US 9,808,542 B2
Pyrrolo[2,3-C]pyridines as imaging agents for neurofibrillary
Abbas W. Walji, Lansdale, PA (US); Eric Hostetler, Collegeville, PA (US); Thomas J. Greshock, Collegeville, PA (US); Jing Li, Lansdale, PA (US); Keith P. Moore, Doylestown, PA (US); Idriss Bennacef, Ambler, PA (US); James Mulhearn, Elkins, PA (US); Harold Selnick, Ambler, PA (US); Yaode Wang, Beijing (CN); Kun Yang, Beijing (CN); and Jianmin Fu, Beijing (CN)
Assigned to Merck Sharp & Dohme Corp., Rahway, NJ (US)
Appl. No. 15/317,333
Filed by MERCK SHARP & DOHME CORP., Rahway, NJ (US)
PCT Filed Jun. 9, 2015, PCT No. PCT/US2015/034794
§ 371(c)(1), (2) Date Dec. 12, 2016,
PCT Pub. No. WO2015/191506, PCT Pub. Date Dec. 17, 2015.
Claims priority of application No. PCT/CN2014/079834 (WO), filed on Jun. 13, 2014.
Prior Publication US 2017/0119912 A1, May 4, 2017
Int. Cl. A61K 51/04 (2006.01); C07D 519/00 (2006.01); C07D 471/04 (2006.01)
CPC A61K 51/0455 (2013.01) [A61K 51/0459 (2013.01); C07D 471/04 (2013.01); C07D 519/00 (2013.01); C07B 2200/05 (2013.01)] 37 Claims
 
1. A compound of formula (I):

OG Complex Work Unit Drawing
or a pharmaceutically acceptable salt thereof wherein;
X represents CH, or N;
R represents hydrogen, or —C1-6alkyl, said alkyl optionally substituted with 1 to 3 groups of Ra;
R1 represents hydrogen, —C1-6alkyl, —CN, —(CH2)nNH(CH2)nN(R)2, —C2-6alkenyl, —(CH2)nOR, or —(CH2)nhalogen;
R2 represents —OC1-6 alkyl, —C2-6alkenylR3—(CH2)nOR, —(CH2)nhalogen, —O(CH2)nhalogen, —C6-10 aryl, —C5-10 heterocyclyl, —O(CH2)nRa, —N(CH3)(CH2)nOR, —NRC(O)R, —NH(CH2)nhalo, —NC(O)C6-10 aryl, —NC(O)C5-10 heterocyclyl, —N(CH3)(CH2)nhalogen, —C(O)NC6-10 aryl, said alkyl, aryl, and heterocyclyl optionally substituted with 1 to 3 groups of Ra;
or an adjacent R1 can combine with R2 to form a nine to ten membered bicyclic ring together with the ring to which R1 and R2 are attached, optionally interrupted with N, S, and/or O, said bicyclic ring optionally substituted with 1 to 3 groups of Ra;
R3 represents hydrogen, —C1-6alkyl, —(CH2)nhalogen, —(CH2)nN(R)2, —(CH2)nNR(CH2)nN(R)2, —C6-10 aryl, —C5-10 heteroaryl, said alkyl, aryl, and heteroaryl optionally substituted with 1 to 3 groups of Ra;
Ra represents —CN, CF3, —C1-6alkyl, —C2-6alkenyl, —C2-6alkynyl, C6-10 aryl, —C5-10 heterocyclyl, —CN, NO2, (CH2) halogen, —O(CH2)nhalogen, (CH2)nOR, —O(CH2)nC6-10 aryl, —(CH2)nN(R)2, —C(O)N(R)2, —N(CH3)(CH2)nOR, —NRCOR, —COR, —NH(CH2)nhalo, —N(CH3)(CH2)nhalogen, C(O)C6-10 aryl, or —CO2R, said alkyl, alkenyl, alkynyl, aryl, and heterocyclyl optionally substituted with 1 to 3 groups of Rb;
R represents hydrogen, —C1-6alkyl, —OR, —(CH2)nN(R)2, or halogen; and
n represents 0-4.
 
35. A method for measuring tau deposits in a patient comprising the steps of administering a detectable quantity of a compound of formula I of claim 1 or a pharmaceutically acceptable salt thereof, and detecting the binding of the compound to tau deposits in the patient.