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US 10,370,345 B2Granted
Amyloid targeting agents and methods of using the same
AssigneesThe Regents of the University of California, Amydis Diagnostics, Inc.
InventorsJerry Yang, Emmanuel A. Theodorakis, Stella Sarraf
Life of this patent
Estimating the term…
Abstract
Provided herein is the design and synthesis of novel molecular rotor fluorophores useful for detection of amyloid or amyloid like proteins. The fluorophores are designed to exhibit enhanced fluorescence emission upon associating with amyloid or amyloid like proteins as compared to unbound compound. Also disclosed herein are methods for treating diseases associated with amyloid or amyloid like proteins.
Claims21
A method for monitoring response to a treatment of a patient having a disease or condition characterized by amyloid deposit in a body part or a body area of the patient, comprising:
- (i) forming a detectable complex in the body part or the body area following the treatment by contacting an effective amount of a compound of Formula Ic, or a salt or solvate thereof, or a pharmaceutical composition thereof, with the amyloid deposit;
- and
- (ii) detecting the detectable complex, wherein a decrease of detectable complex as compared to before the treatment indicates that the patient is responsive to the treatment;
- wherein the compound of Formula Ic has the structure:
- wherein
- EDG is heterocycloalkyl of no more than 10 carbons optionally substituted with one or more R17;
- each R17 is independently halogen, —OR18, —NR19R20, C1-C10 alkyl, or C1-C10 heteroalkyl;
- each of R18, R19 and R20 is independently hydrogen, C1-C10 alkyl, C1-C10 heteroalkyl, or cycloalkyl of no more than 10 carbon atoms, each of which except for hydrogen is optionally substituted with one or more R21;
- each R21 is independently halogen, —OR22, —NR23R24, C1-C10 alkyl, C1-C10 heteroalkyl, cycloalkyl of no more than 10 carbon atoms, heterocycloalkyl of no more than 10 carbon atoms, aryl of no more than 10 carbon atoms, or heteroaryl of no more than 10 carbon atoms;
- each of R22, R23 and R24 is independently hydrogen or C1-C10 alkyl;
- Ar is arylene of no more than 14 carbon atoms optionally substituted with one or more R1;
- each R1 is independently halogen, —OR2, —NR3R4, C1-C10 alkyl, C1-C10 heteroalkyl,
- each of R2, R3 and R4 is independently hydrogen, C1-C10 alkyl, C1-C10 heteroalkyl;
- R84 is hydrogen or C1-C10 alkyl;
- EWG is halogen, —CN, —NO2, or methyl;
- WSG is:
- wherein n is an integer from 2-50, and R81 is hydrogen, a C1-C10 alkyl, a C2-C10 alkenyl, or a C2-C10 alkynyl, wherein the alkyl, alkenyl, or alkynyl is optionally substituted with one or more C1-C10 alkyl, C1-C10 heteroalkyl, cycloalkyl of no more than 10 carbon atoms, heterocycloalkyl of no more than 10 carbon atoms, aryl of no more than 10 carbon atoms, or heteroaryl of no more than 10 carbon atoms;
- each R82 is independently hydrogen or C1-C10 alkyl;
- X is C═O or SO2;
- and
- Y is NH or S.
18 more elements
A method for monitoring response to a treatment of a patient having a disease or condition characterized by amyloid deposit in a body part or a body area of the patient, comprising
- (i) forming a detectable complex in the body part or the body area following the treatment by contacting an effective amount of a compound of the formula:
- or a salt or solvate thereof, or a pharmaceutical composition thereof, with the amyloid deposit;
- and
- (ii) detecting the detectable complex, wherein a decrease of detectable complex as compared to before the treatment indicates that the patient is responsive to the treatment.
1 more element
A method of detecting an amyloid or amyloid like protein comprising
- (i) contacting a compound of Formula Ic, or a salt or solvate thereof, with a body part or a body area of a patient potentially comprising the amyloid or amyloid like protein;
- (ii) forming a detectable complex of the amyloid or amyloid like protein;
- and
- (iii) detecting the detectable complex such that the presence or absence of the detectable complex correlates with the presence or absence of the amyloid or amyloid like protein;
- wherein the compound of Formula Ic has the structure:
- wherein
- EDG is heterocycloalkyl of no more than 10 carbons optionally substituted with one or more R17;
- wherein each R17 is independently halogen, —OR18, —NR19R20, C1-C10 alkyl, or C1-C10 heteroalkyl;
- each of R18, R19 and R20 is independently hydrogen, C1-C10 alkyl, C1-C10 heteroalkyl, or cycloalkyl of no more than 10 carbon atoms, each of which except for hydrogen is optionally substituted with one or more R21;
- each R21 is independently halogen, —OR22, —NR23R24, C1-C10 alkyl, C1-C10 heteroalkyl, cycloalkyl of no more than 10 carbon atoms, heterocycloalkyl of no more than 10 carbon atoms, aryl of no more than 10 carbon atoms, or heteroaryl of no more than 10 carbon atoms;
- each of R22, R23 and R24 is independently hydrogen or C1-C10 alkyl;
- Ar is aryl of no more than 14 carbon atoms optionally substituted with one or more R1;
- each R1 is independently halogen, —OR2, —NR3R4, C1-C10 alkyl, C1-C10 heteroalkyl,
- each of R2, R3 and R4 is independently hydrogen, C1-C10 alkyl, C1-C10 heteroalkyl;
- R84 is hydrogen or C1-C10 alkyl;
- EWG is halogen, —CN, —NO2, or methyl;
- WSG is:
- wherein n is an integer from 2 to 50, and R81 is hydrogen, a C1-C10 alkyl, a C2-C10 alkenyl, or a C2-C10 alkynyl, wherein the alkyl, alkenyl, or alkynyl is optionally substituted with one or more C1-C10 alkyl, C1-C10 heteroalkyl, cycloalkyl of no more than 10 carbon atoms, heterocycloalkyl of no more than 10 carbon atoms, aryl of no more than 10 carbon atoms, or heteroaryl of no more than 10 carbon atoms;
- each R82 is independently hydrogen or C1-C10 alkyl;
- X is C═O or SO2;
- and
- Y is NH or S.
19 more elements
A method for monitoring response to a treatment of a patient having a disease or condition characterized by amyloid deposit in a body part or a body area of the patient, comprising
- (i) forming a detectable complex in the body part or the body area following the treatment by contacting the amyloid deposit with an effective amount of a compound of the formula:
- wherein n is an integer from 2 to 10;
- or a salt or solvate thereof, or a pharmaceutical composition thereof;
- and
- (ii) detecting the detectable complex, wherein a decrease of detectable complex as compared to before the treatment indicates that the patient is responsive to the treatment.
2 more elements
Dependencies are inferred from the claim text.