Pyrimidine derivatives for labeled binding partners

• US 5,502,177 A
• Filed: 09/17/1993
• Issued: 03/26/1996
• Est. Priority Date: 09/17/1993
• Status: Expired due to Term

• Current Assignee: ISIS Pharmaceuticals Incorporated
• Original Assignee: Gilead Sciences Inc.
• Inventors: Jones, Robert J., Lin, Kuei-Ying, Matteucci, Mark D.
• Primary Examiner(s): Jones, W. Gary
• Assistant Examiner(s): HOUTTEMAN, SCOTT W
• Application Number:
  US08/123,505
• Time in Patent Office: 921 Days
• Field of Search: 544/102, 544/103, 544/34, 544/345, 536/26.6, 536/26.7, 536/26.8, 536/28.55
• US Class Current: 536/26.6
• CPC Class Codes: C07D 239/47 One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
• CPC Class Codes: C07D 239/54 as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07F 7/2208 Compounds having tin linked only to carbon, hydrogen and/or halogen
• CPC Class Codes: C07H 19/06 Pyrimidine radicals
• CPC Class Codes: C07H 19/073 with 2-deoxyribosyl as the saccharide radical
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12Q 1/6816 characterised by the detection means C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/686 Polymerase chain reaction [PCR]
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

A compound having the structure: ##STR1## wherein R¹ is an oligonucleotide;

a is 1 and b is 0;

A is C or CH;

X is S, O, NH or NCH₂ R⁶ ;

Z is taken together with A to form an aryl ring structure comprising 6 ring atoms wherein the aryl ring carbon atoms are unsubstituted with other than H or at least 1 nonbridging ring carbon atom is substituted with R⁶ or ═O;

R⁶ is independently H, C₁ -C₆ alkyl, C₂ -C₆ alkenyl, C₂ -C₆ alkynyl, NO₂, N(R³)₂, C.tbd.N or halo, or an R⁶ is taken together with an adjacent Z group R⁶ to complete a phenyl ring; and

R³ is a protecting group or H; and tautomers, solvates and salts thereof.

Claims

1. A compound having the structure:

##STR19## wherein R¹ is an oligonucleotide;

a is 1 and b is 0;

A is C or CH;

X is S, O, NH or NCH₂ R⁶ ;

Z is taken together with A to form an aryl ring structure comprising 6 ring atoms wherein the aryl ring carbon atoms are unsubstituted with other than H or at least 1 nonbridging ring carbon atom is substituted with R⁶ or ═

O;

R⁶ is independently H, C₁ -C₆ alkyl, C₂ -C₆ alkenyl, C₂ -C₆ alkynyl, NO₂, N(R³)₂, C.tbd.N or halo, or an R⁶ is taken together with an adjacent Z group R⁶ to complete a phenyl ring; and

R³ is a protecting group or H; and

tautomers, solvates and salts thereof.

2. The compound of claim 1 wherein Z is ##STR20## A¹ is N or CR⁶ ;

and G is CH.

3. The compound of claim 2 wherein Z is ##STR21## R⁴ is H or C₁ -C₆ alkyl;

and R⁵ is H, NO₂ or C₁ -C₆ alkyl.

4. The compound of claim 2 wherein adjacent R⁶ are taken together to complete a phenyl ring.

5. The compound of claim 1 wherein Z together with CH-A completes a aryl ring containing 6 ring atoms.

6. The compound of claim 5 wherein the aryl ring contains a nonbridging ring carbon atom which is singly substituted with R⁶.

7. The compound of claim 1 wherein Z together with CH-A completes an unsubstituted aryl ring or an aryl ring substituted with R⁶.

8. The compound of claim 1 wherein A is C, b is 0 and a is 1 and X is NHCH₂ R⁶.

9. The compound of claim 1 wherein A is C, and X is NH.

10. The compound of claim 1 wherein A is C, b is 0, a is 1 and X is O.

11. The compound of claim 1 wherein A is C, b is 0, a is 1 and X is S.

12. The compound of claim 1 wherein Z is an aryl ring substituted with C₂ -C₆ alkenyl, C₂ -C₆ alkynyl, NO₂, N(R³)₂, C═

N, or halo.