NOVEL HETEROARYL AND HETEROCYCLE COMPOUNDS, COMPOSITION AND METHODS THEREOFDisclosed are novel heteroaryl and heterocycle compounds of formula I-1, I-2 or I-3 and pharmaceutical compositions comprising them, uses and methods thereof for inhibiting the activity of PI3K and for treating inflammatory and autoimmune diseases and cancer.A compound of formula I-l, 1-2 or 1-3 :I-l 1-2 1-3 and/or its solvates, racemic mixture, enantiomers, diasteromers, tautomers, or mixtures of any ratio, or pharmaceutically acceptable salts thereof, wherein:Z = N or CH;R1 is selected from optionally substituted Ci_6 alkyl, optionally substituted C3-6 cycloalkyl, -(CR'R')n-heterocycle, -(CR'R')n-aryl, and -(CR'R')n-heteroaryl, wherein heterocycle, aryl and heteroaryl independently are 5-6 membered monocyclic ring, which are optionally substituted with one or more groups selected from hydrogen, halo, optionally substituted Ci_6 alkyl, optionally substituted Ci_6 alkoxyl, -CN, -CF3, and -S02R';R2 and R3 are each independently selected from hydrogen and optionally substituted Ci_4 alkyl;R4 is selected from hydrogen, halo, -CN, optionally substituted Ci_6 alkyl, optionally substituted C3_6 cycloalkyl, optionally substituted C2_6 alkenyl, optionally substituted C2_6 alkynyl, -C(0)NR'R', and optionally substituted 5-6 membered monocyclic heteroaryl;R5 is selected from hydrogen and optionally substituted Ci_4 alkyl; or R3, R5 and the atoms they are attached to form an optionally substituted 4-6 membered mono- or bicyclic saturated or partially unsaturated heterocyclic ring; R' and R' are each independently selected from hydrogen, halo, optionally substituted Ci_6 alkyl, optionally substituted C3-6 cycloalkyl, and optionally substituted 4-6 membered monocyclic heterocycle; or R', R' and the nitrogen or carbon atom they are both attached to form an optionally substituted 3-7 membered heterocycle; each of m and n is 0, 1, 2, or 3; each of p is 1 or 2;W is a heteroaryl, which is optionally substituted with one or more groups selected from halo, -CN, -CF3, -N02, -OR', -NR'R', -NR'COR', -(CR'R')n-C(0)R -(CR'R')n-C(=N-OR')-R', -(CR'R')n-C(0)NR'R', -(CR'R')n-S(0)pR -(CR'R')n-SR optionally substituted Ci_6 alkyl, optionally substituted C2_6 alkenyl, optionally substituted C2_6 alkynyl, optionally substituted Ci_6 alkoxy, optionally substituted 5-6 membered monocyclic heterocycle, and optionally substituted 5-6 membered monocyclic heteroaryl; provided that for formula 1-1, when Z = N, R3, R5 and the atoms they are attached to must form an optionally substituted 4-6 membered mono- or bicyclic saturated or partially unsaturated heterocyclic ring, with the provision that when R3, R5 and the atoms they are attached to form an optionally substituted 5 membered mono- or bicyclic saturated or partially unsaturated heterocyclic ring, R4 is not hydrogen, -CN, or aminomethyl.A compound of formula 1-1 according to claim 1, and/or its solvates, racemic mixture, enantiomers, diasteromers, tautomers, or mixtures of any ratio, or pharmaceutically acceptable salts thereof, wherein, R1 is selected from, optionally substituted Ci_6 alkyl, optionally substituted C3-6 cycloalkyl, -(CR'R')n-heterocycle, -(CR'R')n-aryl, and -(CR'R')n-heteroaryl, wherein heterocycle, aryl and heteroaryl independently are 5-6 membered monocyclic ring, which are optionally substituted with one or more groups selected from halo, optionally substituted Ci_6 alkyl, optionally substituted Ci_6 alkoxyl, -CN, -CF3, and -S02R' ;R2 is selected from hydrogen and optionally substituted Ci_4 alkyl;R3, R5 and the atoms they are attached to form an optionally substituted 4-6 membered mono- or bicyclic saturated or partially unsaturated heterocyclic ring;R4 is selected from halo, Ci_6 alkyl, optionally substituted C3_6 cycloalkyl, optionally substituted C2_6 alkenyl, optionally substituted C2_6 alkynyl, -C(0)NR'R', and optionally substituted 5-6 membered monocyclic heteroaryl, wherein Ci_C6 alkyl is optionally substituted with one or more groups selected from Ci_C4 alkoxyl, -OH, and halo;R' and R' are each independently selected from hydrogen, halo, optionally substituted Ci_6 alkyl, optionally substituted C3_6 cycloalkyl, and optionally substituted 5-6 membered monocyclic heterocycle; or R', R' and the nitrogen or carbon atom they are both attached to form an optionally substituted 3-7 membered heterocycle; each of m and n is 0, 1, 2, or 3; each of p is 1 or 2;W is a heteroaryl, which is optionally substituted with one or more groups selected from halo, -CN, -CF3, -N02, -OR', -NR'R', -NR'COR', -(CR'R')n-C(0)R -(CR'R')n-C(=N-OR')-R', -(CR'R')n-C(0)NR'R', -(CR'R')n-S(0)pR -(CR'R')n-SR optionally substituted Ci_6 alkyl, optionally substituted C2_6 alkenyl, optionally substituted C2_6 alkynyl, optionally substituted Ci_6 alkoxy, optionally substituted 5-6 membered monocyclic heterocycle, and optionally substituted 5-6 membered monocyclic heteroaryl.
신규 헤테로아릴 및 헤테로사이클 화합물, 그의 조성물 및 방법본 발명은 화학식 I-1, I-2 또는 I-3의 신규 헤테로아릴 및 헤테로사이클 화합물 및 그를 포함하는 약학 조성물, PI3K의 활성을 저해하고 염증성 및 자가면역 질환 및 암을 치료하기 위한 그의 용도 및 방법에 관한 것이다:화학식 I-1, I-2 또는 I-3의 화합물 및/또는 그의 용매화물, 라세미 혼합물, 거울상이성질체, 부분입체이성질체, 호변이성질체, 또는 임의 비의 혼합물, 또는 그의 약학적으로 허용가능한 염:상기 식에서,Z는 N 또는 CH이고; R1은 임의로 치환된 C1-6 알킬, 임의로 치환된 C3-6 사이클로알킬, -(CR'R")n-헤테로사이클, -(CR'R")n-아릴, 및 -(CR'R")n-헤테로아릴로부터 선택되고, 여기서, 헤테로사이클, 아릴 및 헤테로아릴은 독립적으로 수소, 할로, 임의로 치환된 C1-6 알킬, 임의로 치환된 C1-6 알콕실, -CN, -CF3, 및 -SO2R'로부터 선택되는 하나 이상의 그룹으로 임의로 치환된 5-6 원 모노사이클릭 고리이고;R2 및 R3은 각각 독립적으로 수소 및 임의로 치환된 C1-4 알킬로부터 선택되고;R4는 수소, 할로, -CN, 임의로 치환된 C1-6 알킬, 임의로 치환된 C3-6 사이클로알킬, 임의로 치환된 C2-6 알케닐, 임의로 치환된 C2-6 알키닐, -C(O)NR'R" 및 임의로 치환된 5-6 원 모노사이클릭 헤테로아릴로부터 선택되고; R5는 수소 및 임의로 치환된 C1-4 알킬로부터 선택되거나;또는 R3, R5 및 이들이 결합된 원자는 임의로 치환된 4-6 원 모노- 또는 바이사이클릭 포화 또는 부분 불포화 헤테로사이클릭 고리를 형성하고;R' 및 R"는 각각 독립적으로 수소, 할로, 임의로 치환된 C1-6 알킬, 임의로 치환된 C3-6 사이클로알킬, 및 임의로 치환된 4-6 원 모노사이클릭 헤테로사이클로부터 선택되거나;또는 R', R" 및 이들이 결합된 질소 또는 탄소 원자는 임의로 치환된 3-7 원 헤테로사이클을 형성하고; m 및 n은 각각 0, 1, 2, 또는 3이고;p는 각각 1 또는 2이고;W는 할로, -CN, -CF3, -NO2, -OR', -NR'R", -NR'COR", -(CR'R")n-C(O)R', -(CR'R")n-C(=N-OR')-R", -(CR'R")n-C(O)NR'R" -(CR'R")n-S(O)pR', -(CR'R")n-SR', 임의로 치환된 C1-6 알킬, 임의로 치환된 C2-6 알케닐, 임의로 치환된 C2-6 알키닐, 임의로 치환된 C1-6 알콕시, 임의로 치환된 5-6 원 모노사이클릭 헤테로사이클, 및 임의로 치환된 5-6 원 모노사이클릭 헤테로아릴로부터 선택되는 하나 이상의 그룹으로 임의로 치환된 헤테로아릴이나; 단 화학식 I-1에 대해, Z가 N인 경우, R3, R5 및 이들의 결합된 원자는 임의로 치환된 4-6 원 모노- 또는 바이사이클릭 포화 또는 부분 불포화 헤테로사이클릭 고리를 형성하여야 하되, R3, R5 및 이들이 결합된 원자가 임의로 치환된 5 원 모노- 또는 바이사이클릭 포화 또는 부분 불포화 헤테로사이클릭 고리를 형성하면, R4는 수소, -CN, 또는 아미노메틸이 아니다.