5-azaindazole derivatives as adenosine receptor antagonistsThe present invention relates to novel 5-azaindazole derivatives of formula (I), as described and defined herein, and pharmaceutically acceptable salts, solvates and prodrugs thereof, as well as pharmaceutical compositions comprising such compounds. It has been found that the 5-azaindazole derivatives according to the present invention are highly effective dual A' s2A/A2B(ii) an adenosine receptor antagonist, wherein,and thus may be used as therapeutic agents, particularly in the treatment or prevention of hyperproliferative or infectious diseases or disorders.(I)。A compound of formula (i)(i)wherein:r1aand r1bare linked to each other to form, together with the nitrogen atom to which they are attached, a heterocycloalkyl group optionally substituted by one or more radicals r11substitution;or, alternatively, r1aand r1beach independently selected from hydrogen and c1-5alkyl radical, c2-5alkenyl radical, c2-5alkynyl, -co (c)1-5alkyl), carbocyclyl and heterocyclyl, wherein said alkyl, said alkenyl, said alkynyl and said-co (c) 1-5alkyl) is optionally substituted by one or more radicals r12substituted, and further wherein said carbocyclyl and said heterocyclyl are each optionally substituted with oneone or more radicals r13substitution;each r11independently selected from c1-5alkyl radical, c2-5alkenyl radical, c2-5alkynyl, - (c)0-3alkylene) -oh, - (c)0-3alkylene) -o (c)1-5alkyl), - (c)0-3alkylene) -o (c)1-5alkylene) -oh, - (c)0-3alkylene) -o (c)1-5alkylene) -o (c)1-5alkyl), - (c)0-3alkylene) -sh- (c)0-3alkylene) -s (c)1-5alkyl), - (c)0-3alkylene) -nh2, -(c0-3alkylene) -nh (c)1-5alkyl), - (c)0-3alkylene) -n (c)1-5alkyl) (c1-5alkyl), - (c)0-3alkylene) -halogen, - (c)0-3alkylene group) - (c1-5haloalkyl) - (c)0-3alkylene) -o- (c)1-5haloalkyl) - (c)0-3alkylene) -cf3, -(c0-3alkylene) -cn, - (c)0-3alkylene) -no2, -(c0-3alkylene) -cho, - (c)0-3alkylene) -co- (c)1-5alkyl), - (c)0-3alkylene) -cooh, - (c)0-3alkylene) -co-o- (c)1-5alkyl), - (c)0-3alkylene) -o-co- (c)1-5alkyl), - (c)0-3alkylene) -co-nh2, -(c0-3alkylene) -co-nh (c)1-5alkyl), - (c)0-3alkylene) -co-n (c)1-5alkyl) (c1-5alkyl), - (c)0-3alkylene) -nh-co- (c)1-5alkyl), - (c)0-3alkylene) -n (c)1-5alkyl) -co- (c1-5alkyl), - (c)0-3alkylene) -so2-nh2, -(c0-3alkylene) -so2-nh(c1-5alkyl), - (c)0-3alkylene) -so2-n(c1-5alkyl) (c1-5alkyl), - (c)0-3alkylene) -nh-so 2-(c1-5alkyl), - (c)0-3alkylene) -n (c)1-5alkyl) -so2-(c1-5alkyl), - (c)0-3alkylene) -so- (c1-5alkyl), - (c)0-3alkylene) -so2-(c1-5alkyl), - (c)0-3alkylene) -carboncyclic group, and — (c)0-3alkylene) heterocyclic group, wherein said- (c)0-3carbocyclyl moiety of alkylene) -carbocyclyl and said- (c)0-3alkylene) -heterocyclyl moieties of each of the heterocyclyl groups are optionally substituted with one or more groups independently selected from: c1-5alkyl radical, c2-5alkenyl radical, c2-5alkynyl, -oh, -o (c)1-5alkyl group, -o (c)1-5alkylene) -oh, -o (c)1-5alkylene) -o (c)1-5alkyl), -sh, -s (c)1-5alkyl), -nh2, -nh(c1-5alkyl group), -n (c)1-5alkyl) (c1-5alkyl), halogen, c1-5haloalkyl, -o- (c)1-5haloalkyl), -cf3, -cn, -no2, -cho, -co-(c1-5alkyl), -cooh, -co-o- (c)1-5alkyl group), -o-co- (c)1-5alkyl), -co-nh2, -co-nh(c1-5alkyl), -co-n (c)1-5alkyl) (c1-5alkyl), -nh-co- (c)1-5alkyl group), -n (c)1-5alkyl) -co- (c1-5alkyl), -so2-nh2, -so2-nh(c1-5alkyl), -so2-n(c1-5alkyl) (c1-5alkyl), -nh-so2-(c1-5alkyl group), -n (c)1-5alkyl) -so2-(c1-5alkyl), -so- (c)1-5alkyl), -so2-(c1-5alkyl), cycloalkyl, and heterocycloalkyl;each r12independently selected from-oh, -o (c)1-5alkyl group, -o (c)1-5alkylene) -oh, -o (c)1-5alkylene) -o (c)1-5alkyl), -sh, -s (c)1-5alkyl), -nh2, -nh(c1-5alkyl group), -n (c)1-5alkyl) (c1-5alkyl), halogen, c1-5haloalkyl, -o- (c)1-5haloalkyl), -cf3, -cn, -no2, -cho, -co-(c1-5alkyl), -cooh, -co-o- (c) 1-5alkyl group), -o-co- (c)1-5alkyl), -co-nh2, -co-nh(c1-5alkyl), -co-n (c)1-5alkyl) (c1-5alkyl), -nh-co- (c)1-5alkyl group), -n (c)1-5alkyl) -co- (c1-5alkyl), -so2-nh2, -so2-nh(c1-5alkyl), -so2-n(c1-5alkyl) (c1-5alkyl), -nh-so2-(c1-5alkyl group), -n (c)1-5alkyl) -so2-(c1-5alkyl), -so- (c)1-5alkyl), -so2-(c1-5alkyl), cycloalkyl, and heterocycloalkyl;each r13independently selected from c1-5alkyl radical, c2-5alkenyl radical, c2-5alkynyl, - (c)0-3alkylene) -oh, - (c)0-3alkylene) -o (c)1-5alkyl), - (c)0-3alkylene) -o (c)1-5alkylene) -oh, - (c)0-3alkylene) -o (c)1-5alkylene) -o (c)1-5alkyl), - (c)0-3alkylene) -sh- (c)0-3alkylene) -s (c)1-5alkyl), - (c)0-3alkylene) -nh2, -(c0-3alkylene) -nh (c)1-5alkyl), - (c)0-3alkylene) -n (c)1-5alkyl) (c1-5alkyl), - (c)0-3alkylene) -halogen, - (c)0-3alkylene group) - (c1-5haloalkyl) - (c)0-3alkylene) -o- (c)1-5haloalkyl) - (c)0-3alkylene) -cf3, -(c0-3alkylene) -cn, - (c)0-3alkylene) -no2, -(c0-3alkylene) -cho, - (c)0-3alkylene) -co- (c)1-5alkyl), - (c)0-3alkylene) -cooh, - (c)0-3alkylene) -co-o- (c)1-5alkyl), - (c)0-3alkylene) -o-co- (c)1-5alkyl), - (c)0-3alkylene) -co-nh2, -(c0-3alkylene) -co-nh (c)1-5alkyl), - (c)0-3alkylene) -co-n (c)1-5alkyl) (c1-5alkyl), - (c)0-3alkylene) -nh-co- (c)1-5alkyl), - (c)0-3alkylene) -n (c)1-5alkyl) -co- (c1-5alkyl), - (c)0-3alkylene) -so2-nh2, -(c0-3alkylene) -so 2-nh(c1-5alkyl), - (c)0-3alkylene) -so2-n(c1-5alkyl) (c1-5alkyl), - (c)0-3alkylene) -nh-so2-(c1-5alkyl), - (c)0-3alkylene) -n (c)1-5alkyl) -so2-(c1-5alkyl), - (c)0-3alkylene) -so- (c1-5alkyl), - (c)0-3alkylene) -so2-(c1-5alkyl), - (c)0-3alkylene) -cycloalkyl, and- (c)0-3alkylene) -heterocycloalkyl;r2and r4each independently selected from hydrogen, c1-5alkyl radical, c2-5alkenyl radical, c2-5alkynyl, - (c)0-3alkylene) -oh, - (c)0-3alkylene) -o (c)1-...
아데노신 수용체 안타고니스트로서의 5-아자인다졸 유도체본 발명은 본원에서 기재 및 정의된 바와 같은 식 (I) 의 신규한 5-아자인다졸 유도체, 및 그의 약학적으로 허용가능한 염, 용매화합물 및 전구약물, 뿐만 아니라 그러한 화합물을 포함하는 약학적 조성물에 관한 것이다. 본 발명에 따른 5-아자인다졸 유도체는 고도로 효과적인 이중 A2A/A2B 아데노신 수용체 안타고니스트인 것으로 밝혀졌고, 따라서 치료제로서, 특히 과증식성 또는 전염성 질환 또는 장애의 치료 또는 예방에서 사용될 수 있다.[이미지]식 (I) 의 화합물[이미지]식에서:R1A 및 R1B 는 상호 연결되어, 그들이 부착되어 있는 질소 원자와 함께, 하나 이상의 기 R11 로 임의로 치환되는 헤테로시클로알킬을 형성하거나;또는, 대안적으로, R1A 및 R1B 은 각각 독립적으로 수소, C1-5 알킬, C2-5 알케닐, C2-5 알키닐, -CO(C1-5 알킬), 카르보시클릴, 및 헤테로시클릴로부터 선택되며, 상기 알킬, 상기 알케닐, 상기 알키닐, 및 상기 -CO(C1-5 알킬) 의 알킬 모이어티는 각각 임의로 하나 이상의 기 R12 로 치환되고, 또한 상기 카르보시클릴 및 상기 헤테로시클릴은 각각 임의로 하나 이상의 기 R13 로 치환되고;각각의 R11 은 독립적으로 C1-5 알킬, C2-5 알케닐, C2-5 알키닐, -(C0-3 알킬렌)-OH, -(C0-3 알킬렌)-O(C1-5 알킬), -(C0-3 알킬렌)-O(C1-5 알킬렌)-OH, -(C0-3 알킬렌)-O(C1-5 알킬렌)-O(C1-5 알킬), -(C0-3 알킬렌)-SH, -(C0-3 알킬렌)-S(C1-5 알킬), -(C0-3 알킬렌)-NH2, -(C0-3 알킬렌)-NH(C1-5 알킬), -(C0-3 알킬렌)-N(C1-5 알킬)(C1-5 알킬), -(C0-3 알킬렌)-할로겐, -(C0-3 알킬렌)-(C1-5 할로알킬), -(C0-3 알킬렌)-O-(C1-5 할로알킬), -(C0-3 알킬렌)-CF3, -(C0-3 알킬렌)-CN, -(C0-3 알킬렌)-NO2, -(C0-3 알킬렌)-CHO, -(C0-3 알킬렌)-CO-(C1-5 알킬), -(C0-3 알킬렌)-COOH, -(C0-3 알킬렌)-CO-O-(C1-5 알킬), -(C0-3 알킬렌)-O-CO-(C1-5 알킬), -(C0-3 알킬렌)-CO-NH2, -(C0-3 알킬렌)-CO-NH(C1-5 알킬), -(C0-3 알킬렌)-CO-N(C1-5 알킬)(C1-5 알킬), -(C0-3 알킬렌)-NH-CO-(C1-5 알킬), -(C0-3 알킬렌)-N(C1-5 알킬)-CO-(C1-5 알킬), -(C0-3 알킬렌)-SO2-NH2, -(C0-3 알킬렌)-SO2-NH(C1-5 알킬), -(C0-3 알킬렌)-SO2-N(C1-5 알킬)(C1-5 알킬), -(C0-3 알킬렌)-NH-SO2-(C1-5 알킬), -(C0-3 알킬렌)-N(C1-5 알킬)-SO2-(C1-5 알킬), -(C0-3 알킬렌)-SO-(C1-5 알킬), -(C0-3 알킬렌)-SO2-(C1-5 알킬), -(C0-3 알킬렌)-카르보시클릴, 및 -(C0-3 알킬렌)-헤테로시클릴로부터 선택되며, 상기 -(C0-3 알킬렌)-카르보시클릴의 카르보시클릴 모이어티 및 상기 -(C0-3 알킬렌)-헤테로시클릴의 헤테로시클릴 모이어티는 각각 임의로 C1-5 알킬, C2-5 알케닐, C2-5 알키닐, -OH, -O(C1-5 알킬), -O(C1-5 알킬렌)-OH, -O(C1-5 알킬렌)-O(C1-5 알킬), -SH, -S(C1-5 알킬), -NH2, -NH(C1-5 알킬), -N(C1-5 알킬)(C1-5 알킬), 할로겐, C1-5 할로알킬, -O-(C1-5 할로알킬), -CF3, -CN, -NO2, -CHO, -CO-(C1-5 알킬), -COOH, -CO-O-(C1-5 알킬), -O-CO-(C1-5 알킬), -CO-NH2, -CO-NH(C1-5 알킬), -CO-N(C1-5 알킬)(C1-5 알킬), -NH-CO-(C1-5 알킬), -N(C1-5 알킬)-CO-(C1-5 알킬), -SO2-NH2, -SO2-NH(C1-5 알킬), -SO2-N(C1-5 알킬)(C1-5 알킬), -NH-SO2-(C1-5 알킬), -N(C1-5 알킬)-SO2-(C1-5 알킬), -SO-(C1-5 알킬), -SO2-(C1-5 알킬), 시클로알킬, 및 헤테로시클로알킬로부터 독립적으로 선택되는 하나 이상의 기로 치환되고;각각의 R12 은 독립적으로 -OH, -O(C1-5 알킬), -O(C1-5 알킬렌)-OH, -O(C1-5 알킬렌)-O(C1-5 알킬), -SH, -S(C1-5 알킬), -NH2, -NH(C1-5 알킬), -N(C1-5 알킬)(C1-5 알킬), 할로겐, C1-5 할로알킬, -O-(C1-5 할로알킬), -CF3, -CN, -NO2, -CHO, -CO-(C1-5 알킬), -COOH, -CO-O-(C1-5 알킬), -O-CO-(C1-5 알킬), -CO-NH2, -CO-NH(C1-5 알킬), -CO-N(C1-5 알킬)(C1-5 알킬), -NH-CO-(C1-5 알킬), -N(C1-5 알킬)-CO-(C1-5 알킬), -SO2-NH2, -SO2-NH(C1-5 알킬), -SO2-N(C1-5 알킬)(C1-5 알킬), -NH-SO2-(C1-5 알킬), -N(C1-5 알킬)-SO2-(C1-5 알킬), -SO-(C1-5 알킬), -SO2-(C1-5 알킬), 시클로알킬, 및 헤테로시클로알킬로부터 선택되고;각각의 R13 은 독립적으로 C1-5 알킬, C2-5 알케닐, C2-5 알키닐, -(C0-3 알킬렌)-OH, -(C0-3 알킬렌)-O(C1-5 알킬), -(C0-3 알킬렌)-O(C1-5 알킬렌)-OH, -(C0-3 알킬렌)-O(C1-5 알킬렌)-O(C1-5 알킬), -(C0-3 알킬렌)-SH, -(C0-3 알킬렌)-S(C1-5 알킬), -(C0-3 알킬렌)-NH2, -(C0-3 알킬렌)-NH(C1-5 알킬), -(C0-3 알킬렌)-N(C1-5 알킬)(C1-5 알킬), -(C0-3 알킬렌)-할로겐, -(C0-3 알킬렌)-(C1-5 할로알킬), -(C0-3 알킬렌)-O-(C1-5 할로알킬), -(C0-3 알킬렌)-CF3, -(C0-3 알킬렌)-CN, -(C0-3 알킬렌)-NO2, -(C0-3 알킬렌)-CHO, -(C0-3 알킬렌)-CO-(C1-5 알킬), -(C0-3 알킬렌)-COOH, -(C0-3 알킬렌)-CO-O-(C1-5 알킬), -(C0-3 알킬렌)-O-CO-(C1-5 알킬), -(C0-3 알킬렌)-CO-NH2, -(C0-3 알킬렌)-CO-NH(C1-5 알킬), -(C0-3 알킬렌)-CO-N(C1-5 알킬)(C1-5 알킬), -(C0-3 알킬렌)-NH-CO-(C1-5 알킬), -(C0-3 알킬렌)-N(C1-5 알킬)-CO-(C1-5 알킬), -(C0-3 알킬렌)-SO2-NH2, -(C0-3 알킬렌)-SO2-NH(C1-5 알킬), -(C0-3 알킬렌)-SO2-N(C1-5 알킬)(C1-5 알킬), -(C0-3 알킬렌)-NH-SO2-(C1-5 알킬), -(C0-3 알킬렌)-N(C1-5 알킬)-SO2-(C1-5 알킬), -(C0-3 알킬렌)-SO-(C1-5 알킬), -(C0-3 알킬렌)-SO2-(C1-5 알킬), -(C0-3 알킬렌)-시클로알킬, 및 -(C0-3 알킬렌)-헤테로시클로알킬로부터 선택되고;R2 및 R4 은 각각 독립적으로 수소, C1-5 알킬, C2-5 알케닐, C2-5 알키닐, -(C0-3 알킬렌)-OH, -(C0-3 알킬렌)-O(C1-5 알킬), -(C0-3 알킬렌)-O(C1-5 알킬렌)-OH, -(C0-3 알킬렌)-O(C1-5 알킬렌)-O(C1-5 알킬), -(C0-3 알킬렌)-SH, -(C0-3 알킬렌)-S(C1-5 알킬), -(C0-3 알킬렌)-NH2, -(C0-3 알킬렌)-NH(C1-5 알킬), -(C0-3 알킬렌)-N(C1-5 알킬)(C1-5 알킬), -(C0-3 알킬렌)-할로겐, -(C0-3 알킬렌)-(C1-5 할로알킬), -(C0-3 알킬렌)-O-(C1-5 할로알킬), -(C0-3 알킬렌)-CF3, -(C0-3 알킬렌)-CN, -(C0-3 알킬렌)-NO2, -(C0-3 알킬렌)-CHO, -(C0-3 알킬렌)-CO-(C1-5 알킬), -(C0-3 알킬렌)-COOH, -(C0-3 알킬렌)-CO-O-(C1-5 알킬), -(C0-3 알킬렌)-O-CO-(C1-5 알킬), -(C0-3 알킬렌)-CO-NH2, -(C0-3 알킬렌)-CO-NH(C1-5 알킬), -(C0-3 알킬렌)-CO-N(C1-5 알킬)(C1-5 알킬), -(C0-3 알킬렌)-NH-CO-(C1-5 알킬), -(C0-3 알킬렌)-N(C1-5 알킬)-CO-(C1-5 알킬), -(C0-3 알킬렌)-SO2-NH2, -(C0-3 알킬렌)-SO2-NH(C1-5 알킬), -(C0-3 알킬렌)-SO2-N(C1-5 알킬)(C1-5 알킬), -(C0-3 알킬렌)-NH-SO2-(C1-5 알킬), -(C0-3 알킬렌)-N(C1-5 알킬)-SO2-(C1-5 알킬), -(C0-3 알킬렌)-SO-(C1-5 알킬), -(C0-3 알킬렌)-SO2-(C1-5 알킬), -(C0-3 알킬렌)-카르보시클릴, 및 -(C0-3 알킬렌)-헤테로시클릴로부터 선택되며, 상기 -(C0-3 알킬렌)-카르보시클릴의 카르보시클릴 모이어티 및 상기 -(C0-3 알킬렌)-헤테로시클릴의 헤테로시클릴 모이어티는 각각 임의로 C1-5 알킬, C2-5 알케닐, C2-5 알키닐, -OH, -O(C1-5 알킬), -O(C1-5 알킬렌)-OH, -O(C1-5 알킬렌)-O(C1-5 알킬), -SH, -S(C1-5 알킬), -NH2, -NH(C1-5 알킬), -N(C1-5 알킬)(C1-5 알킬), 할로겐, C1-5 할로알킬, -O-(C1-5 할로알킬), -CF3, -CN, -NO2, -CHO, -CO-(C1-5 알킬), -COOH, -CO-O-(C1-5 알킬), -O-CO-(C1-5 알킬), -CO-NH2, -CO-NH(C1-5 알킬), -CO-N(C1-5 알킬)(C1-5 알킬), -NH-CO-(C1-5 알킬), -N(C1-5 알킬)-CO-(C1-5 알킬), -SO2-NH2, -SO2-NH(C1-5 알킬), -SO2-N(C1-5 알킬)(C1-5 알킬), -NH-SO2-(C1-5 알킬), -N(C1-5 알킬)-SO2-(C1-5 알킬), -SO-(C1-5 알킬), -SO2-(C1-5 알킬), 시클로알킬, 및 헤테로시클로알킬로부터 독립적으로 선택되는 하나 이상의 기로 치환되고;R3 은 수소, C1-5 알킬, C2-5 알케닐, C2-5 알키닐, -(C1-5 알킬렌)-OH, -(C1-5 알킬렌)-O(C1-5 알킬), -(C1-5 알킬렌)-O(C1-5 알킬렌)-OH, -(C1-5 알킬렌)-O(C1-5 알킬렌)-O(C1-5 알킬), -(C1-5 알킬렌)-SH, -(C1-5 알킬렌)-S(C1-5 알킬), -(C1-5 알킬렌)-NH2, -(C...