PYRAZOLOPYRIMIDINONE COMPOUNDS AND USES THEREOFThe present invention relates to pyrazolopyrimidinone compounds. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating autoimmune, inflammatory, and neurodegenerative diseases by administering these compounds and pharmaceutical compositions to subjects in need thereof. The present invention also relates to the use of such compounds for research or other non-therapeutic purposes.A compound of Formula (I):or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate orpharmaceutically acceptable hydrate thereof, whereinY is -CR3= or -N=;R1 is Q1-T1-(X1)n;Q1 is a bond or C1–3alkylene, wherein the C1–3alkylene group is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-6alkyl, C2–6alkenyl, C2–6alkynyl, cyano, C1–6haloalkyl, -ORw2, and -NRw2Rx2;T1 is C3-8cycloalkyl, C6-10aryl, 3- to 12-membered heterocycloalkyl, 5- to 10- membered heteroaryl, -C(=O)C0–3alkylene-C3-8cycloalkyl, -C(=O)-C0–3alkylene-C6–10aryl, -C(=O)-C0-3alkylene-3 to 12-membered heterocycloalkyl, -C(=O)-C0–3alkylene-5 to 10- membered heteroaryl, -NRaRb, -S(=O)2Ra, -NRaC(=O)Ra, -NRaC(=O)NRaRb,-NRaC(=O)ORa, -NRaS(=O)2Ra, -C(=O)NRaS(=O)2Ra, -NRaS(=O)2NRaRb, -C(=O)NRaRb, or -S(=O)2NRaRb;each X1 is independently selected from the group consisting of halo, cyano, oxo, C0-3alkylene-C(=O)Rc, C0–3alkylene-ORc, C0–3alkylene-C(=O)ORc, C0–3alkylene-OC(=O)Rc, C0–3alkylene-NRcRd, C0-3alkylene-N+RcRdRd’, C0–3alkylene-S(=O)mRc,C0-3alkylene-NRcC(=O)Rc, C0–3alkylene-NRcC(=O)NRcRd, C0–3alkylene-OC(=O)NRcRd, C0– 3alkylene-NRcC(=O)ORc, C0–3alkylene-NRcS(=O)2Rc, C0–3alkylene-C(=O)NRcS(=O)2Rc, C0– 3alkylene-NRcS(=O)2NRcRd, C0–3alkylene-C(=O)NRcRd, C0–3alkylene-S(=O)2NRcRd, C0-3alkylene-C(=NRc)NRcRd, C0–3alkylene-NRcC(=NRc)NRcRd, and RS1, in which RS1 is C1– 6alkyl, C2–6alkenyl, C2–6alkynyl, C0–3alkylene-C3–8cycloalkyl, C0–3alkylene-C6–10aryl, C0-3alkylene-3- to 12-membered heterocycloalkyl, or C0–3alkylene-5- to 10-membered heteroaryl;and each RS1 is optionally substituted with one or more substituents independently selected from the group consisting of halo, cyano, nitro, oxo, C1–6alkyl, C2–6alkenyl, C2-6alkynyl, C1–6haloalkyl, C0–3alkylene-NReRf, C0–3alkylene-ORe,C0-3alkylene-NReC(=O)Re, C0–3alkylene-NReC(=O)ORe, C0–3alkylene-NReC(=O)NReRf, C0– 3alkylene-OC(=O)Re, C0–3alkylene-C(=O)ORe, C0–3alkylene-C(=O)NReRf, C0-3alkylene-C(=O)Re, C0–3alkylene-S(=O)mRe, C0–3alkylene-S(=O)2NReRf,C0-3alkylene-NReS(=O)2Re, C0–3alkylene-C(=O)NReS(=O)2Re,C0-3alkylene-NReS(=O)2NReRf, and RS2, in which RS2 is C0–3alkylene-C3-8cycloalkyl, C0-3alkylene-C6–10aryl, C0–3alkylene-3- to 12-membered heterocycloalkyl, or C0–3alkylene- 5- to 10-membered heteroaryl,and each RS2 is optionally substituted with one or more substituents independently selected from the group consisting of halo, oxo, C1–6alkyl, C2–6alkenyl, C2–6alkynyl, cyano, C1–6haloalkyl, -ORw, and -NRwRx;R2 is Q2-T2-(X2)p;Q2 is a bond or C1–3alkylene, wherein the C1–3alkylene group is optionally substituted with one or more substituents independently selected from the group consisting of halo, C1-6alkyl, C2–6alkenyl, C2–6alkynyl, cyano, C1–6haloalkyl, -ORw3, and -NRw3Rx3;T2 is H, halo, cyano, C1–6alkyl, C2–6alkenyl, C2–6alkynyl, C3–8cycloalkyl, C6–10aryl, 3- to 12-membered heterocycloalkyl, 5- to 10-membered heteroaryl,-C(=O)-C0-3alkylene-C3-8cycloalkyl, -C(=O)-C0–3alkylene-C6–10aryl, -C(=O)-C0–3alkylene- 3- to 12-membered heterocycloalkyl, -C(=O)-C0–3alkylene-5- to 10-membered heteroaryl, -ORz, -S(=O)mRk, -P(=O)RkkRmm, -NRkRm, -C(=O)ORk, or -C(=O)NRkRm;each X2 is independently selected from the group consisting of halo, cyano, oxo, C0-3alkylene-ORn, C0–3alkylene-S(=O)mRn, C0–3alkylene-NRnRo, C0–3alkylene-C(=O)NRnRo, C0–3alkylene-C(=O)ORn, and RS3, in which RS3 is C1–6alkyl, C2–6alkenyl, C2–6alkynyl, C0-3alkylene-C3–8cycloalkyl, C0-3alkylene-C6-10aryl, C0–3alkylene-3- to 12-membered heterocycloalkyl, or C0–3alkylene-5- to 10-membered heteroaryl;and RS3 is optionally substituted with one or more substituents independently selected from the group consisting of halo, oxo, cyano, C0–3alkylene-ORp, C0–3alkylene-S(=O)mRp, C0-3alkylene-NRpRq, C0–3alkylene-C(=O)NRpRq, C0–3alkylene-C0–3alkylene-C(=O)ORp, C1-6alkyl, C2–6alkenyl, C2–6alkynyl, C1–6haloalkyl, and RS4, in which RS4 isC0-3alkylene-C3-8cycloalkyl, C0-3alkylene-C6–10aryl, C0–3alkylene-3- to 12-membered heterocycloalkyl, or C0–3alkylene-5- to 10-membered heteroaryl;and each RS4 is optionally substituted with one or more substituents independently selected from the group consisting of halo, oxo, C1–6alkyl, C2–6alkenyl, C2–6alkynyl, cyano, C1–6haloalkyl, -ORw4, and -NRw4Rx4;R3 is C1–3alkyl, C1–3haloalkyl, C2-3alkenyl, C2-3alkynyl, C3–6cycloalkyl, -CN, -ORr, are optionally substituted with one C3–6cycloalkyl;R4 is C1–6alkyl, C1–6haloalkyl, S(=O)mRu, C0–3alkylene-C3–8cycloalkyl,C0-3alkylene-C6–10aryl, C0–3alkylene-3- to 12-membered heterocycloalkyl, or C0–3alkylene- 5- to 10-membered heteroaryl, wherein C0–3alkylene-C3–8cycloalkyl, C0–3alkylene-C6–10aryl, C0–3alkylene-3- to 12-membered heterocycloalkyl, or C0–3alkylene-5- to 10-membered heteroaryl are optionally substituted with one or more substituents independently selected from the group consisting of halo, oxo, C1–6alkyl, C2–6alkenyl, C2–6alkynyl, cyano,C1-6haloalkyl, ORw5, and NRw5Rx5;each of Ra and Rb, independently, is H or RS5, ...
피라졸로피리미디논 화합물 및 그의 용도본 발명은 피라졸로피리미디논 화합물에 관한 것이다. 또한, 본 발명은 이들 화합물을 포함하는 제약 조성물 및 자가면역, 염증성 및 신경변성 질환의 치료를 필요로 하는 대상체에게 이들 화합물 및 제약 조성물을 투여함으로써 자가면역, 염증성 및 신경변성 질환을 치료하는 방법에 관한 것이다. 본 발명은 또한 연구 또는 다른 비치료적 목적을 위한 이러한 화합물의 용도에 관한 것이다.화학식 (I)의 화합물 또는 그의 제약상 허용되는 염, 제약상 허용되는 용매화물 또는 제약상 허용되는 수화물:여기서Y는 -CR3= 또는 -N=이고;R1은 Q1-T1-(X1)n이고;Q1은 결합 또는 C1-3알킬렌이고, 여기서 C1-3알킬렌 기는 할로, C1-6알킬, C2-6알케닐, C2-6알키닐, 시아노, C1-6할로알킬, -ORw2, 및 -NRw2Rx2로 이루어진 군으로부터 독립적으로 선택된 1개 이상의 치환기로 임의로 치환되고;T1은 C3-8시클로알킬, C6-10아릴, 3- 내지 12-원 헤테로시클로알킬, 5- 내지 10-원 헤테로아릴, -C(=O)C0-3알킬렌-C3-8시클로알킬, -C(=O)-C0-3알킬렌-C6-10아릴, -C(=O)-C0-3알킬렌-3 내지 12-원 헤테로시클로알킬, -C(=O)-C0-3알킬렌-5 내지 10-원 헤테로아릴, -NRaRb, -S(=O)2Ra, -NRaC(=O)Ra, -NRaC(=O)NRaRb, -NRaC(=O)ORa, -NRaS(=O)2Ra, -C(=O)NRaS(=O)2Ra, -NRaS(=O)2NRaRb, -C(=O)NRaRb, 또는 -S(=O)2NRaRb이고;각각의 X1은 할로, 시아노, 옥소, C0-3알킬렌-C(=O)Rc, C0-3알킬렌-ORc, C0-3알킬렌-C(=O)ORc, C0-3알킬렌-OC(=O)Rc, C0-3알킬렌-NRcRd, C0-3알킬렌-N+RcRdRd', C0-3알킬렌-S(=O)mRc, C0-3알킬렌-NRcC(=O)Rc, C0-3알킬렌-NRcC(=O)NRcRd, C0-3알킬렌-OC(=O)NRcRd, C0-3알킬렌-NRcC(=O)ORc, C0-3알킬렌-NRcS(=O)2Rc, C0-3알킬렌-C(=O)NRcS(=O)2Rc, C0-3알킬렌-NRcS(=O)2NRcRd, C0-3알킬렌-C(=O)NRcRd, C0-3알킬렌-S(=O)2NRcRd, C0-3알킬렌-C(=NRc)NRcRd, C0-3알킬렌-NRcC(=NRc)NRcRd, 및 RS1로 이루어진 군으로부터 독립적으로 선택되고, 여기서 RS1은 C1-6알킬, C2-6알케닐, C2-6알키닐, C0-3알킬렌-C3-8시클로알킬, C0-3알킬렌-C6-10아릴, C0-3알킬렌-3- 내지 12-원 헤테로시클로알킬, 또는 C0-3알킬렌-5- 내지 10-원 헤테로아릴이고;각각의 RS1은 할로, 시아노, 니트로, 옥소, C1-6알킬, C2-6알케닐, C2-6알키닐, C1-6할로알킬, C0-3알킬렌-NReRf, C0-3알킬렌-ORe, C0-3알킬렌-NReC(=O)Re, C0-3알킬렌-NReC(=O)ORe, C0-3알킬렌-NReC(=O)NReRf, C0-3알킬렌-OC(=O)Re, C0-3알킬렌-C(=O)ORe, C0-3알킬렌-C(=O)NReRf, C0-3알킬렌-C(=O)Re, C0-3알킬렌-S(=O)mRe, C0-3알킬렌-S(=O)2NReRf, C0-3알킬렌-NReS(=O)2Re, C0-3알킬렌-C(=O)NReS(=O)2Re, C0-3알킬렌-NReS(=O)2NReRf, 및 RS2로 이루어진 군으로부터 독립적으로 선택된 1개 이상의 치환기로 임의로 치환되고, 여기서 RS2는 C0-3알킬렌-C3-8시클로알킬, C0-3알킬렌-C6-10아릴, C0-3알킬렌-3- 내지 12-원 헤테로시클로알킬, 또는 C0-3알킬렌-5- 내지 10-원 헤테로아릴이고,각각의 RS2는 할로, 옥소, C1-6알킬, C2-6알케닐, C2-6알키닐, 시아노, C1-6할로알킬, -ORw, 및 -NRwRx로 이루어진 군으로부터 독립적으로 선택된 1개 이상의 치환기로 임의로 치환되고;R2는 Q2-T2-(X2)p이고;Q2는 결합 또는 C1-3알킬렌이고, 여기서 C1-3알킬렌 기는 할로, C1-6알킬, C2-6알케닐, C2-6알키닐, 시아노, C1-6할로알킬, -ORw3, 및 -NRw3Rx3으로 이루어진 군으로부터 독립적으로 선택된 1개 이상의 치환기로 임의로 치환되고;T2는 H, 할로, 시아노, C1-6알킬, C2-6알케닐, C2-6알키닐, C3-8시클로알킬, C6-10아릴, 3- 내지 12-원 헤테로시클로알킬, 5- 내지 10-원 헤테로아릴, -C(=O)-C0-3알킬렌-C3-8시클로알킬, -C(=O)-C0-3알킬렌-C6-10아릴, -C(=O)-C0-3알킬렌-3- 내지 12-원 헤테로시클로알킬, -C(=O)-C0-3알킬렌-5- 내지 10-원 헤테로아릴, -ORz, -S(=O)mRk, -P(=O)RkkRmm, -NRkRm, -C(=O)ORk, 또는 -C(=O)NRkRm이고;각각의 X2는 할로, 시아노, 옥소, C0-3알킬렌-ORn, C0-3알킬렌-S(=O)mRn, C0-3알킬렌-NRnRo, C0-3알킬렌-C(=O)NRnRo, C0-3알킬렌-C(=O)ORn, 및 RS3으로 이루어진 군으로부터 독립적으로 선택되고, 여기서 RS3은 C1-6알킬, C2-6알케닐, C2-6알키닐, C0-3알킬렌-C3-8시클로알킬, C0-3알킬렌-C6-10아릴, C0-3알킬렌-3- 내지 12-원 헤테로시클로알킬, 또는 C0-3알킬렌-5- 내지 10-원 헤테로아릴이고;RS3은 할로, 옥소, 시아노, C0-3알킬렌-ORp, C0-3알킬렌-S(=O)mRp, C0-3알킬렌-NRpRq, C0-3알킬렌-C(=O)NRpRq, C0-3알킬렌-C0-3알킬렌-C(=O)ORp, C1-6알킬, C2-6알케닐, C2-6알키닐, C1-6할로알킬, 및 RS4로 이루어진 군으로부터 독립적으로 선택된 1개 이상의 치환기로 임의로 치환되고, 여기서 RS4는 C0-3알킬렌-C3-8시클로알킬, C0-3알킬렌-C6-10아릴, C0-3알킬렌-3- 내지 12-원 헤테로시클로알킬, 또는 C0-3알킬렌-5- 내지 10-원 헤테로아릴이고;각각의 RS4는 할로, 옥소, C1-6알킬, C2-6알케닐, C2-6알키닐, 시아노, C1-6할로알킬, -ORw4, 및 -NRw4Rx4로 이루어진 군으로부터 독립적으로 선택된 1개 이상의 치환기로 임의로 치환되고;R3은 C1-3알킬, C1-3할로알킬, C2-3알케닐, C2-3알키닐, C3-6시클로알킬, -CN, -ORr, -C(=O)Rr, -S(=O)mRr, NRrRt, 또는 -C(=O)ORr이고, 여기서 C1-3알킬, C2-3알케닐 및 C2-3알키닐은 1개의 C3-6시클로알킬로 임의로 치환되고;R4는 C1-6알킬, C1-6할로알킬, S(=O)mRu, C0-3알킬렌-C3-8시클로알킬, C0-3알킬렌-C6-10아릴, C0-3알킬렌-3- 내지 12-원 헤테로시클로알킬, 또는 C0-3알킬렌-5- 내지 10-원 헤테로아릴이고, 여기서 C0-3알킬렌-C3-8시클로알킬, C0-3알킬렌-C6-10아릴, C0-3알킬렌-3- 내지 12-원 헤테로시클로알킬, 또는 C0-3알킬렌-5- 내지 10-원 헤테로아릴은 할로, 옥소, C1-6알킬, C2-6알케닐, C2-6알키닐, 시아노, C1-6할로알킬, ORw5, 및 NRw5Rx5로 이루어진 군으로부터 독립적으로 선택된 1개 이상의 치환기로 임의로 치환되고;각각의 Ra 및 Rb는 독립적으로 H 또는 RS5이고, 여기서 RS5는 C1-6알킬, C2-6알케닐, C2-6알키닐, C0-3알킬렌-C3-8시클로알킬, C0-3알킬렌-C6-10아릴, C0-3알킬렌-3- 내지 12-원 헤테로시클로알킬, 또는 C0-3알킬렌-5- 내지 10-원 헤테로아릴이고;RS5는 할로, 시아노, 옥소, C1-6할로알킬, C0-3알킬렌-ORc2, C0-3알킬렌-C(=O)Rc2, C0-3알킬렌-C(=O)ORc2, C0-3알킬렌-OC(=O)Rc2, C0-3알킬렌-C(=O)NRc2Rd2, C0-3알킬렌-S(=O)mRc2, C0-3알킬렌-S(=O)2NRc2Rd2, C0-3알킬렌-NRc2Rd2, C0-3알킬렌-NRc2C(=O)Rc2, C0-3알킬렌-NRc2C(=O)ORc2, C0-3알킬렌-NRc2C(=O)NRc2Rd2, C0-3알킬렌-NRc2S(=O)2Rc2, C0-3알킬렌-C(=O)NRc2S(=O)2Rc2, C0-3알킬렌-NRc2S(=O)2NRc2Rd2, C0-3알킬렌-N(S(=O)2Rc2)2, 및 RS6으로 이루어진 군으로부터 독립적으로 선택된 1개 이상의 치환기로 임의로 치환되고, 여기서 RS6은 C1-6알킬, C2-6알케닐, C2-6알키닐, C0-3알킬렌-C3-8시클로알킬, C0-3알킬렌-C6-10아릴, C0-3알킬렌-3- 내지 12-원 헤테로시클로알킬, 또는 C0-3알킬렌-5- 내지 10-원 헤테로아릴이고;각각의 RS6은 할로, 시아노, 옥소, C1-6알킬, C2-6알케닐, C2-6알키닐, C1-6할로알킬, C0-3알킬렌-NRe2Rf2, C0-3알킬렌-ORe2, C0-3알킬렌-NRe2C(=O)Re2, C0-3알킬렌-NRe2C(=O)ORe2, C0-3알킬렌-NRe2C(=O)NRe2Rf2, C0-3알킬렌-OC(=O)Re2, C0-3알킬렌-C(=O)ORe2, C0-3알킬렌-C(=O)NRe2Rf2, C0-3알킬렌-C(=O)Re2, C0-3알킬렌-S(=O)mRe2, C0-3알킬렌-S(=O)2NRe2Rf2, C0-3알킬렌-NRe2S(=O)2Re2, C0-3알킬렌-C(=O)NRe2S(=O)2Re2, C0-3알킬렌-NRe2S(=O)2NRe2Rf2, 및 RS7로 이루어진 군으로부터 독립적으로 선택된 1개 이상의 치환기로 임의로 치환되고, 여기서 RS7은 C0-3알킬렌-C3-8시클로알킬, C0-3알킬렌-C6-10아릴, C0-3알킬렌-3- 내지 12-원 헤테로시클로알킬, 또는 C0-3알킬렌-5- 내지 10-원 헤테로아릴이고;각각의 RS7은 할로, 옥소, C1-6알킬, C2-6알케닐, C2-6알키닐, 시아노, C1-6할로알킬, -ORw6, 및 -NRw6Rx6으로 이루어진 군으로부터 독립적으로 선택된 1개 이상의 치환기로 임의로 치환되고;각각의 Rc, Rc2, Rd, Rd', 및 Rd2는 독립적으로 H 또는 RS8이고, 여기서 RS8은 C1-6알킬, C2-6알케닐, C2-6알키닐, C0-3알킬렌-C3-8시클로알킬, C0-3알킬렌-C6-10아릴, C0-3알킬렌-3- 내지 12-원 헤테로시클로알킬, 또는 C0-3알킬렌-5- 내지 10-원 헤테로아릴이고;각각의 RS8은 할로, 시아노, 옥소, C1-6알킬, C2-6알케닐, C2-6알키닐, C1-6할로알킬, C0-3알킬렌-NRe3Rf3, C0-3알킬렌-ORe3, C0-3알킬렌-C(=O)ORe3, C0-3알킬렌-C(=O)NRe3Rf3, C0-3알킬렌-C(=O)Re3, C0...