5-oxo-isoxazoles as inhibitors of lipases and phospholipasesThe present invention relates to 5-oxo-isoxazole derivatives of the general formula (I) with the meanings disclosed in the description, the pharmaceutically applicable salts thereof, and the use thereof as drugs.The tautomeric form of the compound of formula i, this compound and physiology thereof the salt that can tolerateimplication wherein is:r1 is (c 5-c 16)-alkyl, y-aryl, y-heteroaryl, wherein aryl or heteroaryl can be replaced one or many: f, cl, br, i, oh, cf by following group 3, no 2, cn, ocf 3, o-(c 1-c 6)-alkyl, o-(c 1-c 4)-alkoxyl group-(c 1-c 4)-alkyl, s-(c 1-c 6)-alkyl, (c 1-c 6)-alkyl, (c 2-c 4)-haloalkyl, o-(c 2-c 4)-haloalkyl, (c 2-c 6)-alkenyl, (c 3-c 8)-cycloalkyl, o-(c 3-c 8)-cycloalkyl, (c 2-c 6)-alkynyl, (c 0-c 8)-alkylidene group-aryl, o-(c 0-c 8)-alkylidene group-aryl, s-aryl, (c 0-c 8)-alkylidene group-heteroaryl, n (r4) (r5), so 2-ch 3, so 2-nh 2, sf 5, cooh, coo-(c 1-c 6)-alkyl, con (r6) (r7), n (r8) co (r9), n (r10) so 2(r11), co (r12), (cr13r14) x-o (r15), o-co-n (r16) (r17), o-co-(c 1-c 6)-alkylidene group-co-o-(c 1-c 6)-alkyl, o-co-(c 1-c 6)-alkylidene group-co-oh, o-co-(c 1-c 6)-alkylidene group-co-n (r18) (r19), aryl wherein or heteroaryl can be replaced one or many by following group again: f, cl, br, i, oh, cf 3, no 2, cn, ocf 3, o-(c 1-c 6)-alkyl, o-(c 1-c 4)-alkoxyl group-(c 1-c 4)-alkyl, s-(c 1-c 6)-alkyl, (c 1-c 6)-alkyl, (c 2-c 4)-haloalkyl, (c 2-c 6)-alkenyl, (c 3-c 8)-cycloalkyl, o-(c 3-c 8)-cycloalkyl, (c 2-c 6)-alkynyl, n (r4a) (r5a), so 2-ch 3, sf 5, cooh, coo-(c 1-c 6)-alkyl, con (r6a) (r7a), n (r8a) co (r9a), n (r10a) so 2(r11a), co (r12a), (cr13ar14a) x '-o (r15a), o-co-n (r16a) (r17a), o-co-(c 1-c 6)-alkylidene group-co-o-(c 1-c 6)-alkyl, o-co-(c 1-c 6)-alkylidene group-co-oh, o-co-(c 1-c 6)-alkylidene group-co-n (r18a) (r19a); x, x ' are 0,1,2,3,4,5,6;r4, r5, r6, r7, r9, r10, r11, r12, r13, r14, r15, r16, r17, r18, r19, r4a, r5a, r6a, r7a, r9a, r10a, r11a, r12a, r13a, r14a, r15a, r16a, r17a, r18a, r19a are hydrogen, (c independently of one another 1-c 8)-alkyl; or the group of formula iawherein w is-c (r26) (r27)-,-c (r26) (r27)-c (r28) (r29)-,-c (r26) (r27)-o-; r20, r21, r22, r23, r24, r25, r26, r27, r28, r29 are identical or different, are hydrogen, f, cl, br, i, oh, cf 3, no 2, cn, ocf 3, sf 5, o-(c 1-c 6)-alkyl, o-(c 1-c 4)-alkoxyl group-(c 1-c 4)-alkyl, s-(c 1-c 6)-alkyl, (c 1-c 6)-alkyl, (c 2-c 4)-haloalkyl, o-(c 2-c 4)-haloalkyl, (c 2-c 6)-alkenyl, (c 3-c 8)-cycloalkyl, o-(c 3-c 8)-cycloalkyl, (c 3-c 8)-cycloalkenyl group, (c 2-c 6)-alkynyl, n (r30) (r31), so 2-ch 3, cooh, coo-(c 1-c 6)-alkyl, con (r32) (r33), n (r34) co (r35), n (r36) so 2(r37), co (r38), (cr39r40) x '-o (r41), o-co-n (r42) (r43), o-co-(c 1-c 6)-alkylidene group-co-o-(c 1-c 6)-alkyl, o-co-(c 1-c 6)-alkylidene group-co-oh, o-co-(c 1-c 6)-alkylidene group-co-n (r44) (r45); x ' is 0,1,2,3,4,5,6;r30、r31、r32、r33、r34、r35、r36、r37、r38、r39、r40、r41、r42、r43、r44、r45identical or different, be hydrogen, (c 1-c 6)-alkyl; perhapsr20 and r26 or r21 and r27 with the carbon atom that carries them form monocyclic, 5 or 6 yuan saturated, part is undersaturated or aromatic ring system, the single member of described ring system can by-chr46-,-cr46r47-,=(c-r46)-replace;perhapsr22 and r24 or r23 and r25 with the carbon atom that carries them form monocyclic, 5 or 6 yuan saturated, part is undersaturated or aromatic ring system, the single member of described ring system can by-chr46-,-cr46r47-,=(c-r46)-replace;r46, r47 are identical or different, are f, cl, br, i, oh, cf 3, no 2, cn, ocf 3, sf 5, o-(c 1-c 6)-alkyl, o-(c 1-c 4)-alkoxyl group-(c 1-c 4)-alkyl, s-(c 1-c 6)-alkyl, (c 1-c 6)-alkyl, (c 2-c 4)-haloalkyl, o-(c 2-c 4)-haloalkyl, (c 2-c 6)-alkenyl, (c 3-c 8)-cycloalkyl, o-(c 3-c 8)-cycloalkyl, (c 2-c 6)-alkynyl, n (r48) (r49), so 2-ch 3, cooh, coo-(c 1-c 6)-alkyl, con (r50) (r51), n (r52) co (r53), n (r54) so 2(r55), co (r56), (cr57r58) x ' '-o (r59), o-co-n (r60) (r61), o-co-(c 1-c 6)-alkylidene group-co-o-(c 1-c 6)-alkyl, o-co-(c 1-c 6)-alkylidene group-co-oh, o-co-(c 1-c 6)-alkylidene group-co-n (r62) (r63); x′″0、1、2、3、4、5、6；r48、r49、r50、r51、r52、r53、r54、r55、r56、r57、r58、r59、r60、r61、r62、r63identical or different, be hydrogen, (c 1-c 6)-alkyl; y, z are identical or different, are (c 1-c 2)-alkylidene group, it can be by f, cl, ch 3or oh replaces; r2 is hydrogen, (c 1-c 12)-alkyl, z-aryl, wherein aryl or heteroaryl can randomly be substituted, (c 3-c 12)-cycloalkyl; r3 is (c 1-c 12)-alkyl, aryl, heteroaryl, wherein aryl or heteroaryl can randomly be substituted, (c 3-c 12)-cycloalkyl; perhaps r2 and r3 form ring system monocyclic, saturated or the undersaturated 4-to 8-of part unit with the carbon atom that carries them, the single member of described ring system can by one to three be selected from-chr64-,-cr64r65-,=(c-r66)-,-nr67-,-c (=o)-,-atom or the group of o-replace, condition be selected from-two unit of o-cannot be adjacent;r64, r65, r66, r67 are identical or different, are hydrogen, f, cl, br, i, oh, cf 3, no 2, cn, ocf 3, sf 5, o-(c 1-c 6)-alkyl, o-(c 1-c 4)-alkoxyl group-(c 1-c 4)-alkyl, s-(c 1-c 6)-alkyl, (c 1-c 6)-alkyl, (c 2-c 4)-haloalkyl, o-(c 2-c 4)-haloalkyl, (c 2-c 6)-alkenyl, (c 3-c 8)-c...
리파제 및 포스포리파제의 억제제로서의 5-옥소-이속사졸본 발명은 본 명세서에 기재된 의미를 갖는 화학식 I의 5-옥소-이속사졸 유도체, 약제학적으로 사용가능한 이의 염 및 약물로서의 이의 용도에 관한 것이다. 화학식 I  화학식 I의 화합물, 당해 화합물의 토오토머 형태 또는 생리학적으로 허용되는 이의 염. 화학식 I [이미지] 위의 화학식 I에서, R1은 (C5-C16)-알킬, Y-아릴 또는 Y-헤테로아릴이고, 여기서 상기 아릴 또는 헤테로아릴은 F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, O-(C1-C6)-알킬, O-(C1-C4)-알콕시-(C1-C4)-알킬, S-(C1-C6)-알킬, (C1-C6)-알킬, (C2-C4)-할로알킬, O-(C2-C4)-할로알킬, (C2-C6)-알케닐, (C3-C8)-사이클로알킬, O-(C3-C8)-사이클로알킬, (C2-C6)-알키닐, (C0-C8)-알킬렌-아릴, O-(C0-C8)-알킬렌-아릴, S-아릴, (C0-C8)-알킬렌-헤테로아릴, N(R4)(R5), SO2-CH3, SO2-NH2, SF5, COOH, COO-(C1-C6)-알킬, CON(R6)(R7), N(R8)CO(R9), N(R10)SO2(R11), CO(R12), (CR13R14)x-O(R15), O-CO-N(R16)(R17), O-CO-(C1-C6)-알킬렌-CO-O-(C1-C6)-알킬, O-CO-(C1-C6)-알킬렌-CO-OH 또는 O-CO-(C1-C6)-알킬렌-CO-N(R18)(R19)로 1회 이상 치환될 수 있고, 여기서 상기 아릴 또는 헤테로아릴은 다시 F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, O-(C1-C6)-알킬, O-(C1-C4)-알콕시-(C1-C4)-알킬, S-(C1-C6)-알킬, (C1-C6)-알킬, (C2-C4)-할로알킬, (C2-C6)-알케닐, (C3-C8)-사이클로알킬, O-(C3-C8)-사이클로알킬, (C2-C6)-알키닐, N(R4a)(R5a), SO2-CH3, SF5, COOH, COO-(C1-C6)-알킬, CON(R6a)(R7a), N(R8a)CO(R9a), N(R10a)SO2(R11a), CO(R12a), (CR13aR14a)x'-O(R15a), O-CO-N(R16a)(R17a), O-CO-(C1-C6)-알킬렌-CO-O-(C1-C6)-알킬, O-CO-(C1-C6)-알킬렌-CO-OH 또는 O-CO-(C1-C6)-알킬렌-CO-N(R18a)(R19a)로 1회 이상 치환될 수 있고; x 및 x'는 0, 1, 2, 3, 4, 5 또는 6이고; R4, R5, R6, R7, R9, R10, R11, R12, R13, R14, R15, R16, R17, R18, R19, R4a, R5a, R6a, R7a, R9a, R10a, R11a, R12a, R13a, R14a, R15a, R16a, R17a, R18a 및 R19a는 서로 독립적으로 수소 또는 (C1-C8)-알킬이거나; R1은 화학식 Ia의 라디칼이고; 화학식 Ia [이미지] 위의 화학식 Ia에서, W는 -C(R26)(R27)-, -C(R26)(R27)-C(R28)(R29)- 또는 -C(R26)(R27)-O-이고; R20, R21, R22, R23, R24, R25, R26, R27, R28 및 R29는 동일하거나 상이하게 수소, F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, SF5, O-(C1-C6)-알킬, O-(C1-C4)-알콕시-(C1-C4)-알킬, S-(C1-C6)-알킬, (C1-C6)-알킬, (C2-C4)-할로알킬, O-(C2-C4)-할로알킬, (C2-C6)-알케닐, (C3-C8)-사이클로알킬, O-(C3-C8)-사이클로알킬, (C3-C8)-사이클로알케닐, (C2-C6)-알키닐, N(R30)(R31), SO2-CH3, COOH, COO-(C1-C6)-알킬, CON(R32)(R33), N(R34)CO(R35), N(R36)SO2(R37), CO(R38), (CR39R40)x"-O(R41), O-CO-N(R42)(R43), O-CO-(C1-C6)-알킬렌-CO-O-(C1-C6)-알킬, O-CO-(C1-C6)-알킬렌-CO-OH 또는 O-CO-(C1-C6)-알킬렌-CO-N(R44)(R45)이고; x"는 0, 1, 2, 3, 4, 5 또는 6이고; R30, R31, R32, R33, R34, R35, R36, R37, R38, R39, R40, R41, R42, R43, R44 및 R45는 동일하거나 상이하게 수소 또는 (C1-C6)-알킬이거나; R20과 R26, 또는 R21과 R27은 이들을 함유하는 탄소 원자와 함께 5 또는 6원의 모노사이클릭 포화, 부분 불포화 또는 방향족 환 시스템을 형성하고, 상기 환 시스템의 개별적인 구성원은 -CHR46-, -CR46R47- 또는 =(C-R46)-에 의해 대체될 수 있거나; R22와 R24, 또는 R23과 R25는 이들을 함유하는 탄소 원자와 함께 5 또는 6원의 모노사이클릭 포화, 부분 불포화 또는 방향족 환 시스템을 형성하고, 상기 환 시스템의 개별적인 구성원은 -CHR46-, -CR46R47- 또는 =(C-R46)-에 의해 대체될 수 있고; R46 및 R47은 동일하거나 상이하게 F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, SF5, O-(C1-C6)-알킬, O-(C1-C4)-알콕시-(C1-C4)-알킬, S-(C1-C6)-알킬, (C1-C6)-알킬, (C2-C4)-할로알킬, O-(C2-C4)-할로알킬, (C2-C6)-알케닐, (C3-C8)-사이클로알킬, O-(C3-C8)-사이클로알킬, (C2-C6)-알키닐, N(R48)(R49), SO2-CH3, COOH, COO-(C1-C6)-알킬, CON(R50)(R51), N(R52)CO(R53), N(R54)SO2(R55), CO(R56), (CR57R58)x"'-O(R59), O-CO-N(R60)(R61), O-CO-(C1-C6)-알킬렌-CO-O-(C1-C6)-알킬, O-CO-(C1-C6)-알킬렌-CO-OH 또는 O-CO-(C1-C6)-알킬렌-CO-N(R62)(R63)이고; x"'는 0, 1, 2, 3, 4, 5 또는 6이고; R48, R49, R50, R51, R52, R53, R54, R55, R56, R57, R58, R59, R60, R61, R62 및 R63은 동일하거나 상이하게 수소 또는 (C1-C6)-알킬이고; Y 및 Z는 동일하거나 상이하게 (C1-C2)-알킬렌이고, 이는 F, Cl, CH3 또는 OH로 1회 치환될 수 있고; R2는 수소, (C1-C12)-알킬, Z-아릴(여기서, 아릴은 임의로 치환될 수 있다) 또는 (C3-C12)-사이클로알킬이고; R3은 (C1-C12)-알킬, 아릴, 헤테로아릴(여기서, 아릴 또는 헤테로아릴은 임의로 치환될 수 있다) 또는 (C3-C12)-사이클로알킬이거나; R2와 R3은 이들을 함유하는 탄소 원자와 함께 4 내지 8원의 모노사이클릭 포화 또는 부분 불포화 환 시스템을 형성하고, 상기 환 시스템의 개별적인 구성원은 일련의 -CHR64-, -CR64R65-, =(C-R66)-, -NR67-, -C(=O)- 및 -O-로부터의 1 내지 3개의 원자 또는 원자 그룹에 의해 대체될 수 있고, 단 일련의 -O-로부터의 2개의 단위는 인접할 수 없으며; R64, R65, R66 및 R67은 동일하거나 상이하게 수소, F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, SF5, O-(C1-C6)-알킬, O-(C1-C4)-알콕시-(C1-C4)-알킬, S-(C1-C6)-알킬, (C1-C6)-알킬, (C2-C4)-할로알킬, O-(C2-C4)-할로알킬, (C2-C6)-알케닐, (C3-C8)-사이클로알킬, O-(C3-C8)-사이클로알킬, (C3-C8)-사이클로알케닐, (C2-C6)-알키닐, N(R68)(R69), SO2-CH3, COOH, COO-(C1-C6)-알킬, CON(R70)(R71), N(R72)CO(R73), N(R74)SO2(R75), CO(R76), (CR77R78)x""-O(R79), O-CO-N(R80)(R81), O-CO-(C1-C6)-알킬렌-CO-O-(C1-C6)-알킬, O-CO-(C1-C6)-알킬렌-CO-OH 또는 O-CO-(C1-C6)-알킬렌-CO-N(R82)(R83)이고; x""는 0, 1, 2, 3, 4, 5 또는 6이고; R68, R69, R70, R71, R72, R73, R74, R75, R76, R77, R78, R79, R80, R81, R82 및 R83은 동일하거나 상이하게 수소 또는 (C1-C6)-알킬이고; 단, R1이 사이클로헥실이고, R2가 H이고, R3이 페닐인 화합물은 제외된다. 