Diagnostic probes and remedies for diseases with accumulation of prion protein, and stains for prion protein
First Claim
Patent Images
1. A compound, which is used as a probe for diagnosing diseases in which prion protein is accumulated, represented by the formula (I) or (II):
- wherein D is NR′
, S, O, CH═
CH, or CH2, R′
is H, alkyl having 1 to 4 carbons hereinafter, referred to as C1-4 alkyl), or phenyl, wherein the C1-4 alkyl is optionally substituted with halogen(s), E is N or CH, Ra is, each independently, selected from the group consisting of H, C1-4 alkyl, halogen, OH, C1-4 alkyl-OH, C1-4 alkyl-O—
C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, NO2, O—
C1-4 alkyl, COOH, and SO3H, wherein the C1-4 alkyl is optionally substituted with halogen(s), Q is N or CRb, Rb is selected from the group consisting of H, C1-4 alkyl, halogen, OH, C1-4 alkyl-OH, C1-4 alkyl-O—
C1-4 alkyl, NH(C1-4 alkyl), NH2, N(C1-4 alkyl)2, NO2, O—
C1-4 alkyl, COOH, and SO3H, wherein the C1-4 alkyl is optionally substituted with halogen(s), m is an integer of 0 to 4, R1 and R2 are independently selected from the group consisting of H, C1-4 alkyl, halogen, OH, C1-4 alkyl-OH, C1-4 alkyl-O—
C1-4 alkyl, NH(C1-4 alkyl), NH2, N(C1-4 alkyl)2, NO2, O—
C1-4 alkyl, COOH, and SO3H, wherein the C1-4 alkyl is optionally substituted with halogen(s), or alternatively, R1 and R2, together, form a benzene or naphthalene ring which is optionally substituted with one to four R4, R3 is selected from the group consisting of H, C1-4 alkyl, halogen, OH, C1-4 alkyl-OH, C1-4 alkyl-O—
C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, NO2, O—
C1-4 alkyl, COOH, SO3H, wherein the C1-4 alkyl is optionally substituted with halogen(s), and any one of the moieties represented by (a) to (e);
wherein each Rx is independently selected from the group consisting of H, C1-4 alkyl, halogen, OH, C1-4 alkyl-OH, C1-4 alkyl-O—
C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, N═
CH-allyl, NO2, O—
C1-4 alkyl, COOH, and SO3H, wherein the C1-4 alkyl is optionally substituted with halogen(s), each R4 is independently selected from the group consisting of H, C1-4 alkyl, halogen, OH, C1-4 alkyl-OH, C1-4 alkyl-O—
C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, NO2, O—
C1-4 alkyl, COOH, SO3H, wherein the C1-4 alkyl is optionally substituted with halogen(s), and any one of the moieties represented by (f) to (l);
wherein two R4s attached on adjacent carbons may form a methylenedioxy group, and wherein the C1-4 alkyl is optionally substituted with halogen(s), each Ry is independently selected from the group consisting of H, C1-4 alkyl, halogen, OH, C1-4 alkyl-OH, C1-4 alkyl-O—
C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, NO2, O—
C1-4 alkyl, COOH, and SO3H, wherein the C1-4 alkyl is optionally substituted with halogen(s), A is any one of the rings represented by (i) to (ix);
wherein each Rz is independently selected from the group consisting of H, C1-4 alkyl, halogen, OH, C1-4 alkyl-OH, C1-4 alkyl —
O—
C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, NO2, O—
C1-4 alkyl, phenyl, COOH, and SO3H, wherein the C1-4 alkyl is optionally substituted with halogen(s), X is N or CH, Y is N or CH, Z is O, S, CH2, N—
CpH2p+1, and p is an integer of 0 to 4, or a salt or solvate thereof.
1 Assignment
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Accused Products
Abstract
A compound, which is used for the diagnosis and the prophylaxis/treatment of diseases in which prion protein is accumulated, or specific staining of abnormal prion protein in samples, represented by the formula (I) or (II):
68 Citations
43 Claims
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1. A compound, which is used as a probe for diagnosing diseases in which prion protein is accumulated, represented by the formula (I) or (II):
-
wherein D is NR′
, S, O, CH═
CH, or CH2,R′
is H, alkyl having 1 to 4 carbons hereinafter, referred to as C1-4 alkyl), or phenyl, wherein the C1-4 alkyl is optionally substituted with halogen(s),E is N or CH, Ra is, each independently, selected from the group consisting of H, C1-4 alkyl, halogen, OH, C1-4 alkyl-OH, C1-4 alkyl-O—
C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, NO2, O—
C1-4 alkyl, COOH, and SO3H, wherein the C1-4 alkyl is optionally substituted with halogen(s),Q is N or CRb, Rb is selected from the group consisting of H, C1-4 alkyl, halogen, OH, C1-4 alkyl-OH, C1-4 alkyl-O—
C1-4 alkyl, NH(C1-4 alkyl), NH2, N(C1-4 alkyl)2, NO2, O—
C1-4 alkyl, COOH, and SO3H, wherein the C1-4 alkyl is optionally substituted with halogen(s),m is an integer of 0 to 4, R1 and R2 are independently selected from the group consisting of H, C1-4 alkyl, halogen, OH, C1-4 alkyl-OH, C1-4 alkyl-O—
C1-4 alkyl, NH(C1-4 alkyl), NH2, N(C1-4 alkyl)2, NO2, O—
C1-4 alkyl, COOH, and SO3H, wherein the C1-4 alkyl is optionally substituted with halogen(s),or alternatively, R1 and R2, together, form a benzene or naphthalene ring which is optionally substituted with one to four R4, R3 is selected from the group consisting of H, C1-4 alkyl, halogen, OH, C1-4 alkyl-OH, C1-4 alkyl-O—
C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, NO2, O—
C1-4 alkyl, COOH, SO3H, wherein the C1-4 alkyl is optionally substituted with halogen(s), and any one of the moieties represented by (a) to (e);
wherein each Rx is independently selected from the group consisting of H, C1-4 alkyl, halogen, OH, C1-4 alkyl-OH, C1-4 alkyl-O—
C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, N═
CH-allyl, NO2, O—
C1-4 alkyl, COOH, and SO3H, wherein the C1-4 alkyl is optionally substituted with halogen(s),each R4 is independently selected from the group consisting of H, C1-4 alkyl, halogen, OH, C1-4 alkyl-OH, C1-4 alkyl-O—
C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, NO2, O—
C1-4 alkyl, COOH, SO3H, wherein the C1-4 alkyl is optionally substituted with halogen(s), and any one of the moieties represented by (f) to (l);
wherein two R4s attached on adjacent carbons may form a methylenedioxy group, and wherein the C1-4 alkyl is optionally substituted with halogen(s), each Ry is independently selected from the group consisting of H, C1-4 alkyl, halogen, OH, C1-4 alkyl-OH, C1-4 alkyl-O—
C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, NO2, O—
C1-4 alkyl, COOH, and SO3H, wherein the C1-4 alkyl is optionally substituted with halogen(s),A is any one of the rings represented by (i) to (ix);
wherein each Rz is independently selected from the group consisting of H, C1-4 alkyl, halogen, OH, C1-4 alkyl-OH, C1-4 alkyl —
O—
C1-4 alkyl, NH2, NH(C1-4 alkyl), N(C1-4 alkyl)2, NO2, O—
C1-4 alkyl, phenyl, COOH, and SO3H, wherein the C1-4 alkyl is optionally substituted with halogen(s),X is N or CH, Y is N or CH, Z is O, S, CH2, N—
CpH2p+1, andp is an integer of 0 to 4, or a salt or solvate thereof. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 40, 41, 42)
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- 38. Use of a compound of the present invention for manufacturing a medicament for the prophylaxis and/or treatment of a disease in which the accumulation of prion protein in the body constitutes or partially constitutes the etiology.
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43. A labeled precursor of BF-168, BF-224, or N-227, wherein the precursor is a tosylate derivative.
Specification