 1-17 and a pharmaceutically acceptable excipient.

### Claim 19 (depends on 18)

The composition of claim 18, wherein the composition is formulated as a unit dose.

### Claim 20 (depends on 18)

The composition of claim 18, wherein the composition is formulated for subcutaneous administration.

### Claim 21 (depends on 18)

The composition of claim 18, wherein the composition is formulated for intravenous administration.

### Claim 22 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)

A method of treating and/or controlling obesity, comprising administering to a patient in need thereof an effective amount of a compound of any one of claims 1-17.

### Claim 23 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)

A method of inducing weight loss in a patient in need thereof, comprising administering to said patient an effective amount of a compound of any one of claims 1-17.

### Claim 24 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17)

A method of substantially preventing weight gain in a patient in need thereof, comprising administering to said patient an effective amount of a compound of any one of claims 1-17.

### Claim 25 (depends on 22, 23, 24)

The method of any one of claims 22-24, wherein the patient is a human.

### Claim 26 (depends on 22, 23, 24)

The method of any one of claims 22-24, wherein the patient is a cat or dog.

### Claim 27 (depends on 22, 23, 24)

The method of any one of claims 22-24, wherein the patient has a body mass index greater than or equal to about 30 kg/m2 before the administration.

### Claim 28 (depends on 22, 23, 24, 25, 26, 27)

The method of any one of claims 22-27, wherein administering comprises subcutaneous administration.

### Claim 29 (depends on 22, 23, 24, 25, 26, 27)

The method of any one of claims 22-27, wherein administering comprises intravenous administration.

### Claim 30 (depends on 22, 23, 24, 25, 26, 27, 28, 29)

The method of any one of claims 22-29, wherein administering comprises once, twice, or thrice weekly administration.

### Claim 31 (depends on 22, 23, 24, 25, 26, 27, 28, 29, 30)

The method of any one of claims 22-30, comprising administering said compound in an amount sufficient to establish inhibition of intracellular MetAP2 effective to increase thioredoxin production in the patient and to induce multi organ stimulation of anti-obesity processes in the subject.

### Claim 32 (depends on 31)

The method of claim 31, comprising administering said compound in an amount insufficient to reduce angiogenesis in the patient.