Imidazopyrazine derivatives, process for preparation thereof, and their uses as luciferins
The present invention is in the field of bioluminescence in biology and/or medicine. In particular, the invention provides imidazopyrazine derivatives, processes for preparation thereof, and their uses as luciferins.
1. A kit comprising:
i) A compound of following formula:
wherein:
R 1 represents H or a group selected from C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 6 -C 10 aryl, aralkyl and C 5 -C 10 -membered heteroaryl groups, said C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 6 -C 10 aryl, aralkyl and C 5 -C 10 -membered heteroaryl groups are optionally substituted by at least one Y 1 group;
R 2 represents a group selected from C 6 -C 10 aryl and C 5 -C 10 -membered heteroaryl groups, said C 6 -C 10 aryl and C 5 -C 10 -membered heteroaryl groups are optionally substituted by at least one Y 2 group;
or R 1 and R 2 together form with the two carbon atom to which they are respectively attached a C 5 -C 7 cycloalkene group, a C 4 -C 7 heterocycloalkene group, or a C 6 -C 10 arene, said C 5 -C 7 cycloalkene group and C 4 -C 7 heterocycloalkene groups are fused with a C 6 -C 10 arene, said C 5 -C 7 cycloalkene group, C 4 -C 7 heterocycloalkene group, C 6 -C 10 arene, C 5 -C 7 cycloalkene group and C 4 -C 7 heterocycloalkene groups are optionally substituted by at least one Y 12 group;
R 3 represents H, a C 1 -C 6 alkyl, an aralkyl group, a hetaralkyl group or a heterocycloalkyl-CH 2 — group, said C 1 -C 6 alkyl, aralkyl group, hetaralkyl group and heterocycloalkyl-CH 2 — group are optionally substituted by at least one Y 3 group;
R 4 represents H or a group selected from C 1 -C 6 alkyl and C 3 -C 7 cycloalkyl groups, said C 1 -C 6 alkyl and C 3 -C 7 cycloalkyl groups are optionally substituted by at least one Y 4 group;
R 5 represents a —C(═O)R a group or a —C(═O)OR a group, said C(═O)R a group and —C(═O)OR a group are optionally substituted by at least one Y 5 group;
R a represents H, a C 1 -C 6 alkyl group, a C 3 -C 7 cycloalkyl group, a C 6 -C 10 aryl, or an aralkyl group, said C 1 -C 6 alkyl group, C 3 -C 7 cycloalkyl group, C 6 -C 10 aryl, and aralkyl group are optionally substituted by at least one Y a group;
Z represents a C 6 -C 10 aryl, a C 5 -C 10 -membered heteroaryl groups, a C 1 -C 6 alkyl, a C 3 -C 7 cycloalkyl, a C 4 -C 7 heterocycloalkyl, said C 6 -C 10 aryl, C 5 -C 10 -membered heteroaryl groups, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl and C 4 -C 7 heterocycloalkyl are optionally substituted by at least one Y Z group;
said Y 1 , Y 2 , Y 12 , Y 3 , Y 4 , Y 5 , Y a and Y Z groups are each independently selected from:
a C 1 -C 6 alkyl;
a C 3 -C 7 cycloalkyl;
a C 6 -C 10 aryl;
a C 5 -C 10 -membered heteroaryl group;
an halogen;
a —CF 3 group;
a —CN group;
a —OR i group;
a —OSO 3 H group;
a —NR i R ii group;
a guanidinyl group;
a —C(═O)OR a group, R a is as defined above;
R i and R ii each independently represent H, a C 1 -C 6 alkyl group, a C 3 -C 10 cycloalkyl group, an aralkyl group; or together form with the nitrogen atom to which they are attached a C 4 -C 7 heterocycloalkyl group;
and
ii) a solution comprising a strong acid.
2. A compound of following formula:
wherein:
R 1 represents H or a group selected from C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 6 -C 10 aryl, aralkyl and C 5 -C 10 -membered heteroaryl groups, said C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 6 -C 10 aryl, aralkyl and C 5 -C 10 -membered heteroaryl groups are optionally substituted by at least one Y 1 group;
R 2 represents a group selected from C 6 -C 10 aryl and C 5 -C 10 -membered heteroaryl groups, said C 6 -C 10 aryl and C 5 -C 10 -membered heteroaryl groups are optionally substituted by at least one Y 2 group;
or R 1 and R 2 together form with the two carbon atom to which they are respectively attached a C 5 -C 7 cycloalkene group, a C 4 -C 7 heterocycloalkene group, or a C 6 -C 10 arene, said C 5 -C 7 cycloalkene group and C 4 -C 7 heterocycloalkene groups are fused with a C 6 -C 10 arene, said C 5 -C 7 cycloalkene group, C 4 -C 7 heterocycloalkene group, C 6 -C 10 arene, C 5 -C 7 cycloalkene group and C 4 -C 7 heterocycloalkene groups are optionally substituted by at least one Y 12 group;
R 3 represents H, a C 1 -C 6 alkyl, an aralkyl group, a hetaralkyl group or a heterocycloalkyl-CH 2 — group, said C 1 -C 6 alkyl, aralkyl group, hetaralkyl group and heterocycloalkyl-CH 2 — group are optionally substituted by at least one Y 3 group;
R 4 represents H or a group selected from C 1 -C 6 alkyl and C 3 -C 7 cycloalkyl groups, said C 1 -C 6 alkyl and C 3 -C 7 cycloalkyl groups are optionally substituted by at least one Y 4 group;
R 5 represents a —C(═O)R a group or a —C(═O)OR a group, said C(═O)R a group and —C(═O)OR a group are optionally substituted by at least one Y 5 group;
R a represents H, a C 1 -C 6 alkyl group, a C 3 -C 7 cycloalkyl group, a C 6 -C 10 aryl, or an aralkyl group, said C 1 -C 6 alkyl group, C 3 -C 7 cycloalkyl group, C 6 -C 10 aryl, and aralkyl group are optionally substituted by at least one Y a group;
Z represents a C 6 -C 10 aryl, a C 5 -C 10 -membered heteroaryl groups, a C 1 -C 6 alkyl, a C 3 -C 7 cycloalkyl, a C 4 -C 7 heterocycloalkyl, said C 6 -C 10 aryl, C 5 -C 10 -membered heteroaryl groups, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl and C 4 -C 7 heterocycloalkyl are optionally substituted by at least one Y Z group;
said Y 1 , Y 2 , Y 12 , Y 3 , Y 4 , Y 5 , Y a and Y Z groups are each independently selected from:
a C 1 -C 6 alkyl;
a C 3 -C 7 cycloalkyl;
a C 6 -C 10 aryl;
a C 5 -C 10 -membered heteroaryl group;
an halogen;
a —CF 3 group;
a —CN group;
a —OR i group;
a —OSO 3 H group;
a —NR i R ii group;
a guanidinyl group;
a —C(═O)OR a group, R a is as defined above;
R i and R ii each independently represent H, a C 1 -C 6 alkyl group, a C 3 -C 10 cycloalkyl group, an aralkyl group; or together form with the nitrogen atom to which they are attached a C 4 -C 7 heterocycloalkyl group;
with the proviso that when R 1 and R 4 represent H, then:
R 2 is not unsubstituted phenyl, or 4-hydroxy-phenyl, or
R 3 is not unsubstituted benzyl, or
Z is not unsubstituted phenyl, 4-hydroxy-phenyl, or unsubstituted furan.
3. A compound of following formula:
wherein:
R 1 represents H or a group selected from C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 6 -C 10 aryl, aralkyl and C 5 -C 10 -membered heteroaryl groups, said C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 6 -C 10 aryl, aralkyl and C 5 -C 10 -membered heteroaryl groups are optionally substituted by at least one Y 1 group;
R 2 represents a group selected from C 6 -C 10 aryl and C 5 -C 10 -membered heteroaryl groups, said C 6 -C 10 aryl and C 5 -C 10 -membered heteroaryl groups are optionally substituted by at least one Y 2 group;
R 3 represents an aralkyl group, said aralkyl group is optionally substituted by at least one Y 3 group;
R 4 represents H or a group selected from C 1 -C 6 alkyl and C 3 -C 7 cycloalkyl groups, said C 1 -C 6 alkyl and C 3 -C 7 cycloalkyl groups are optionally substituted by at least one Y 4 group;
Z represents a prow of following formula:
or an oxazolyl, or an oxadiazolyl;
R, R′, R″ and R′″ each independently represent H or a group selected from:
a C 1 -C 6 alkyl group;
a C 3 -C 7 cycloalkyl group;
an halogen;
a —OR i group;
a —CF 3 group;
X represents O or S;
said Y 1 , Y 2 , Y 3 and Y 4 , groups are each independently selected from:
a C 1 -C 6 alkyl group;
a C 3 -C 7 cycloalkyl group;
an halogen;
a —OR ii group;
R i and R ii each independently represent H, a C 1 -C 6 alkyl group, a C 3 -C 10 cycloalkyl group or an aralkyl group;
provided that:
when Z═Z1:
at least one of R, R′ and R″ does not represent H; or
when R, R′ and R″ represent H, then R 2 represents a group selected from C 6 -C 10 aryl and C 5 -C 10 -membered heteroaryl groups substituted by at least an halogen group; or R 3 represents a group selected from C 6 -C 10 aralkyl groups substituted by at least an halogen group;
when Z═Z2:
at least one of R, R′, R″ and R′″ does not represent H; or
when R, R′, R″ and R′″ represent H; then R 2 represents a group selected from C 6 -C 10 aryl and C 5 -C 10 -membered heteroaryl groups substituted by at least a halogen group; or R 3 represents a group selected from C 6 -C 10 aralkyl groups substituted by at least an halogen group; or
when R, R′ and R′″ represent H and R″ represents a C 1 -C 6 alkyl group or a —OR i group; then R 2 does not represent a 4-HO-phenyl- group; or R 3 represents a group selected from C 6 -C 10 aralkyl groups substituted by at least an halogen group,
R 5 represents a —C(═O)R a group or a —C(═O)OR a group, said C(═O)R a group and —C(═O)OR a group are optionally substituted by at least one Y 5 group, wherein R a represents H, a C 1 -C 6 alkyl group, a C 3 -C 7 cycloalkyl group, a C 6 -C 10 aryl, or an aralkyl group, said C 1 -C 6 alkyl group, C 3 -C 7 cycloalkyl group, C 6 -C 10 aryl, and aralkyl group are optionally substituted by at least one Y a group.
4. A kit comprising:
i) A compound of following formula:
wherein:
R 1 represents H or a group selected from C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 6 -C 10 aryl, aralkyl and C 5 -C 10 -membered heteroaryl groups, said C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 6 -C 10 aryl, aralkyl and C 5 -C 10 -membered heteroaryl groups are optionally substituted by at least one Y 1 group;
R 2 represents a group selected from C 6 -C 10 aryl and C 5 -C 10 -membered heteroaryl groups, said C 6 -C 10 aryl and C 5 -C 10 -membered heteroaryl groups are optionally substituted by at least one Y 2 group;
or R 1 and R 2 together form with the two carbon atom to which they are respectively attached a C 5 -C 7 cycloalkene group, a C 4 -C 7 heterocycloalkene group, or a C 6 -C 10 arene, said C 5 -C 7 cycloalkene group and C 4 -C 7 heterocycloalkene groups are fused with a C 6 -C 10 arene, said C 5 -C 7 cycloalkene group, C 4 -C 7 heterocycloalkene group, C 6 -C 10 arene, C 5 -C 7 cycloalkene group and C 4 -C 7 heterocycloalkene groups are optionally substituted by at least one Y 12 group;
R 3 represents H, a C 1 -C 6 alkyl, an aralkyl group, a hetaralkyl group or a heterocycloalkyl-CH 2 — group, said C 1 -C 6 alkyl, aralkyl group, hetaralkyl group and heterocycloalkyl-CH 2 — group are optionally substituted by at least one Y 3 group;
R 4 represents H or a group selected from C 1 -C 6 alkyl and C 3 -C 7 cycloalkyl groups, said C 1 -C 6 alkyl and C 3 -C 7 cycloalkyl groups are optionally substituted by at least one Y 4 group;
R 5 represents a —C(═O)R a group or a —C(═O)OR a group, said C(═O)R a group and —C(═O)OR a group are optionally substituted by at least one Y 5 group;
R a represents H, a C 1 -C 6 alkyl group, a C 3 -C 7 cycloalkyl group, a C 6 -C 10 aryl, or an aralkyl group, said C 1 -C 6 alkyl group, C 3 -C 7 cycloalkyl group, C 6 -C 10 aryl, and aralkyl group are optionally substituted by at least one Y a group;
Z represents a C 6 -C 10 aryl, a C 5 -C 10 -membered heteroaryl groups, a C 1 -C 6 alkyl, a C 3 -C 7 cycloalkyl, a C 4 -C 7 heterocycloalkyl, said C 6 -C 10 aryl, C 5 -C 10 -membered heteroaryl groups, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl and C 4 -C 7 heterocycloalkyl are optionally substituted by at least one Y Z group;
said Y 1 , Y 2 , Y 12 , Y 3 , Y 4 , Y 5 , Y a and Y Z groups are each independently selected from:
a C 1 -C 6 alkyl;
a C 3 -C 7 cycloalkyl;
a C 6 -C 10 aryl;
a C 5 -C 10 -membered heteroaryl group;
an halogen;
a —CF 3 group;
a —CN group;
a —OR i group;
a —OSO 3 H group;
a —NR i R ii group;
a guanidinyl group;
a —C(═O)OR a group, R a is as defined above;
R i and R ii each independently represent H, a C 1 -C 6 alkyl group, a C 3 -C 10 cycloalkyl group, an aralkyl group; or together form with the nitrogen atom to which they are attached a C 4 -C 7 heterocycloalkyl group;
ii) a solution comprising a strong acid; and
iii) a buffered media.