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US 11,466,158 B2Granted
Phthalocyanine dye compounds, conjugates and methods of use thereof
AssigneeRakuten Medical, Inc.
InventorsJuan Betancort, Lew Makings, Torsten Wiemann
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Abstract
Disclosed herein are phthalocyanine dyes, and conjugates thereof, useful as fluorescent reporters for bioassays, for optical imaging and as therapeutic conjugates as the photosensitizing agents in light-based therapies including photoimmuno therapy (PIT). Certain phthalocyanine dyes disclosed herein are water soluble, and possess photophysical and photochemical profiles useful for use in imaging or therapy.
Claims29
A phthalocyanine dye having the Formula (I):
- or a salt, stereoisomer, or tautomer thereof, wherein,
- M is Si;
- X is
- Y is
- R1 and R2 are each independently alkyl;
- R3, R4 or R5 are selected from substituent group (a) substituent group (b) wherein,
- (a) R3 is hydrogen, -L3-H, -L3-A, or -L3-Z;
- R4 is -L4-H, —(NH)m-L4-A, —(NH)m-L4-Z, —(O)m-L4-A, or —(O)m-L4-Z;
- R5 is -L4-H or -L5-A;
- and
- (b) R3 is -L3-H, or -L3-A;
- R4 is -L4-H, —(NH)m-L4-A;
- wherein R3 and R4 are connected with a bond to form a heterocyclyl substituted with -L4-A;
- and
- R5 is -L4-H or -L5-A;
- provided at least one of R3, R4 and R5 is a group containing A;
- A is a group selected from —C(O)OR11 or —NR12R13, wherein each R11 is independently hydrogen, alkyl, haloalkyl, alkenyl, heterocyclyl, aryl or heteroaryl, and each R11 is independently optionally substituted with one to five groups each independently selected from halo, —SO3H and —SO2F;
- each R12 is independently hydrogen, alkyl or haloalkyl;
- each R13 is aryl or heteroaryl, and each R13 is independently optionally substituted with one to five groups each independently selected from halo, —SO3H and —SO2F;
- or optionally R12 and R13, together with the nitrogen to which they are attached, form a cyclic imide;
- R6 and R7 are each independently alkyl;
- R8, R9 or R10 are selected from substituent group (a) or substituent group (b) wherein,
- (a) R8 is hydrogen, -L8-H or -L8-Z;
- R9 is -L9-H, —(NH)n-L9-Z or —(O)n-L9-Z;
- R10 is -L10-Z;
- and
- (b) R8 and R9 are connected with a bond to form a heterocyclyl substituted with -L9-Z and R10 is -L10-H or -L10-Z;
- provided at least one of R8, R9 and R10 is a group containing Z;
- Z is selected from:
- —(CH2)q(OCH2CH2)vOR22,
- —(CH2)qO(CH2)vN[(CH2CH2O)wCH2CH2OR22]t,
- —(CH2)qN[(CH2)p(OCH2CH2)vOR22]t,
- —(CH2)qN[(CH2)pSO3H]t,
- —(CH2)qNRb[(CH2)pSO3H]u,
- —(CH2)qNRb[(CH2)pCH(SO3H)2]u,
- —SO3H,
- —CH(SO3H)2,
- —PO3H,
- —(CH2)qN[(CH2)pPO3H]t,
- —(CH2)qNRb[(CH2)pPO3H]u, or
- —(CH2)qNRb(CH2)pCH(PO3H)2,
- each R22 is independently alkyl, haloalkyl, cycloalkyl or aryl;
- each Rb is independently hydrogen, alkyl, haloalkyl or cycloalkyl;
- each v, w and p are independently an integer from 1 to 10;
- each q is independently an integer from 0 to 10;
- t is 2 or 3;
- and
- u is 1 or 2,
- L1 and L2 are each independently optionally substituted C2-4 alkylene;
- L3, L4, L5, L8, L9 and L10 are each independently optionally substituted alkylene, or optionally substituted heteroalkylene, where the carbon atom of the alkylene, or heteroalkylene is further optionally substituted with Z and each nitrogen atom of the heteroalkylene or heteroalkenylene is optionally substituted with one or two L′-Z;
- L′ is each independently optionally substituted alkylene, or optionally substituted heteroalkylene;
- a is 0 or 1;
- b is 0 or 1;
- c is 0 or 1;
- d is 0 or 1;
- m is 0 or 1;
- n is 0 or 1;
- provided that if b is 1, then a is 0;
- if d is 1, then c is 0;
- if m is 1, b is 1;
- and
- if n is 1, c is 1;
- and
- provided that when R6 and R7 are both methyl, and L2 is propylene, c is 1 and d is 0, then
- L8, L9 and L10 are each not propylene.
62 more elements
Dependencies are inferred from the claim text.