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 prodrug thereof, as well as pharmaceutical compositions comprising such compounds. The 5-azaindazole derivatives according to the invention have been found to be highly effective dual A2A/A2B adenosine receptor antagonists, and can thus be used as therapeutic agents, particularly in the treatment or prevention of hyperproliferative or infectious diseases or disorders.A compound of formula (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 r12and further wherein said carbocyclyl and said heterocyclyl are each optionally substituted with one or more groups 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 radical)-cooh, -(c0-3alkylene) -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) -nh-co-o- (c)1-5alkyl), - (c)0-3alkylene) -n (c)1-5alkyl) -co-o- (c)1-5alkyl), - (c)0-3alkylene) -o-co-nh- (c)1-5alkyl), - (c)0-3alkylene) -o-co-n (c)1-5alkyl group) - (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-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) -carbocyclyl, 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), -cf 3, -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), -nh-co-o- (c)1-5alkyl group), -n (c)1-5alkyl) -co-o- (c)1-5alkyl group), -o-co-nh- (c)1-5alkyl group), -o-co-n (c)1-5alkyl group) - (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), -nh-co-o- (c)1-5alkyl group), -n (c)1-5alkyl) -co-o- (c)1-5alkyl group), -o-co-nh- (c)1-5alkyl group), -o-co-n (c)1-5alkyl group) - (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) -nh-co-o- (c)1-5...
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)-NH-CO-O-(C1-5 알킬), -(C0-3 알킬렌)-N(C1-5 알킬)-CO-O-(C1-5 알킬), -(C0-3 알킬렌)-O-CO-NH-(C1-5 알킬), -(C0-3 알킬렌)-O-CO-N(C1-5 알킬)-(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), -NH-CO-O-(C1-5 알킬), -N(C1-5 알킬)-CO-O-(C1-5 알킬), -O-CO-NH-(C1-5 알킬), -O-CO-N(C1-5 알킬)-(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), -NH-CO-O-(C1-5 알킬), -N(C1-5 알킬)-CO-O-(C1-5 알킬), -O-CO-NH-(C1-5 알킬), -O-CO-N(C1-5 알킬)-(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)-NH-CO-O-(C1-5 알킬), -(C0-3 알킬렌)-N(C1-5 알킬)-CO-O-(C1-5 알킬), -(C0-3 알킬렌)-O-CO-NH-(C1-5 알킬), -(C0-3 알킬렌)-O-CO-N(C1-5 알킬)-(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)-NH-CO-O-(C1-5 알킬), -(C0-3 알킬렌)-N(C1-5 알킬)-CO-O-(C1-5 알킬), -(C0-3 알킬렌)-O-CO-NH-(C1-5 알킬), -(C0-3 알킬렌)-O-CO-N(C1-5 알킬)-(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 알...