Luminogenic and fluorogenic compounds and methods to detect molecules or conditions

Patent metadata

Field	Value
Publication number	US-10077244-B2
Application number	US-201414553445-A
Country	US
Kind code	B2
Filing date	Nov 25, 2014
Priority date	May 31, 2005
Publication date	Sep 18, 2018
Grant date	Sep 18, 2018

Abstract

A method to detect the presence of amount of at least one molecule in a sample which employs a derivative of luciferin or a derivative of a fluorophore is provided. Compounds and compositions for carrying out the methods of the invention are also provided.

First claim

The invention claimed is:

1. A compound according to formula IIA:

wherein
Z is OR 1 ;
Z″ is O;
R is H, (C 1-6 )alkyl, saccharide, or M + wherein M is an alkali metal;
R 1 is (C 6-30 )aryl, heteroaryl, piperidinyl, (C 1-20 )alkylthio, (C 1-20 )alkyl-S(O)—, (C 1-20 )alkyl-SO 2 —, (C 1-20 )alkyl-SO 3 —, (C 1-20 )alkylphosphate, (C 1-20 )alkylphosphonate, (C 6-30 )arylthio, (C 6-30 )aryl-S(O)—, (C 6-30 )aryl-SO 2 —, (C 6-30 )aryl-SO 3 —, (C 6-30 )arylphosphate, (C 6-30 )arylphosphonate, or (C 1-20 )alkyl substituted by R 2 ;
R 2 is (C 3-20 )cycloalkyl, (C 1-20 )alkoxyl, (C 1-20 )alkylcarbonyl, (C 1-20 )alkylcarboxyl, hydroxyl, —COOR x , —SO 3 R x , (C 1-20 )alkylthio, (C 6-30 )arylthio, (C 1-20 )alkyl-S(O)—, (C 1-20 )alkyl-S(O) 2 —, nitro, amino, NH(C 1-6 )alkyl, NH(C 1-6 )alkynyl, N((C 1-6 )alkyl) 2 , N((C 1-6 )alkynyl) 2 , mercapto, saccharide, or trifluoromethyl;
W 1 is H, halo, hydroxyl, (C 1-6 ) alkyl or (C 1-6 ) alkoxy;
wherein any alkyl, alkenyl, cycloalkyl, alkoxy, amino, aryl, heteroaryl or heterocycle group is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of (C 1-6 )alkyl, phenyl, halo, hydroxyl, —COOR x , —SO 2 R x , —SO 3 R x , nitro, amino, NH(C 1-6 )alkyl, NH(C 1-6 )alkynyl, N((C 1-6 )alkyl) 2 , N((C 1-6 )alkynyl) 2 , and mercapto;
R x is H or (C 1-6 )alkyl;
or formula IIA is optionally a dimer connected at Z via a linker comprising a (C 1-12 )alkyl diradical that is optionally interrupted by one to four O atoms, N atoms, or an optionally substituted aryl, heteroaryl or heterocycle group to form a bridge between the dimer of formula IIA, and the R 1 group of each Z group connecting the dimer for formula IIA is replaced by the linker;
or a salt thereof, provided that the compound is not

or a salt thereof.

2. A compound according to claim 1 , wherein R is H or methyl.

3. A compound according to claim 2 , wherein R 1 is (C 1-20 ) alkyl substituted by R 2 .

4. A compound according to claim 3 , wherein R 2 is amino.

5. A compound according to claim 1 , wherein R 1 is selected from the group consisting of —SO 2 (C 6-30 )aryl and —S(O) 3 (C 6-30 )aryl, wherein the aryl in —SO 2 (C 6-30 )aryl and —S(O) 3 (C 6-30 )aryl is optionally substituted.

6. A compound according to claim 5 , wherein the aryl in —SO 2 (C 6-30 ) a and —S(O) 3 (C 6-30 )aryl is substituted with one or more substituents.

7. A compound according to claim 6 , wherein the one or more substituents are selected from the group consisting of nitro, phenyl and (C 1-6 )alkyl.

8. A compound selected from the group consisting of:

9. A compound of claim 8 , wherein the compound is

10. The compound claim 1 , wherein R 1 is (C 6-30 )aryl, heteroaryl, piperidinyl, (C 1-20 )alkylthio, (C 1-20 )alkyl-S(O)—, (C 1-20 )alkyl-SO 2 —, (C 1-20 )alkyl-SO 3 —, (C 1-20 )alkylphosphate, (C 1-20 )alkylphosphonate, (C 6-30 )arylthio, (C 6-3-0 )aryl-S(O)—, (C 6-30 )aryl-SO 2 —, (C 6-30 )aryl-SO 3 —, (C 6-30 )arylphosphate, or (C 6-30 )arylphosphonate.

11. The compound of claim 3 , wherein R 2 is (C 3-20 )cycloalkyl, (C 1-20 )alkoxyl, (C 1-20 )alkylcarbonyl, (C 1-20 )alkylcarboxyl, hydroxyl, —COOR x , —SO 3 R x , (C 1-20 )alkylthio, (C 6-30 )arylthio, (C 1-20 )alkyl-S(O)—, (C 1-20 )alkyl-S(O) 2 —, nitro, NH(C 1-6 )alkynyl, N((C 1-6 )alkynyl) 2 , mercapto, saccharide, or trifluoromethyl.

12. A compound of formula (VI), or a salt thereof,

wherein
R 1 is —OCH 2 CH 2 CH 2 —NR a R b , wherein R a and R b are independently H or C 1-20 alkyl;
R 6 is —COR 11 , wherein R 11 is H, OH, C 1-20 alkoxy, C 2-20 alkenyl, or NR 12 R 13 , wherein R 12 and R 13 are independently H or C 1-20 alkyl; and
R 7 is H, halo, (C 1-6 ) alkyl, (C 1-6 ) alkoxy, or C 2-20 alkenyl.

13. The compound of claim 12 , or a salt thereof, wherein
R 11 is OH or C 1-20 alkoxy.

14. The compound of claim 12 , wherein the compound is

or a salt thereof.

15. The compound of claim 1 , wherein in formula IIA
Z is OR;
Z″ is O;
R is H, (C 1-6 )alkyl, saccharide, or M + wherein M is an alkali metal;
R 1 is (C 6-30 )aryl, heteroaryl, piperidinyl, (C 1-20 )alkylthio, (C 1-20 )alkyl-S(O)—, (C 1-20 )alkyl-SO 2 —, (C 1-20 )alkyl-SO 3 —, (C 1-20 )alkylphosphate, (C 1-20 )alkylphosphonate, (C 6-30 )arylthio, (C 6-30 )aryl-S(O)—, (C 6-30 )aryl-SO 2 —, (C 6-30 )aryl-SO 3 —, (C 6-30 )arylphosphate, (C 6-30 )arylphosphonate, or (C 1-20 )alkyl substituted by R 2 ;
R 2 is (C 3-20 )cycloalkyl, (C 1-20 )alkoxyl, (C 1-20 )alkylcarbonyl, (C 1-20 )alkylcarboxyl, hydroxyl, —COOR x , —SO 3 R x , (C 1-20 )alkylthio, (C 6-30 )arylthio, (C 1-20 )alkyl-S(O)—, (C 1-20 )alkyl-S(O) 2 —, nitro, amino, NH(C 1-6 )alkyl, NH(C 1-6 )alkynyl, N((C 1-6 )alkyl) 2 , N((C 1-6 )alkynyl) 2 , mercapto, saccharide, or trifluoromethyl;
W 1 is H, halo, hydroxyl, (C 1-6 ) alkyl or (C 1-6 ) alkoxy;
wherein any alkyl, alkenyl, cycloalkyl, alkoxy, amino, aryl, heteroaryl or heterocycle group is optionally substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of (C 1 - 6 )alkyl, phenyl, halo, hydroxyl, —COOR x , —SO 2 R x , —SO 3 R x , nitro, amino, NH(C 1-6 )alkyl, NH(C 1-6 )alkynyl, N((C 1-6 )alkyl) 2 , N((C 1-6 )alkynyl) 2 , and mercapto; and
R x is H or (C 1-6 )alkyl,
or a salt thereof.

16. The compound of claim 1 , wherein formula IIA is a dimer connected at Z via a linker comprising a (C 1-12 )alkyl diradical that is optionally interrupted by one to four O atoms, N atoms, or an optionally substituted aryl, heteroaryl or heterocycle group to form a bridge between the dimer of formula IIA, and the R 1 group of each Z group connecting the dimer for formula IIA is replaced by the linker, or a salt thereof.

Assignees

• Promega Corp

Inventors

• Cali James J
• Daily William
• Hawkins Erika
• Klaubert Dieter
• Liu Jianquan
• Meisenheimer Poncho
• Scurria Michael
• Shultz John W
• Unch James
• Valley Michael P
• Wood Keith V
• Zhou Wenhui

Classifications

• C07D417/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D417/14

  containing three or more hetero rings · CPC title

• C07D277/66 Primary

  with aromatic rings or ring systems directly attached in position 2 · CPC title

• C07D277/68

  with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2 · CPC title

• C09B57/02

  Coumarine dyes · CPC title