| 主权项 |
1. A method for determining the likelihood of a living patient having Alzheimer's disease pathology (AD pathology) comprising the steps of
a) determining the amount of one or more of a protein-protein complex i) α7nAChR/FLNA, ii) TLR4/FLNA and iii) α7nAChR/Aβ present in a first portion of a lymphocyte preparation from said living patient; b) determining the amount of said one or more of i) α7nAChR /FLNA, ii) TLR4/FLNA and iii) α7nAChR/Aβ present as a protein-protein complex in a second portion of said lymphocyte preparation, said second portion of said lymphocyte portion further containing admixed therein a FLNA binding-effective amount of a compound that binds to a pentapeptide of filamin A (FLNA) of SEQ ID NO: 1, or a pharmaceutically acceptable salt said compound; and c) comparing the values so determined, whereby a determined amount of said one or more of i) α7nAChR /FLNA, ii) TLR4/FLNA and iii) α7nAChR/Aβ present as a protein-protein complex in a second portion of said lymphocyte preparation that is significantly decreased in the presence of said compound or said pharmaceutically acceptable salt of said compound indicates that the patient had AD pathology at the time the body sample was taken, whereas no significant difference between the two determined values indicates that the patient was free of AD pathology at the time the body sample was taken; wherein said compound is a compound of Series C-2 that corresponds in structure to the Formula A below:wherein
Q is CHR9 or C(O), Z is CHR10or C(O), and only one of Q and Z is C(O); each of m and n is zero or one and the sum of m+n is 1 or 2; each of G, P and W is selected from the group consisting of NR20, NR2, NR7, S and O, where R7 and R2 are the same or different and are H, C(H)v(D)h where each of v and h is 0, 1, 2 or 3 and v+h=3, C(H)q(D)r-aliphatic C1-C11 hydrocarbyl where each of q and r is 0, 1, or 2 and q+r=0, 1 or 2, aliphatic C1-C12 hydrocarbyl sulfonyl or aliphatic C1-C12 hydrocarboyl, and R20is X-circle A-R1 as defined hereinafter; each of d, e, f and k is either zero or one and the sum of (d+e+f+k)=2; D and F are the same or different and are CH or CD; E and K are the same or different and are CH2, CHD or CD2; X is SO2, C(O), CH2, CD2, OC(O), NHC(NH), NHC(S) or NHC(O); circle A is an aromatic or heteroaromatic ring system that contains a single ring or two fused rings; R1 is H or represents up to three substituents, R1a, R1b, and R1c, that themselves can be the same or different, wherein each of those three groups, R1a-c, is separately selected from the group consisting of H, C1-C6 hydrocarbyl, C1-C6 hydrocarbyloxy, C1-C6 hydrocarbyloxycarbonyl, trifluoromethyl, trifluoromethoxy, C1-C7 hydrocarboyl, hydroxy-, trifluoromethyl- or halogen-substituted C1-C7 hydrocarboyl, C1-C6 hydrocarbylsulfonyl, C1-C6 hydrocarbyloxysulfonyl, halogen, nitro, phenyl, cyano, carboxyl, C1-C7 hydrocarbyl carboxylate, carboxamide or sulfonamide, wherein the amido nitrogen in either amide group has the formula NR3R4 in which R3 and R4 are the same or different and are H, C1-C4 hydrocarbyl, or R3 and R4 together with the depicted nitrogen form a 5-7membered ring that optionally contains 1 or 2 additional hetero atoms that independently are nitrogen, oxygen or sulfur,MAr, where M is —CH2—, —O— or —N═N—and Ar is a single-ringed aryl or heteroaryl group and NR5R6 wherein R5 and R6 are the same or different and are H, C1-C4 hydrocarbyl, C1-C4 acyl, C1-C4 hydrocarbylsulfonyl, or R5 and R6 together with the depicted nitrogen form a 5-7-membered ring that optionally contains 1 or 2 additional hetero atoms that independently are nitrogen, oxygen or sulfur; R8, R9, and R10are each H, or two of R8, R9, and R10 are H and one is a C1-C8 hydrocarbyl group that is unsubstituted or is substituted with up to three atoms that are the same or different and are oxygen or nitrogen atoms; R11, R12, R13and R14 are all H, or R11 and R13 are H and R12 and R14 are H or D, or one of the pair R11 and R12 or the pair R13 and R14 together with the depicted ring form a saturated or unsaturated 6-membered ring, and the other pair are each H or they are H and D. |
