Traitement en cours

Veuillez attendre...

Paramétrages

Paramétrages

Aller à Demande

1. WO2020108720 - NOUVEAUX COMPOSÉS DE TÉTRAZINE POUR L'IMAGERIE IN VIVO

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

[ EN ]

Claims

1. A tetrazine compound having the following formula I:


Formula I

wherein one of R1-R5 is 18F,

at least two of the remaining R1-R5 are H, and the other remaining R1-R5 are the same or different and are selected from H, alkyl, halogen, - CF3, -CN, -O-alkyl, -S-alkyl, -NH-alkyl, -N(alkyl)2, -NH(C=0)-alkyl, -N-alkyl-(C=0)-alkyl, -S02-alkyl, - S02-NH2, -S02-NHalkyl, -S02-N(alkyl)2 -C(=0)-NH2, -C(=0)-NH-alkyl, -C(=0)- N(alkyl)2, -C(=0)-OH, -C(=0)-0-alkyl, -CH2-NH2, .CH2-NH-alkyl, -OH, CH2-0-al- kyl, CH2-0-aryl, CH2-0-phenyl, CH2-0-naphthyl,


, wherein n is an integer from 1 to 4, and

R6 is selected from H, CH3, phenyl,
, wherein the curly bond indicates the link to the tetrazine moiety.

2. A compound according to claim 1 , wherein alkyl is selected from linear or

branched Oi-Ob alkyl, cyclic Oi-Ob alkyl, optionally substituted with -OH, -NH2 or halogen.

3. A compound according to claim 1 or 2, wherein alkyl is selected from linear or branced methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert. butyl, pentyl, and hexyl.

4. A compound according to any of the preceding claims, wherein halogen is se lected from I, Br, or Cl.

5. A compound according to any of the preceding claims selected from the com pounds, wherein:

a) Ri is 18F and all other R’s are H; or

b) R2 is 18F and all other R’s are H; or

c) R3 is 18F and all other R’s are H.

A compound according to any of claims 1-4, selected from compounds wherein:

a) are


b) R2 is 18F and Ri, R3, R4, and R5 are

c) R3 is 18F and Ri, R2, R4, and R5 are


7. A tetrazine precursor having the formula III:


Formula III

wherein one of R1-R5 is SnR3, B(OR)2, B(OH)2 or similar tin or boronic acid/es- ter species. R is an alkyl as defined herein that may contain one or more het eroatoms selected from oxygen and nitrogen; and at least two of the remaining R1-R5 are H, and the other remaining R1-R5 are the same or different and are selected from H, alkyl, halogen, - CF3, -CN, -O-alkyl, -S-alkyl, -NH-alkyl, -N(al- kyl)2, -NH(C=0)-alkyl, -N-alkyl-(C=0)-alkyl, -S02-alkyl, -SO2-NH2, -S02-NHalkyl, -S02-N(alkyl)2 -C(=0)-NH2, -C(=0)-NH-alkyl, -C(=0)-N(alkyl)2, -C(=0)-OH, - C(=0)-0-alkyl, -CH2-NH2, .C-NH-alkyl, -OH, CH2-0-alkyl, CH2-0-aryl, CH2-0- phenyl, CH2-0-naphthyl


, wherein n is an integer from 1 to 4, and

R6 is selected from H, CH3, phenyl,
wherein the curly bond indicates the link to the tetrazine moiety.

8. A tetrazine precursor having the formula IV:


Formula IV

wherein one of R1-R5 is iodine (I), at least two of the remaining R1-R5 are H, and the other remaining R1-R5 are the same or different and are selected from H, al kyl, halogen, - CF3, -CN, -O-alkyl, -S-alkyl, -NH-alkyl, -N(alkyl)2, -NH(C=0)-al- kyl, -N-alkyl-(C=0)-alkyl, -S02-alkyl, -S02-NH2, -S02-NHalkyl, -S02-N(alkyl)2 - C(=0)-NH2, -C(=0)-NH-alkyl, -C(=0)-N(alkyl)2, -C(=0)-OH, -C(=0)-0-alkyl, - CH2-NH2, -CH2-NH-alkyl, -OH, CH2-0-alkyl, CH2-0-aryl, CH2-0-phenyl, CH2-0- naphthyl

, wherein n is an integer from 1 to 4, and

R6 is selected from H, CH3, phenyl,
wherein the curly bond indicates the link to the tetrazine moiety

9. A compound as defined in any of claims 1-6 for use in bioorthogonal chemistry.

10. A compound as defined in any of claims 1-6 for use in diagnostics.

11. A compound as defined in any of claims 1-6 for use in in vivo imagining.

12. A compound for use as defined in any of claims 9-11 , wherein the compound penetrates the blood-brain-barrier.

13. A method for preparing a compound as defined in any of claims 1-6, the method comprises converting a suitably functionalized benzonitrile to the corresponding tetrazine as detailed in section“1.3 General Procedure for synthesis of 3-H-6- aryl-1 ,2,4,5-tetrazine”.

14. A method according to claim 13 comprising reacting


wherein RI-R6 are as defined herein, in the presence of hydrazine monohydrate to obtain a compound according to any of claims 1-6.

15. A method according to claim 13, wherein the reaction is carried out at a temper ature range of from 50 to 70 °C.

16. A method according to claim 14, wherein water is added after cooling to room temperature followed by addition of HCI and extraction with EtOAc.