PYRROLO[1,2-B]PYRIDAZINE DERIVATIVES AS IRAK4 INHIBITORSA compound of Formula (I), pharmaceutically acceptable salts thereof, deuterated analogs thereof, compositions thereof, and methods of treating disease using a compound thereof are disclosed.A compound of formula (I):wherein“Het” is selected from: X and Y are each independently selected from: -H, -F, -Cl, -Br, -CN, -CF3, -CF2H, -OH, or -OCH3;R1 and R2 are each independently selected from: a) Ci-10 alkyl optionally substituted with Z1;b) C3-10 cycloalkyl optionally substituted with Z1;c) 5-10 membered heteroaryl optionally substituted with Z1;d) C6-10 aryl optionally substituted with Z1;e) 4-12 membered heterocyclyl optionally substituted with Z1;f) -N(R12)(R12), -S(0)2R12, -S(0)2 N(R12)(R12), or -H;Z1 is independently oxo, halo, -NO2, -N3, -CN, C1-9 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-15 cycloalkyl, C1-8 haloalkyl, aryl, heteroaryl, heterocyclyl, -O-R12, -C(0)-R12, -C(0)0- R12, -C(0)-N(R12)( R12), -N(R12)( R12), -N(R12)2(R12)+, -N(R12)C(0)-R12, -N(R12)C(0)0- R12, -N(R12)C(0)N(R12)( R12), -N(R12)S(0)2(R12), -NR12S(0)2N(R12)( R12), - NR12S(0)20(R12), -0C(0)R12, -0C(0)0R12, -0C(0)-N(R12)( R12), -Si(R12)3, -S- R12, -S(0)R12, -S(0)(NH)R12, -S(0)2R12 or -S(0)2N(R12)( R12); wherein any alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, aryl, heteroaryl orheterocyclyl is optionally substituted with Zla; each Zla is independently oxo, halo, -NCte, -CN, -N3, C1-9 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-15 cycloalkyl, C1-8 haloalkyl, aryl, heteroaryl, heterocyclyl, -O-R12, -C(0)R12, -C(0)0- R12, -C(0)N(R12)( R12), -N(R12)( R12), -N(R12)2(R12) +, -N(R12)-C(0)R12, - N(R12)C(0)0(R12), -N(R12)C(0)N(R12)( R12), -N(R12)S(0)2(R12), -N(R12)S(0)2- N(R12)( R12), -N(R12)S(0)20(R12), -0C(0)R12, -0C(0)0R12, -0C(0)- N(R12)( R12), -Si(R12)3, -S-R12, -S(0)R12, -S(0)(NH)R12, -S(0)2R12or -S(0)2N(R12)( R12); wherein any alkyl, alkenyl, alkynyl, cycloalkyl, haloalkyl, aryl, heteroaryl orheterocyclyl is optionally substituted with Zlb; each R12 is independently H, C1-9 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-15 cycloalkyl, aryl, heteroaryl or heterocyclyl; wherein any alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl or heterocyclyl is optionally substituted with Zla; each Zlb is independently oxo, hydroxy, halo, -NCte, -N3, -CN, C1-9 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-15 cycloalkyl, C1-8 haloalkyl, aryl, heteroaryl, heterocyclyl, -0(Ci-9 alkyl), -0(C2-6 alkenyl), -0(C2-6 alkynyl), -0(C3-i5 cycloalkyl), -0(Ci-8 haloalkyl), -O(aryl), -O(heteroaryl), -O(heterocyclyl), -NIL·, -NH(CI-9 alkyl), -NH(C2-6alkenyl), -NH(C2-6 alkynyl), -NH(C3-i5 cycloalkyl), -NH(CI-8 haloalkyl), -NH(aryl), -NH(heteroaryl), -NH(heterocyclyl), -N(CI-9 alkyl)2, -N(C3-is cycloalkyl)2, -N(C2-6 alkenyl)2, -N(C2-6 alkynyl)2, -N(C3-i5 cycloalkyl)2, -N(Ci-s haloalkyl)2, -N(aryl)2, - N(heteroaryl)2, -N(heterocyclyl)2, -N(CI-9 alkyl)(C3-i5 cycloalkyl), -N(CI-9 alkyl)(C2-6 alkenyl), -N(CI-9 alkyl)(C2-6 alkynyl), -N(CI-9 alkyl)(C3-is cycloalkyl), -N(CI-9 alkyl)(Ci-8 haloalkyl), -N(CI-9 alkyl)(aryl), -N(CI-9 alkyl)(heteroaryl), -N(CI-9alkyl)(heterocyclyl), -C(0)(Ci-9 alkyl), -C(0)(C2-6 alkenyl), -C(0)(C2-6alkynyl), -C(0)(C3-i5 cycloalkyl), -C(0)(Ci-8 haloalkyl), -C(0)(aryl), -C(0)(heteroaryl), -C(0)(heterocyclyl), -C(0)0(Ci-9 alkyl), -C(0)0(C2-6 alkenyl), -C(0)0(C2-6alkynyl), -C(0)0(C3-is cycloalkyl), -C(0)0(Ci-8 haloalkyl), -C(0)0(aryl), - C(0)0(heteroaryl), -C(0)0(heterocyclyl), -C(0)NH2, -C(0)NH(Ci-9alkyl), -C(0)NH(C2-6 alkenyl), -C(0)NH(C2-6 alkynyl), -C(0)NH(C3-i5cycloalkyl), -C(0)NH(CI-8 haloalkyl), -C(0)NH(aryl), -C(0)NH(heteroaryl), - C(0)NH(heterocyclyl), -C(0)N(CI-9 alkyl)2, -C(0)N(C3-i5 cycloalkyl)2, -C(0)N(C2-6 alkenyl)2, -C(0)N(C2-6 alkynyl)2, -C(0)N(C3-i5 cycloalkyl)2, -C(0)N(CI-8 haloalkyl)2, - C(0)N(aryl)2, -C(0)N(heteroaryl)2, -C(0)N(heterocyclyl)2, -NHC(0)(CI-9alkyl), -NHC(0)(C2-6 alkenyl), -NHC(0)(C2-6 alkynyl), -NHC(0)(C3-i5cycloalkyl), -NHC(0)(CI-8 haloalkyl), -NHC(0)(aryl), -NHC(0)(heteroaryl), - NHC(0)(heterocyclyl), -NHC(0)0(Ci-9 alkyl), -NHC(0)0(C2-6 alkenyl), -NHC(0)0(C2- 6 alkynyl), -NHC(0)0(C3-i5 cycloalkyl), -NHC(0)0(CI-8 haloalkyl), -NHC(0)0(aryl), - NHC(0)0(heteroaryl), -NHC(0)0(heterocyclyl), -NHC(0)NH(Ci-9alkyl), -NHC(0)NH(C2-6 alkenyl), -NHC(0)NH(C2-6 alkynyl), -NHC(0)NH(C3-i5 cycloalkyl), -NHC(0)NH(CI-8 haloalkyl), -NHC(0)NH(aryl), - NHC(0)NH(heteroaryl), -NHC(0)NH(heterocyclyl), -SH, -S(Ci-9 alkyl), -S(C2-6 alkenyl), -S(C2-6 alkynyl), -S(C3-i5 cycloalkyl), -S(Ci-8 haloalkyl), -S(aryl), - S(heteroaryl), -S(heterocyclyl), -NHS(0)(Ci-9 alkyl), -N(CI-9 alkyl)(S(0)(Ci-9 alkyl), - S(0)N(CI-9 alkyl)2, -S(0)(Ci-9 alkyl), -S(0)(NH)(Ci-9 alkyl), -S(0)(C2-6alkenyl), -S(0)(C2-6 alkynyl), -S(0)(C3-i5 cycloalkyl), -S(0)(Ci-8 haloalkyl), -S(0)(aryl), -S(0)(heteroaryl), -S(0)(heterocyclyl), -S(0)2(Ci-9 alkyl), -S(0)2(C2-6 alkenyl), -S(0)2(C2-6 alkynyl), -S(0)2(C3-i5 cycloalkyl), -S(0)2(Ci-8 haloalkyl), - S(0)2(aryl), -S(0)2(heteroaryl), -S(0)2(heterocyclyl), -S(0)2NH(CI-9 alkyl),or -S(0)2N(CI-9 alkyl)2;wherein any alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl is optionally substituted with one or more halo, C1-9 alkyl, C1-8 haloalkyl, -OH, -NH2, -NH(CI-9 alkyl), -NH(C3-i5 cycloalkyl), -NH(CI-8 haloalkyl), -NH(aryl), -NH(heteroaryl), -...
IRAK4 억제제로서의 피롤로[1,2-B]피리다진 유도체화학식 (I)의 화합물 또는 그의 제약상 허용되는 염, 그의 중수소화 유사체, 그의 조성물, 및 그의 화합물을 사용하여 질환을 치료하는 방법이 개시된다.화학식 (I)의 화합물 또는 그의 제약상 허용되는 염, 입체이성질체, 입체이성질체의 혼합물 또는 중수소화 유사체.여기서"Het"는로부터 선택되고;X 및 Y는 각각 독립적으로 -H, -F, -Cl, -Br, -CN, -CF3, -CF2H, -OH, 또는 -OCH3으로부터 선택되고;R1 및 R2는 각각 독립적으로 a) Z1로 임의로 치환된 C1-10 알킬; b) Z1로 임의로 치환된 C3-10 시클로알킬; c) Z1로 임의로 치환된 5-10원 헤테로아릴; d) Z1로 임의로 치환된 C6-10 아릴; e) Z1로 임의로 치환된 4-12원 헤테로시클릴; f) -N(R12)(R12), -S(O)2R12, -S(O)2N(R12)(R12), 또는 -H로부터 선택되고;Z1은 독립적으로 옥소, 할로, -NO2, -N3, -CN, C1-9 알킬, C2-6 알케닐, C2-6 알키닐, C3-15 시클로알킬, C1-8 할로알킬, 아릴, 헤테로아릴, 헤테로시클릴, -O-R12, -C(O)-R12, -C(O)O-R12, -C(O)-N(R12)(R12), -N(R12)(R12), -N(R12)2(R12)+, -N(R12)C(O)-R12, -N(R12)C(O)O-R12, -N(R12)C(O)N(R12)(R12), -N(R12)S(O)2(R12), -NR12S(O)2N(R12)(R12), -NR12S(O)2O(R12), -OC(O)R12, -OC(O)OR12, -OC(O)-N(R12)(R12), -Si(R12)3, -S-R12, -S(O)R12, -S(O)(NH)R12, -S(O)2R12 또는 -S(O)2N(R12)(R12)이고;여기서 임의의 알킬, 알케닐, 알키닐, 시클로알킬, 할로알킬, 아릴, 헤테로아릴 또는 헤테로시클릴은 Z1a로 임의로 치환되고;각각의 Z1a는 독립적으로 옥소, 할로, -NO2, -CN, -N3, C1-9 알킬, C2-6 알케닐, C2-6 알키닐, C3-15 시클로알킬, C1-8 할로알킬, 아릴, 헤테로아릴, 헤테로시클릴, -O-R12, -C(O)R12, -C(O)O-R12, -C(O)N(R12)(R12), -N(R12)(R12), -N(R12)2(R12)+, -N(R12)-C(O)R12, -N(R12)C(O)O(R12), -N(R12)C(O)N(R12)(R12), -N(R12)S(O)2(R12), -N(R12)S(O)2-N(R12)(R12), -N(R12)S(O)2O(R12), -OC(O)R12, -OC(O)OR12, -OC(O)-N(R12)(R12), -Si(R12)3, -S-R12, -S(O)R12, -S(O)(NH)R12, -S(O)2R12 또는 -S(O)2N(R12)(R12)이고;여기서 임의의 알킬, 알케닐, 알키닐, 시클로알킬, 할로알킬, 아릴, 헤테로아릴 또는 헤테로시클릴은 Z1b로 임의로 치환되고;각각의 R12는 독립적으로 H, C1-9 알킬, C2-6 알케닐, C2-6 알키닐, C3-15 시클로알킬, 아릴, 헤테로아릴 또는 헤테로시클릴이고;여기서 임의의 알킬, 알케닐, 알키닐, 시클로알킬, 아릴, 헤테로아릴 또는 헤테로시클릴은 Z1a로 임의로 치환되고;각각의 Z1b는 독립적으로 옥소, 히드록시, 할로, -NO2, -N3, -CN, C1-9 알킬, C2-6 알케닐, C2-6 알키닐, C3-15 시클로알킬, C1-8 할로알킬, 아릴, 헤테로아릴, 헤테로시클릴, -O(C1-9 알킬), -O(C2-6 알케닐), -O(C2-6 알키닐), -O(C3-15 시클로알킬), -O(C1-8 할로알킬), -O(아릴), -O(헤테로아릴), -O(헤테로시클릴), -NH2, -NH(C1-9 알킬), -NH(C2-6 알케닐), -NH(C2-6 알키닐), -NH(C3-15 시클로알킬), -NH(C1-8 할로알킬), -NH(아릴), -NH(헤테로아릴), -NH(헤테로시클릴), -N(C1-9 알킬)2, -N(C3-15 시클로알킬)2, -N(C2-6 알케닐)2, -N(C2-6 알키닐)2, -N(C3-15 시클로알킬)2, -N(C1-8 할로알킬)2, -N(아릴)2, -N(헤테로아릴)2, -N(헤테로시클릴)2, -N(C1-9 알킬)(C3-15 시클로알킬), -N(C1-9 알킬)(C2-6 알케닐), -N(C1-9 알킬)(C2-6 알키닐), -N(C1-9 알킬)(C3-15 시클로알킬), -N(C1-9 알킬)(C1-8 할로알킬), -N(C1-9 알킬)(아릴), -N(C1-9 알킬)(헤테로아릴), -N(C1-9 알킬)(헤테로시클릴), -C(O)(C1-9 알킬), -C(O)(C2-6 알케닐), -C(O)(C2-6 알키닐), -C(O)(C3-15 시클로알킬), -C(O)(C1-8 할로알킬), -C(O)(아릴), -C(O)(헤테로아릴), -C(O)(헤테로시클릴), -C(O)O(C1-9 알킬), -C(O)O(C2-6 알케닐), -C(O)O(C2-6 알키닐), -C(O)O(C3-15 시클로알킬), -C(O)O(C1-8 할로알킬), -C(O)O(아릴), -C(O)O(헤테로아릴), -C(O)O(헤테로시클릴), -C(O)NH2, -C(O)NH(C1-9 알킬), -C(O)NH(C2-6 알케닐), -C(O)NH(C2-6 알키닐), -C(O)NH(C3-15 시클로알킬), -C(O)NH(C1-8 할로알킬), -C(O)NH(아릴), -C(O)NH(헤테로아릴), -C(O)NH(헤테로시클릴), -C(O)N(C1-9 알킬)2, -C(O)N(C3-15 시클로알킬)2, -C(O)N(C2-6 알케닐)2, -C(O)N(C2-6 알키닐)2, -C(O)N(C3-15 시클로알킬)2, -C(O)N(C1-8 할로알킬)2, -C(O)N(아릴)2, -C(O)N(헤테로아릴)2, -C(O)N(헤테로시클릴)2, -NHC(O)(C1-9 알킬), -NHC(O)(C2-6 알케닐), -NHC(O)(C2-6 알키닐), -NHC(O)(C3-15 시클로알킬), -NHC(O)(C1-8 할로알킬), -NHC(O)(아릴), -NHC(O)(헤테로아릴), -NHC(O)(헤테로시클릴), -NHC(O)O(C1-9 알킬), -NHC(O)O(C2-6 알케닐), -NHC(O)O(C2-6 알키닐), -NHC(O)O(C3-15 시클로알킬), -NHC(O)O(C1-8 할로알킬), -NHC(O)O(아릴), -NHC(O)O(헤테로아릴), -NHC(O)O(헤테로시클릴), -NHC(O)NH(C1-9 알킬), -NHC(O)NH(C2-6 알케닐), -NHC(O)NH(C2-6 알키닐), -NHC(O)NH(C3-15 시클로알킬), -NHC(O)NH(C1-8 할로알킬), -NHC(O)NH(아릴), -NHC(O)NH(헤테로아릴), -NHC(O)NH(헤테로시클릴), -SH, -S(C1-9 알킬), -S(C2-6 알케닐), -S(C2-6 알키닐), -S(C3-15 시클로알킬), -S(C1-8 할로알킬), -S(아릴), -S(헤테로아릴), -S(헤테로시클릴), -NHS(O)(C1-9 알킬), -N(C1-9 알킬)(S(O)(C1-9 알킬), -S(O)N(C1-9 알킬)2, -S(O)(C1-9 알킬), -S(O)(NH)(C1-9 알킬), -S(O)(C2-6 알케닐), -S(O)(C2-6 알키닐), -S(O)(C3-15 시클로알킬), -S(O)(C1-8 할로알킬), -S(O)(아릴), -S(O)(헤테로아릴), -S(O)(헤테로시클릴), -S(O)2(C1-9 알킬), -S(O)2(C2-6 알케닐), -S(O)2(C2-6 알키닐), -S(O)2(C3-15 시클로알킬), -S(O)2(C1-8 할로알킬), -S(O)2(아릴), -S(O)2(헤테로아릴), -S(O)2(헤테로시클릴), -S(O)2NH(C1-9 알킬), 또는 -S(O)2N(C1-9 알킬)2이고;여기서 임의의 알킬, 시클로알킬, 아릴, 헤테로아릴, 또는 헤테로시클릴은 1개 이상의 할로, C1-9 알킬, C1-8 할로알킬, -OH, -NH2, -NH(C1-9 알킬), -NH(C3-15 시클로알킬), -NH(C1-8 할로알킬), -NH(아릴), -NH(헤테로아릴), -NH(헤테로시클릴), -N(C1-9 알킬)2, -N(C3-15 시클로알킬)2, -NHC(O)(C3-15 시클로알킬), -NHC(O)(C1-8 할로알킬), -NHC(O)(아릴), -NHC(O)(헤테로아릴), -NHC(O)(헤테로시클릴), -NHC(O)O(C1-9 알킬), -NHC(O)O(C2-6 알키닐), -NHC(O)O(C3-15 시클로알킬), -NHC(O)O(C1-8 할로알킬), -NHC(O)O(아릴), -NHC(O)O(헤테로아릴), -NHC(O)O(헤테로시클릴), -NHC(O)NH(C1-9 알킬), -S(O)(NH)(C1-9 알킬), S(O)2(C1-9 알킬), -S(O)2(C3-15 시클로알킬), -S(O)2(C1-8 할로알킬), -S(O)2(아릴), -S(O)2(헤테로아릴), -S(O)2(헤테로시클릴), -S(O)2NH(C1-9 알킬), -S(O)2N(C1-9 알킬)2, -O(C3-15 시클로알킬), -O(C1-8 할로알킬), -O(아릴), -O(헤테로아릴), -O(헤테로시클릴), 또는 -O(C1-9 알킬)로 임의로 치환된다.