IP Library Granted Patent US 11,535,754
Granted Patent B2
US 11,535,754 · App. 17/737,899 · Granted Dec 27, 2022

Silicon containing detectable compounds and uses thereof

Inventors: Megha Cila (San Diego, CA); Ronald Graham (Carlsbad, CA); Rodrigo Rodriguez (San Diego, CA)
Assignee: Singular Genomics Systems, Inc.
C09B62/365C09K11/06G01N33/582C09K2211/1018
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Quick Facts
Patent No.
US 11,535,754
App. No.
17/737,899
Granted
Dec 27, 2022
Kind
B2
Abstract

Disclosed herein, inter alia, are silicon containing detectable compounds and methods of use thereof. In an aspect is provided a monovalent nucleotide or monovalent nucleoside covalently bound to a monovalent form of a compound described herein (e.g., wherein the R13 moiety of a compound described herein has reacted with a bioconjugate reactive group to form a bioconjugate linker thereby covalently bonding the monovalent compound to the monovalent nucleotide or monovalent nucleoside).

Claims (69)

1. A compound, or salt thereof, having the formula:

wherein

R 1 , R 8 , R 9 , R 10 , R 11 , and R 12 are each independently -L 1 -R 13 , hydrogen, halogen, —CCl 3 , —CBr 3 , —CF 3 , —CI 3 , —CHCl 2 , —CHBr 2 , —CHF 2 , —CHI 2 , —CH 2 Cl, —CH 2 Br, —CH 2 F, —CH 2 I, —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCI 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , —OCH 2 Cl, —OCH 2 Br, —OCH 2 I, —OCH 2 F, —N 3 , —SF 5 , —PO 3 H, substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl;

R 2 and R 3 are each independently -L 1 -R 13 , substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl;

R 4 , R 5 , R, and R 7 are each independently -L 1 -R 13 , hydrogen, halogen, —CF 3 , —CBr 3 , —CCl 3 , —CI 3 , —CHF 2 , —CHBr 2 , —CHCl 2 , —CHI 2 , —CH 2 F, —CH 2 Br, —CH 2 Cl, —CH 2 I, —OH, —COOH, —CONH 2 , —SH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R 4 and R 5 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 6 and R 7 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 4 and R 9 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 7 and R 10 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 5 and R 11 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 6 and R 12 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 1 and R 9 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl; substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 8 and R 10 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl; substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

wherein no more than one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 is -L 1 -R 13 ;

R 13 is a monovalent nucleotide, a bioconjugate reactive moiety, a monovalent nucleoside, or a monovalent nucleic acid; and

L 1 is a covalent linker or a bond wherein one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 and R 12 is -L 1 -R 13 .

2. The compound of claim 1 , having the formula:

3. The compound of claim 1 , wherein L 1 is a bond, —S(O) 2 —, —S(O) 2 NH—, —NHS(O) 2 —, —NH—, —O—, —S—, —C(O)—, —C(O)NH—, —NHC(O)—, —NHC(O)NH—, —C(O)O—, —OC(O)—, substituted or unsubstituted alkylene, substituted or unsubstituted heteroalkylene, substituted or unsubstituted cycloalkylene, substituted or unsubstituted heterocycloalkylene, substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, or a polymer.

4. The compound of claim 1 , wherein R 13 is hydrogen,

5. The compound of claim 1 , wherein R 2 and R 3 are each independently substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted 2 to 6 membered heteroalkyl.

6. The compound of claim 1 , wherein R 4 , R 5 , R 6 , and R 7 are each independently hydrogen, substituted or unsubstituted C 1 -C 6 alkyl, or substituted or unsubstituted 2 to 6 membered heteroalkyl.

7. The compound of claim 1 , wherein R 4 and R 5 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted 3 to 6 membered heterocycloalkyl.

8. The compound of claim 1 , wherein R 6 and R 7 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted 3 to 6 membered heterocycloalkyl.

9. The compound of claim 1 , wherein R 1 , R 8 , R 9 , R 10 , R 11 , and R 12 are each independently hydrogen, halogen, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —SF 5 , —PO 3 H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, or -L 1 -R 13 .

10. The compound of claim 1 , wherein the compound has the formula:

11. The compound of claim 1 , having the formula:

wherein

R 14 and R 15 are each independently halogen, —CCl 3 , —CBr 3 , —CF 3 , —CI 3 , —CHCl 2 , —CHBr 2 , —CHF 2 , —CHI 2 , —CH 2 Cl, —CH 2 Br, —CH 2 F, —CH 2 I, —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCI 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , —OCH 2 Cl, —OCH 2 Br, —OCH 2 I, —OCH 2 F, —N 3 , —SF 5 , —PO 3 H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, or -L 1 -R 13 ;

wherein no more than one of R 1 , R 2 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 14 , and R 15 is -L 1 -R 13 ; and

z14 and z15 are each independently an integer from 0 to 8.

12. The compound of claim 1 , having the formula:

wherein

R 16 and R 17 are each independently halogen, —CCl 3 , —CBr 3 , —CF 3 , —CI 3 , —CHCl 2 , —CHBr 2 , —CHF 2 , —CHI 2 , —CH 2 Cl, —CH 2 Br, —CH 2 F, —CH 2 I, —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCI 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , —OCH 2 Cl, —OCH 2 Br, —OCH 2 I, —OCH 2 F, —N 3 , —SF 5 , —PO 3 H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, or -L 1 -R 13 ; and

wherein no more than one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 16 , and R 17 is -L 1 -R 13 ; and

z16 and z17 are each independently an integer from 0 to 4.

13. The compound of claim 12 , having the formula:

14. The compound of claim 12 , having the formula:

15. The compound of claim 12 , having the formula:

16. The compound of claim 1 , wherein R 13 is

wherein

B is a divalent base;

R 27 is independently a 5′-nucleoside protecting group, monophosphate moiety, polyphosphate moiety, or nucleic acid moiety;

R 18 is hydrogen or —OR 18A ; and

R 18A and R 19 are each independently hydrogen, or a reversible terminator moiety.

17. The compound of claim 16 , wherein R 19 is a reversible terminator moiety, and the reversible terminator moiety is:

R 18 is hydrogen or —OH;

R 27 is a triphosphate moiety; or

B is a divalent cytosine or a derivative thereof, divalent guanine or a derivative thereof, divalent adenine or a derivative thereof, divalent thymine or a derivative thereof, divalent uracil or a derivative thereof, divalent hypoxanthine or a derivative thereof, divalent xanthine or a derivative thereof, divalent 7-methylguanine or a derivative thereof, divalent 5,6-dihydrouracil or a derivative thereof, divalent 5-methylcytosine or a derivative thereof, or divalent 5-hydroxymethylcytosine or a derivative thereof.

18. The compound of claim 1 , having the formula:

wherein,

Ring A and Ring B are each independently a heterocycloalkyl;

R 34 and R 36 are each independently halogen, —CCl 3 , —CBr 3 , —CF 3 , —CI 3 , —CHCl 2 , —CHBr 2 , —CHF 2 , —CHI 2 , —CH 2 Cl, —CH 2 Br, —CH 2 F, —CH 2 I, —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCI 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , —OCH 2 Cl, —OCH 2 Br, —OCH 2 I, —OCH 2 F, —N 3 , —SF 5 , —PO 3 H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, or -L 1 -R 13 ;

wherein no more than one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 34 , and R 36 is -L 1 -R 13 ; and

z34 and z36 are each independently an integer from 0 to 12.

19. The compound of claim 18 , having the formula:

20. A method of detecting the presence of an agent, wherein said agent is covalently bound to a monovalent form of a compound, and said agent is an oligonucleotide, protein, or compound, wherein said monovalent form of the compound has the formula:

wherein,

R 1 , R 8 , R 9 , R 10 , R 11 , and R 12 are each independently hydrogen, halogen, —CCl 3 , —CBr 3 , —CF 3 , —CI 3 , —CHCl 2 , —CHBr 2 , —CHF 2 , —CHI 2 , —CH 2 Cl, —CH 2 Br, —CH 2 F, —CH 2 I, —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, NHC(O)H, —NHC(O)OH, —NHOH, —OCCl 3 , —OCF 3 , —OCBr 3 , —OCI 3 , —OCHCl 2 , —OCHBr 2 , —OCHI 2 , —OCHF 2 , —OCH 2 Cl, —OCH 2 Br, —OCH 2 I, —OCH 2 F, —N 3 , —SF 5 , —PO 3 H, substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl;

R 2 and R 3 are each independently substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl;

R 4 , R 5 , R 6 , and R 7 are each independently hydrogen, halogen, —CF 3 , —CBr 3 , —CCl 3 , —CI 3 , —CHF 2 , —CHBr 2 , —CHCl 2 , —CHI 2 , —CH 2 F, —CH 2 Br, —CH 2 Cl, —CH 2 I, —OH, —COOH, —CONH 2 , —SH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R 4 and R 5 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 6 and R 7 substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 4 and R 9 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 7 and R 10 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 5 and R 11 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 6 and R 12 substituents may optionally be joined to form a substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 1 and R 9 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl; substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl;

R 8 and R 10 substituents may optionally be joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl; substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heteroaryl; and

L 1 is a covalent linker.

Assignments (3)
SECURITY INTEREST Recorded Mar 7, 2025
From: SINGULAR GENOMICS SYSTEMS, INC.
To: FIRST-CITIZENS BANK & TRUST COMPANY
Reel/Frame 070440/0465 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 11, 2022
From: CILA, MEGHA; GRAHAM, RONALD; RODRIGUEZ, RODRIGO
To: SINGULAR GENOMICS SYSTEMS, INC
Reel/Frame 061744/0257 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 4, 2022
From: CILA, MEGHA; GRAHAM, RONALD; RODRIGUEZ, RODRIGO
To: SINGULAR GENOMICS SYSTEMS, INC.
Reel/Frame 060721/0014 →
Continuity (3)
Continuation PCTUS2020058916 · Nov 4, 2020
Provisional Application 62932296 · Nov 7, 2019
Related Publication 20220267603A1 · Aug 25, 2022
Cited By (2)
US 12,331,199 US 12,365,801