NOVEL HETEROARYL SUBSTITUTED IMIDAZO Ý1,2 -A¨PYRIDINE DERIVATIVESThe present invention relates to novel heteroaryl substituted imidazopyridine derivatives, precursors thereof, and therapeutic uses of such compounds, having the structural formula (Ia) and to their pharmaceutically acceptable salt, compositions and methods of use. Furthermore, the invention relates to novel heteroaryl substituted imidazopyridine derivatives that are suitable for imaging amyloid deposits in living patients, their compositions, methods of use and processes to make such compounds. More specifically, the present invention relates to a method of imaging amyloid deposits in brain in vivo to allow antemortem diagnosis of Alzheimer's disease as well as measureing clinical efficacy of Alzheimer's disease therapeutic agents.A compound according to formula Ia(Ia) whereinRl is selected from H, halo, Ci-5 alkyl, Ci-5 fluoroalkyl, Ci-3 alkyleneOCi-3 alkyl, Ci-3 alkyleneOCi-3 fluorolkyl, Ci-3 alkyleneNH2, Cx-3 alkyleneNHCi-3 alkyl, d-3 alky leneN(C i-3 alkyl)2, Ci-3 alkyleneNHCi-3 fluoroalkyl, Ci-3 alkyleneN(Ci-3 fluoroalkyl^, Ci-3 alkyleneN(Cj-3 alkyl) C 1.3 fluoroalkyl, hydroxy, Ci-5 alkoxy, Ci-5 fluoroalkoxy, Ci-5 Salkyl, Ci-5 Sfluoroalkyl, amino, NHCj-3 alkyl, NHCi-3 fluoroalkyl, N(Ci-3 alkyl)2, N(Ci-3 alkyl)Ci-3 fluoroalkyl, NH(CO)Ci-3 alkyl, NH(CO)Ci-3 fluorolkyl, NH(CO)Ci-3 alkoxy, NH(CO)Ci-3 fluoroalkoxy, NHSO2Ci-3 alkyl, NHSO2Ci-3 fluoroalkyl, (CO)Ci-3 alkyl, (CO)Ci-3 fluoroalkyl, (CO)C1-3 alkoxy, (CO)C1-3 fluoroalkoxy, (CO)NH2, (CO)NHCL3 alkyl, (CO)NHC1-3 fluoroalkyl, (CO)N(CL3 alkyl)2, (CO)N(Ci-3 alkyl)Ci.3 fluoroalkyl, (CO)N(C4-6 alkylene), (CO)N(C4-6 fluoroalkylene), cyano, SO2NHCi-3 fluoroalkyl, nitro and SO2NH2;R2 is selected from H, halo, Ci-5 alkyl, Ci-5 fluoroalkyl, Ci-3 alkyleneOCi-3 alkyl, Ci-3 alkyleneOCi-3 fluorolkyl, Ci-3 alkyleneNH2j Ci-3 alkyleneNHCi-3 alkyl, Ci-3 alkyleneN(Ci-3 alkyl)2, Ci-3 alkyleneNHCi-3 fluoroalkyl, Ci-3 alkyleneN(Ci-3 fluoroalkyl)2, Ci-3 alkyleneN(C i-3 alky I)C i-3 fluoroalkyl, hydroxy, Ci-5 alkoxy, Ci-5 fluoroalkoxy, Ci-5 Salkyl, Ci-5 Sfluoroalkyl, amino, NHCi-3 alkyl, NHd-3 fluoroalkyl, N(Ci-3 alkyl)2, N(Ci-3 alkyl)d.3 fluoroalkyl, NH(CO)Ci-3 alkyl, NH(CO)Ci-3 fluorolkyl, NH(CO)Ci-3 alkoxy, NH(CO)Ci-3 fluoroalkoxy, NHSO2Ci-3 alkyl, NHSO2Ci-3 fluoroalkyl, (CO)Ci-3 alkyl, (CO)C1-3 fluoroalkyl, (CO)Ci-3 alkoxy, (CO)C1-3 fluoroalkoxy, (CO)NH2, (CO)NHCL3 alkyl, (CO)NHC1-3 fluoroalkyl, (CO)N(Ci-3 alkyl)2, (CO)N(Ci-3 alkyl)C1-3 fluoroalkyl, (CO)N(C4.6 alkylene), (CO)N(C4-0 fluoroalkylene), cyano, SO2NHCi-3 fluoroalkyl., nitro and SO2NH2; or Rl and R2 together forms a ring;Q is a nitrogen-containing aromatic heterocycle selected from Hetl to Het8;whereinHetl is a 6-membered aromatic heterocycle containing one or two N atoms, wherein X1, X2, X3 and X4 are independently selected from N or C; and wherein one or two of X1, X2, X3 and X4 is N and the remaining is C and wherein the atom Xi is C, said C is optionally substituted with R4; and wherein the atom X2 is C, said C is optionally substituted with R5;R3 is selected from halo, C1-4 alkyl, Ci-4 fluoroalkyl, Ci-3 alkyleneOCi-3 alkyl, Ci.3 alkyleneOQ.3 fluoroalkyl, Ci-3 alkyleneNHCi-3 alkyl, C1-3 alkyleneN(Ci-3 alkyl)2, Ci-3 alkyleneNHCi-3 fluoroalkyl, Ci-3 alkyleneN(Ci-3 alkyl)Ci.3 fluoroalkyl, Ci-4 alkoxy, CM fluoroalkoxy, NHCi-3 alkyl, NHCi-3 fluoroalkyl, N(C1-3 alkyl)2, N(Ci-3 alkyl)Ci-3 fluoroalkyl, NH(C0-3 alkylene)G2, N(C0-I alkyl)N(C0._ alkyl)2, N(C0-3 fluoroalkyl)N(C0-i alkyl)2, N(C0-J alkyl)N(C0-i alkyl)C0-3 fluoroalkyl, N(C0-I alkyl)OC0-i alkyl, N(C0-3 fluoroalkyl)OCo-i alkyl, N(C0-I alkyl)OCo-3 fluoroalkyl, NH(CO)C1-3 alkyl, NH(CO)C1-3 fluoroalkyl, NH(C0)G2, (CO)C1-3 alkyl, (CO)C1-3 fluorolkyl, (CO)C1-3 alkoxy, (CO)Ci-3 fluoroalkoxy, (CO)NH2, (CO)NHC1-3 alkyl, (CO)NHC1-3 fluoroalkyl, (CO)N(C1-3 alkyl)2, (CO)N(C1-3 alkyl)C1-3 fluoroalkyl, (CO)N(C4-6 alkylene), (CO)N(C4-6 fluoroalkylene), (C0)G2, (C0)NHG2, SO2NH2, SO2NHC1-3 alkyl, SO2NHCi-3 fluoroalkyl, SO2N(C1-3 alkyl)2, SO2N(C1-3 alkyl)C1-3 fluoroalkyl, cyano, SO2Ci-6 alkyl, SO2Ci-6 fluoroalkyl, SCi-6 alkyl, SCi-6 fluoroalkyl, N(C4-6 alkylene) and Gl, wherein Gl is;X5 is selected from O, NH, NC1-3 alkyl, N(CO)OCi-4 alkyl, N(CO)C14 alkyl, N(C0)CM fluorolkyl and NC1-3 fluorolkyl;G2 is phenyl or a 5- or 6-membered aromatic heterocycle, optionally substituted with a substituent selected from fluoro, bromo, iodo, methyl and methoxy;R4 is H or halo;R5 is H or halo;R6 is selected from H, methyl and Ci-4 fluoroalkyl; andone or more of the constituting atoms optionally is a detectable isotope;as a free base or a pharmaceutically acceptable salt, solvate or solvate of a salt thereof.
신규 헤테로아릴 치환된 이미다조〔１，２­Ａ〕피리딘 유도체본 발명은 하기 화학식 Ia의 신규 헤테로아릴 치환된 이미다조피리딘 유도체, 그의 전구체, 상기 화합물의 치료 용도, 및 상기 화합물의 제약상 허용되는 염, 조성물 및 사용 방법에 관한 것이다. <화학식 Ia>  또한, 본 발명은 살아있는 환자에서 아밀로이드 침착물의 이미지화에 적합한 신규 헤테로아릴 치환된 이미다조피리딘 유도체, 이들의 조성물, 사용 방법 및 이러한 화합물의 제조 방법에 관한 것이다. 보다 구체적으로, 본 발명은 생체내에서 뇌의 아밀로이드 침착물을 이미지화하여 알쯔하이머병을 사망 전에 진단할 뿐만 아니라 알쯔하이머병 치료제의 임상 효능을 측정하는 방법에 관한 것이다.유리 염기로서 하기 화학식 Ia의 화합물 또는 이의 제약상 허용되는 염, 용매화물 또는 염의 용매화물. <화학식 Ia>  상기 식에서, R1은 H, 할로, C1-5알킬, C1-5플루오로알킬, C1-3알킬렌OC1-3알킬, C1-3알킬렌OC1-3플루오로알킬, C1-3알킬렌NH2, C1-3알킬렌NHC1-3알킬, C1-3알킬렌N(C1-3알킬)2, C1-3알킬렌NHC1-3플루오로알킬, C1-3알킬렌N(C1-3플루오로알킬)2, C1-3알킬렌N(C1-3알킬)C1-3플루오로알킬, 히드록시, C1-5알콕시, C1-5플루오로알콕시, C1-5S알킬, C1-5S플루오로알킬, 아미노, NHC1-3알킬, NHC1-3플루오로알킬, N(C1-3알킬)2, N(C1-3알킬)C1-3플루오로알킬, NH(CO)C1-3알킬, NH(CO)C1-3플루오로알킬, NH(CO)C1-3알콕시, NH(CO)C1-3플루오로알콕시, NHSO2C1-3알킬, NHSO2C1-3플루오로알킬, (CO)C1-3알킬, (CO)C1-3플루오로알킬, (CO)C1-3알콕시, (CO)C1-3플루오로알콕시, (CO)NH2, (CO)NHC1-3알킬, (CO)NHC1-3플루오로알킬, (CO)N(C1-3알킬)2, (CO)N(C1-3알킬)C1-3플루오로알킬, (CO)N(C4-6알킬렌), (CO)N(C4-6플루오로알킬렌), 시아노, SO2NHC1-3플루오로알킬, 니트로, 및 SO2NH2로부터 선택되고; R2는 H, 할로, C1-5알킬, C1-5플루오로알킬, C1-3알킬렌OC1-3알킬, C1-3알킬렌OC1-3플루오로알킬, C1-3알킬렌NH2, C1-3알킬렌NHC1-3알킬, C1-3알킬렌N(C1-3알킬)2, C1-3알킬렌NHC1-3플루오로알킬, C1-3알킬렌N(C1-3플루오로알킬)2, C1-3알킬렌N(C1-3알킬)C1-3플루오로알킬, 히드록시, C1-5알콕시, C1-5플루오로알콕시, C1-5S알킬, C1-5S플루오로알킬, 아미노, NHC1-3알킬, NHC1-3플루오로알킬, N(C1-3알킬)2, N(C1-3알킬)C1-3플루오로알킬, NH(CO)C1-3알킬, NH(CO)C1-3플루오로알킬, NH(CO)C1-3알콕시, NH(CO)C1-3플루오로알콕시, NHSO2C1-3알킬, NHSO2C1-3플루오로알킬, (CO)C1-3알킬, (CO)C1-3플루오로알킬, (CO)C1-3알콕시, (CO)C1-3플루오로알콕시, (CO)NH2, (CO)NHC1-3알킬, (CO)NHC1-3플루오로알킬, (CO)N(C1-3알킬)2, (CO)N(C1-3알킬)C1-3플루오로알킬, (CO)N(C4-6알킬렌), (CO)N(C4-6플루오로알킬렌), 시아노, SO2NHC1-3플루오로알킬, 니트로, 및 SO2NH2로부터 선택되거나; 또는 R1 및 R2는 함께  고리를 형성하고; Q는 하기 Het1 내지 Het8로부터 선택된 질소-함유 방향족 헤테로사이클이고  여기서, Het1은 1 또는 2개의 N 원자를 함유하는 6-원 방향족 헤테로사이클이고, 여기서 X1, X2, X3 및 X4는 N 또는 C로부터 독립적으로 선택되고; X1, X2, X3 및 X4 중 1 또는 2개는 N이고, 나머지는 C이고, 원자 X1이 C인 경우 상기 C는 R4로 임의로 치환되고; 원자 X2가 C인 경우 상기 C는 R5로 임의로 치환되고; R3은 할로, C1-4알킬, C1-4플루오로알킬, C1-3알킬렌OC1-3알킬, C1-3알킬렌OC1-3플루오로알킬, C1-3알킬렌NHC1-3알킬, C1-3알킬렌N(C1-3알킬)2, C1-3알킬렌NHC1-3플루오로알킬, C1-3알킬렌N(C1-3알킬)C1-3플루오로알킬, C1-4알콕시, C1-4플루오로알콕시, NHC1-3알킬, NHC1-3플루오로알킬, N(C1-3알킬)2, N(C1-3알킬)C1-3플루오로알킬, NH(C0-3알킬렌)G2, N(C0-1알킬)N(C0-1알킬)2, N(C0-3플루오로알킬)N(C0-1알킬)2, N(C0-1알킬)N(C0-1알킬)C0-3플루오로알킬, N(C0-1알킬)OC0-1알킬, N(C0-3플루오로알킬)OC0-1알킬, N(C0-1알킬)OC0-3플루오로알킬, NH(CO)C1-3알킬, NH(CO)C1-3플루오로알킬, NH(CO)G2, (CO)C1-3알킬, (CO)C1-3플루오로알킬, (CO)C1-3알콕시, (CO)C1-3플루오로알콕시, (CO)NH2, (CO)NHC1-3알킬, (CO)NHC1-3플루오로알킬, (CO)N(C1-3알킬)2, (CO)N(C1-3알킬)C1-3플루오로알킬, (CO)N(C4-6알킬렌), (CO)N(C4-6플루오로알킬렌), (CO)G2, (CO)NHG2, SO2NH2, SO2NHC1-3알킬, SO2NHC1-3플루오로알킬, SO2N(C1-3알킬)2, SO2N(C1-3알킬)C1-3플루오로알킬, 시아노, SO2C1-6알킬, SO2C1-6플루오로알킬, SC1-6알킬, SC1-6플루오로알킬, N(C4-6알킬렌) 및 G1로부터 선택되고, 여기서 G1은 이고; X5는 O, NH, NC1-3알킬, N(CO)OC1-4알킬, N(CO)C1-4알킬, N(CO)C1-4플루오로알킬 및 NC1-3플루오로알킬로부터 선택되고; G2는 플루오로, 브로모, 요오도, 메틸 및 메톡시로부터 선택된 치환기로 임의로 치환된, 페닐 또는 5-원 또는 6-원 방향족 헤테로사이클이고; R4는 H 또는 할로이고; R5는 H 또는 할로이고; R6은 H, 메틸, 및 C1-4플루오로알킬로부터 선택되고; 상기 구성 원자들 중 하나 이상은 임의로는, 검출가능한 동위원소이다.