Tagging compounds and process for use in aida libraries

• US 20040077019A1
• Filed: 11/12/2003
• Published: 04/22/2004
• Est. Priority Date: 10/30/2000
• Status: Abandoned Application

• Current Assignee: Hubert Gstach
• Original Assignee: Hubert Gstach
• Inventors: Gstach, Hubert
• Application Number:
  US10/415,280
• Publication Number:
  US 20040077019A1
• Time in Patent Office: Days
• US Class Current: 435/7.1
• CPC Class Codes: C07B 2200/11 Compounds covalently bound to a solid support
• CPC Class Codes: C07D 231/56 Benzopyrazoles; Hydrogenated benzopyrazoles
• CPC Class Codes: C40B 40/04 Libraries containing only organic compounds
• CPC Class Codes: C40B 50/16 involving encoding steps
• CPC Class Codes: C40B 70/00 Tags or labels specially adapted for combinatorial chemistry or libraries, e.g. fluorescent tags or bar codes

Abstract

A compound of formula A—B—D—X—D′—E or formula A—B—D—E—D′—X wherein A is the residue of a solid support, originating from standard materials applied in solid phase and solution phase organic chemistry, B is a linker residue having a group which allows cleavage of a compound of a formula II or a compound of formula III to liberate an D—X—D′—E, or D—E—D′—X fragment, respectively, D and D′ independently of each other are a bond or a spacer residue, E is the residue of a molecule to be investigated produced via combinatorial chemistry, and X is the residue of a fluorescent dye, which is characterized in that a compound of A—B—D—X—D′—E or of formula A—B—D—E—D′—X is tagged by at least one tag residue, and the use of such compounds in the decoding step of a screening process.

Claims

1. A compound of formula

A—

B—

D—

X—

D′

—

E 

 

II

or a compound of formula

A—

B—

D—

E—

D′

—

X 

 

II,

wherein

A is the residue of a solid support, originating from standard materials applied in solid phase and solution phase organic chemistry,

B is a linker residue having a group which allows cleavage of a compound of formula II or a compound of formula III to liberate an D—

X—

D′

—

E, or D—

E—

D′

—

X fragment, respectively,

D and D′

independently of each other are a bond or a spacer residue,

E is the residue of a molecule to be investigated produced via combinatorial chemistry, and

X is the residue of a fluorescent dye,

characterized in that a compound of formula II or of formula III is tagged by at least one tag residue.

2. A compound of formula

D— X—

D′

—

E 

 

IV, orD—

E—

D′

—

X 

 

V, orE—

D′

—

X 

 

VI

wherein E, and X are as defined in claim 1 and D and D′

independently of each other are the residue of a spacer, or are a bond, or are not present, characterized in that a compound of formula IV or of formula V or of formula VI is tagged by at least one tag residue.

4. Use of a compound of any one of claims 1 to 3 in the decoding step of a screening process.

5. A process for the synthesis of generic fluorescence labelled libraries (AIDA-libraries) on a conventionally used linker cleavable by light wherein the first combinatorial step of fluorescence labelled libraries is partial-encoded comprising providing a set of compounds bound to at least to on tag residue, which s t of compounds consists in compounds as claimed in any one of claims 1 to 3, wherein the tag residues have different molecular weights.

6. A process for the synthesis of generic fluorescence labelled libraries (AIDA-libraries) on a conventionally used linker cleavable by acid, wherein the first combinatorial step of fluorescence labelled libraries is partial-encoded, comprising providing a set of compounds of the present invention covalently bound to at least one tag residue which set of compounds consists in compounds as claimed in any one of claims 1 to 3, wherein the tag residues have different molecular weights.

7. A process for the decoding of building blocks of generic fluorescence labelled libraries (AIDA-libraries) comprising reading a tag residue in a compound of formula I, IV, V, or VI according to any one of claims 1 to 3 by use of MS-spectrography.

8. A process for the decoding of building blocks obtained by more than one combinatorial step of generic fluorescence labelled libraries (AIDA-libraries) comprising a split-and-mix-and-divide production of generically fluorescence (AIDA) labelled compound libraries in more than one combinatorial step and reading a tag residue, e.g. R_tag, in a compound of formula I, IV, V, or VI according to any one of claims 1 to 3 by use of MS-spectrography.

9. A process for the decoding of building blocks of generic fluorescence labelled libraries (AIDA-libraries) comprising

a) tagging a first combinatorial step with a tag residue and carrying out the first combinatorial step, in different vials for each building block expected to be obtained,

b) mixing the content of the vials containing the different building blocks obtained in the first combinatorial step,

c) carrying out a second combinatorial step such, that the building blocks obtained after the second combinatorial step have different molecular weights in a mixture obtained in b), for each building block in separate vials, and, if desired,

d) mixing the content of the vials obtained in step c) and carrying out a third combinatorial step, for each building block in different vials, and if desired,

e) carrying out a fourth combinatorial step for each building block in at least one of the vials obtained in step d), and

f) reading a tag residue in a compound of formula I, IV, V, or VI according to any one of claims 1 to 3 by use of MS-spectrography.

10. Use of a compound comprising a tag residue according to any one of claims 1 to 3 in the modification of physio-chemical properties of generic fluorescence labelled conjugated ligands.

11. Use according to claim 10 in the improvement of the solubility of generic fluorescence labelled conjugated ligands.

3. A compound of formula I, wherein

one of R₁ and R₂ and one of R₃ and R₄ is hydrogen, and the other R₁ or R₂;

and R₃ or R₄ is independently of each other

—

COOH, —

COOR₇, —

CONHR_tag, —

CONR_tag (CH₂)_nOH, —

CONR₈R₉, —

CH₂OH, —

CH₂NHR_tag, —

NO₂, —

NR₁₀R₁₁, —

NR_tagCOR₁₂, Cl, Br, F, —

CF₃, unsubstituted alkoxy and alkoxy substituted by

-aryl, —

N═

C═

O, —

N═

C═

S, —

SO₃H, —

SO₂NR_tag(CH₂)_nNH₂, —

SO₂NH(CH₂)_nNR_tagH, —

CONR_tag(CH₂)_nNH₂, —

CONH(CH₂)_nNR_taH,

unsubstituted alkyl or alkyl substituted by

—

COOH, —

COOR₇, —

CONR_tagH, —

CONR₈R₉, —

CONR_tag(CH₂)_nOH, —

CH₂OH, —

CH₂NH₂, —

N═

C═

O, —

N═

C═

S, —

SO₃H, —

SO₂NR_tag(CH₂)_nNH₂, —

SO₂NH(CH₂)_nNR_tagH, —

CONR_tag(CH₂)_nNH₂, —

CONH(CH₂)_nNR_tagH;

R₅ and R₆ are hydrogen, or one of R₅ and R₆ is hydrogen and the other is hydrogen, halogen, unsubstituted alkoxy or alkoxy substituted by

-aryl, —

NO₂, —

NR₁₀R₁₁, —

NR_tagCOR₁₂;

unsubstituted alkyl or alkyl substituted by

—

COOH, —

COOR₇, —

CONHR_tag, —

CONR₈R₉, —

CONR_tag(CH₂)_nOH, —

CH₂OH, —

CH₂NHR_tag, —

N═

C═

O, —

N═

C═

S, —

SO₃H, —

SO₂NR_tag(CH₂)_nNH₂, —

SO₂NH(CH₂)_nNHR_tag, —

CONR_tag(CH₂)_nNH₂, —

CONH(CH₂)_nNHR_tag;

n=2 to 8,

R₇ is a carboxyl-protecting or carboxyl-activating group

R₈ and R₉ together with the nitrogen atom to which they are attached form heterocyclyl, with the proviso that piperazine is excluded;

R₁₀ and R₁₁ are independently of each other hydrogen or R_tag,

R₁₂ is alkyl, aryl, aralkyl, unprotected or protected amino or halogen;

R_tag is hydrogen, alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, heterocyclylalkyl, with the proviso that unsubstituted methyl and unsubstituted cyclopropylmethyl are excluded;

with the proviso that in a compound of formula I

at least one R_tag is present,

at least one R_tag is other than hydrogen, and

at least one functional groups are present in the meanings of R₁, R₂, R₃, R₄, R₅, and R₆ which have the ability to covalently bind to one or two further reactants.