# US 2014/0193340 A1 · Luciferin Amides

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- Number: US 2014/0193340 A1
- Document ID: US20140193340A1
- Status: Published application
- Kind: A1
- Application number: 13/839,791
- Filed: 2013-03-15
- Published: 2014-07-10
- Earliest claimed: 2013-01-04
- Assignees: University of Massachusetts
- Applicants: University of Massachusetts
- Inventors: Stephen C. Miller
- Web page: https://patentgrep.com/patent/US20140193340A1

## CPC

- A61K 49/0021: {the fluorescent group being a small organic molecule}
- A61K 49/0045: {the fluorescent agent being a peptide or protein used for imaging or diagnosis in vivo}
- C07D 277/66: with aromatic rings or ring systems directly attached in position 2
- C07D 417/04: directly linked by a ring-member-to-ring-member bond
- C07D 513/04: Ortho-condensed systems
- C07D 513/06: Peri-condensed systems
- G01N 21/763: {Bioluminescence}
- A61K 49/0017: {Fluorescence in vivo}
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

This disclosure relates to luciferin amides of formula (I) shown below: Each variable in formula (I) is defined in the specification. These compounds can be used to detect fatty acid amide hydrolase activities in vitro, in live cells, or in vivo.

## Claims

### Claim 1

A compound of formula (I):
wherein
n is 0 or 1;
is deleted, a single bond, or a double bond; provided that, when n is 0, is deleted;
each of X1 and X2, independently, is O, S, Se, N, N(Ra), C(Ra), or C(RaRa′), in which each of Ra and Ra′, independently, is H or C1-C10 alkyl; provided that, when is a double bond, X1 is N or C(Ra);
each of Y1 and Y2, independently, is N or C(Rb), in which Rb is H or C1-C10 alkyl;
Z is C(Rc) or C(RcRc′), in which each of Rc and Re, independently, is H or C1-C10 alkyl; provided that, when is a single bond, Z is C(RcRc′) and that, when is a double bond, Z is C(Rc);
R2 is H, N(RdRd′), or ORd, in which each of Rd and Rd′, independently, is H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C20 cycloalkyl, C3-C20 cycloalkenyl, C1-C20 heterocycloalkyl, C1-C20 heterocycloalkenyl, aryl, or heteroaryl;
each of R1, R3, R4, R5, and R6, independently, is H, halo, CN, ORe, SRe, NO2, N(ReRe′), C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C20 cycloalkyl, C3-C20 cycloalkenyl, C1-C20 heterocycloalkyl, C1-C20 heterocycloalkenyl, aryl, heteroaryl, in which each of Re and Re′, independently, is H or C1-C10 alkyl; or R1 and R2, together with the carbon atoms to which they are attached, are a substituted or unsubstituted 5, 6, or 7-membered ring optionally fused with one or more substituted or unsubstituted 5, 6, or 7-membered rings; or R2 and R3, together with the carbon atoms to which they are attached, are a substituted or unsubstituted 5, 6, or 7-membered ring optionally fused with one or more substituted or unsubstituted 5, 6, or 7-membered rings; and
each of R7 and R8, independently, is H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C20 cycloalkyl, C3-C20 cycloalkenyl, C1-C20 heterocycloalkyl, C1-C20 heterocycloalkenyl, aryl, or heteroaryl.

### Claim 2 (depends on 1)

The compound of claim 1, wherein n is 0 and is deleted.

### Claim 3 (depends on 2)

The compound of claim 2, wherein each of X1 and X2 is S and each Y1 and Y2 is N.

### Claim 4 (depends on 3)

The compound of claim 3, wherein R2 is N(RdRd′), in which each of Rd and Rd′, independently, is H or C1-C10 alkyl optionally substituted with OH.

### Claim 5 (depends on 4)

The compound of claim 4, wherein each of Rd and Rd′, independently, is H, CH3, CH2CH3, CH(CH3)2, (CH2)3—OH, or CH2CH(CH3)2.

### Claim 6 (depends on 5)

The compound of claim 5, wherein each of R1, R3, R4, R5, and R6 is H.

### Claim 7 (depends on 6)

The compound of claim 6, wherein each of R7 and R8, independently, is H or C1-C10 alkyl optionally substituted with OH.

### Claim 8 (depends on 7)

The compound of claim 7, wherein each of R7 and R8, independently, is H, CH3, or CH2CH2OH.

### Claim 9 (depends on 6)

The compound of claim 6, wherein the compound is

### Claim 10 (depends on 3)

The compound of claim 3, wherein R2 and R3, together with the carbon atoms to which they are attached, are a 5 or 6-membered ring, each of which is optionally substituted with C1-C10 alkyl or optionally fused with a 5 or 6-membered ring.

### Claim 11 (depends on 10)

The compound of claim 10, wherein R2 and R3, together with the carbon atoms to which they are attached, are a 5-membered ring optionally substituted with CH3, or a 6-membered ring optionally substituted with CH3 or optionally fused with a 5-membered ring.

### Claim 12 (depends on 11)

The compound of claim 11, wherein each of R1 and R4, independently, is H, OH, or C1-C10 alkyl.

### Claim 13 (depends on 12)

The compound of claim 12, wherein each of R5 and R6 is H and each of R7 and R8, independently, is H or C1-C10 alkyl.

### Claim 14 (depends on 13)

The compound of claim 13, wherein the compound is

### Claim 15 (depends on 3)

The compound of claim 3, wherein R1 and R2, together with the carbon atoms to which they are attached, are a 6-membered ring optionally substituted with C1-C10 alkyl.

### Claim 16 (depends on 15)

The compound of claim 15, wherein R1 and R2, together with the carbon atoms to which they are attached, are a 6-membered ring optionally substituted with CH3.

### Claim 17 (depends on 16)

The compound of claim 16, wherein each of R3, R4, R5, R6, R7, and R8 is H.

### Claim 18 (depends on 15)

The compound of claim 15, wherein the compound is

### Claim 19 (depends on 3)

The compound of claim 3, wherein R1 and R2, together with the carbon atoms to which they are attached, are a 6-membered ring optionally substituted with C1-C10 alkyl and R2 and R3, together with the carbon atoms to which they are attached, are a 6-membered ring optionally substituted with C1-C10 alkyl.

### Claim 20 (depends on 19)

The compound of claim 19, wherein R1 and R2, together with the carbon atoms to which they are attached, are a 6-membered ring and R2 and R3, together with the carbon atoms to which they are attached, are a 6-membered ring.

### Claim 21 (depends on 20)

The compound of claim 20, wherein each of R4, R5, R6, R7, and R8 is H.

### Claim 22 (depends on 21)

The compound of claim 21, wherein the compound is

### Claim 23 (depends on 3)

The compound of claim 3, wherein R2 is ORd, in which Rd is H or C1-C10 alkyl optionally substituted with aryl.

### Claim 24 (depends on 23)

The compound of claim 23, wherein R2 is OH, OCH3, or OCH2Ph.

### Claim 25 (depends on 24)

The compound of claim 24, wherein each of R1, R3, R4, R5, R6, R7, and R8 is H.

### Claim 26 (depends on 25)

The compound of claim 25, wherein the compound is

### Claim 27 (depends on 3)

The compound of claim 3, wherein R2 is H.

### Claim 28 (depends on 27)

The compound of claim 27, wherein the compound is

### Claim 29 (depends on 1)

The compound of claim 1, wherein the compound is a D-isomer.

### Claim 30 (depends on 1)

An imaging method, comprising:
contacting a cell comprising a luciferase and a fatty acid amide hydrolase with the compound of claim 1; and
detecting bioluminescent emission from the cell.

### Claim 31 (depends on 30)

The method of claim 30, wherein the luciferase is a wild-type luciferase.

### Claim 32 (depends on 31)

The method of claim 31, wherein the wild-type luciferase is a beetle luciferase.

### Claim 33 (depends on 32)

The method of claim 32, wherein the beetle luciferase is a firefly, click beetle, or railroad worm luciferase.

### Claim 34 (depends on 30)

The method of claim 30, wherein the luciferase is a mutated luciferase.

### Claim 35 (depends on 30)

The method of claim 30, wherein the contacting step is performed in a brain of a subject.

### Claim 36 (depends on 1)

An imaging method, comprising:
contacting a cell comprising a fatty acid amide hydrolase with the compound of claim 1;
introducing a luciferase; and
detecting bioluminescent emission.