WO 2019/090111 Al 09 May 2019 (09.05.2019) W 1P O PCT

WO 2019/090111 Al 09 May 2019 (09.05.2019) W 1P O PCT

(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2019/090111 Al 09 May 2019 (09.05.2019) W 1P O PCT (51) International Patent Classification: (84) Designated States (unless otherwise indicated, for every A61K 31/7064 (2006.01) A61P 33/14 (2006.01) kind of regional protection available): ARIPO (BW, GH, A61K 45/06 (2006.01) A61P 25/28 (2006.01) GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, A61P 35/00 (2006.01) C07F 9/6561 (2006.01) UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, A61P 31/12 (2006.01) TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, ΓΕ , IS, IT, LT, LU, LV, (21) International Application Number: MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, PCT/US20 18/059004 TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, (22) International Filing Date: KM, ML, MR, NE, SN, TD, TG). 02 November 2018 (02. 11.2018) Declarations under Rule 4.17: (25) Filing Language: English — as to applicant's entitlement to apply for and be granted a (26) Publication Language: English patent (Rule 4.17(H)) — as to the applicant's entitlement to claim the priority of the (30) Priority Data: earlier application (Rule 4.17(Hi)) 62/581,574 03 November 2017 (03. 11.2017) US 62/664,841 30 April 2018 (30.04.2018) US Published: — with international search report (Art. 21(3)) (71) Applicant: ORIC PHARMACEUTICALS, INC. — before the expiration of the time limit for amending the [US/US]; 240 E . Grand Avenue, 2nd Floor, South San Fran¬ claims and to be republished in the event of receipt of cisco, California 94080 (US). amendments (Rule 48.2(h)) (72) Inventors: DU, Xiaohui; 240 E . Grand Avenue, 2nd Floor, South San Francisco, California 94080 (US). EKSTEROWICZ, John; 240 E . Grand Avenue, 2nd Floor, South San Francisco, California 94080 (US). FANTIN, Va¬ leria R.; 240 E . Grand Avenue, 2nd Floor, South San Fran¬ cisco, California 94080 (US). JACKSON, Erica L.; 240 E . Grand Avenue, 2nd Floor, South San Francisco, Califor¬ nia 94080 (US). SUN, Daqing; 240 E . Grand Avenue, 2nd Floor, South SanFrancisco, California 94080 (US). YE, Qi- uping; 240 E . Grand Avenue, 2nd Floor, South SanFrancis¬ co, California 94080 (US). MOORE, Jared; 240 E . Grand Avenue, 2nd Floor, South San Francisco, California 94080 (US). ZAVOROTINSKAYA, Tatiana; 240 E . Grand Av¬ enue, 2nd Floor, South San Francisco, California 94080 (US). (74) Agent: SMITH, Deborah M.; Wilson Sonsini Goodrich & Rosati, 650 Page Mill Road, Palo Alto, California 94304 (US). (81) Designated States (unless otherwise indicated, for every kind of national protection available) : AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. ©O S o (54) Title: CD73 INHIBITORS (57) Abstract: Described herein are CD73 inhibitors and pharmaceutical compositions comprising said compounds. The subject com¬ pounds and compositions are useful for the treatment of cancer, infections, and neurodegenerative diseases. CD73 INHIBITORS CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims the benefit of U.S. Provisional Application Serial Number 62/581,574, filed November 3, 2017, and U.S. Provisional Application Serial Number 62/664,841, filed April 30, 2018 which are all hereby incorporated by reference in their entirety. BACKGROUND [0002] A need exists in t e art for an effective treatment of cancer, infections, and neurodegenerative diseases. BRIEF SUMMARY OF THE INVENTION [0003] Provided herein are compounds of Formulas (I), (II), (Ila), (lib), (III), and (IV) or pharmaceutically acceptable salts, solvates, or stereoisomers thereof, and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful as CD73 inhibitors. Furthermore, the subject compounds and compositions are useful for the treatment of cancers, infections, and neurodegenerative diseases. [0004] Provided herein are compounds having the structure of Formula (Ila), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof: Formula (Ila); wherein: A is -O- or -CH2-; Q1 is CW and Q2 is N; or Q1 is N and Q2 is N; a a a a W is hydrogen, halogen, -CN, -OH, -OR , -SH, -SR , -S(=0)R , -N0 2, -NR R , -S(=0) 2R , - a a a b b NHS(=0) 2R , -S(=0) NR R , -C(=0)R , -OC(=0)R , -C(=0)OR , -OC(=0)OR , -C(=0)NR R , -OC(=0)NR R , -NRbC(=0)NR R , -NRbC(=0)R a, -NRbC(=0)OR b, C C alkyl, C -C alkenyl, C2-C alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C alkyl(aryl), Ci-C alkyl(heteroaryl), Ci-C alkyl(cycloalkyl), or Ci-C alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R 0; Z is -N^R 2, -OR60, -SR6 1, or -CR R R64; 1 2 R and R are each independently hydrogen, C -C alkyl, C2-C alkenyl, C2-C alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C -C alkyl(aryl), C -C alkyl(heteroaryl), C -C 1 a a a alkyl(cycloalkyl), C C alkyl(heterocycloalkyl), -S(=0) 2R , -S(=0) 2NR R , or -C(=0) R ; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R ; or R1 and R2 are taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three R b ; 60 1 1 1 1 R is hydrogen, -C(=0)R , -C(=0)OR , -C(=0)NR R , C C alkyl, C2-C alkenyl, C -C alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C alkyl(aryl), Ci-C alkyl(heteroaryl), C -C alkyl(cycloalkyl), C -C alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R m; R6 1 is hydrogen, -C(=0)R 1 , -C(=0)OR 1 , -C(=0)NR 1 R1 , C C alkyl, C -C alkenyl, C -C alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C -C alkyl(aryl), C -C alkyl(heteroaryl), C -C alkyl(cycloalkyl), C -C alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R ; R62, R63, and R64 are each independently hydrogen, halogen, -CN, -OH, -OR1 , -SH, -SR1 , - S(=0)R 1 , -N0 , -NR 1 R1 , -S(=0) R1 , -NHS(=0) R1 , -S(=0) NR1 R1 , -C(=0)R 1 , - OC(=0)R 1 , -C(=0)OR 1 , -OC(=0)OR 1 , -C(=0)NR 1 R1 , -OC(=0)NR 1 R1 , - NR1 C(=0)NR 1 R1 , -NR 1 C(=0)R 1 , -NR 1 C(=0)OR 1 , C C alkyl, C -C alkenyl, C -C alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C -C alkyl(aryl), C -C alkyl(heteroaryl), C -C alkyl(cycloalkyl), or C -C alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R °; R3 is halogen, -CN, -OH, -OR1 b , -SR1 b , -NR 1 bR1 , C C alkyl, C -C alkenyl, C -C alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, Ci-C alkyl(aryl), Ci-C alkyl(heteroaryl), Ci-C alkyl(cycloalkyl), or C -C alkyl(heterocycloalkyl); wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R ; 4 7 1 1 1 R and R are each independently hydrogen, halogen, -OH, -OR , -NR S(=0) 2R , - 1 1 NR C(=0)R , C -C alkyl, C2-C alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R ; 5 6 1 1 1 R and R are each independently hydrogen, halogen, -OH, -OR , -NR S(=0) 2R , - 1 1 NR C(=0)R , Ci-Ce alkyl, C2-C alkenyl, C2-C alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R ; X1 is a bond; Y 1 is -S(=0) -; R45 and R4 are each independently hydrogen, halogen, -OH, -ORa, -NR R , C C alkyl, or C C haloalkyl; v2 is 1-3; 1 a 1 b 1 1 1 1 1 R , R , R , R , R , R , R are each independently C C alkyl, C2-C alkenyl, C2-C alkynyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl is independently optionally substituted with one, two, or three R ; R1 a, R1 b , R1 , R1 , R1 , R1 , R1 , R1 a, R1 , R1 , R1 , and R1 are each independently hydrogen, C -C alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, or heterocycloalkyl; wherein each alkyl, alkenyl, alkynyl, cycloalkyl, and heterocycloalkyl is independently optionally substituted with one, two, or three R ; or R1 a and R1 a or R1 b and R1 or R1 and R1 or R1 and R1 or R1 and R1 are taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl optionally substituted with one, two, or three halogen, C -C alkyl, or C -C haloalkyl; R1 b is C -C alkyl, C2-C6 alkenyl, C2-C6 alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, C r C alkyl(aryl), C

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