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首页> 外国专利> GUANIDINE DERIVATIVES, PROCESS FOR PREPARING THE SAME, PHARMACEUTICAL COMPOSITION FOR INHIBITING PROTEOLYSIS IN A MAMMAL, METHOD OF TREATING, METHOD OF INHIBITING: PROTEOLYSIS IN A MAMMAL, THROMBIN-INDUCED PLATELET AGGREGATION AND CLOTTING OF FIBRINOGEN IN PLASMA, THROMBIN IN BLOOD, FORMATION OF BLOOD PLATELET AGGREGATES IN BLOOD, THROMBUS FORMATION, A DEVICE USED IN BLOOD COLLECTION, BLOOD CIRCULATION AND BLOOD STORAGE

GUANIDINE DERIVATIVES, PROCESS FOR PREPARING THE SAME, PHARMACEUTICAL COMPOSITION FOR INHIBITING PROTEOLYSIS IN A MAMMAL, METHOD OF TREATING, METHOD OF INHIBITING: PROTEOLYSIS IN A MAMMAL, THROMBIN-INDUCED PLATELET AGGREGATION AND CLOTTING OF FIBRINOGEN IN PLASMA, THROMBIN IN BLOOD, FORMATION OF BLOOD PLATELET AGGREGATES IN BLOOD, THROMBUS FORMATION, A DEVICE USED IN BLOOD COLLECTION, BLOOD CIRCULATION AND BLOOD STORAGE

机译：胍基衍生物，制备相同药物的方法，用于抑制哺乳动物中蛋白水解的药物组合物，治疗方法，抑制方法：哺乳动物中的蛋白水解，凝血酶诱导的血小板凝集和血浆中纤维蛋白的形成，血浆中血栓的形成血小板聚集在血液，血栓形成，用于血液收集，血液循环和血液储存的设备上

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摘要

1. A compound having the Formula I: or a solvate, hydrate or pharmaceutically acceptable salt or prodrug thereof; wherein R1 is phenyl, naphthyl, dihydrodioxobenzo[b]thiophenyl or heteroaryl group, each of which is optionally substituted with at least one substituent, independently selected from the group, consisting of C1-6 alkyl, hydroxy, nitro, trifluoromethyl, trifluoromethoxy, halo, C1-6 alkoxy, cyano, amino, hydroxyamino, mono (C1-6) alkylamino, di(C1-6) alkylamino, heterocycle, aryl(C1-6) alkoxy, (C1-6) alkylsulfonyl, (C1-6) alkylsulfinyl, (C1-6) alkylcarbonyl, arylsulfonyl, and R13R14NSO2, wherein R13 and R14 are independently selected from the group consisting of hydrogen, C1-6alkyl, C2-6alkenyl, aryl, optionally substituted C1-6 alkyl, C1-6alkoxy, C1-6alkoxycarbonyl, or carboxy group, ar(C1-6)alkyl, wherein aryl group is optionally substituted with C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxycarbonyl or carboxy group, heterocycle, optionally substituted with benzyl or C1-6 alkyl, heterocyclo (C1-6)alkyl, carboxy (C1-6)alkyl, C1-6 alkoxycarbonyl (C1-6)alkyl, cyano(C1-6)alkyl, hydroxy(C1-6)alkyl, C1-6alkoxy(C1-6)alkyl, mono- and di(C1-6)alkylamino-(C1-6)alkyl, or R13 and R14 can be taken together with the nitrogen atom to atom to which they are attached to form a four to seven membered ring, optionally containing at least one heteroatom in addition to said nitrogen, such as oxygen, sulfur, or nitrogen (NR15), said ring being saturated, and said ring having at least one optional substituent, wherein said optional substituents and R15 are independently selected from the group consisting of hydrogen, C1-6alkyl, aryl, optionally substituted C1-6alkoxy, ar(C1-6)alkyl, heterocycle, carboxy(C1-6)alkyl, C1-6alkoxycarbonyl(C1-6)alkyl, carboxy, C1-6. alkoxycarbonyl, carboxamido, C1-6alkoxysulfonamido, sulfonamido, C1-6. alkanoyl, and C1-6. alkylsulfonyl. Z is one of -NR10SO2-, -SO2NR10-, -OSO2-, -SO2O-, -OCH2-, -CH2O-, -NR10CO- or -CONR10-; R4 is hydrogen, alkyl, halo, hydroxyalkyl, amino, alkoxy, or hydroxy; R2 and R3 are each hydrogen; Y is one of -O-, -NH-, -S-, or -CH2-; X is oxygen or NH; R6 and R7 are hydrogen; R12 is hydrogen or C1-6alkyl; R8 and R12 are each independently hydrogen, hydroxy, hydroxymethyl, or R8 and R12 are joined to form -(CH2)r-, wherein r is from 2 to 5; R10 is hydrogen or C1-6alkyl; Ra, Rb and Rc are independently hydrogen, C1-6 alkyl or -CO2Rw group; Rw - C1-6 alkyl; n is from 0 to 8, m is from 0 to 4. 2. A compound of Claim 1, wherein R1 is phenyl or naphthyl, each of which is optionally substituted as it is defined in Claim 1. 3. A compound of Claim 1, wherein R1 is heteroaryl which is optionally substituted by at least one substituents independently selected from the group consisting of hydroxy, nitro, trifluoromethyl, trifluoromethoxy, halogen, C1-6alkoxy, C1-6alkyl, amino, mono(C1-6)alkylamino, di(C1-6)alkylamino, or cyano group. 3. A compound of Claim 1, wherein R1 is pyridyl, pyrazolyl, thiophenyl, chromenyl, benzoxazolyl, benzthiadiazolyl, quinazolinyl, quinolinyl, isoquinolinyl or tetrahydroquinolinyl, any of which is optionally substituted by one or more substituents independently selected from the group consisting of hydroxy, nitro, trifluoromethyl, trifluoromethoxy, halogen, C1-6alkoxy, C1-6alkyl, amino, mono(C1-6)alkylamino, di(C1-6)alkylamino, and cyano. 5. A compound of Claim 1, wherein Y is -O- or -NH-. 6. A compound of Claim 5, wherein Y is -O-. 7. A compound of Claim 1, wherein Z is -SO2NR10-, -SO2O- or -CH2O-. 8. A compound of Claim 1, wherein Ra, Rb and Rc are hydrogen. 9. A compound of Claim 1, wherein n is from 1 to 4. 10. A compound of Claim 1, wherein m is zero, 1, 2 or 3. 11. A compound of Claim 1, wherein m and n are each zero and R7, R8, R11 and R12 are each hydrogen. 12. A compound of Claim 1, wherein R2 and R3 are hydrogen and R4 is methyl or chloro. 13. A compound of Claim 1, wherein R1 is one of the following groups phenyl, naphtyl, pyridinyl, thiophenyl (i.e., thiophene), quinazolinyl, quinolinyl or tetrahydroquinolinyl, any of which is optionally substituted by one or two of hydroxy, nitro, trifluoromethyl, trifluoromethoxy, halo, C1-6 alkyl, phenyl, C1-6 alkoxy, amino, mono (C1-4) alkylamino, di(C1-4) alkylamino, hydroxyamino, C6-10 ar(C1-6) alkoxy, C1-6 alkylcarbonyl, C1-6 alkylsulfonyl, C1-6alkylsulfinyl, cyano and R13R14NSO2-; R13 and R14 are independently selected from the group consisting of hydrogen, C1-6alkyl, C2-6alkenyl, aryl, optionally substituted C1-6 alkyl, C1-6alkoxy, C1-6alkoxycarbonyl, or carboxy group, ar(C1-6)alkyl, wherein aryl group is optionally substituted with C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxycarbonyl or carboxy group, heterocycle, optionally substituted with benzyl or C1-6 alkyl, heterocyclo (C1-6)alkyl, carboxy (C1-6)alkyl, C1-6 alkoxycarbonyl (C1-6)alkyl, cyano(C2-6)alkyl, hydroxy(C2-6)alkyl, C1-6alkoxy(C2-6)alkyl, mono- and di(C1-6)alkylamino-(C2-6)alkyl, or R13 and R14 can be taken together with the nitrogen atom to which they are attached to form a four to seven membered ring, optionally containing at least one heteroatom in addition to said nitrogen, such as oxygen, sulfur, or nitrogen (NR15), said ring being saturated, and said ring having one or two optional substituents, wherein said optional substituents and R15 are independently selected from the group consisting of hydrogen, C1-6alkyl, ar(C1-6)alkyl, heterocycle, C1-6alkoxycarbonyl(C1-6)alkyl, carboxy, (C1-6.)alkoxycarbonyl, carboxamido, C1-6. alkanoyl, C1-6. alkylsulfonyl, C1-6. alkoxysulfonyl, and sulfonamido. Z is one of -SO2O-, -SO2NR10-, -CH2O- or -OCH2-; R4 is hydrogen, C1-4alkyl, halo, hydroxy(C1-4)alkyl, or C1-4alkoxy; R10 is hydrogen or alkyl; Y is one of -O-, -S-, or -NH-; and Ra, Rb and Rc are each hydrogen or C1-4 alkyloxycarbonyl. 14. A compound of Claim 1, wherein R1 is one of phenyl, naphthyl, pyridyl, thiophenyl, quinolinyl or isoquinolinyl, optionally substituted by one or two of chloro, methoxy, methyl, trifluoromethyl, cyano, nitro, or amino; Z is one of -SO2O-, -SO2NR10-, -CH2O- or -OCH2-; R2 and R3 are hydrogen; R4 is one of hydrogen, methyl, methoxy; Y is one of -O- or -NH-; Ra, Rb and Rc are hydrogen; R6 and R7 are hydrogen; R12 is hydrogen or C1-6 alkyl; R8 and R11 are independently one of hydrogen, hydroxy, hydroxymethyl, or C1-4 alkoxy, or R8 and R11 are joint with forming -(CH2)r-, wherein r is 2, 3 or 4; R10 is hydrogen or C1-6 alkyl; n is 0-4, m is zero, 1, 2, 3. 15. A compound of Claim 1, wherein R1 is phenyl, substituted by C1-6 alkylsulfonyl, phenylsulfonyl, or R13R14NSO2-, wherein R13 and R14 are independently selected from the group consisting of hydrogen, C1-6 alkyl, C2-6alkenyl, C6-10 aryl, optionally substituted C1-6alkyl, C1-6alkoxy, C1-6 alkoxycarbonyl or carboxy group, C6-10 ar(C1-4)alkyl, wherein aryl group is optionally substituted with C1-6alkyl, C1-6alkoxy, C1-6 alkoxycarbonyl or carboxy group, pyridyl, pyridyl(C1-4)alkyl, carboxy(C1-6)alkyl, C1-4 alkoxycarbonyl(C1-4)alkyl, cyano(C2-6)alkyl, hydroxy(C2-6)alkyl, C1-4alkoxy(C2-6)alkyl, mono- and di(C1-4)alkylamino-(C2-6)alkyl, or R13 and R14 can be taken together with the nitrogen atom to which they are attached to form a heterocyclic ring, which is selected from the group comprising N-morpholino, N-piperazinyl (optionally N' substituted with C1-6 alkyl, C6-10 aryl, C6-10 aryl (C1-6)alkyl, C1-6alkylsulfonyl, or C1-6alkylcarbonyl), N-pyrrolyl, N-piperidinyl, N-pyrrolidinyl, N-dihydropyridyl, N-indolyl, wherein said heterocyclic ring can be optionally substituted with one or two of C1-4 alkyl, C6-10 aryl, optionally substituted C1-6alkoxy, C6-10 ar(C1-4)alkyl, heterocycle, carboxy(C1-6)alkyl, C1-4 alkoxycarbonyl(C1-4)alkyl, carboxy, C1-6 alkoxycarbonyl, carboxamido, C1-6alkanoyl, or C1-6alkylsulfonyl; Z is one of -SO2O-, -SO2NR10-, -CH2O- or -OCH2-; R2 and R3 are hydrogen; R4 is one of hydrogen, methyl, methoxy; Y is one of -O-, -NH-; Ra, Rb and Rc are hydrogen, C1-6alkyl or -CO2Rw; Rw - C1-6alkyl; R6 and R7 are hydrogen; R12 is hydrogen or C1-6alkyl; R8 and R11 are independently hydrogen, hydroxy, hydroxymethyl, or C1-4alkoxy, or R8 and R11 are taken together to form -(CH2)r- where r is 2, 3 or 4 R10 is hydrogen or alkyl; n is from zero to 4; and m is zero, 1, 2 or 3. 16. A compound of Claim 1, wherein the moiety -Z-R1 is attached to the benzene ring in a position meta- to Y. 17. A compound having the formula: or a solvate, hydrate, pharmaceutically acceptable salt or prodrug thereof: wherein R21 is one of phenyl, naphthyl, thiophenyl, quinolinyl or isoquinolinyl, optionally substituted by one or two substituents independently selected from the group consisting of halogen, C1-4 alkyl, C1-4 alkoxy, methoxy, trifluoromethyl, cyano, nitro, or amino; and when R21 is phenyl, said phenyl can be optionally substituted by C1-6 alkylsulfonyl, arylsulfonyl, or R22R23NSO2-, where R22 and R23 are independently selected from the group consisting of hydrogen, C1-6 alkyl, C6-10 aryl, optionally substituted C1-6alkyl, C1-6alkoxy, C1-6alkoxycarbonyl, or carboxy, C6-10ar(C1-4)alkyl, wherein aryl group is optionally substituted with C1-6alkyl, C1-6alkoxy, C1-6alkoxycarbonyl, or carboxy, pyridyl, pyridyl(C1-4)alkyl, carboxy(C1-6)alkyl, C1-4 alkoxycarbonyl(C1-4)alkyl, cyano(C2-6)alkyl, hydroxy(C2-6)alkyl, C1-4alkoxy(C2-6)alkyl, mono- and di(C1-4)alkylamino-(C2-6)alkyl, or R22 and R23 can be taken together with the nitrogen atom to which they are attached to form a heterocyclic ring, which is selected from the group comprising N-morpholino, N-piperazinyl (optionally N' substituted with C1-6 alkyl, C6-10 aryl, C6-10 aryl (C1-6)alkyl, C1-6alkylsulfonyl, or C1-6alkylcarbonyl), N-pyrrolyl, N-piperidinyl, N-pyrrolidinyl, N-dihydropyridyl, N-indolyl, wherein said heterocyclic ring can be opti
机译：1.具有式I的化合物：或其溶剂化物，水合物或药学上可接受的盐或前药;其中R 1为苯基，萘基，二氢二氧代苯并[b]噻吩基或杂芳基，其各自任选地被至少一个独立地选自C 1-6烷基，羟基，硝基，三氟甲基的取代基取代，三氟甲氧基，卤素，C1-6烷氧基，氰基，氨基，羟氨基，单（C1-6）烷基氨基，二（C1-6）烷基氨基，杂环，芳基（C1-6）烷氧基，（C1-6）烷基磺酰基，（C1 -6）烷基亚磺酰基，（C1-6）烷基羰基，芳基磺酰基和R 13 R 14 NSO 2，其中R 13和R 14独立地选自氢，C 1-6烷基，C 2 -6烯基，芳基，任选取代的C1-6烷基，C1-6烷氧基，C1-6烷氧羰基或羧基芳（C1-6）烷基，其中芳基任选被C1-6烷基，C1-6烷氧基，C1取代-6烷氧羰基或羧基，杂环基，可选地被苄基或C1-6烷基取代，杂环（C1-6）烷基，羧基（C1-6）烷基，C1-6烷氧羰基（C1-6）烷基，氰基（C1- 6）烷基，羟基（C1 -6）烷基，C 1-6烷氧基（C 1-6）烷基，单和二（C 1-6）烷基氨基-（C 1-6）烷基或R 13和R 14可以与氮一起使用原子与它们连接的原子形成一个四元至七元环，除了所述氮外，还任选包含至少一个杂原子，例如氧，硫或氮（NR 15），所述环是饱和的，和所述环具有至少一个任选的取代基，其中所述任选的取代基和R 15独立地选自氢，C 1-6烷基，芳基，任选取代的C 1-6烷氧基，芳（C 1-6）烷基，杂环，羧基（C1-6）烷基，C1-6烷氧基羰基（C1-6）烷基，羧基，C1-6。烷氧基羰基，羧酰胺基，C 1-6烷氧基磺酰胺基，磺酰胺基，C 1-6。烷酰基和C1-6。烷基磺酰基。 Z为-NR 10 SO 2-，-SO 2 NR 10-，-OSO 2-，-SO 2 O-，-OCH 2-，-CH 2 O-，-NR 10 CO-或-CONR 10-之一。 R 4为氢，烷基，卤素，羟基烷基，氨基，烷氧基或羟基; R 2和R 3各自为氢。 Y为-O-，-NH-，-S-或-CH 2-之一。 X是氧或NH; R 6和R 7为氢; R 12为氢或C 1-6烷基; R 8和R 12各自独立地为氢，羟基，羟甲基，或R 8和R 12连接形成-（CH 2）r-，其中r为2至5; R 10为氢或C 1-6烷基; R a，R b和R c独立地为氢，C 1-6烷基或-CO 2 R w基团; R w-C 1-6烷基; n为0至8，m为0至4。2.权利要求1的化合物，其中R 1为苯基或萘基，其各自如权利要求1所定义的被取代。3.化合物2.权利要求1的化合物，其中R 1是杂芳基，其任选地被至少一个独立地选自羟基，硝基，三氟甲基，三氟甲氧基，卤素，C 1-6烷氧基，C 1-6烷基，氨基，单（C 1）的取代基取代的杂芳基。 -6）烷基氨基，二（C1-6）烷基氨基或氰基。 3.权利要求1的化合物，其中R 1是吡啶基，吡唑基，噻吩基，色烯基，苯并恶唑基，苄二重氮基，喹唑啉基，喹啉基，异喹啉基或四氢喹啉基，它们中的任何一个任选地被一个或多个独立地选自以下的取代基取代：由羟基，硝基，三氟甲基，三氟甲氧基，卤素，C1-6烷氧基，C1-6烷基，氨基，单（C1-6）烷基氨基，二（C1-6）烷基氨基和氰基组成。 5.权利要求1的化合物，其中Y是-O-或-NH-。 6.权利要求5的化合物，其中Y是-O-。 7.权利要求1的化合物，其中Z是-SO 2 NR 10-，-SO 2 O-或-CH 2 O-。 8.权利要求1的化合物，其中R a，R b和R c为氢。 9.权利要求1的化合物，其中n为1-4。10.权利要求1的化合物，其中m为零，1、2或3。11.权利要求1的化合物，其中m和n各自为零。 R 7，R 8，R 11和R 12分别为氢。 12.权利要求1的化合物，其中R 2和R 3是氢，R 4是甲基或氯。 13.权利要求1的化合物，其中R 1为以下基团之一：苯基，萘基，吡啶基，噻吩基（即噻吩），喹唑啉基，喹啉基或四氢喹啉基，它们中的任何一个任选地被一个或两个羟基取代，硝基，三氟甲基，三氟甲氧基，卤素，C1-6烷基，苯基，C1-6烷氧基，氨基，单（C1-4）烷基氨基，二（C1-4）烷基氨基，羟基氨基，C6-10 ar（C1-6）烷氧基，C 1-6烷基羰基，C 1-6烷基磺酰基，C 1-6烷基亚磺酰基，氰基和R 13 R 14 NSO 2-; R 13和R 14独立地选自氢，C 1-6烷基，C 2-6烯基，芳基，任选取代的C 1-6烷基，C 1-6烷氧基，C 1-6烷氧基羰基或羧基， C1-6）烷基，其中芳基任选地被C 1-6烷基，C 1-6烷氧基，C 1-6烷氧基羰基或羧基取代，杂环基，任选地被苄基或C 1-6烷基取代，杂环（C 1-6）烷基，羧基（C 1- 6）烷基，C1-6烷氧羰基（C1-6）烷基，氰基（C2-6）烷基，羟基（C2-6）烷基，C1-6烷氧基（C2-6）烷基，单和二（C1-6）烷基氨基-（C 2-6）烷基或R 13和R 14可以与它们所连接的氮原子一起形成四元至七元环，除了还包含至少一个杂原子所述氮，例如氧，硫或氮（NR 15），所述环是饱和的，并且所述环具有一个或两个任选的取代基，其中所述任选的取代基和R 15独立地选自：氢，C 1-6烷基，芳（C 1-6）烷基，杂环，C 1-6烷氧羰基（C 1-6）烷基，羧基，（C 1-6）烷氧羰基，羧酰胺基，C 1-6。烷酰基，C 1-6。烷基磺酰基，C 1-6。烷氧基磺酰基和磺酰胺基Z为-SO 2 O-，-SO 2 NR 10-，-CH 2 O-或-OCH 2-之一。 R 4为氢，C 1-4烷基，卤素，羟基（C 1-4）烷基或C 1-4烷氧基; R 10为氢或烷基; Y是-O-，-S-或-NH-之一; R a，R b和R c分别为氢或C 1-4烷氧羰基。 14.权利要求1的化合物，其中R 1是苯基，萘基，吡啶基，硫代苯基，喹啉基或异喹啉基中的一种，其任选地被氯，甲氧基，甲基，三氟甲基，氰基，硝基或氨基中的一个或两个取代; Z为-SO 2 O-，-SO 2 NR 10-，-CH 2 O-或-OCH 2-之一。 R 2和R 3为氢; R 4为氢，甲基，甲氧基之一; Y是-O-或-NH-之一; R a，R b和R c为氢; R 6和R 7为氢; R 12为氢或C 1-6烷基; R 8和R 11独立地为氢，羟基，羟甲基或C 1-4烷氧基之一，或R 8和R 11结合形成-（CH 2）r-，其中r为2 ，3或4; R 10为氢或C 1-6烷基; n是0-4，m是0、1、2、3。15.权利要求1的化合物，其中R 1是苯基，被C 1-6烷基磺酰基，苯基磺酰基或R 13 R 14取代。 NSO 2-，其中R 13和R 14独立地选自氢，C 1-6烷基，C 2-6烯基，C 6-10芳基，任选取代的C 1-6烷基，C 1-6烷氧基，C 1-6烷氧基羰基或羧基，C6-10 ar（C1-4）烷基，其中芳基任选地被C1-6烷基，C1-6烷氧基，C1-6烷氧基羰基或羧基，吡啶基，吡啶基（C1-4）烷基，羧基取代（C1-6）烷基，C1-4烷氧基羰基（C1-4）烷基，氰基（C2-6）烷基，羟基（C2-6）烷基，C1-4烷氧基（C2-6）烷基，单和二（C1） -4）烷基氨基-（C 2-6）烷基，或R 13和R 14可以与它们所连接的氮原子一起形成杂环，该杂环选自N-吗啉代，N-哌嗪基（可选地被C1-6烷基，C6-10芳基，C6-10芳基（C1-6）烷基，C1-6烷基磺酰基或C1-6烷基羰基取代的N'），N-吡咯lyl，N-哌啶基，N-吡咯烷基，N-二氢吡啶基，N-吲哚基，其中所述杂环可任选地被C1-4烷基，C6-10芳基，任选取代的C1-6烷氧基，C6-10中的一个或两个取代芳（C1-4）烷基，杂环，羧基（C1-6）烷基，C1-4烷氧羰基（C1-4）烷基，羧基，C1-6烷氧羰基，羧酰胺基，C1-6烷酰基或C1-6烷基磺酰基; Z为-SO 2 O-，-SO 2 NR 10-，-CH 2 O-或-OCH 2-之一。 R 2和R 3为氢; R 4为氢，甲基，甲氧基之一; Y是-O-，-NH-之一; R a，R b和R c为氢，C 1-6烷基或-CO 2 R w; R w-C 1-6烷基; R 6和R 7为氢; R 12为氢或C 1-6烷基; R 8和R 11独立地为氢，羟基，羟甲基或C 1-4烷氧基，或R 8和R 11一起形成-（CH 2）r-，其中r为2、3或4 R 10为氢或烷基; n从零到4; 16.根据权利要求1所述的化合物，其中-ZR 1部分在Y的间位与苯环连接。17.一种具有下式的化合物：m和0为1、1、2或3。溶剂化物，水合物，药学上可接受的盐或前药：其中R 21为苯基，萘基，噻吩基，喹啉基或异喹啉基中的一种，任选地被一个或两个独立地选自卤素，C 1-4烷基的取代基取代，C 1-4烷氧基，甲氧基，三氟甲基，氰基，硝基或氨基;当R 21为苯基时，所述苯基可以任选地被C 1-6烷基磺酰基，芳基磺酰基或R 22 R 23 NSO 2-取代，其中R 22和R 23独立地选自由氢，C 1-6烷基，C 6-10芳基，任选取代的C 1-6烷基，C 1-6烷氧基，C 1-6烷氧基羰基或羧基，C 6-10芳（C 1-4）烷基组成的基团，其中芳基任选地被C 1-6烷基，C 1-6烷氧基，C 1-6烷氧基羰基或羧基，吡啶基，吡啶基（C 1-4）烷基，羧基（C 1-6）烷基，C 1-4烷氧基羰基（C 1-4）取代烷基，氰基（C2-6）烷基，羟基（C2-6）烷基，C1-4烷氧基（C2-6）烷基，单和二（C1-4）烷基氨基-（C2-6）烷基或R <22 R 2和R 23可以与它们所连接的氮原子一起形成杂环，该杂环选自N-吗啉代，N-哌嗪基（任选地被C 1-6烷基取代的N'， C6-10芳基，C6-10芳基（C1-6）烷基，C1-6烷基磺酰基或C1-6烷基羰基），N-吡咯基，N-哌啶基，N-吡咯烷基，N-二氢吡啶基，N-吲哚基，其中所述杂环可以优化

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