US 10,889,581 B2
Cyclopropyl fused thiazine derivatives as beta-secretase inhibitors and methods of use
Jennifer R. Allen, Newbury Park, CA (US); Albert Amegadzie, Moorpark, CA (US); Matthew P. Bourbeau, Woodland Hills, CA (US); Jian J. Chen, Camarillo, CA (US); Michael J. Frohn, Thousand Oaks, CA (US); Paul E. Harrington, Thousand Oaks, CA (US); Jonathan D. Low, Reseda, CA (US); Vu V. Ma, Oak Park, CA (US); Thomas T. Nguyen, Newbury Park, CA (US); Alexander Pickrell, Westlake Village, CA (US); and Corey Reeves, Sherman Oaks, CA (US)
Assigned to Amgen Inc., Thousand Oaks, CA (US)
Appl. No. 16/466,199
Filed by AMGEN INC., Thousand Oaks, CA (US)
PCT Filed Dec. 13, 2017, PCT No. PCT/US2017/066184
§ 371(c)(1), (2) Date Jun. 3, 2019,
PCT Pub. No. WO2018/112086, PCT Pub. Date Jun. 21, 2018.
Claims priority of provisional application 62/434,721, filed on Dec. 15, 2016.
Prior Publication US 2020/0231585 A1, Jul. 23, 2020
Int. Cl. C07D 471/14 (2006.01); C07D 417/14 (2006.01); C07D 417/10 (2006.01)
CPC C07D 417/14 (2013.01) [C07D 417/10 (2013.01)] 21 Claims
 
1. A compound of Formula I

OG Complex Work Unit Drawing
or a tautomer thereof, or a pharmaceutically acceptable salt of said compound or tautomer, wherein
A is N, CH, or CR4;
R1 is H, —CN, C1-6alkyl, C2-6alkenyl, —C1-4alkyl-C(O)NR1′R1′, —C1-4alkyl-C(O)-heterocycloalkyl, —(HC═CH)—C(O)NR1′R1′, —(HC═CH)—C(O)-heterocycloalkyl, —C(O)NR1′R1′, or —C(O)-heterocycloalkyl, wherein the C1-6alkyl and the C2-6alkenyl are (i) optionally substituted with one to three fluoro substituents or (ii) optionally substituted with CN, OH, methoxy, or a 5-membered nitrogen-containing heteroaryl, wherein the 5-membered nitrogen-containing heteroaryl is optionally substituted with C1-4 alkyl;
R1′ is, independently, H or C1-4alkyl;
R2 and R2′ are independently H or halogen;
R3 is C1-4alkyl, wherein the C1-4alkyl is optionally substituted with one to three fluoro substituents;
R4 is halogen;
R5 is H, C3-6cycloalkyl, phenyl, or 5- or 6-membered heteroaryl, wherein the phenyl or heteroaryl is optionally substituted with one to three substituents independently selected from halogen, —CN, C1-4alkyl, 2-propynyloxy, 2-butynyloxy, or oxazolylmethoxy.