CN1216540A - 具有内皮素受体拮抗效应的2,1,3-苯并噻(噁)二唑衍生物 - Google Patents
具有内皮素受体拮抗效应的2,1,3-苯并噻(噁)二唑衍生物 Download PDFInfo
- Publication number
- CN1216540A CN1216540A CN97193959A CN97193959A CN1216540A CN 1216540 A CN1216540 A CN 1216540A CN 97193959 A CN97193959 A CN 97193959A CN 97193959 A CN97193959 A CN 97193959A CN 1216540 A CN1216540 A CN 1216540A
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- CN
- China
- Prior art keywords
- diazosulfide
- phenyl
- benzyl
- hydroxyl
- furans
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 108050001739 Endothelin receptor Proteins 0.000 title abstract description 4
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- 239000002253 acid Substances 0.000 claims description 322
- 238000006243 chemical reaction Methods 0.000 claims description 300
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 42
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
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- HNHVTXYLRVGMHD-UHFFFAOYSA-N n-butyl isocyanate Chemical compound CCCCN=C=O HNHVTXYLRVGMHD-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 150000002828 nitro derivatives Chemical class 0.000 description 1
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 150000004866 oxadiazoles Chemical class 0.000 description 1
- BSCHIACBONPEOB-UHFFFAOYSA-N oxolane;hydrate Chemical compound O.C1CCOC1 BSCHIACBONPEOB-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- RFPMGSKVEAUNMZ-UHFFFAOYSA-N pentylidene Chemical group [CH2+]CCC[CH-] RFPMGSKVEAUNMZ-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 208000002815 pulmonary hypertension Diseases 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- HNKJADCVZUBCPG-UHFFFAOYSA-N thioanisole Chemical compound CSC1=CC=CC=C1 HNKJADCVZUBCPG-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D285/00—Heterocyclic compounds containing rings having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by groups C07D275/00 - C07D283/00
- C07D285/01—Five-membered rings
- C07D285/02—Thiadiazoles; Hydrogenated thiadiazoles
- C07D285/14—Thiadiazoles; Hydrogenated thiadiazoles condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/12—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms condensed with carbocyclic rings or ring systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明涉及式(Ⅰ)的化合物或一种环化的互变异构形式,其中R为(i),(ii)或(iii),n为0,1或2;X指O或S,而R1,R2,R3和R4具有不同的含义。本发明还涉及具有内皮素受体拮抗性能的这些化合物的(E)异构体和盐。
Description
本发明涉及式Ⅰ化合物或一种互变异构的闭环形式,以及(E)异构体和所有异构体的盐:其中R是或
X是O或S,R1是H、Hal、OH、OA、A、亚烷基-O-A、NO2、NH2、NH酰基、SO2NH2、SO3-A、SO2NHA、CN或甲酰基,R2、R3、R4各自相互独立地是苯基,该苯基未被取代或由Hal、OH、OA、O-亚烷基-R5、A、S-A、S-OA、SO2A、S-OR5、SO2R5、NO2、NH2、NHA、NA2、NH酰基、NHSO2A、NHSO2R5、NASO2A、NASO2-R5、NH(CO)NH2、NH(CO)NHA、甲酰基、NH(CO)NHR5、NHCOOA、NA酰基、NHCOOCH2R5、NHSO2CH2R5、NHCOO-亚烷基-OA、NH(CO)NA2、1-哌啶基-CO-NH、1-吡咯烷基-CONH、O(CH2)nCOOA、O(CH2)nCOOH、O(CH2)nOH、O(CH2)nOA、CH2OA、CH2OH、COOH、COOA、CH2COOH或CH2COOA单取代或多取代,或为如下基团其中R2还可以为A或环烷基,R5为苯基,该苯基未被取代或由Hal、OH、OA、A、S-A、NO2、NH2、NHA、NA2、NH酰基、NHSO2A、NASO2A、NH(CO)NH2、NH(CO)NHA、甲酰基、NHCOOA、NA酰基、NHCOO-亚烷基-OA、NH(CO)NA2、N-哌啶基-CO-NH、N-吡咯烷基-CONH、O(CH2)nCOOA、O(CH2)nCOOH、O(CH2)nOH、O(CH2)nOA、CH2OH、CH2OA、COOH、COOA、CH2COOH或CH2COOA单取代或多取代,A为具有1-6个碳原子的烷基,其中一个或两个CH2基团可以用O或S原子或用-CR6=CR6'基团替代和/或1-7个H原子可以用F替代,D为羰基或〔C(R6R6')〕m,E为CH2、S或O,Y为O或S,R6和R6'各自相互独立地为H、F或A,Hal为氟、氯、溴或碘,n为0、1或2,以及m为1或2。
类似化合物公开于WO95/05376中。
本发明的目的是寻找具有有用性能的新型化合物,特别是那些能用于药物生产的化合物。
已经发现式Ⅰ的化合物及其盐类具有非常有用的药理性能及良好的耐受性。特别是它们显示内皮素受体拮抗性能,因此可用于一些疾病的治疗,如高血压、心机能不全、冠心病、肾部、大脑和心肌局部缺血、肾机能不全、脑梗塞、蛛网膜下出血、动脉硬化、肺性高血压、发炎、哮喘、***增生、内毒素休克及服用一些物质如环孢素后的并发症、及其它与内皮素活动有关的疾病。
该化合物尤其显示对内皮素亚受体ETA和ETB的高亲和力。这些作用可用常规的体外或体内方法进行确定,例如P.D.Stein等在《医药化学杂志》1994年第37卷第329~331页和E.Ohlstein等在1994年《美国国家科学院院报》第91卷第8052~8056页所述。
确定降压作用的适宜方法例如由M.K.Bazil等在1993年《心血管药理学杂志》第22卷第897~905页和J.Lange等在1991年《试验室动物》第20卷应用号1016上说明。
式Ⅰ的化合物可以作为人药和兽药中的药物活性化合物,特别用于预防和/或治疗心脏、循环和血管疾病,特别是高血压和心机能不全。
R2-(CH2)k-CHO Ⅲ其中R2具有权利要求1中所述含义,而k为0或1,然后使酯断裂,或者,为了制备根据权利要求1的式Ⅰ化合物及其盐,其中b)R为
使式Ⅳ化合物其中R1、R4和X具有权利要求1所述含义,而A为具有1-4个碳原子的烷基或苄基,与上述式Ⅲ化合物反应,然后使酯断裂,或者,为了制备根据权利要求1的式Ⅰ化合物及其盐,其中c)R为
使式Ⅴ化合物其中R3和R4具有权利要求1所述含义,而A为具有1-4个碳原子的烷基或苄基,与式Ⅵ化合物反应,其中R1和X具有权利要求1所述含义,而k为0或1,然后使酯断裂,和/或其特征在于,使式Ⅰ化合物中的一个或多个基团R1、R2、R3和/或R4通过例如如下方式转化为一个或多个基团R1、R2、R3和/或R4:
ⅰ)将硝基还原为氨基,
ⅱ)酰基化或烷基化氨基,
ⅲ)将氨基转化为磺酰氨基,和/或将式Ⅰ的碱或酸转化为其盐的一种。
对于出现几次的所有基团,例如R3、R4或R5,它们的含义相互独立。
对于X和Y而言,它们的含义同样相互独立。
上下文中的基团或参数R、X、R1、R2、R3、R4、A、k和n具有对式Ⅰ-Ⅵ所示的含义,除非另有指明。
在上式中,A为烷基且具有1-6,优选1、2、3或4个碳原子。A优选为甲基,还有乙基,丙基,异丙基,丁基,异丁基,仲丁基或叔丁基,另外还有戊基,1-、2-或3-甲基丁基,1,1-、1,2-或2,2-二甲基丙基,1-乙基丙基,己基,1-、2-、3-或4-甲基戊基,1,1-、1,2-、1,3-、2,2-、2,3-或3,3-二甲基丁基,1-或2-乙基丁基,1-乙基-1-甲基丙基,1-乙基-2-甲基丙基,1,1,2-或1,2,2-三甲基丙基,以及三氟甲基,五氟乙基,烯丙基或丁烯基。
环烷基优选为环丙基,环丁基,环戊基或环己基。
亚烷基优选为亚甲基,亚乙基,亚丙基,亚丁基和亚戊基或亚己基。
酰基优选为甲酰基、乙酰基、丙酰基和丁酰基,戊酰基或己酰基。
E优选为O,还有CH2或S。
D优选为CH2,但羰基也是优选的。
Hal优选的是F、Cl或Br,但还优选为Ⅰ。
R1优选为H、氟、氯、溴、碘、甲氧基、乙氧基、丙氧基、甲氧甲基、硝基、氨基、甲酰氨基、乙酰氨基、磺酰氨基、甲磺酰氨基、N-甲基磺酰氨基、氰基和甲酰基。
R2、R3和R4各自相互独立地为未取代的苯基,或优选由氟、氯、溴、碘、羟基、甲氧基、乙氧基、丙氧基、丁氧基、戊氧基、苄氧基、苯乙氧基、甲硫基、乙硫基、甲基亚磺酰基、乙基亚磺酰基、甲磺酰基、乙磺酰基、苯基亚磺酰基、苯磺酰基、硝基、氨基、甲氨基、乙氨基、二甲氨基、二乙氨基、甲酰氨基、乙酰氨基、N-甲基乙酰氨基、N-乙基乙酰氨基、N-丙基乙酰氨基、N-丁基乙酰氨基、丙酰氨基、丁酰氨基、甲磺酰氨基、乙磺酰氨基、丙磺酰氨基、丁磺酰氨基、N-甲基甲磺酰氨基、N-甲基乙磺酰氨基、N-乙基甲磺酰氨基、N-乙基乙磺酰氨基、N-丙基甲磺酰氨基、N-丙基乙磺酰氨基、N-丁基甲磺酰氨基、N-丁基乙磺酰氨基、苯磺酰氨基、(4-甲基苯基)磺酰氨基、脲基、甲基脲基、苯基脲基、甲氧羰基氨基、乙氧羰基氨基、甲酰基、羟甲基、甲氧甲基、乙氧甲基、苯胺基、苯氧羰基氨基、苄氧羰基氨基、苄基磺酰氨基、N,N-二甲基脲基、1-哌啶基-CONH-、1-吡咯烷基-CONH、羟基乙氧羰基氨基、甲氧基乙氧羰基氨基、羧基甲氧基、羧基乙氧基、甲氧羰基甲氧基、甲氧羰基乙氧基、羟基乙氧基、甲氧基乙氧基、羧基、甲氧羰基、乙氧羰基、羧甲基、甲氧羰基甲基或乙氧羰基甲基单取代的苯基,其中R2还优选为A或环烷基。
R2、R3和R4优选为邻-、间-或对甲苯基,邻-、间-或对-乙基苯基,邻-、间-或对-丙基苯基,邻-、间-或对-异丙基苯基,邻-、间-或对-叔丁基苯基,邻-、间-或对-羟基苯基,邻-、间-或对-硝基苯基,邻-、间-或对-氨基苯基,邻-、间-或对-(N-甲氨基)苯基,邻-、间-或对-乙酰氨基苯基,邻-、间-或对-甲氧苯基,邻-、间-或对-乙氧苯基,邻-、间-或对-(N,N-二甲氨基)苯基,邻-、间-或对-(N-乙氨基)苯基,邻-、间-或对-(N,N-二乙氨基)苯基,邻-、间-或对-氟苯基,邻-、间-或对-溴苯基,邻-、间-或对-氯苯基,邻-、间-或对-甲酰基苯基,邻-、间-或对-(苯磺酰氨基)苯基,邻-、间-或对-(甲磺酰氨基)苯基,邻-、间-或对-甲硫基苯基,邻-、间-或对-苄氧苯基,邻-、间-或对-脲基苯基,邻-、间-或对-(N-甲基脲基)苯基,邻-、间-或对-(羟甲基)苯基,邻-、间-或对-(甲氧基甲基)苯基,还优选2,3-亚甲二氧基苯基,3,4-亚甲二氧基苯基,2,3-亚乙二氧基苯基,3,4-亚乙二氧基苯基,3,4-(二氟代亚甲二氧基)苯基,2,3-二氢苯并呋喃-5-或-6-基,2,3-(2-氧代亚甲二氧基)苯基,2,3-、2,4-、2,5-、2,6-、3,4-或3,5-(二氟甲氧基)(羧基甲氧基)苯基,2,3-、2,4-、2,5-、2,6-、3,4-或3,5-甲氧基(羧基甲氧基)苯基,2,3-、2,4-、2,5-、2,6-、3,4-或3,5-羟基(羧基甲氧基)苯基,还优选为2,3-、2,4-、2,5-、2,6-、3,4-或3,5-二氟苯基,2,3-、2,4-、2,5-、2,6-、3,4-或3,5-二氯苯基,2,3-、2,4-、2,5-、2,6-、3,4-或3,5-二溴苯基,2,4-或2,5-二硝基苯基,2,5-或3,4-二甲氧苯基,3-硝基-4-氯苯基,2-氨基-3-氯-、2-氨基-4-氯-、2-氨基-5-氯-或2-氨基-6-氯苯基,2-硝基-4-N,N-二甲基氨基-或3-硝基-4-N,N-二甲氨基苯基,2,3,4-、2,3,5-、2,3,6-、2,4,6-或3,4,5-三氯苯基,2,4,6-三甲氧基苯基,2-羟基-3,5-二氯苯基,对碘代苯基,3,6-二氯-4-氨基苯基,4-氟-3-氯苯基,2-氟-4-溴苯基,2,5-二氟-4-溴苯基,3-溴-6-甲氧苯基,3-氯-6-甲氧苯基,3-氯-4-乙酰氨基苯基,3-氟-4-甲氧苯基,或还优选2,3-二氢苯并呋喃基,2,3-二氢-2-氧代呋喃基,2,1,3-苯并噻二唑-4-或-5-基或2,1,3-苯并噁二唑-5-基。
R5为未取代苯基,或优选由氟、氯、溴、碘、羟基、甲氧基、乙氧基、丙氧基、丁氧基、戊氧基、己氧基、甲硫基、乙硫基、硝基、氨基、甲氨基、乙氨基、二甲氨基、二乙氨基、甲酰氨基、乙酰氨基、N-甲基乙酰氨基、N-乙基乙酰氨基、N-丙基乙酰氨基、N-丁基乙酰氨基、丙酰氨基、丁酰氨基、甲磺酰氨基、乙磺酰氨基、丙碘酰氨基、丁磺酰氨基、N-甲基甲磺酰氨基、N-甲基乙磺酰氨基、N-乙基甲磺酰氨基、N-乙基乙磺酰氨基、N-丙基甲磺酰氨基、N-丙基乙磺酰氨基、N-丁基甲磺酰氨基、N-丁基乙磺酰氨基、脲基、甲基脲基、苯基脲基、甲氧羰基氨基、乙氧羰基氨基、甲酰基、羟甲基、甲氧甲基、乙氧甲基、N,N-二甲基脲基、N-哌啶基-CONH-、N-吡咯烷基-CONH、羟基乙氧羰基氨基、甲氧基乙氧羰基氨基、羧基甲氧基、羧基乙氧基、甲氧羰基甲氧基、甲氧基羰基乙氧基、羟基乙氧基或甲氧基乙氧基单取代的苯基。
R5优选为邻-、间-或对甲苯基,邻-、间-或对-乙基苯基,邻-、间-或对-丙基苯基,邻-、间-或对-异丙基苯基,邻-、间-或对-叔丁基苯基,邻-、间-或对-羟基苯基,邻-、间-或对-硝基苯基,邻-、间-或对-氨基苯基,邻-、间-或对-(N-甲氨基)苯基,邻-、间-或对-乙酰氨基苯基,邻-、间-或对-甲氧苯基,邻-、间-或对-乙氧苯基,邻-、间-或对-(N,N-二甲氨基)苯基,邻-、间-或对-(N-乙氨基)苯基,邻-、间-或对-(N,N-二乙氨基)苯基,邻-、间-或对-氟苯基,邻-、间-或对-溴苯基,邻-、间-或对-氯苯基,邻-、间-或对-甲酰基苯基,邻-、间-或对-(甲磺酰氨基)苯基,邻-、间-或对-甲硫基苯基,邻-、间-或对-脲基苯基,邻-、间-或对-(N-甲基脲基)苯基,邻-、间-或对-(羟甲基)苯基,邻-、间-或对-(甲氧基甲基)苯基,还优选2,3-亚甲二氧基苯基,3,4-亚甲二氧基苯基,2,3-亚乙二氧基苯基,3,4-亚乙二氧基苯基,3,4-(二氟代亚甲二氧基)苯基,2,3-二氢苯并呋喃-5-或-6-基,2,3-(2-氧代亚甲二氧基)苯基,2,3-、2,4-、2,5-、2,6-、3,4-或3,5-(二氟甲氧基)(羧基甲氧基)苯基,2,3-、2,4-、2,5-、2,6-、3,4-或3,5-甲氧基(羧基甲氧基)苯基,2,3-、2,4-、2,5-、2,6-、3,4-或3,5-羟基(羧基甲氧基)苯基,还优选为2,3-、2,4-、2,5-、2,6-、3,4-或3,5-二氟苯基,2,3-、2,4-、2,5-、2,6-、3,4-或3,5-二氯苯基,2,3-、2,4-、2,5-、2,6-、3,4-或3,5-二溴苯基,2,4-或2,5-二硝基苯基,2,5-或3,4-二甲氧苯基,3-硝基-4-氯苯基或2-氨基-6-氯苯基,2-硝基-4-N,N-二甲基氨基-或3-硝基-4-N,N-二甲氨基苯基,2,3,4-、2,3,5-、2,3,6-、2,4,6-或3,4,5-三氯苯基,2,4,6-三甲氧基苯基,2-羟基-3,5-二氯苯基,对碘代苯基,3,6-二氯-4-氨基苯基,4-氟-3-氯苯基,2-氟-4-溴苯基,2,5-二氟-4-溴苯基,3-溴-6-甲氧苯基,3-氯-6-甲氧苯基或3-氯-4-乙酰氨基苯基。
式Ⅰ化合物可以具有一个或多个手性中心,因而以各种立体异构形式存在。式Ⅰ包括所有这些形式。
式Ⅰ的Z异构体是特别优选的,即基团R中的C=C双键以Z构型存在的化合物。
因此,本发明尤其涉及其中至少一个上述基团具有上述优选含义之一的那些式Ⅰ化合物。某些优选的化合物可以由下述亚式Ⅰa-Ⅰe表示,它们与式Ⅰ相对应且其中未更详细描述的基团具有式Ⅰ中所示含义,但是在Ⅰa中,R为
R1为H,X为S以及n为1;在Ⅰb中,R为
R1为H,X为O以及n为1;在Ⅰc中,R为
R1为H,X为S以及n为1;在Ⅰd中,R为
R1为H,X为S以及n为1;在Ⅰe中,R为
R1为H,
R2和R3各自相互独立地为未取代或由Hal、OH、OA、O-亚烷基-R5、A、S-A、S-OA、SO2A、S-OR5、SO2R5、NO2、NH2、NHA、NA2、NH酰基、NHSO2A、NHSO2R5、NASO2A、NASO2-R5、NH(CO)NH2、NH(CO)NHA、甲酰基、NH(CO)NHR5、NHCOOA、NA酰基、NHCOOCH2R5、NHSO2CH2R5、NHCOO-亚烷基-OA、NH(CO)NA2、1-哌啶基-CONH、1-吡咯烷基-CONH、O(CH2)nCOOA、O(CH2)nCOOH、O(CH2)nOH、O(CH2)nOA、CH2OH、CH2OA、COOH、COOA、CH2COOH、CH2COOA、-O-CH2-CH2-O-、-O-CH2-CH2-、-O-CF2-O-或-O-CF2-CF2-O-单取代或多取代的苯基,下式基团或其中R2还为A或环烷基,
X为S以及
n为0、1或2。
式Ⅰ化合物以及其制备所用原料可由本身已知的方法,例如在文献中(例如在标准著作如Houben-Weyl,有机化学方法(Methoden derorganischen Chemie),Georg-Thieme-Verlag,Stuttgart中)所述的方法制备,即在已知且适于上述反应的反应条件下制备。在这种情况下也可以使用本身已知的改进方法,但本文不作更详细的说明。
通常情况下,该反应在惰性溶剂中,优选在碱存在下进行。所用碱例如为钾或钠的醇盐如甲醇钾或钠、乙醇钾或钠或叔丁醇钾或钠。优选的溶剂特别是下述醇类。
取决于所用条件,反应时间为几分钟至14天,反应温度为约0℃至150℃,优选20-130℃。
合适的惰性溶剂例如是烃类如己烷、石油醚、苯、甲苯或二甲苯;氯代烃类如三氯乙烯、1,2-二氯乙烷、四氯化碳、氯仿或二氯甲烷;醇类如甲醇、乙醇、异丙醇、正丙醇、正丁醇或叔丁醇;醚类如***、二异丙醚、四氢呋喃(THF)或二噁烷;乙二醇醚类如乙二醇单甲醚或单***(甲基乙二醇或乙基乙二醇)、乙二醇二甲醚(二甘醇二甲醚);酮类如丙酮或丁酮;酰胺类如乙酰胺、二甲基甲酰胺(DMF)或二甲基乙酰胺;腈类如乙腈;亚砜类如二甲亚砜(DMSO);二硫化碳;羧酸如甲酸或乙酸;硝基化合物如硝基甲烷或硝基苯;酯类如乙酸乙酯或上述溶剂的混合物。
通常,式Ⅱ的起始化合物是新颖的,而式Ⅲ的那些则通常是已知的。
然而,式Ⅱ的化合物可以由本身已知的方法制备。因此,例如2-(2,1,3-苯并噻二唑-5-基)-4-(4-甲氧苯基)-4-氧代丁酸乙酯可以由2-(2,1,3-苯并噻二唑-5-基)乙酸乙酯与2′-溴-4-甲氧基苯乙酮反应而得到,所述反应在惰性溶剂中进行,且加入酸结合试剂,优选碱金属或碱土金属的氢氧化物、碳酸盐或碳酸氢盐或碱金属或碱土金属的另一弱酸盐,优选钾、钠、钙或铯的另一弱酸盐。加入有机碱如三乙胺、二甲基苯胺、吡啶或喹啉也是有利的。
通常情况下,该反应在惰性溶剂中于酸结合试剂存在下在上述温度下进行。
通常情况下式Ⅳ的起始化合物是新颖的,但也可由本身已知的方式制备。
因此,例如通过使式Ⅶ化合物其中X为O或S,与式Ⅷ化合物反应,
随后通过加入氢氰酸得,得到式X化合物该化合物随后可以通过将腈基转化为COOH基团,然后酯化而转化为式Ⅳ化合物,其中R1为H。其中R为的式Ⅰ化合物优选通过式Ⅴ化合物与式Ⅵ化合物反应,然后使酯断裂而得到。
通常情况下,该反应在惰性溶剂中在酸结合试剂存在下在上述温度下进行。
例如可以使用乙酸或使用NaOH或KOH在水、水-THF或水-二噁烷中于0-100℃下水解酯。
通常情况下,式Ⅴ的起始化合物是新颖的,但可以类似于式X化合物的制备方法制得,随后将腈基转化为酯官能基。
通常,式Ⅵ的起始化合物是已知的或可由已知方法制备。
也可以通过将一个或多个基团R1、R2、R3和/或R4转化为一个或多个基团R1、R2、R3和/或R4而将式Ⅰ化合物转化为另一式Ⅰ化合物,例如将硝基还原(例如通过在惰性溶剂如甲醇或乙醇中于Raney镍或Pd/C上进行氢化)成氨基。
游离氨基可以进一步由常规方式使用酰氯或酸酐酰化或使用未取代或取代的烷基卤化物烷基化,有利的是在惰性溶剂如二氯甲烷或THF和/或在碱如三乙胺或吡啶存在下于-60℃至+30℃的温度下进行上述反应。
若需要,可以根据常规方法通过溶剂分解或氢解而释放式Ⅰ化合物中官能改性的氨基和/或羟基。因此,例如可以将含有NH-酰基或COOA基团的式Ⅰ化合物转化为含NH2或HOOC基团的相应式Ⅰ化合物。
式Ⅰ的碱可以用酸转化为缔合的酸加成盐,例如通过等量的碱与酸在惰性溶剂如乙醇中反应,然后蒸发。适用于该反应的酸特别是那些给出生理上可接受的盐的酸。因此可以使用无机酸如硫酸、硝酸、氢卤酸如盐酸或氢溴酸、磷酸如正磷酸、氨基磺酸,还有有机酸,特别是脂族、脂环族、芳脂族、芳族或杂环族一元羧酸或多元羧酸、磺酸或硫酸,如甲酸、乙酸、丙酸、新戊酸、二乙基乙酸、丙二酸、琥珀酸、庚二酸、富马酸、马来酸、乳酸、酒石酸、苹果酸、柠檬酸、葡糖酸、抗坏血酸、烟酸、异烟酸、甲磺酸、乙磺酸、乙二磺酸、2-羟基乙磺酸、苯磺酸、对甲苯磺酸、萘一磺酸和萘二磺酸以及月桂基硫酸。与生理上不可接受的酸形成的盐如苦味酸盐可以用于式Ⅰ化合物的分离和/或提纯。
另一方面,式Ⅰ化合物可以使用碱(如钠或钾的氢氧化物或碳酸盐)转化为相应的金属盐,特别是碱金属盐或碱土金属盐,或转化为相应的铵盐。
本发明还涉及式Ⅰ化合物和/或其生理上可接受的盐在生产药物制剂中的用途,特别是由非化学途径生产药物制剂。在这点上,它们可与至少一种固体、液体和/或半液体赋形剂或助剂一起制成合适的剂形,合适的话与一种或多种其他活性化合物组合。
本发明还涉及药物制剂,它们包含至少一种式Ⅰ化合物和/或其一种生理上可接受的盐。
这些制剂可用作人药或兽药中的药物。可能的赋形剂是有机或无机物,它们适于肠部(如口服)或肠胃外给药或局部用药且不与新颖化合物反应,例如为水、植物油、苄醇、亚烷基二醇、聚乙二醇、甘油三乙酸酯、明胶、碳水化合物如乳糖或淀粉、硬脂酸镁、滑石、凡士林。具体来说,片剂、丸剂、包衣片剂、胶囊、粉剂、颗粒、糖浆、汁液或液滴用于口服给药,栓剂用于直肠给药,溶液、优选油性或水溶液、还有悬浮液、乳液或植入物用于肠胃外给药,而软膏、霜剂或粉剂用于局部用药。这些新颖化合物也可以冻干并将所得冻干物用于例如生产注射制剂。上述制剂可以被杀菌和/或含有助剂如润滑剂、防腐剂、稳定剂和/或润湿剂、乳化剂、影响渗透压的盐、缓冲物质、着色剂、调味剂和/或一种或多种其他活性化合物,如一种或多种维生素。
式Ⅰ化合物及其生理上可接受的盐可以用于控制疾病,特别是高血压和心机能不全。
在这种情况下,本发明的物质通常优选以约1-500mg/剂量单位,特别是5-100mg/剂量单位的剂量给药。日剂量优选为约0.02-10mg/kg体重。然而,每一患者所用具体剂量取决于各种因素,如所用具体化合物的活性,年龄,体重,通常的健康状况,性别,饮食,给药时间和途径,***速率,药物组合以及治疗所涉及的特定疾病的严重程度。优选口服给药。
上下文中所有温度均示为℃。在下列实施例中,“常规处理”指:若需要,加入水,若需要,根据最终产物的组成将混合物调至pH2-10,用乙酸乙酯或二氯甲烷萃取,分离出有机相,用硫酸钠干燥,蒸发并用硅胶色谱法和/或结晶法提纯。Rf为在硅胶上的;洗脱剂:乙酸乙酯/甲醇9∶1。质谱(MS):EI(电子碰撞离子化)M+,FAB(快速原子轰击)(M+H)+实施例1
将0.38g苯甲醛和1.20g 2-(2,1,3-苯并噻二唑-5-基)-4-(4-甲氧苯基)-4-氧代丁酸乙酯(“A”),m.p.89℃,(可通过5.5g 2-(2,1,3-苯并噻二唑-5-基)乙酸乙酯与5.5g 2'-溴-4-甲氧基苯乙酮和4g碳酸钾在200ml丙酮中在回流下反应18小时而得到;2-(2,1,3-苯并噻二唑-5-基)乙酸乙酯,m.p.40-41℃,通过24.3g 3,4-二氨基苯基乙酸乙酯和26.9ml亚硫酰基苯胺在80ml甲苯中于回流下反应4小时而得到)加入80mg钠在5ml甲醇中的溶液中并在回流下加热混合物1小时。加入5ml乙酸后,再加热16小时。除去溶剂并按常规方式处理残余物。得到3-(2,1,3-苯并噻二唑-5-基)-4-苄基-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,FAB 431。
类似地,由“A”与2-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(2-甲氧苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2酮,m.p.131℃与3-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲氧苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2酮,FAB 460与4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲氧苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2酮,m.p.70℃以及作为副产物的2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲氧苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸,m.p.184℃与3,4-二甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.62℃与3,4,5-三甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.164℃,FAB 543与3,4-二异丙氧基-5-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.136℃与3,4,5-三异丙氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三异丙氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.149℃与4-三氟甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-三氟甲基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,与4-氰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-氰基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,与4-甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.58℃与3-甲基-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲基-4-甲氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,与4-叔丁基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-叔丁基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,与(2-甲氧羰基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,与(2-羧基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-羧基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,与4-乙氧羰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-乙氧羰基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,与4-苄氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-苄氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,与4-二甲氨基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-二甲氨基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.70℃,与4-硝基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-硝基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,与(1,3-苯并间二氧杂环戊烯-5-基)甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.67℃与3-氟-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-氟-4-甲氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.66℃与3-(N,N-二甲氨基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔3-(N,N-二甲氨基)苄基〕-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,与环己烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环己基甲基-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.153℃,以及与环戊烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环戊基甲基-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮。
类似地,通过2-(2,1,3-苯并噻二唑-5-基)-4-(1,4-苯并二噁烷-6-基)-4-氧代丁酸乙酯与苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-苄基-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,m.p.98℃与2-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(2-甲氧苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与3-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲氧苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲氧苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与3,4-二甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与3,4,5-三甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,m.p.82℃与3,4-二异丙氧基-5-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,m.p.173℃与3,4,5-三异丙氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三异丙氧基苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与4-三氟甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-三氟甲基苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与4-氰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-氰基苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与4-甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲基苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与3-甲基-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲基-4-甲氧基苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与4-叔丁基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-叔丁基苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与(2-甲氧羰基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与(2-羧基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-羧基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与4-乙氧羰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-乙氧羰基苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与4-苄氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-苄氧基苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与4-二甲氨基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-二甲氨基苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与4-硝基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-硝基苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与(1,3-苯并间二氧杂环戊烯-5-基)甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与3-氟-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-氟-4-甲氧苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与3-(N,N-二甲氨基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔3-(N,N-二甲氨基)苄基〕-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,与环己烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环己基甲基-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,m.p.81℃,以及与环戊烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环戊基甲基-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮。
类似地,由2-(2,1,3-苯并噻二唑-5-基)-4-(4-甲基苯基)-4-氧代丁酸乙酯与苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-苄基-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与2-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(2-甲氧基苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与3-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲氧基苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲氧基苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与3,4-二甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与3,4,5-三甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与3,4-二异丙氧基-5-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与3,4,5-三异丙氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三异丙氧基苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与4-三氟甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-三氟甲基苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与4-氰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-氰基苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与4-甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲基苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与3-甲基-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲基-4-甲氧苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与4-叔丁基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-叔丁基苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与(2-甲氧羰基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与(2-羧基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-羧基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与4-乙氧羰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-乙氧羰基苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与4-苄氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-苄氧基苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与4-二甲氨基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-二甲氨基苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与4-硝基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-硝基苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与(1,3-苯并间二氧杂环戊烯-5-基)甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与3-氟-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-氟-4-甲氧基苄基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与3-(N,N-二甲氨基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔3-(N,N-二甲氨基)苄基〕-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与环己烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(环己基甲基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,以及与环戊烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(环戊基甲基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮。
类似地,由2-(2,1,3-苯并噻二唑-5-基)-4-苯基-4-氧代丁酸乙酯与苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-苄基-5-羟基-5-苯基-5H-呋喃-2-酮,与2-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(2-甲氧苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,与3-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲氧苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,与4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲氧苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,与3,4-二甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧基苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,与3,4,5-三甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,m.p.174℃与3,4-二异丙氧基-5-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧基苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,与3,4,5-三异丙氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三异丙氧基苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,与4-三氟甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-三氟甲基苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,与4-氰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-氰基苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,与4-甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲基苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,与3-甲基-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲基-4-甲氧苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,与4-叔丁基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-叔丁基苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,与(2-甲氧羰基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-5-羟基-5-苯基-5H-呋喃-2-酮,与(2-羧基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-羧甲基甲氧基-4-甲氧基)苄基〕-5-羟基-5-苯基-5H-呋喃-2-酮,与4-乙氧羰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-乙氧羰基苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,与4-苄氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-苄氧基苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,与4-二甲氨基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-二甲氨基苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,与4-硝基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-硝基苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,与(1,3-苯并间二氧杂环戊烯-5-基)甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-5-羟基-5-苯基-5H-呋喃-2-酮,与3-氟-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-氟-4-甲氧基苄基)-5-羟基-5-苯基-5H-呋喃-2-酮,与3-(N,N-二甲氨基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔3-(N,N-二甲氨基)苄基〕-5-羟基-5-苯基-5H-呋喃-2-酮,与环己烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环己基甲基-5-羟基-5-苯基-5H-呋喃-2-酮,和与环戊烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环戊基甲基-5-羟基-5-苯基-5H-呋喃-2-酮。
类似地,由2-(2,1,3-苯并噻二唑-5-基)-4-(4-异丙氧基苯基)-4-氧代丁酸乙酯与苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-苄基-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与2-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(2-甲氧苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与3-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲氧苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲氧苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与3,4-二甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧基苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与3,4,5-三甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,m.p.180℃与3,4-二异丙氧基-5-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧基苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,m.p.170℃与3,4,5-三异丙氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三异丙氧基苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与4-三氟甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-三氟甲基苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与4-氰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-氰基苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与4-甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲基苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与3-甲基-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲基-4-甲氧苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与4-叔丁基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-叔丁基苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与(2-甲氧羰基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与(2-羧基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-羧基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与4-乙氧羰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-乙氧羰基苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与4-苄氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-苄氧基苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与4-二甲氨基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-二甲氨基苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与4-硝基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-硝基苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与(1,3-苯并间二氧杂环戊烯-5-基)甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与3-氟-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-氟-4-甲氧基苄基)-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与3-(N,N-二甲氨基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔3-(N,N-二甲氨基)苄基〕-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,与环己烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环己基甲基-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮,和与环戊烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环戊基甲基-5-羟基-5-(4-异丙氧苯基)-5H-呋喃-2-酮。
类似地,由2-(2,1,3-苯并噻二唑-5-基)-4-(4-苄氧苯基)-4-氧代丁酸乙酯与苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-苄基-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与2-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(2-甲氧苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与3-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲氧苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲氧苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与3,4-二甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧基苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与3,4,5-三甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与3,4-二异丙氧基-5-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧基苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与3,4,5-三异丙氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三异丙氧基苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与4-三氟甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-三氟甲基苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与4-氰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-氰基苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与4-甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲基苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与3-甲基-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲基-4-甲氧苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与4-叔丁基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-叔丁基苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与(2-甲氧羰基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与(2-羧基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-羧基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与4-乙氧羰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-乙氧羰基苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与4-苄氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-苄氧基苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与4-二甲氨基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-二甲氨基苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与4-硝基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-硝基苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与(1,3-苯并间二氧杂环戊烯-5-基)甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与3-氟-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-氟-4-甲氧基苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与3-(N,N-二甲氨基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔3-(N,N-二甲氨基)苄基〕-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与环己烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环己基甲基-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,和与环戊烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环戊基甲基-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮。
类似地,由2-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲基苯基)-4-氧代丁酸乙酯与苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-苄基-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与2-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(2-甲氧苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与3-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲氧苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲氧苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与3,4-二甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧基苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与3,4,5-三甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与3,4-二异丙氧基-5-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧基苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与3,4,5-三异丙氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三异丙氧基苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与4-三氟甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-三氟甲基苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与4-氰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-氰基苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与4-甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲基苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与3-甲基-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲基-4-甲氧苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与4-叔丁基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-叔丁基苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与(2-甲氧羰基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与(2-羧基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-羧基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与4-乙氧羰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-乙氧羰基苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与4-苄氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-苄氧基苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与4-二甲氨基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-二甲氨基苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与4-硝基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-硝基苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与(1,3-苯并间二氧杂环戊烯-5-基)甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与3-氟-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-氟-4-甲氧基苄基)-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与3-(N,N-二甲氨基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔3-(N,N-二甲氨基)苄基〕-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,与环己烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环己基甲基-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮,和与环戊烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环戊基甲基-5-羟基-5-(3,4-二甲基苯基)-5H-呋喃-2-酮。
类似地,由2-(2,1,3-苯并噻二唑-5-基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代丁酸乙酯与苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-苄基-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,m.p.71℃与2-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(2-甲氧苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与3-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲氧苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲氧苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与3,4-二甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧基苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与3,4,5-三甲氧基苯甲醛反应得到3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,m.p.86℃与3,4-二异丙氧基-5-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧基苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与3,4,5-三异丙氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三异丙氧基苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-三氟甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-三氟甲基苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-氰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-氰基苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲基苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与3-甲基-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲基-4-甲氧苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-叔丁基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-叔丁基苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与(2-甲氧羰基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与(2-羧基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-羧基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-乙氧羰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-乙氧羰基苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-苄氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-苄氧基苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-二甲氨基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-二甲氨基苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-硝基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-硝基苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与(1,3-苯并间二氧杂环戊烯-5-基)甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与3-氟-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-氟-4-甲氧基苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与3-(N,N-二甲氨基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔3-(N,N-二甲氨基)苄基〕-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与环己烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环己基甲基-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,和与环戊烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环戊基甲基-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮。
类似地,由2-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苯基)-4-氧代丁酸乙酯与苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-苄基-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与2-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(2-甲氧苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与3-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲氧苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲氧苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与3,4-二甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧基苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与3,4,5-三甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,m.p.70℃与3,4-二异丙氧基-5-甲氧基苯甲醛反应得到3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧基苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,m.p.61℃与3,4,5-三异丙氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三异丙氧基苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与4-三氟甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-三氟甲基苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与4-氰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-氰基苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与4-甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲基苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与3-甲基-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲基-4-甲氧苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与4-叔丁基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-叔丁基苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与(2-甲氧羰基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与(2-羧基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-羧基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与4-乙氧羰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-乙氧羰基苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与4-苄氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-苄氧基苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与4-二甲氨基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-二甲氨基苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与4-硝基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-硝基苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与(1,3-苯并间二氧杂环戊烯-5-基)甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与3-氟-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-氟-4-甲氧基苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与3-(N,N-二甲氨基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔3-(N,N-二甲氨基)苄基〕-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与环己烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环己基甲基-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,和与环戊烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环戊基甲基-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮。
类似地,由2-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧基苯基)-4-氧代丁酸乙酯与苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-苄基-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与2-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(2-甲氧苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与3-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲氧苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲氧苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与3,4-二甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧基苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与3,4,5-三甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与3,4-二异丙氧基-5-甲氧基苯甲醛反应得到3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧基苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与3,4,5-三异丙氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三异丙氧基苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与4-三氟甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-三氟甲基苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与4-氰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-氰基苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与4-甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲基苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与3-甲基-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲基-4-甲氧苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与4-叔丁基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-叔丁基苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与(2-甲氧羰基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与(2-羧基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-羧基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与4-乙氧羰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-乙氧羰基苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与4-苄氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-苄氧基苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与4-二甲氨基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-二甲氨基苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与4-硝基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-硝基苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与(1,3-苯并间二氧杂环戊烯-5-基)甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与3-氟-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-氟-4-甲氧基苄基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与3-(N,N-二甲氨基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔3-(N,N-二甲氨基)苄基〕-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与环己烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环己基甲基-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,和与环戊烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环戊基甲基-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮。
类似地,由2-(2,1,3-苯并噻二唑-5-基)-4-(4-甲硫基苯基)-4-氧代丁酸乙酯与苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-苄基-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与2-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(2-甲氧苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与3-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲氧苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲氧苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与3,4-二甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧基苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与3,4,5-三甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与3,4-二异丙氧基-5-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧基苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与3,4,5-三异丙氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三异丙氧基苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与4-三氟甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-三氟甲基苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与4-氰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-氰基苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与4-甲基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲基苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与3-甲基-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲基-4-甲氧苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与4-叔丁基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-叔丁基苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与(2-甲氧羰基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与(2-羧基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(2-羧基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与4-乙氧羰基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-乙氧羰基苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与4-苄氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-苄氧基苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与4-二甲氨基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-二甲氨基苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与4-硝基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-硝基苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与(1,3-苯并间二氧杂环戊烯-5-基)甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与3-氟-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-氟-4-甲氧基苄基)-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与3-(N,N-二甲氨基)苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔3-(N,N-二甲氨基)苄基〕-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,与环己烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环己基甲基-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮,和与环戊烷甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-环戊基甲基-5-羟基-5-(4-甲硫基苯基)-5H-呋喃-2-酮。
类似地,由2-(2,1,3-苯并噁二唑-5-基)-4-(4-甲氧基苯基)-4-氧代丁酸乙酯与苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-苄基-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与2-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(2-甲氧苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与3-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(3-甲氧苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(4-甲氧苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与3,4-二甲氧基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(3,4-二甲氧基苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与3,4,5-三甲氧基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与3,4-二异丙氧基-5-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧基苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与3,4,5-三异丙氧基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(3,4,5-三异丙氧基苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与4-三氟甲基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(4-三氟甲基苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与4-氰基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(4-氰基苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与4-甲基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(4-甲基苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与3-甲基-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(3-甲基-4-甲氧苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与4-叔丁基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(4-叔丁基苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与(2-甲氧羰基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与(2-羧基甲氧基-4-甲氧基)苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-〔(2-羧基甲氧基-4-甲氧基)苄基〕-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与4-乙氧羰基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(4-乙氧羰基苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与4-苄氧基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(4-苄氧基苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与4-二甲氨基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(4-二甲氨基苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与4-硝基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(4-硝基苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与(1,3-苯并间二氧杂环戊烯-5-基)甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与3-氟-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-(3-氟-4-甲氧基苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与3-(N,N-二甲氨基)苯甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-〔3-(N,N-二甲氨基)苄基〕-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,与环己烷甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-环己基甲基-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮,和与环戊烷甲醛反应得到
3-(2,1,3-苯并噁二唑-5-基)-4-环戊基甲基-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮。实施例2
将0.7ml 0.1N NaOH加入30mg 3-(2,1,3-苯并噻二唑-5-基)-4-苄基-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮在1ml甲醇中的悬浮液中并在室温下搅拌混合物。除去溶剂,将残余物分配于水和***之间,然后冻干水相。得到2-(2,1,3-苯并噻二唑-5-基)-3-苄基-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,FAB 453。
类似地,用NaOH处理实施例1中所述的呋喃衍生物,得到相应开链4-氧代-2-丁烯酸衍生物的钠盐:
2-(2,1,3-苯并噻二唑-5-基)-3-(2-甲氧苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲氧苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲氧苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二甲氧苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三甲氧苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,m.p.245℃(分解)
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二异丙氧基-5-甲氧苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,FAB 599
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三异丙氧基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-三氟甲基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-氰基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲基-4-甲氧基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-叔丁基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-羧基甲氧基-4-甲氧基)苄基〕-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-乙氧羰基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-苄氧基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-硝基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-二甲氨基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-氟-4-甲氧基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔3-(N,N-二甲氨基)苄基〕-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(环己基甲基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(环戊基甲基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠。
2-(2,1,3-苯并噻二唑-5-基)-3-苄基-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,FAB 481
2-(2,1,3-苯并噻二唑-5-基)-3-(2-甲氧苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲氧苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲氧苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二甲氧苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三甲氧苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,m.p.76℃
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二异丙氧基-5-甲氧苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,m.p.70℃
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三异丙氧基苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-三氟甲基苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-氰基苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲基苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲基-4-甲氧基苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-叔丁基苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-羧基甲氧基-4-甲氧基)苄基〕-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-乙氧羰基苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-苄氧基苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-硝基苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-二甲氨基苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-氟-4-甲氧基苄基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔3-(N,N-二甲氨基)苄基〕-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(环己基甲基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(环戊基甲基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠。
2-(2,1,3-苯并噻二唑-5-基)-3-苄基-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(2-甲氧苄基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲氧苄基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲氧苄基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二甲氧苄基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三甲氧苄基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二异丙氧基-5-甲氧苄基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三异丙氧基苄基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-三氟甲基苄基)-5-羟基-5-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-氰基苄基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲基苄基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲基-4-甲氧基苄基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-叔丁基苄基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-羧基甲氧基-4-甲氧基)苄基〕-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-乙氧羰基苄基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-苄氧基苄基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-硝基苄基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-二甲氨基苄基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-氟-4-甲氧基苄基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔3-(N,N-二甲氨基)苄基〕-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(环己基甲基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠,和
2-(2,1,3-苯并噻二唑-5-基)-3-(环戊基甲基)-4-(4-甲基苯基)-4-氧代-2-丁烯酸钠。
2-(2,1,3-苯并噻二唑-5-基)-3-苄基-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(2-甲氧苄基)-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲氧苄基)-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲氧苄基)-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二甲氧苄基)-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三甲氧苄基)-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二异丙氧基-5-甲氧苄基)-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三异丙氧基苄基)-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-三氟甲基苄基)-5-羟基-5-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-氰基苄基)-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲基苄基)-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲基-4-甲氧基苄基)-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-叔丁基苄基)-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-羧基甲氧基-4-甲氧基)苄基〕-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-乙氧羰基苄基)-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-苄氧基苄基)-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-硝基苄基)-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-二甲氨基苄基)-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-氟-4-甲氧基苄基)-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔3-(N,N-二甲氨基)苄基〕-4-苯基-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(环己基甲基)-4-苯基-4-氧代-2-丁烯酸钠,和
2-(2,1,3-苯并噻二唑-5-基)-3-(环戊基甲基)-4-苯基-4-氧代-2-丁烯酸钠。
2-(2,1,3-苯并噻二唑-5-基)-3-苄基-4-(4-异丙氧基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(2-甲氧苄基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲氧苄基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲氧苄基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二甲氧苄基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三甲氧苄基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二异丙氧基-5-甲氧苄基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三异丙氧基苄基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-三氟甲基苄基)-5-羟基-5-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-氰基苄基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲基苄基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲基-4-甲氧基苄基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-叔丁基苄基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-羧基甲氧基-4-甲氧基)苄基〕-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-乙氧羰基苄基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-苄氧基苄基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-硝基苄基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-二甲氨基苄基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-氟-4-甲氧基苄基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔3-(N,N-二甲氨基)苄基〕-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(环己基甲基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠,和
2-(2,1,3-苯并噻二唑-5-基)-3-(环戊基甲基)-4-(4-异丙氧苯基)-4-氧代-2-丁烯酸钠。
2-(2,1,3-苯并噻二唑-5-基)-3-苄基-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(2-甲氧苄基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲氧苄基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲氧苄基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二甲氧苄基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三甲氧苄基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二异丙氧基-5-甲氧苄基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三异丙氧基苄基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-三氟甲基苄基)-5-羟基-5-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-氰基苄基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲基苄基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲基-4-甲氧基苄基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-叔丁基苄基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-羧基甲氧基-4-甲氧基)苄基〕-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-乙氧羰基苄基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-苄氧基苄基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-硝基苄基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-二甲氨基苄基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-氟-4-甲氧基苄基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔3-(N,N-二甲氨基)苄基〕-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(环己基甲基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠,和
2-(2,1,3-苯并噻二唑-5-基)-3-(环戊基甲基)-4-(4-苄氧苯基)-4-氧代-2-丁烯酸钠。
2-(2,1,3-苯并噻二唑-5-基)-3-苄基-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(2-甲氧苄基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲氧苄基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲氧苄基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二甲氧苄基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三甲氧苄基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二异丙氧基-5-甲氧苄基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三异丙氧基苄基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-三氟甲基苄基)-5-羟基-5-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-氰基苄基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲基苄基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲基-4-甲氧基苄基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-叔丁基苄基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-羧基甲氧基-4-甲氧基)苄基〕-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-乙氧羰基苄基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-苄氧基苄基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-硝基苄基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-二甲氨基苄基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-氟-4-甲氧基苄基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔3-(N,N-二甲氨基)苄基〕-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(环己基甲基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠,和
2-(2,1,3-苯并噻二唑-5-基)-3-(环戊基甲基)-4-(3,4-二甲基苯基)-4-氧代-2-丁烯酸钠。
2-(2,1,3-苯并噻二唑-5-基)-3-苄基-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(2-甲氧苄基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲氧苄基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲氧苄基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二甲氧苄基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三甲氧苄基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,FAB 557
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二异丙氧基-5-甲氧苄基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三异丙氧基苄基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-三氟甲基苄基)-5-羟基-5-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-氰基苄基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲基苄基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲基-4-甲氧基苄基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-叔丁基苄基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-羧基甲氧基-4-甲氧基)苄基〕-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-乙氧羰基苄基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-苄氧基苄基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-硝基苄基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-二甲氨基苄基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-氟-4-甲氧基苄基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔3-(N,N-二甲氨基)苄基〕-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(环己基甲基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠,和
2-(2,1,3-苯并噻二唑-5-基)-3-(环戊基甲基)-4-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代-2-丁烯酸钠。
2-(2,1,3-苯并噻二唑-5-基)-3-苄基-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(2-甲氧苄基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲氧苄基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲氧苄基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二甲氧苄基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三甲氧苄基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二异丙氧基-5-甲氧苄基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三异丙氧基苄基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-三氟甲基苄基)-5-羟基-5-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-氰基苄基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲基苄基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲基-4-甲氧基苄基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-叔丁基苄基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-羧基甲氧基-4-甲氧基)苄基〕-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-乙氧羰基苄基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-苄氧基苄基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-硝基苄基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-二甲氨基苄基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-氟-4-甲氧基苄基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔3-(N,N-二甲氨基)苄基〕-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(环己基甲基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠,和
2-(2,1,3-苯并噻二唑-5-基)-3-(环戊基甲基)-4-(3,4,5-三甲氧苯基)-4-氧代-2-丁烯酸钠。
2-(2,1,3-苯并噻二唑-5-基)-3-苄基-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(2-甲氧苄基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲氧苄基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲氧苄基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二甲氧苄基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三甲氧苄基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二异丙氧基-5-甲氧苄基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三异丙氧基苄基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-三氟甲基苄基)-5-羟基-5-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-氰基苄基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲基苄基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲基-4-甲氧基苄基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-叔丁基苄基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-羧基甲氧基-4-甲氧基)苄基〕-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-乙氧羰基苄基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-苄氧基苄基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-硝基苄基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-二甲氨基苄基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-氟-4-甲氧基苄基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔3-(N,N-二甲氨基)苄基〕-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(环己基甲基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠,和
2-(2,1,3-苯并噻二唑-5-基)-3-(环戊基甲基)-4-(3,4-二甲氧苯基)-4-氧代-2-丁烯酸钠。
2-(2,1,3-苯并噻二唑-5-基)-3-苄基-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(2-甲氧苄基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲氧苄基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲氧苄基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二甲氧苄基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三甲氧苄基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二异丙氧基-5-甲氧苄基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三异丙氧基苄基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-三氟甲基苄基)-5-羟基-5-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-氰基苄基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲基苄基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-甲基-4-甲氧基苄基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-叔丁基苄基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(2-羧基甲氧基-4-甲氧基)苄基〕-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-乙氧羰基苄基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-苄氧基苄基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-硝基苄基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(4-二甲氨基苄基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(3-氟-4-甲氧基苄基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-〔3-(N,N-二甲氨基)苄基〕-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噻二唑-5-基)-3-(环己基甲基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠,和
2-(2,1,3-苯并噻二唑-5-基)-3-(环戊基甲基)-4-(4-甲硫基苯基)-4-氧代-2-丁烯酸钠。
2-(2,1,3-苯并噁二唑-5-基)-3-苄基-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(2-甲氧苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(3-甲氧苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(4-甲氧苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(3,4-二甲氧苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(3,4,5-三甲氧苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(3,4-二异丙氧基-5-甲氧苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(3,4,5-三异丙氧基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(4-三氟甲基苄基)-5-羟基-5-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(4-氰基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(4-甲基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(3-甲基-4-甲氧基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(4-叔丁基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-〔(2-甲氧羰基甲氧基-4-甲氧基)苄基〕-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-〔(2-羧基甲氧基-4-甲氧基)苄基〕-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(4-乙氧羰基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(4-苄氧基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(4-硝基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(4-二甲氨基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(3-氟-4-甲氧基苄基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-〔3-(N,N-二甲氨基)苄基〕-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,
2-(2,1,3-苯并噁二唑-5-基)-3-(环己基甲基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠,和
2-(2,1,3-苯并噁二唑-5-基)-3-(环戊基甲基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠。实施例3
将0.38g苯甲醛和1.20g 4-(2,1,3-苯并噻二唑-5-基)-2-(1,3-苯并间二氧杂环戊烯-5-基)-4-氧代丁酸乙酯(“B”)加入80mg钠在5ml甲醇中的溶液中并在回流下加热混合物1小时。加入5ml乙酸后,再加热混合物16小时。除去溶剂并按常规方式处理。得到无定形5-(2,1,3-苯并噻二唑-5-基)-4-苄基-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮。
类似地,由“B”与4-甲氧基苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(4-甲氧苯基甲基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与3,4-二甲氧基苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧基苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与3,4,5-三甲氧基苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与3,4-二异丙氧基-5-甲氧基苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与3,4,5-三异丙氧基苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三异丙氧基苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-氯苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(4-氯苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-溴苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(4-溴苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-三氟甲基苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(4-三氟甲基苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-氰基苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(4-氰基苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-甲基苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(4-甲基苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与3-甲基-4-甲氧基苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(3-甲基-4-甲氧苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-叔丁基苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(4-叔丁基苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与(2-甲氧羰基甲氧基-4-甲氧基)苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-[(2-甲氧羰基甲氧基-4-甲氧基)苄基]-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与(2-羧基甲氧基-4-甲氧基)苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-[(2-羧基甲氧基-4-甲氧基)苄基]-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-乙氧羰基苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(4-乙氧羰基苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-甲磺酰基苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(4-甲磺酰基苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-苄氧基苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(4-苄氧基苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-二甲氨基苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(4-二甲氨基苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-硝基苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(4-硝基苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与4-甲酰基苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(4-甲酰基苄基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与(1,3-苯并间二氧杂环戊烯-5-基)甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-〔(1,3-苯并间二氧杂环戊烯-5-基)甲基〕-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基氧基)苯甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-〔2-(1,3-苯并间二氧杂环戊烯-5-基氧基)苄基]-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,与环己烷甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(环己基甲基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮,和与环戊烷甲醛反应得到
5-(2,1,3-苯并噻二唑-5-基)-4-(环戊基甲基)-5-羟基-3-(1,3-苯并间二氧杂环戊烯-5-基)-5H-呋喃-2-酮。实施例4
将0.5g(2,1,3-苯并噻二唑-5-基)甲醛(“C”)和1.20g 2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(4-甲氧苯基)-4-氧代丁酸乙酯加入80mg钠在5ml甲醇中的溶液中并在回流下加热混合物1小时。加入5ml乙酸后,再加热16小时。除去溶剂并按常规方式处理残余物。得到4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(甲氧苯基)-5H-呋喃-2-酮,m.p.172℃。
类似地,由“C”与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(3,4-二甲氧苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(3,4-二甲氧苯基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(3,4,5-三甲氧苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(3,4,5-三甲氧苯基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(3,4-二异丙氧基-5-甲氧苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(3,4-二异丙氧基-5-甲氧苯基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(3,4,5-三异丙氧基苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(3,4,5-三异丙氧基苯基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(4-氯苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(4-氯苯基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(4-溴苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(4-溴苯基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(4-三氟甲基苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(4-三氟甲基苯基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(4-氰基苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(4-氰基苯基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(4-甲基苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(4-甲基苯基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(3-甲基-4-甲氧苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(3-甲基-4-甲氧苯基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(4-叔丁基苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(4-叔丁基苯基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-〔(2-甲氧羰基甲氧基-4-甲氧基)苯基])-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(2-甲氧羰基甲氧基-4-甲氧基)苯基]-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-〔(2-羧基甲氧基-4-甲氧基)苯基]-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(2-羧基甲氧基-4-甲氧基)苯基]-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(4-乙氧羰基苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(4-乙氧羰基苯基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(4-甲磺酰基苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(4-甲磺酰基苯基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(4-苄氧苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(4-二甲氨基苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(4-二甲氨基苯基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(4-硝基苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(4-硝基苯基)-5H-呋喃-2-酮,与2-(1,3-苯并间二氧杂环戊烯-5-基)-3-(4-甲酰基苯基)-4-氧代丁酸乙酯反应得到
4-(2,1,3-苯并噻二唑-5-基甲基)-3-(1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(4-甲酰基苯基)-5H-呋喃-2-酮。实施例5
将1g 3-(2,1,3-苯并噻二唑-5-基)-4-(4-硝基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮在25ml甲醇中的溶液在常压和20℃下在1g Raney镍上氢化完全。过滤混合物,除去溶剂,得到3-(2,1,3-苯并噻二唑-5-基)-4-(4-氨基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮。实施例6
通过与等摩尔量的乙酰氯和催化量的二甲氨基吡啶在吡啶中反应,由3-(2,1,3-苯并噻二唑-5-基)-4-(4-氨基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-乙酰氨基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮。实施例7
通过与等摩尔量的异氰酸苯基酯在二氯甲烷中反应,由3-(2,1,3-苯并噻二唑-5-基)-4-(4-氨基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔4-(苯基脲基)苄基〕-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮。实施例8
通过与等摩尔量的异氰酸丁基酯在二氯甲烷中反应,由3-(2,1,3-苯并噻二唑-5-基)-4-(4-氨基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮得到
3-(2,1,3-苯并噻二唑-5-基)-4-[4-(丁基脲基)苄基]-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮。实施例9
通过与等摩尔量的NaH和丁基碘在THF中反应由3-(2,1,3-苯并噻二唑-5-基)-4-(4-乙酰氨基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔4-(N-丁基乙酰氨基)苄基〕-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮。实施例10
通过与等摩尔量的丁基磺酰氯和碳酸铯在DMF中反应由3-(2,1,3-苯并噻二唑-5-基)-4-(4-氨基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔4-(丁基磺酰氨基)苄基〕-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮。
通过与甲苯磺酰氯的类似反应由3-(2,1,3-苯并噻二唑-5-基)-4-(4-氨基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔4-(甲苯磺酰氨基)苄基〕-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮。实施例11
通过用10ml KOH溶液在20ml乙醇中处理0.25g 3-(2,1,3-苯并噻二唑-5-基)-4-〔4-(N-丁基乙酰氨基)苄基〕-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,在常规处理后得到2-(2,1,3-苯并噻二唑-5-基)-3-〔4-(N-丁基氨基)苄基〕-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钾。实施例12
通过使等摩尔量的4,4'-二甲氧基苯偶酰与1-(2,1,3-苯并噻二唑-5-基)乙酸乙酯和等摩尔量的乙醇钠在乙醇中反应,在常规处理之后得到2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲氧苯基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸乙酯。
随后用氢氧化钠溶液进行酯的水解,得到2-(2,1,3-苯并噻二唑-5-基)-3-(4-甲氧苯基)-4-(4-甲氧苯基)-4-氧代-2-丁烯酸钠。实施例13
类似于实施例1,由2-(2,1,3-苯并噻二唑-6-甲氧基-5-基)-4-(1,4-苯并二噁烷-6-基)-4-氧代丁酸乙酯与环己烷甲醛反应得到
3-(2,1,3-苯并噻二唑-6-甲氧基-5-基)-4-环己基甲基-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮。
通过用氢氧化钠溶液类似于实施例2进行处理,得到2-(2,1,3-苯并噻二唑-6-甲氧基-5-基)-3-(环己基甲基)-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸钠。实施例14
类似于实施例1,由2-(2,1,3-苯并噻二唑-5-基)-4-(3-氟-4-甲氧苯基)-4-氧代丁酸乙酯(“D”)与苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-苄基-5-羟基-5-(3-氟-4-甲氧苯基)-5H-呋喃-2-酮,m.p.65℃由“D”与3,4,5-三甲氧基苯甲醛(“E”)反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧苄基)-5-羟基-5-(3-氟-4-甲氧苯基)-5H-呋喃-2-酮,FAB 539,类似于实施例2,由该化合物得到
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三甲氧基苄基)-4-(3-氟-4-甲氧苯基)-4-氧代-2-丁烯酸钠,m.p.254℃(分解),由“A”与(7-甲氧基-1,3-苯并间二氧杂环戊烯-5-基)甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-〔(7-甲氧基-13-苯并间二氧杂环戊烯-5-基)甲基〕-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.61℃由2-(2,1,3-苯并噻二唑-5-基)-4-(3-甲氧苯基)-4-氧代丁酸乙酯与“E”反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧苄基)-5-羟基-5-(3-甲氧苯基)-5H-呋喃-2-酮,m.p.61℃由2-(2,1,3-苯并噻二唑-5-基)-4-(2-甲氧苯基)-4-氧代丁酸乙酯与“E”反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧苄基)-5-羟基-5-(2-甲氧苯基)-5H-呋喃-2-酮,m.p.180℃由“A”与4-甲硫基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲硫基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.64 ℃由“A”与3-苄氧基-4-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3-苄氧基-4-甲氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮m.p.58℃由“A”与(2,3-二氢苯并呋喃-5-基)甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(2,3-二氢苯并呋喃-5-基甲基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.74℃由“A”与异丁醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(2-甲基丙基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.129℃由“A”与3,5-二甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,5-二甲氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.54℃由“A”与4-叔丁氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-叔丁氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.68℃,通过与TFA反应,由该化合物得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-羟基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.83℃由“A”与4-三氟甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-三氟甲氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.56℃由“A”与3,5-二甲氧基-4-异丙氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,5-二甲氧基-4-异丙氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.62℃由“A”与4-3,5-二甲氧基-4-戊氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,5-二甲氧基-4-戊氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,FAB 576由“A”与3,5-二甲氧基-4-己氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,5-二甲氧基-4-己氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,FAB 590由“A”与4-苯氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4-苯氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.70℃由“A”与4,5-二甲氧基-3-异丙氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(4,5-二甲氧基-3-异丙氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,EI 548由2-(2,1,3-苯并噻二唑-5-基)-4-(2,5-二甲氧基苯基)-4-氧代丁酸乙酯与“E”反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(2,5-二甲氧苯基)-5H-呋喃-2-酮,m.p.73℃由2-(2,1,3-苯并噻二唑-5-基)-4-(3-氯-4-甲氧苯基)-4-氧代丁酸乙酯与“E”反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(3-氯-4-甲氧苯基)-5H-呋喃-2-酮,m.p.158℃由2-(2,1,3-苯并噻二唑-5-基)-4-(3-甲基-4-甲氧苯基)-4-氧代丁酸乙酯与“E”反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(3-甲基-4-甲氧苯基)-5H-呋喃-2-酮,m.p.80℃由2-(2,1,3-苯并噻二唑-5-基)-4-(2,5-二甲氧基苯基)-4-氧代丁酸乙酯与3,4-二异丙氧基-5-甲氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧基苄基)-5-羟基-5-(2,5-二甲氧苯基)-5H-呋喃-2-酮,m.p.70℃由2-(2,1,3-苯并噻二唑-5-基)-4-(2,3-二氢苯并呋喃-5-基)-4-氧代丁酸乙酯与“E”反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(2,3-二氢苯并呋喃-5-基)-5H-呋喃-2-酮,EI 532由2-(2,1,3-苯并噻二唑-5-基)-4-(3-氟-4-甲氧苯基)-4-氧代丁酸乙酯与3,5-二甲氧基-4-异丙氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,5-二甲氧基-4-异丙氧基苄基)-5-羟基-5-(3-氟-4-甲氧苯基)-5H-呋喃-2-酮,EI 566由“A”与3,4-二甲氧基-5-丙氧基苯甲醛反应得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧基-5-丙氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.70℃
类似地,得到下列化合物:
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧基苄基)-5-羟基-5-(4-丙氧苯基)-5H-呋喃-2-酮,m.p.150℃
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧基苄基)-5-羟基-5-(2,4-二甲氧苯基)-5H-呋喃-2-酮,m.p.164℃
3-(2,1,3-苯并噻二唑-5-基)-4-(4-苄氧基-2-甲氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,EI 566
3-(2,1,3-苯并噻二唑-5-基)-4-(2,3,4-三甲氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.70℃
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(2,4-二甲氧苯基)-5H-呋喃-2-酮,m.p.70℃
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三乙氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.139℃
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(4-二氟甲氧苯基)-5H-呋喃-2-酮,FAB 557
3-(2,1,3-苯并噻二唑-5-基)-4-(3-羟基-4-甲氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,FAB 477
3-(2,1,3-苯并噻二唑-5-基)-4-(2,4-二甲氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,EI 490
3-(2,1,3-苯并噻二唑-5-基)-4-(2,4,5-三甲氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.70℃
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(3-氟-4-异丙氧苯基)-5H-呋喃-2-酮,FAB 567
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(3-氟-4-丙氧苯基)-5H-呋喃-2-酮,FAB 567
3-(2,1,3-苯并噻二唑-6-甲基-5-基)-4-(3,5-二甲氧基-4-异丙氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.74℃
3-(2,1,3-苯并噻二唑-5-基)-4-(3,5-二甲氧基-4-苄氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.61℃,通过与三氟乙酸/茴香硫醚反应由该化合物得到
3-(2,1,3-苯并噻二唑-5-基)-4-(3,5-二甲氧基-4-羟基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.69℃
3-(2,1,3-苯并噻二唑-5-基)-4-(3,5-二甲氧基-4-丙氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.60℃
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧基-5-异丙氧基苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,FAB 577
3-(2,1,3-苯并噻二唑-6-甲基-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.183℃
3-(2,1,3-苯并噻二唑-5-基)-4-(4-异丙氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,FAB489
3-(2,1,3-苯并噻二唑-5-基)-4-(4-己氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,FAB 531
3-(2,1,3-苯并噻二唑-5-基)-4-(3,5-二甲氧基-4-异丙氧基苄基)-5-羟基-5-(1,4-苯并二噁烷-6-基)-5H-呋喃-2-酮,m.p.145℃
3-(2,1,3-苯并噻二唑-5-基)-4-(3-甲氧基-5-丁氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,FAB 533
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.52℃
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(2-氟-4-甲氧苯基)-5H-呋喃-2-酮,FAB 539
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧基-5-异丙氧基苄基)-5-羟基-5-(3-氟-4-甲氧苯基)-5H-呋喃-2-酮,m.p.126℃
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二甲氧基-5-苄氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,FAB 597
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(4-氟-2-甲氧苯基)-5H-呋喃-2-酮,FAB 539
3-(2,1,3-苯并噻二唑-5-基)-4-(3,5-二甲氧基-5-乙氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.123℃
3-(2,1,3-苯并噻二唑-5-基)-4-(4-甲氧羰基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.71℃
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基苄基)-5-羟基-5-(3-氟-4-甲氧苯基)-5H-呋喃-2-酮,FAB 565
3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(4-苄氧苯基)-5H-呋喃-2-酮,FAB 489
3-(2,1,3-苯并噻二唑-4-甲基-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.168℃
3-(2,1,3-苯并噻二唑-5-基)-4-(3,5-二甲氧基-4-异丁氧基苄基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.154℃以及实施例15
通过“C”与2-(7-甲氧基-1,3-苯并间二氧杂环戊烯-5-基)-4-(4-甲氧苯基)-4-氧代丁酸乙酯反应,类似于实施例4得到下列化合物:
4-(2,1,3-苯并噻二唑-5-基)-3-(7-甲氧基-1,3-苯并间二氧杂环戊烯-5-基)-5-羟基-5-(4-甲氧苯基)-5H-呋喃-2-酮,m.p.191℃。实施例16
类似于实施例2,由3-(2,1,3-苯并噻二唑-5-基)-4-(3,4-二异丙氧基-5-甲氧基苄基)-5-羟基-5-(3-氟-4-甲氧基苯基)-5H-呋喃-2-酮得到
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二异丙氧基-5-甲氧基苄基)-4-(3-氟-4-甲氧基苯基)-4-氧代-2-丁烯酸钠,FAB 617
由3-(2,1,3-苯并噻二唑-5-基)-4-(3,5-二甲氧基-4-异丙氧基苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮得到
2-(2,1,3-苯并噻二唑-5-基)-3-(3,5-二甲氧基-4-异丙氧基苄基)-4-(4-甲氧基苯基)-4-氧代-2-丁烯酸钠,m.p.65℃。
类似地得到下列化合物:
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4-二甲氧基-5-异丙氧基苄基)-4-(4-甲氧基苯基)-4-氧代-2-丁烯酸钠,m.p.57℃和
2-(2,1,3-苯并噻二唑-5-基)-3-(3,5-二甲氧基-4-异丙氧基苄基)-4-(3-氟-4-甲氧基苯基)-4-氧代-2-丁烯酸钠,FAB 589。
类似地,用KOH处理得到下列化合物:
2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三甲氧基苄基)-4-(4-甲氧基苯基)-4-氧代-2-丁烯酸钾,m.p.202℃。
下列实施例涉及药物制剂:
实施例A:注射瓿:
将100g式Ⅰ活性化合物和5g磷酸氢二钠在3升二次蒸馏水中的溶液用2N盐酸调节至pH6.5,无菌过滤,填充到注射瓿中并在无菌条件下冻干,无菌密封该瓿。各注射瓿含5mg活性化合物。
实施例B:栓剂
将20g式Ⅰ活性化合物与100g大豆卵磷脂和1400g可可脂的混合物融合,倾入模具中并冷却。各栓剂含20mg活性化合物。
实施例C:溶液
由1g式Ⅰ活性化合物、9.38g NaH2PO4·2H2O、28.48gNa2HPO4·12H2O和0.1g氯苄烷铵制备在940ml二次蒸馏水中的溶液。将pH调至6.8,将该溶液配成1升并辐照灭菌。
实施例D:软膏
将500mg式Ⅰ活性化合物与99.5g凡士林在无菌条件下混合。
实施例E:片剂
将1kg式Ⅰ活性化合物、4kg乳糖、1.2kg土豆淀粉、0.2kg滑石和0.1kg硬脂酸镁的混合物以常规方式压缩,得到各片含有10mg活性化合物的片剂。
实施例F:包衣片剂
类似于实施例E,压制片剂,然后用蔗糖、土豆淀粉、滑石、黄蓍胶和着色剂的涂料以常规方式包覆。
实施例G:胶囊
将2kg式Ⅰ活性化合物以常规方式填充到硬明胶胶囊中,各胶囊含有20mg活性化合物。
实施例H:安瓿
将1kg式Ⅰ活性化合物在60升二次蒸馏水中的溶液无菌过滤,填充到安瓿中,在无菌条件下冻干,并无菌密封安瓿。各安瓿含10mg活性化合物。
Claims (9)
1.式Ⅰ化合物或一种互变异构的闭环形式,以及(E)异构体和所有异构体的盐:其中R是 或
X是O或S,R1是H、Hal、OH、OA、A、亚烷基-O-A、NO2、NH2、NH酰基、SO2NH2、SO3-A、SO2NHA、CN或甲酰基,R2、R3、R4各自相互独立地是苯基,该苯基未被取代或由Hal、OH、OA、O-亚烷基-R5、A、S-A、S-OA、SO2A、S-OR5、SO2R5、NO2、NH2、NHA、NA2、NH酰基、NHSO2A、NHSO2R5、NASO2A、NASO2-R5、NH(CO)NH2、NH(CO)NHA、甲酰基、NH(CO)NHR5、NHCOOA、NA酰基、NHCOOCH2R5、NHSO2CH2R5、NHCOO-亚烷基-OA、NH(CO)NA2、1-哌啶基-CO-NH、1-吡咯烷基-CONH、O(CH2)nCOOA、O(CH2)nCOOH、O(CH2)nOH、O(CH2)nOA、CH2OA、CH2OH、COOH、COOA、CH2COOH或CH2COOA单取代或多取代,或为如下基团其中R2还可以为A或环烷基,R5为苯基,该苯基未被取代或由Hal、OH、OA、A、S-A、NO2、NH2、NHA、NA2、NH酰基、NHSO2A、NASO2A、NH(CO)NH2、NH(CO)NHA、甲酰基、NHCOOA、NA酰基、NHCOO-亚烷基-OA、NH(CO)NA2、N-哌啶基-CO-NH、N-吡咯烷基-CONH、O(CH2)nCOOA、O(CH2)nCOOH、O(CH2)nOH、O(CH2)nOA、CH2OH、CH2OA、COOH、COOA、CH2COOH或CH2COOA单取代或多取代,A为具有1-6个碳原子的烷基,其中一个或两个CH2基团可以用O或S原子或用-CR6=CR6'基团替代和/或1-7个H原子可以用F替代,D为羰基或〔C(R6R6')〕m,E为CH2、S或O,Y为O或S,R6和R6'各自相互独立地为H、F或A,Hal为氟、氯、溴或碘,n为0、1或2,以及m为1或2。
2.根据权利要求1的如下化合物及其盐:a)2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三甲氧基苄基)-4-(4-甲氧基苯基)-4-氧代-2-丁烯酸;b)2-(2,1,3-苯并噻二唑-5-基)-3-(3,4,5-三甲氧基苄基)-4-(3-氟-4-甲氧基苯基)-4-氧代-2-丁烯酸;c)3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(4-甲氧基苯基)-5H-呋喃-2-酮;d)3-(2,1,3-苯并噻二唑-5-基)-4-(3,4,5-三甲氧基苄基)-5-羟基-5-(3-氟-4-甲氧基苯基)-5H-呋喃-2-酮;e)2-(2,1,3-苯并噻二唑-5-基)-3-苄基-4-(1,4-苯并二噁烷-6-基)-4-氧代-2-丁烯酸;f)2-(2,1,3-苯并噻二唑-5-基)-3-苄基-4-(3-氟-4-甲氧基苯基)-4-氧代-2-丁烯酸;g)2-(2,1,3-苯并噻二唑-5-基)-3-环己基甲基-4-(3-氟-4-甲氧基苯基)-4-氧代-2-丁烯酸;h)2-(2,1,3-苯并噻二唑-5-基)-3-[3-(N,N-二甲氨基)苄基]-4-(4-甲氧基苯基)-4-氧代-2-丁烯酸。
R2-(CH2)k-CHO Ⅲ其中R2具有权利要求1中所述含义,而k为0或1,然后使酯断裂,或者,为了制备根据权利要求1的式Ⅰ化合物及其盐,其中b)R为
使式Ⅳ化合物其中R1、R4和X具有权利要求1所述含义,而A为具有1-4个碳原子的烷基或苄基,与上述式Ⅲ化合物反应,然后使酯断裂,或者,为了制备根据权利要求1的式Ⅰ化合物及其盐,其中c)R为
使式Ⅴ化合物其中R3和R4具有权利要求1所述含义,而A为具有1-4个碳原子的烷基或苄基,与式Ⅵ化合物反应,其中R1和X具有权利要求1所述含义,而k为0或1,然后使酯断裂,和/或其特征在于,使式Ⅰ化合物中的一个或多个基团R1、R2、R3和/或R4通过例如如下方式转化为一个或多个基团R1、R2、R3和/或R4:
ⅰ)将硝基还原为氨基,
ⅱ)酰基化或烷基化氨基,
ⅲ)将氨基转化为磺酰氨基,和/或将式Ⅰ的碱或酸转化为其盐的一种。
4.生产药物制剂的方法,其特征在于将根据权利要求1的式Ⅰ化合物和/或其一种生理上可接受的盐与至少一种固体、液体或半液体赋形剂或助剂一起制成适当的剂形。
5.药物制剂,其特征在于它含有至少一种根据权利要求1的式Ⅰ化合物和/或其一种生理上可接受的盐。
6.根据权利要求1的式Ⅰ化合物和其生理上可接受的盐,用于控制高血压,心机能不全,肾机能不全,脑梗塞,冠心病,肾部、大脑和心肌局部缺血,蛛网膜下出血,发炎,哮喘和内毒素休克。
7.根据权利要求1的式Ⅰ药物及其生理上可接受的盐,用作内皮素受体拮抗剂。
8.根据权利要求1的式Ⅰ化合物和/或其生理上可接受的盐在生产药物中的用途。
9.根据权利要求1的式Ⅰ化合物和/或其生理上可接受的盐在控制高血压,心机能不全,肾机能不全,脑梗塞,冠心病,肾部、大脑和心肌局部缺血,蛛网膜下出血,发炎,哮喘和内毒素休克中的用途。
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DE19710831A1 (de) * | 1997-03-15 | 1998-09-17 | Merck Patent Gmbh | Endothelin-Rezeptor-Antagonisten |
DE19712141A1 (de) * | 1997-03-22 | 1998-09-24 | Merck Patent Gmbh | Endothelin-Rezeptor-Antagonisten |
DE19731571A1 (de) * | 1997-07-23 | 1999-01-28 | Merck Patent Gmbh | Endothelin-Rezeptor-Antagonisten |
DE10155076A1 (de) * | 2001-11-09 | 2003-05-22 | Merck Patent Gmbh | Verwendung von Endothelin-Rezeptor-Antagonisten zur Behandlung von Tumorerkrankungen |
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DE19509950A1 (de) * | 1995-03-18 | 1996-09-19 | Merck Patent Gmbh | Endothelin-Rezeptor-Antagonisten |
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1996
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- 1997-02-20 UA UA98094979A patent/UA51696C2/uk unknown
- 1997-02-20 EP EP97905065A patent/EP0882030B1/de not_active Expired - Lifetime
- 1997-02-20 RU RU98117806/04A patent/RU2175320C2/ru not_active IP Right Cessation
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- 1997-02-20 CN CN97193959A patent/CN1072660C/zh not_active Expired - Fee Related
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AU1875797A (en) | 1997-09-10 |
US6017939A (en) | 2000-01-25 |
DE19607096A1 (de) | 1997-08-28 |
CN1072660C (zh) | 2001-10-10 |
UA51696C2 (uk) | 2002-12-16 |
EP0882030B1 (de) | 2001-09-12 |
AU721203B2 (en) | 2000-06-29 |
PT882030E (pt) | 2002-03-28 |
ATE205486T1 (de) | 2001-09-15 |
EP0882030A1 (de) | 1998-12-09 |
DE59704603D1 (de) | 2001-10-18 |
RU2175320C2 (ru) | 2001-10-27 |
ES2164328T3 (es) | 2002-02-16 |
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