Granted Patent B2

US 12,285,250 · App. 16/455,038 · Granted Apr 29, 2025

Inventors: Soya Gamsey (San Francisco, CA); Viachaslau Bernat (Burlingame, CA); Alex Kutyavin (Lake Stevens, WA); Jacob William Clary (Moss Beach, CA); Sulolit Pradhan (Foster City, CA)

Assignee: Profusa, Inc

A61B5/14532A61B5/1459A61B5/14865A61B5/6847C07F7/0816C07F7/30C07F9/657172C09B23/083C09B23/10C09B57/00C09K11/06

Abstract

Claims (46)

1. A compound of formula (IV-IA):

or a tautomer, a solvate, or a salt thereof, wherein:

each R 1 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 11 , R 12 , and R 14 is independently H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 2 -C 10 heteroalkyl, halogen, —C(O)R′, —COOR′, —C(O)NH 2 , —C(O)NR′R″, —CF 3 , —CN, —SO 3 H, —SO 2 CF 3 , —SO 2 R′, —SO 2 NR′R″, —N(R′) 2 , —N(R′) 3 + , —NO 2 , —OR′, —NHC(O)R′, —OC(O)R′, or phenyl;

R′ and R″ are each independently H or C 1 -C 6 alkyl; or R′ and R″ can together form a 5- or 6-membered heterocycle with the nitrogen atom to which they are attached, wherein the heterocycle optionally comprises one additional heteroatom selected from S, O, and N;

R d and R e are each H, C 1 -C 6 alkyl, C 6 -C 10 aryl, C 1 -C 6 alkoxy, or C 6 -C 10 aryloxy;

each R 2 and R 15 is independently, H or C 1 -C 6 alkyl;

R 9 and R 10 are independently H, C 1 -C 6 alkyl, or —NHC(O)C(CH 3 )CH 2 ;

L 1 and L 3 are independently a bond or a linker group selected from optionally substituted C 1 -C 10 alkylene, optionally substituted C 2 -C 10 alkenylene, optionally substituted C 2 -C 10 alkynylene, optionally substituted C 2 -C 20 heteroalkylene, optionally substituted —(CH 2 CH 2 O) n CH 2 —, optionally substituted —CH 2 (CH 2 CH 2 O) n —, optionally substituted —(CH 2 CH 2 O) n CH 2 CH 2 —, optionally substituted —CH 2 CH 2 (CH 2 CH 2 O) n —, or optionally substituted (CH 2 CH 2 O) n —, wherein n is an integer between 1 and 5;

L 2 is a bond, optionally substituted phenylene, optionally substituted -alkylene-phenylene-, optionally substituted -phenylene-alkylene-, or optionally substituted 5- or 6-membered heteroarylene;

R 20 , R 21 , R 23 , and R 24 are each independently H, C 1 -C 6 alkyl optionally substituted with —NH 2 or —NH 3 + , C 2 -C 6 alkenyl, or benzyl optionally substituted with —B(OR 2 ) 2 ;

R 22 , R 25 , R 26 , and R 27 are each independently H or C 1 -C 6 alkyl;

alternatively, (R 21 and R 20 ) and/or (R 23 and R 24 ) together with the nitrogen atom to which they are attached, form a 6-, 5-, or 4-membered saturated or partially saturated ring;

alternatively, (R 21 and R 22 ), (R 24 and R 25 ), (R 23 and R 27 ), and/or (R 26 and R 20 ), together with the atoms to which they are attached, form an optionally substituted 6- or 5-membered saturated, unsaturated, or partially saturated ring;

provided that the compound is not

 or a salt thereof.

2. The compound of claim 1 , wherein L 2 is a bond; phenylene optionally substituted with at least one substituent selected from C 1 -C 3 alkyl, C 1 -C 3 alkoxy, or halogen;

3. The compound of claim 1 , wherein L 2 is a bond, optionally substituted phenylene, optionally substituted -alkylene-phenylene-, optionally substituted -phenylene-alkylene-, or optionally substituted 5- or 6-membered heteroarylene; wherein the optional substituent is halogen, C 1 -C 3 alkyl, or C 1 -C 3 alkoxy.

4. The compound of claim 1 , wherein L 2 is a bond,

5. The compound of claim 1 , wherein L 2 is

each is optionally substituted.

6. The compound of claim 1 , wherein R d and R e are each methyl.

7. The compound of claim 1 , wherein R 9 , R 10 , or both, is —NHC(O)C(CH 3 )CH 2 .

8. The compound of claim 1 , wherein L 1 , L 3 , or both, is C 1 -C 10 alkylene, C 2 -C 20 heteroalkylene, —(CH 2 CH 2 O) n CH 2 —, —(CH 2 CH 2 O) n CH 2 CH 2 —, or —(CH 2 CH 2 O) n —.

9. The compound of claim 1 , wherein L 1 and L 3 are independently —CH 2 —CH 2 —CH 2 — or —(CH 2 CH 2 O) 4 CH 2 CH 2 —.

10. The compound of claim 1 , wherein R 11 , R 14 and R 12 are H.

11. The compound of claim 1 , wherein R 22 , R 25 , R 26 , and R 27 are H.

12. The compound of claim 1 , wherein R 1 , R 5 , and R 6 are H.

13. The compound of claim 1 , wherein at least one of R 3 , R 4 , R 7 , and R 8 is C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkoxy, halogen, —SO 2 NR′R″, —CN, or —NO 2 .

14. The compound of claim 1 , wherein at least one of R 3 , R 4 , R 7 , and R 8 is methyl, —CF 3 , methoxy, halogen, —SO 2 N(Me) 2 , —SO 2 NHMe, —CN, —NO 2 , or

15. The compound of claim 1 , wherein R 2 and R 15 are H.

16. The compound of claim 1 , wherein R 20 , R 21 , R 23 , and R 24 are each independently H; C 1 -C 4 alkyl optionally substituted with —NH 2 or —NH 3 ; C 2 -C 4 alkenyl; or benzyl optionally substituted with —B(OR 2 ) 2 ; or alternatively, (R 21 and R 22 ), (R 24 and R 25 ), (R 23 and R 27 ), and/or (R 26 and R 20 ), together with the atoms to which they are attached, form an optionally substituted 6- or 5-membered saturated, unsaturated, or partially saturated ring.

17. The compound of claim 1 , wherein R 20 , R 21 , R 23 , and R 24 are each independently H, C 1 -C 6 alkyl, or benzyl optionally substituted with —B(OR 2 ) 2 .

18. A compound selected from:

a)

 or a tautomer, a solvate, or a salt thereof, or

b)

19. A sensor comprising a polymer, wherein the polymer comprises one or more residues of the compound of claim 1 .

20. A method of measuring blood glucose concentration in a mammalian subject, comprising:

a) implanting a sensor of claim 19 into subcutaneous tissue of the mammalian subject;

b) measuring at least one wavelength of light in the glucose-concentration-dependent luminescent signal from the sensor with a detector to produce a detected luminescent signal; and

c) processing the detected luminescent signal to produce a glucose concentration.

21. A sensor comprising a polymer, wherein the polymer comprises one or more residues of the compound of claim 18 .

22. A method of measuring blood glucose concentration in a mammalian subject, comprising:

a) implanting a sensor of claim 21 into subcutaneous tissue of the mammalian subject;

b) measuring at least one wavelength of light in the glucose-concentration-dependent luminescent signal from the sensor with a detector to produce a detected luminescent signal; and

c) processing the detected luminescent signal to produce a glucose concentration.

Assignments (3)

Continuity (2)

References Cited (217)