Pyrazolone derivatives as nitroxyl donorsThe disclosed subject matter provides pyrazolone derivative compounds, pharmaceutical compositions comprising such compounds, kits comprising such compounds, and methods of using such compounds or pharmaceutical compositions. In particular, the disclosed subject matter provides methods of using such compounds or pharmaceutical compositions for treating heart failure.Formula 1. (Ia) compound or pharmaceutically acceptable salt thereofWherein：R1For phenyl, wherein the phenyl is unsubstituted or substitution has 1,2,3,4 or 5 to be independently selected from substituent group below：Halogen Element, (C1-C6) alkyl, halogenated (C1-C4) alkyl, perhalogeno (C1-C4) alkyl, (C1-C6) alkoxy, halogenated (C1-C4) alcoxyl Base, perhalogeno (C1-C4) alkoxy ,-C (=O) OH ,-C (=O) O (C1-C6) alkyl ,-C (=O) NR4R5,-C (=O)-(5-, 6- or 7- members) Heterocyclylalkyl, (5-, 6- or 7- member) Heterocyclylalkyl, (C1-C6) alkyl sulfenyl, halogenated (C1-C4) alkyl sulfenyl, complete Halogenated (C1-C4) alkyl sulfenyl, (C1-C6) alkyl sulphinyl, (C1-C6) alkyl sulphonyl, (C3-C6) naphthene sulfamide base, halogen Generation (C1-C4) alkyl sulphinyl, halogenated (C1-C4) alkyl sulphonyl, perhalogeno (C1-C4) alkyl sulphinyl, perhalogeno (C1-C4) alkyl sulphonyl ,-S (O)2-NH2、-S(O)2-NR6R7、-S(O)2Phenyl ,-S (O)2(5-, 6- or 7- member) heterocycle alkane Base ,-S (=O) (=NR8)(C1-C6) alkyl ,-NR4R5、N-(C1-C6) bis- (C of alkyl amino sulfonyl and N, N-1-C6) alkyl ammonia Base sulfonyl；R4、R5、R6And R7Respectively stand alone as H or (C1-C6) alkyl；R8For H ,-(C=O) (C1-C6) alkyl or-(C=O) perhalogeno (C1-C4) alkyl；R2For (C1-C6) alkyl；R3For-C (=NOR9)R10, wherein R9For (C1-C6) alkyl, and R10For phenyl；AndR is hydrogen ,-COH ,-CO- (C1-C6) alkyl ,-CO- (C2-C4) alkenyl ,-CO- phenyl ,-CO- benzyls ,-CO- cyclopenta ,- CO- cyclohexyl ,-CO- (5-, 6- or 7- member) Heterocyclylalkyl ,-CO- benzyls oxygroup ,-CO-O- (C1-C6) alkyl ,-CO-NH2、- CO-NH-(C1-C4) alkyl or-CO-N ((C1-C4) alkyl)2, wherein described-(C1-C6) alkyl ,-(C2-C4) alkenyl, phenyl, benzyl Base, cyclopenta, cyclohexyl ,-(5-, 6- or 7- member) Heterocyclylalkyl, benzyl oxygroup ,-O- (C1-C6) alkyl ,-NH- (C1-C4) alkane Base or-N ((C1-C4) alkyl)2Can be unsubstituted or substitution has 1,2 or 3 substituent group selected from the following：Halogen ,-(C1-C6) Alkyl ,-(C2-C4) alkenyl ,-(C2-C3) alkynyl ,-(5- or 6- member) heteroaryl ,-O- (C1-C6) alkyl ,-S- (C1-C6) alkyl ,- C (halogen)3,-CH (halogen)2、-CH2(halogen) ,-CN ,-NO2、-NH2、-NH-(C1-C4) alkyl ,-N (- (C1-C4) alkyl)2、- C(O)(C1-C4) alkyl ,-C (O) O (C1-C4) alkyl ,-OC (O) (C1-C4) alkyl ,-OC (O) NH2、-S(O)(C1-C4) alkyl ,- S(O)2(C1-C4) alkyl or 5- methyl-2- oxo-2H-1,3- Dioxol-4 -yl methyl.
니트록실 공여자로서의 피라졸론 유도체개시된 대상은 피라졸론 유도체 화합물, 이러한 화합물을 포함하는 제약 조성물, 이러한 화합물을 포함하는 키트, 및 이러한 화합물 또는 제약 조성물을 사용하는 방법을 제공한다. 특히, 개시된 대상은 심부전을 치료하기 위해 이러한 화합물 또는 제약 조성물을 사용하는 방법을 제공한다.화학식 (Ia)의 화합물 또는 그의 제약상 허용되는 염.[이미지]여기서:R1은 페닐이며, 여기서 상기 페닐은 비치환되거나 또는 할로, (C1-C6)알킬, (C1-C4)할로알킬, (C1-C4)퍼할로알킬, (C1-C6)알콕시, (C1-C4)할로알콕시, (C1-C4)퍼할로알콕시, -C(=O)OH, -C(=O)O(C1-C6)알킬, -C(=O)NR4R5, -C(=O)-(5-, 6-, 또는 7-원)헤테로시클로알킬, (5-, 6-, 또는 7-원)헤테로시클로알킬, (C1-C6)알킬술파닐, (C1-C4)할로알킬술파닐, (C1-C4)퍼할로알킬술파닐, (C1-C6)알킬술피닐, (C1-C6)알킬술포닐, (C3-C6)시클로알킬술포닐, (C1-C4)할로알킬술피닐, (C1-C4)할로알킬술포닐, (C1-C4)퍼할로알킬술피닐, (C1-C4)퍼할로알킬술포닐, -S(O)2-NH2, -S(O)2-NR6R7, -S(O)2-페닐, -S(O)2-(5-, 6-, 또는 7-원)헤테로시클로알킬, -S(=O)(=NR8)(C1-C6)알킬, -NR4R5, N-(C1-C6)알킬아미노술포닐 및 N,N-디(C1-C6)알킬아미노술포닐로부터 독립적으로 선택되는 1, 2, 3, 4 또는 5개의 치환기(들)로 치환되고;R4, R5, R6 및 R7은 각각 독립적으로 H 또는 (C1-C6)알킬이고;R8은 H, -(C=O)(C1-C6)알킬 또는 -(C=O)(C1-C4)퍼할로알킬이고;R2는 (C1-C6)알킬이고;R3은 -C(=NOR9)R10이며, 여기서 R9는 (C1-C6)알킬이고 R10은 페닐이고;R은 수소, -COH, -CO-(C1-C6)알킬, -CO-(C2-C4)알케닐, -CO-페닐, -CO-벤질, -CO-시클로펜틸, -CO-시클로헥실, -CO-(5-, 6-, 또는 7-원)헤테로시클로알킬, -CO-벤질옥시, -CO-O-(C1-C6)알킬, -CO-NH2, -CO-NH-(C1-C4)알킬 또는 -CO-N((C1-C4)알킬)2이며, 여기서 상기 -(C1-C6)알킬, -(C2-C4)알케닐, 페닐, 벤질, 시클로펜틸, 시클로헥실, -(5-, 6-, 또는 7-원)헤테로시클로알킬, 벤질옥시, -O-(C1-C6)알킬, -NH-(C1-C4)알킬 또는 -N((C1-C4)알킬)2는 비치환되거나 또는 할로, -(C1-C6)알킬, -(C2-C4)알케닐, -(C2-C3)알키닐, -(5- 또는 6-원)헤테로아릴, -O-(C1-C6)알킬, -S-(C1-C6)알킬, -C(할로)3, -CH(할로)2, -CH2(할로), -CN, -NO2, -NH2, -NH-(C1-C4)알킬, -N(-(C1-C4)알킬)2, -C(O)(C1-C4)알킬, -C(O)O(C1-C4)알킬, -OC(O)(C1-C4)알킬, -OC(O)NH2, -S(O)(C1-C4)알킬, -S(O)2(C1-C4)알킬 또는 5-메틸-2-옥소-2H-1,3-디옥솔-4-일메틸로부터 선택되는 1, 2 또는 3개의 치환기로 치환될 수 있다.