CN1120837A - 吡唑衍生物 - Google Patents
吡唑衍生物 Download PDFInfo
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- CN1120837A CN1120837A CN94191705A CN94191705A CN1120837A CN 1120837 A CN1120837 A CN 1120837A CN 94191705 A CN94191705 A CN 94191705A CN 94191705 A CN94191705 A CN 94191705A CN 1120837 A CN1120837 A CN 1120837A
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- aromatic series
- alkyl
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- 150000003217 pyrazoles Chemical class 0.000 title abstract description 4
- -1 5-tetrazolyl group Chemical group 0.000 claims abstract description 263
- 125000005843 halogen group Chemical group 0.000 claims abstract description 68
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 37
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 35
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 21
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 8
- 206010019280 Heart failures Diseases 0.000 claims abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 59
- 125000003118 aryl group Chemical group 0.000 claims description 41
- 201000010099 disease Diseases 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 125000003342 alkenyl group Chemical class 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical class 0.000 claims description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 10
- 125000002252 acyl group Chemical class 0.000 claims description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
- 230000001684 chronic effect Effects 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000005161 aryl oxy carbonyl group Chemical class 0.000 claims description 5
- 239000008280 blood Substances 0.000 claims description 5
- 210000004369 blood Anatomy 0.000 claims description 5
- 125000000304 alkynyl group Chemical class 0.000 claims description 4
- 125000000392 cycloalkenyl group Chemical class 0.000 claims description 4
- 125000006717 (C3-C10) cycloalkenyl group Chemical group 0.000 claims description 3
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 3
- 239000002220 antihypertensive agent Substances 0.000 claims description 3
- CFHIDWOYWUOIHU-UHFFFAOYSA-N oxomethyl Chemical compound O=[CH] CFHIDWOYWUOIHU-UHFFFAOYSA-N 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 abstract description 170
- 102000005862 Angiotensin II Human genes 0.000 abstract description 16
- 101800000733 Angiotensin-2 Proteins 0.000 abstract description 16
- CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 abstract description 15
- 229950006323 angiotensin ii Drugs 0.000 abstract description 15
- 206010020772 Hypertension Diseases 0.000 abstract description 6
- 230000003042 antagnostic effect Effects 0.000 abstract description 5
- 230000002265 prevention Effects 0.000 abstract description 3
- 229910052757 nitrogen Inorganic materials 0.000 abstract 2
- 206010020571 Hyperaldosteronism Diseases 0.000 abstract 1
- 208000020832 chronic kidney disease Diseases 0.000 abstract 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 abstract 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1303
- 239000000460 chlorine Substances 0.000 description 342
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 322
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 307
- 125000001309 chloro group Chemical group Cl* 0.000 description 137
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 112
- 238000006243 chemical reaction Methods 0.000 description 107
- 125000006017 1-propenyl group Chemical group 0.000 description 103
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 103
- 239000002585 base Substances 0.000 description 97
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 89
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 79
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 78
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 77
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 76
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 63
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 61
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 59
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 49
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- 238000000034 method Methods 0.000 description 34
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 31
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 29
- 238000003786 synthesis reaction Methods 0.000 description 29
- 230000015572 biosynthetic process Effects 0.000 description 28
- 239000000243 solution Substances 0.000 description 27
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- 238000004519 manufacturing process Methods 0.000 description 24
- 238000010511 deprotection reaction Methods 0.000 description 23
- 230000006837 decompression Effects 0.000 description 19
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- 150000002148 esters Chemical class 0.000 description 14
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 125000001462 1-pyrrolyl group Chemical group [*]N1C([H])=C([H])C([H])=C1[H] 0.000 description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 11
- 229910052794 bromium Inorganic materials 0.000 description 11
- 229910052801 chlorine Inorganic materials 0.000 description 11
- 229910052751 metal Inorganic materials 0.000 description 11
- 239000002184 metal Substances 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 238000010898 silica gel chromatography Methods 0.000 description 11
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 10
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 10
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 10
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 10
- 239000001301 oxygen Substances 0.000 description 10
- 229910052760 oxygen Inorganic materials 0.000 description 10
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- 238000000605 extraction Methods 0.000 description 9
- 229910052736 halogen Inorganic materials 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 150000002367 halogens Chemical class 0.000 description 8
- 229910052744 lithium Inorganic materials 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 8
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 229910052802 copper Inorganic materials 0.000 description 7
- 239000010949 copper Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 6
- 239000012141 concentrate Substances 0.000 description 6
- 235000008504 concentrate Nutrition 0.000 description 6
- 125000003963 dichloro group Chemical group Cl* 0.000 description 6
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 235000015320 potassium carbonate Nutrition 0.000 description 6
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 5
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 229910052740 iodine Inorganic materials 0.000 description 5
- 235000010755 mineral Nutrition 0.000 description 5
- 239000011707 mineral Substances 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 125000004430 oxygen atom Chemical group O* 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 238000005684 Liebig rearrangement reaction Methods 0.000 description 4
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 4
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- ZRALSGWEFCBTJO-UHFFFAOYSA-N anhydrous guanidine Natural products NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
- 125000001246 bromo group Chemical group Br* 0.000 description 4
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 4
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
- 230000000007 visual effect Effects 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 3
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
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- 229920000168 Microcrystalline cellulose Polymers 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- VEQPNABPJHWNSG-UHFFFAOYSA-N Nickel(2+) Chemical compound [Ni+2] VEQPNABPJHWNSG-UHFFFAOYSA-N 0.000 description 3
- TZRXHJWUDPFEEY-UHFFFAOYSA-N Pentaerythritol Tetranitrate Chemical compound [O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O TZRXHJWUDPFEEY-UHFFFAOYSA-N 0.000 description 3
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- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
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- 229960002478 aldosterone Drugs 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 150000001336 alkenes Chemical class 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 210000000709 aorta Anatomy 0.000 description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
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- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 3
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- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 3
- 229940016286 microcrystalline cellulose Drugs 0.000 description 3
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- 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 3
- XIKYYQJBTPYKSG-UHFFFAOYSA-N nickel Chemical compound [Ni].[Ni] XIKYYQJBTPYKSG-UHFFFAOYSA-N 0.000 description 3
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- 125000001979 organolithium group Chemical group 0.000 description 3
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 3
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 3
- 229910000105 potassium hydride Inorganic materials 0.000 description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 229910052703 rhodium Inorganic materials 0.000 description 3
- 239000010948 rhodium Substances 0.000 description 3
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 3
- BDDWSAASCFBVBK-UHFFFAOYSA-N rhodium;triphenylphosphane Chemical compound [Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 BDDWSAASCFBVBK-UHFFFAOYSA-N 0.000 description 3
- 230000000630 rising effect Effects 0.000 description 3
- 150000003303 ruthenium Chemical class 0.000 description 3
- VIHDTGHDWPVSMM-UHFFFAOYSA-N ruthenium;triphenylphosphane Chemical compound [Ru].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 VIHDTGHDWPVSMM-UHFFFAOYSA-N 0.000 description 3
- 229910052710 silicon Inorganic materials 0.000 description 3
- 239000010703 silicon Substances 0.000 description 3
- 235000017550 sodium carbonate Nutrition 0.000 description 3
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- 239000000829 suppository Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
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- C07D—HETEROCYCLIC COMPOUNDS
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- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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- C07—ORGANIC CHEMISTRY
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- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
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Abstract
本发明是有关以上式(1)所示的吡唑化合物、其互变异构体及其盐。
[式中R1表示烷基等，R2表示羧基等，R3表示卤素原子、烷基或苯基等，R4、R5、R6分别表示氢原子或卤素原子等，R7表示羧基或5-四唑基等，X表示氮原子等，Y及Z表示CH或氮原子，A及E亚甲基等，D表示苯基等，G表示共价键]
本发明化合物对血管紧张素II具有拮抗作用，对于治疗高血压症、淤血性心脏器质性病变、慢性肾脏器质性病变、醛固酮症、眼内压上升等极为有用。
Description
本发明涉及一种新型吡唑化合物及其互变异构体及其盐，该化合物及其互变异构体及其盐在治疗各种心血管疾病、尤其在治疗高血压、心脏器质性病变及进行静脉器质性病变的处置，以及青光眼、糖尿病性网膜症及各种中枢神经系统疾病，例如在治疗不安、忧郁症、记忆减退、阿尔察默病或慢性肾病变的治疗时、作为血管紧张素II的拮抗剂极为有用。
高血压蛋白原酶-血管紧张素是通常在调节血压时可以发挥其中心的作用，与高血压及淤血性心脏器质性病变的发病有密切的关系。血管紧张素II是一种八肽激素，可由血管紧张素转换酶(ACE)切断十肽的血管紧张素I，主要在血液中生成。此ACE存在于肺、肾及其它许多器官的血管内皮。作为高血压蛋白原酶-血管紧张素系的强力动脉收缩剂的血管紧张素II会作用于细胞膜表面的特异性细胞受体。因此，控制高血压蛋白原酶-血管紧张素系的方法之一即，由血管紧张素II细胞受体中的拮抗。一些血管紧张素II的肽类似物拮抗性地阻塞细胞受体，来阻碍这种激素的作用，但由于有一部分的肽类似物具有激动剂活性、经口吸收效果不好、所以临床上的使用受到限制。[M.Antonaccio，Clin.Exp.Hypertents，A4,27-46(1982)]。
最近有几篇有关几种非肽类化合物可作为血管紧张素II拮抗剂的报告，如美国专利4,207,324号、4,340,598号、4,576,958号、4,582,847号及4,880,804号、欧洲专利公开公报028,834号、245,637号、253,310号、291,969号及475,206号、WO93/17681号、93/17682号等。A.T.Chiu等、Eur.J.Pharm.Exp.Therap.，157,13-21(1988)及P.C.Wong等、J.Pharm.Exp.Therap.，247,1-7(1988)，S.E.Laszlo等、J.Med.Chem.1993,36,3207-3210等。
但上述的美国专利说明书、欧洲专利公开说明书、PCT国际专利公开公报及论文中，都没有揭示本发明的吡唑化合物及其互变异构体及其盐类。
本发明是关于在高血压、淤血性心脏器质性病变、慢性肾脏器质性病变、醛固酮症、眼内压上升等疾病的治疗中可作为血管紧张素II的拮抗药极为有用的新型吡唑化合物及其互变异构体及其盐类。
根据本发明人等深入研究的结果，意外地发现本发明的吡唑化合物及其互变异构体和盐不同于上述文献所揭示的任一化合物，作为不但可与AT1受体结合、还可以与AT2受体结合的血管紧张素II的拮抗药极为有用，还发现其作为抗高血压剂是极优良的化合物，可以作为预防及治疗淤血性心脏器质性病变、慢性肾脏器质性病变、醛固酮症、眼内压上升等疾病的药物的活性成分，完成了本发明。
即，本发明是有关以式(1)所示的吡唑化合物、其互变异构体及其盐类。
[式中R1表示氢原子、C1-C10烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基，NR8R8’(R8及R8’可分别独立表示氢原子、C1-C10的烷基及C6-C10的芳香族基)、SR9(R9与R8相同)、C6-C10的芳香族基或杂环基所取代}、C2-C10链烯基{该链烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’可分别独立表示与上述相同)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、C2-C10的炔基{该炔基可任意被卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’分别独立表示与上述相同)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、C3-C10环烷基{该环烷基可任意被卤素原子、羟基、C1-C10烷氧基、NR8R8’(R8及R8’可分别独立表示与上述相同)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、C3-C10的环烯基{该环烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’可分别独立表示如上所述)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、C6-C10的芳香族基{该芳香族基可任意被C1-C10的烷基、卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’可分别独立表示如上所述)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、杂环基{该杂环基可任意被C1-C10的烷基、卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’可分别独立表示如上述)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、C1-C10酰基{该酰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’可分别独立表示如上所述)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、C1-C10烷氨甲酰基{该烷氨甲酰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’可分别与上述)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、C1-C10烷氧羰基{该烷氧羰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’与上述相同)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、C6-C10芳氧羰基{该芳氧羰基可任意被C1-C10的烷基、卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’分别如上述)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}。
R2表示卤素原子、硝基、氰基、甲酰基、磺酸基、磺酰氨基、PO2H2，PO3H2，5-四唑基、5-四唑甲基、5-四唑乙基、C1-C10烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示氢原子、C1-C10的烷基及C6-C10的芳香族基)、SR11(R11与R10相同)、C6-C10的芳香族基或杂环基所取代}、C2-C10的链烯基{该链烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C2-C10的炔基{该炔基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C3-C10的环烷基{该环烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C3-C10的环烯基{该环烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C6-C10芳香基{该芳香基可任意被C1-C10的烷基、卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、杂环基{该杂环基可任意被C1-C10的烷基、卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C1-C10酰基{该酰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C1-C10烷氨甲酰基{该烷氨甲酰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C1-C10烷氧羰基{该烷氧羰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C6-C10芳氧羰基{该芳氧羰基可任意被C1-C10的烷基、卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、(CH2)m1COX1R12[m1表示0、1、或2、R12表示氢原子或C1-C10的烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、X1表示氧原子、硫原子或NR13(R13与R10相同)1、(CH2)n1X2R14[n1表示0、1或2、R14表示氢原子或C1-C10的烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、或C1-C10的酰基{该酰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、X2表示氧原子、S(O)n2(n2表示0、1、2或3)或NR15(R15与R12相同、或为SO2R16(R16表示C1-C10的烷基(该烷基可任意被卤素原子取代))}]或表示以下所示的噁二唑基。
(式中、R17、R17’、R17”与R10相同)
R3表示卤素原子、羟基、硝基、氰基、甲酰基、胍基、脒基、磺酸基、磺酰氨基、PO2H2，PO3H2，5-四唑基、5-四唑甲基、5-四唑乙基、C1-C10的烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示氢原子、C1-C10的烷基或C6-C10的芳香族基)、SR19(R19与上述相同)、C9-C10的芳香族基、或杂环基所取代}、C2-C10的链烯基{该链烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C2-C10的炔基{该炔基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C3-C10的环烷基{该环烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C3-C10的环烯基{该环烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C6-C10的芳香族基〔该芳香族基可任意被卤素原子、羟基、硝基、氰基、甲酰基、胍基、脒基、磺酸基、磺酰氨基、PO2H2，PO3H2，5-四唑基、C1-C10的烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C2-C10的链烯基{该链烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C2-C10的链烯基{该链烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C3-C10的环烷基{该环烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、(CH2)m2COX3R20[m2为0、1或2、R20表示氢原子或C1-C10的烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18’及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、X3表示氧原子、硫原子或NR21(R21与R18相同)〕、(CH2)n3X4R22[n3表示0、1或2，R22表示氢原子、C1-C10的烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C1-C10的酰基{该酰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6～C10的芳香族基、或杂环基所取代}、X4表示氧原子、S(O)n4(n4表示0、1、2或3)、或NR23(R43与R20相同、或表示SO2R24(R24表示C1-C10的烷基(该烷基可任意被卤素原子所取代))}]、C6-C10的芳香族基、杂环基、或以R2所示的噁二唑基中的任意1-5个所取代〕、杂环基{该杂环基可任意被C1-C10的烷基、卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所述)、SR19(R19与上相同)、C6-C10芳香基、或杂环基所取代}、C1-C10的酰基{该酰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所述)、SR19(R19与上相同)、C6-C10芳香基、或杂环基所取代}、C1-C10的烷氨甲酰基{该烷氨甲酰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所述)、SR19(R19与上相同)、C6-C10芳香基、或杂环基所取代}、C1-C10的烷氧羰基{该烷氧羰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所述)、SR19(R19与上相同)、C6-C10芳香基、或杂环基所取代}、C6-C10的芳氧羰基{该芳氧羰基可任意被C1-C10的烷基、卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所述)、SR19(R19与上相同)、C6-C10芳香基、或杂环基所取代}、(CH2)m3COX5R25(m3表示0、1或2，R25与R1相同、X5表示共价键、氧原子、硫原子或NR26(R26与R18相同)}，(CH2)n5X6R27[n5表示0、1或2、R27与R1相同、或表示硝基、氰基、甲酰基、胍基、脒基、磺酸基、磺酰氨基、PO2H2，PO3H2，5-四唑基、或以R2表示的噁二唑基、X6表示共价键、氧原子、S(O)n6(n6表示0、1、2或3)、NR28{R28与R20相同或表示SO2R29(R29表示C1-C10的烷基(该烷基可任意被卤素原子取代)}]，(CH2)m4X7COR30[m4表示0、1或2、R30表示氢原子、C1-C10的烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所述)、SR19(R19与上相同)、C6-C10芳香基、或杂环基所取代}、或NR31R31’(R31及R31’是分别独立与R18相同)，X7是表示氧原子、硫原子或NR32(R32是与R18相同)〕；R4、R5及R6是分别独立表示卤素原子、羟基、硝基、氰基、甲酰基、胍基、脒基、羧基、磺酸基、磺酰氨基、PO2H2、PO3H2、5-四唑基、C1～C10烷基{该烷基是可任意地被卤素原子、羟基、C1～C10烷氧基、NR33R33’(R33及R33’分别独立表示氢原子、C1～C10烷基及C6～C10芳香族基)、SR34(R34与R33一样)、C6～C10芳香族基、或杂环基所取代}、C1～C10酰基{该酰基可任意地被卤素原子、羟基、C1～C10烷氧基、NR33R33’(R33及R33’是分别独立与上述相同)、SR34(R34与上述相同)、C6～C10芳香族基、或杂环基所取代}，C1～C10烷氧基、NR33R33’(R33及R33’分别独立与上述相同)；
R7表示羧基(该羧基可以被甲基、叔丁基等所保护)、磺酸基、磺酰氨基、PO2H2、PO3H2、5-四唑基(该四唑基可被三苯甲基、甲氧甲基、甲氧.乙氧甲基、苯甲基等所保护)、以R2所示的噁二唑基、X8R35{(R35与R12相同、X8表示氧原子、硫原子或NR36(R36与R33相同)、或SO2R37(R37表示C1～C10烷基(该烷基可任意被卤素原子所取代))}、或杂环基{该杂环基可以任意地被C1～C10烷基、卤素原子、羟基、C1～C10烷氧基、NR38R38’(R38及R38’可分别独立表示氢原子、C1～C10烷基及C6～C10芳香族基)、SR39(R39与R38相同)、C6～C10芳香族基、或杂环基所取代}、或以下所示取代基。
X表示氮原子或N→O；
Y及Z分别独立表示氮原子或CR40(R40与R4相同)；
A表示(CR41R41’)m7-L-(CR42R42’)n7(m7及n7分别独立表示0、1、2、或3、R41、R41’、R42及R42’分别独立与R4相同、L表示共价键、氧原子、羰基、NR43(R43表示氢原子、C1～C10烷基及C6～C10芳香族基)、NR44-CO(R44与R43一样)、CO-NR45(R45与R43相同)、S(O)m5(m5表示0、1或2)、NR46-CO-NR47(R46及R17分别独立表示与R43相同)、CR48＝CR49(R48及R49分别独立表示与R43相同)、C≡C、或NR50-NR51(R50及R51分别独立表示与R43相同)}。
D表示C6～C10芳香族基(该芳香族基可任意被1～5个R3所示取代基所取代)。
E是表示(CR52R53)m6X9(m6是表示0、1、或2、R52及R53是分别独立表示与R4相同、X9是表示共价键、氧原子、硫原子或NR54(R54是表示氢原子、C1～C10烷基及C6～C10芳香族基)}。
G是表示共价键、氧原子、S(O)m8(m8是表示0、1或2)、NR55(R55是表示氢原子、C1～C10烷基及C6～C10芳香族基)、羰基、(CR55R56)n8(n8是表示0、1、或2、R55及R56是表示氢原子、C1～C10烷基及C6～C10芳香族基)、CONR57(R57是表示氢原子、C1～C10烷基及C6～C10芳香族基)、或NR58-CO(R58是表示氢原子、C1～C10烷基及C6～C10芳香族基)}。
以下就上述式(1)化合物的取代基具体举例说明。
C1～C10的烷基是可为例如甲基、乙基、正丁基、仲丁基、叔丁基、正戊基、新戊基及己基等。
C2～C10链烯基可为例如乙烯基、烯丙基、并丙烯基、1-丁烯基、2-丁烯基、3-丁烯基、1、3-丁二烯基、1-戊烯基、2-戊烯基、3-戊烯基、4-戊烯基、1-己烯基、2-己烯基、3-己烯基、4-己烯基及五己烯基等。
C2～C10炔基可为例如乙炔基、1-丙炔基、2-丙炔基、1-丁炔基、2-丁炔/基、3-丁炔基、1-戊炔基、2-戊炔基、3-戊炔基、4-戊炔基、1-己炔基、2-己炔基、3-己炔基、4-己炔基及5-己炔基等。
C3～C10环烷基是包含烷基环烷基或环烷基、烷基、可为例如环丙基、环丁基、环戊基、环己基、4-甲基-环己基及环丙基、甲基等。
C3～C10环烯基是包括烷基环烯基或环烯烷基、可为例如1-环戊烯基、2-环戊烯基、2、4-环戊二烯基、1-环己烯基、2-环己烯基、3-环己烯基、4-甲基-1-环己烯基、1-环戊烯甲基等。
C6～C10芳香族基是例如有苯基、1-茚基、2-茚基、3-茚基、4-茚基、5-茚基、6-茚基、7-茚基、1-萘基、2-萘基、1-四氢萘基、2-四氢萘基、5-四氢萘基、6-四氢萘基、1-并环戊二烯基、2-并环戊二烯基、1-薁基、2-薁基、4-薁基、5-薁基、6-薁基等。
杂环基可为芳香族是杂环基以及非芳香族是杂环基。
芳香族是杂环基可包括5～7员环的单环式杂环基、构成原子数为8～10的缩合二环式杂环基、氧原子、氮原子或硫原子为单独或为1～5个原子的组合、
非芳香族是杂环基可为包含3～10员环的单环式杂环基、构成原子数为6～10个的缩合二环式杂环基、或构成原子数为10个以内的交连环式杂环基、氧原子、氮原子或硫原子为单独或为1～5个原子的组合。
芳香族是杂环基可为例如2-噻嗯基、3-噻嗯基、2-呋喃基、3-呋喃基、2-吡喃基、3-吡喃基、4-吡喃基、2-苯并呋喃基、3-苯并呋喃基、4-苯并呋喃基、5-苯并呋喃基、6-苯并呋喃基、7-苯并呋喃基、1-异苯并呋喃基、4-异苯并呋喃基、5-异苯并呋喃基、2-苯并噻嗯基、3-苯并噻嗯基、4-苯并噻嗯基、5-苯并噻嗯基、6-苯并噻嗯基、7-苯并噻嗯基、1-异苯并噻嗯基、4-异苯并噻嗯基、5-异苯并噻嗯基、2-苯并吡喃基、3-苯并吡喃基、4-苯并吡喃基、5-苯并吡喃基、6-苯并吡喃基、7-苯并吡喃基、8-苯并吡喃基、1-吡咯基、2-吡咯基、3-吡咯基、1-咪唑基、2-咪唑基、4-咪唑基、1-吡唑基、3-吡唑基、4-吡唑基、2-噻唑基、4-噻唑基、5-噻唑基、3-异噻唑基、4-异噻唑基、5-异噻唑基、2-噁唑基、4-噁唑基、5-噁唑基、3-异噁唑基、4-异噁唑基、5-异噁唑基、2-吡啶基、3-吡啶基、4-吡啶基、2-吡嗪基、2-嘧啶基、4-嘧啶基、5-嘧啶基、3-哒嗪基、4-哒嗪基、1-吲哚嗪基、2-吲哚嗪基、3-吲哚嗪基、5-吲哚嗪基、6-吲哚嗪基、7-吲哚嗪基、8-吲哚嗪基、1-异吲哚基、4-异吲哚基、5-异吲哚基、1-吲哚基、2-吲哚基、3-吲哚基、4-吲哚基、5-吲哚基、6-吲哚基、7-吲哚基、1-吲唑基、2-吲唑基、3-吲唑基、4-吲唑基、5-吲唑基、6-吲唑基、7-吲唑基、1-嘌呤基、2-嘌呤基、3-嘌呤基、6-嘌呤基、7-嘌呤基、8-嘌呤基、2-喹啉基、3-喹啉基、4-喹啉基、5-喹啉基、6-喹啉基、7-喹啉基、8-喹啉基、1-异喹啉基、3-异喹啉基、4-异喹啉基、5-异喹啉基、6-异喹啉基、7-异喹啉基、8-异喹啉基、1-酞嗪基、5-酞嗪基、6-酞嗪基、2-萘啶基、3-萘啶基、4-萘啶基、2-喹喔啉基、5-喹喔啉基、6-喹喔啉基、2-喹唑啉基、4-喹唑啉基、5-喹唑啉基、6-喹唑啉基、7-喹唑啉基、8-喹唑啉基、3-噌啉基、4-噌啉基、5-噌啉基、6-噌啉基、7-噌啉基、8-噌啉基、2-喋啶基、4-喋啶基、6-喋啶基、7-喋啶基、3-呋咱基等，这些基团可被羟基、卤素原子、氧基(＝O)、氨基、烷基等所取代。
又、非芳香族是杂环基例如有2-色满基、3-色满基、4-色满基、5-色满基、6-色满基、7-色满基、8-色满基、1-异色满基、3-异色满基、4-异色满基、5-异色满基、6-异色满基、7-异色满基、8-异色满基、1-吡咯烷基、2-吡咯烷基、3-吡咯烷基、1-吡咯啉基、2-吡咯啉基、3-吡咯啉基、4-吡咯啉基、5-吡咯啉基、1-咪唑啶基、2-咪唑啶基、4-咪唑啶基、1-咪唑啉基、2-咪唑啉基、4-咪唑啉基、1-吡唑烷基、3-吡唑烷基、4-吡唑烷基、1-吡唑啉基、2-吡唑啉基、3-吡唑啉基、4-吡唑啉基、5-吡唑啉基、1-哌啶基、2-哌啶基、3-哌啶基、4-哌啶基、1-哌嗪基、2-哌嗪基、3-哌嗪基、1-吲哚满基、2-吲哚满基、3-吲哚满基、4-吲哚满基、5-吲哚满基、6-吲哚满基、7-吲哚满基、1-异吲哚满基、2-异吲哚满基、4-异吲哚满基、5-异吲哚满基、2-奎宁环基、3-奎宁环基、4-奎宁环基、2-吗啉基、3-吗啉基、4-吗啉基、1-吖丁啶基、2-吖丁啶基、3-吖丁啶基、1-吖丁啶酮基、3-吖丁啶酮基、4-吖丁啶酮基等、这些基团可被羟基、卤素原子、氧基(＝O)、氨基、烷基所取代。
C1～C10酰基例如有甲酰基、乙酰基、丙酰基、丁酰基、异丁酰基、戊酰基、异戊酰基、三甲基乙酰基、丙烯酰基、丙炔酰基、甲基丙烯酰基、巴豆酰基、苯甲酰基、2-呋喃甲酰基、3-呋喃甲酰基、2-噻吩甲酰基、3-噻吩甲酰基、烟酰基、环丙羰基、氢化阿托酰基、肉桂酰基等。
C1～C10烷氨甲酰基例如有N-甲基氨甲酰基、N、N-二甲基氨甲酰基、N-乙基氨甲酰基、N-丙基氨甲酰基、N-丁基-N-甲基氨甲酰基、N-苯氨甲酰基、氨羰丙酰基等。
C1～C10烷氧羰基例如有甲氧羰基、乙氧羰基、正丙氧羰基、异丙氧羰基、正丁氧羰基、仲丁氧羰基、叔丁氧羰基、苯甲氧羰基等。
C6～C10芳氧羰基例如有苯氧羰基、1-萘氧羰基、2-萘氧羰基、8-喹啉氧羰基等。
C1～C10烷氧基例如有甲氧基、乙氧基、正丙氧基、异丙氧基、正丁氧基、仲丁氧基、叔丁氧基、苯甲氧基、苯氧基、1-萘氧基、2-萘氧基、8-喹啉氧基等。
卤素原子为氟原子、氯原子、溴原子及碘原子等。
本发明的式(1)吡唑化合物、其互变异构物及盐可以依以下方法制造。反应式(1)
(式中R2、R3、R4、R5、R6、R7、A、D、E、G、X、Y及Z如上述。V表示氯原子、溴原子、碘原子等卤素及甲磺酰氧基、对甲苯磺酰氧基、三氟甲烷磺酰氧基等脱离基)。
反应式(1)使通式〔2b〕化合物与〔3a〕化合物、生成式(5)化合物后、视其需要进行脱保护、制造式〔1〕化合物中的R1为氢的化合物。
此反应可在碳酸钾、碳酸钠、碳酸锂、碳酸氢钾、碳酸氢钠、氢氧化锂等无机碱存在下进行。又、除上述无机碱之外还可以使用氢化钠、氢化钾、正丁基锂等金属氢化物、甲醇钠、乙醇钠、叔丁醇钾等醇金属、氨基钠、二异丙氨基锂、六甲基二硅叠氮锂、2、2、6、6-四甲基哌啶锂等金属酰胺及三甲胺、三乙胺、吡啶、二异丙乙胺等有机碱。
反应溶剂是只要不影响反应，通常可为苯、甲苯、己烷等烃类溶剂、四氢呋喃、二乙醚、1，4-二噁烷等醚系溶剂、甲酰胺、N，N-二甲基甲酰胺、N，N-二甲基乙酰胺、N-甲基吡咯酮等酰胺系溶剂、甲醇、乙醇、丙醇等醇系溶剂、氯仿、二氯甲烷、二氯乙烷等卤素系溶剂、及其他乙腈、二甲亚砜等溶剂、水等、或这些的混合溶剂等。
反应温度可以采用-78℃～反应中使用的溶剂的沸点范围温度。
原料的摩尔比可以任意设定，只对式〔3a〕的化合物通常使用0.8～1.5倍摩尔式〔2b〕化合物即可。
脱保护可以按公知的方法进行。例如为甲酯、乙酯时可在水-醇溶剂中，使用氢氧化钠、氢氧化钾等，于冰冷下～室温下反应即可以脱离。又为三苯甲基时可用水性乙酸、或盐酸-乙醇、或乙醇在回流条件下予以脱离。
苯甲基时可以使用钯-碳催化剂，由氢气的水解即可脱离、甲氧甲醚基时可由盐酸-乙醇予以脱离。反应式(2)
(式中R2，R3，R4，R5，R6，R7，A，D，E，G，X，Y，及Z是如上述)。
反应式(2)是使式〔3b〕化合物与〔2a〕化合物反应，生成式(5)化合物后、视其需要进行脱保护、制造式〔1〕化合物中的R1为氢的化合物。
此反应可以在与反应式(1)一样的条件下进行反应。脱保护的条件亦如上述。
原料的摩尔比可以任意设定，只对式〔3b〕的化合物通常使用0.8～1.5倍摩尔式〔2a〕化合物即可。反应式(3)(式中R1、R2、R3、R4、R5、R6、R7、A、D、E、G、X、Y及Z是与上述相同。R1表示氢原子、烷基、链烯基、炔基或芳烷基时，V表示氯原子、溴原子、碘原子、甲磺酰氧基、对甲苯磺酰氧基、三氟甲磺酰氧基等卤素及脱离基，R1为酰基时，V表示氯原子、溴原子、碘原子等卤素及甲氧基、乙氧基、甲硫基、乙硫基等)。
反应式(3)是使式〔5〕化合物与〔4a〕化合物反应，生成式(1a)化合物后，视其需要进行脱保护，制造式〔1〕化合物中的R1为氢以外的化合物。此反应可以在与反应式(1)同样的条件下进行。又、脱保护的条件亦如上述。反应式(4)
(式中R1，R2，R3，R4，R5，R6，R7，A，D，E，G，X，Y及Z是如上述)。
反应式(4)是使式〔6〕化合物与〔3a〕化合物反应，生成式(1a)化合物后，视其需要进行脱保护，制造式〔1〕化合物中的R1为氢以外的化合物。此反应可以在与反应式(1)同样的条件下进行。又、脱保护的条件亦如上述。反应式(5)
(式中R1，R2，R3，R4，R5，R6，R7，A，D，E，G，X，Y，Z及V是与上述相同)。
反应式(5)是使式〔7〕化合物与〔2a〕化合物反应，生成式(1a)化合物后，视其需要进行脱保护，制造式〔1〕化合物中的R1为氢以外的化合物。此反应可以在与反应式(1)同样的条件下进行。又、脱保护的条件亦如上述。反应式(6)
(式中R1，R2，R3，R4，R5，R6，R7，A，D，E，G，X，Y及Z是与上述相同)。反应式(6)可以用碱去除式〔1b〕化合物的5位氢原子后，使其与亲电子试剂反应，合成式〔1a〕化合物，视其需要进行脱保护用以制造式(1)化合物。
此反应通常可使用二异丙胺锂、六甲二硅叠氮锂、2，2，6，6-四甲基哌啶锂等金属酰胺、锂、钠等金属碱、氢化钾等金属氢化物或甲基锂、正丁基锂等烷基金属等进行反应。
亲电子试剂可以使用氟、氯、溴、碘等卤素类、1，1，2，2-四氟-1，2-二溴乙烷、1，2-二溴乙烷、甲基碘、丙基碘等卤代烷基类、甲基异氰酸酯、环己基异氰酸酯等异氰酸酯类、乙酰氯、氯甲酸乙酯等卤代酸类、N-甲氧基-N-甲基苯甲酰胺、二甲基甲酰胺等酰胺类、乙酸乙酯、硼酸三乙酯等酯类或二氧化碳等。
反应溶剂、反应温度及反应试剂的摩尔比等反应条件可以在与反应式(1)一样的条件下进行。又、脱保护条件是与上述相同。反应式(7)
(式中R1、R2、R3、R4、R5、R6、R7、A、D、E、G、X、Y及Z是与上述相同，W是表示氯、溴、碘等卤素。)。
反应式(7)是以有机锂试剂或碱金属对于式〔1c〕化合物中5位的卤素进行卤素-金属交换后、在无催化剂或催化剂存在下使其与亲电子剂反应、合成为式〔1a〕化合物、视其需要进行脱保护、以制造式(1)的化合物的方法。
此反应中通常可以使用丁基锂、甲基锂等有机锂试药或锂、钠、钾等金属等进行。
可视其需要使用作为催化剂的四(三苯膦)钯(0)、氯化钯(II)等钯类、二氯〔1、3、-双(二本膦基)丙烷〕镍(II)、四(三对磷酸三苯酯)镍(0)等镍类、二氯三(三苯膦)钌等钌类、氯三(三苯膦)铑等铑类。
此反应可以在与反应式(6)一样的条件下进行。又、脱保护条件亦与上述相同。反应式(8)
(式中R1，R2，R3，R4，R5，R6，R7，A，D，E，G，X，Y，及V是与上述相同)。
反应式(8)是在无催化剂或催化剂存在下，使式〔1d〕化合物与有机金属试剂或炔类或烯类反应，合成〔1a〕化合物，视其需要进行脱保护，用以制造式〔1〕的化合物的方法。
本反应中可以做为有机金属试剂使用的有甲基锂、正丁基锂、苯基锂、4-甲苯基锂等有机锂类、甲基溴化镁、苯基溴化镁等有机镁类、二异甲基-1-己烯铝等有机铝类、甲基溴化锌、苯基溴化锌等有机锌类、三甲基乙烯基锡等有机锡类、3-甲苯基硼酸等有机硼类、甲基铜、苯基酮、甲基铜酸锂等有机铜类、甲醇钠、酚钠等金属醇类、甲基硫醇钠、苯基硫醇钠等硫醇化金属类等。亦可使用苯乙炔、三甲基甲硅烷基乙炔等炔类、或丙烯醛、丙烯腈等烯类等。
可视其需要使用作为催化剂的四(三苯膦)钯(0)、氯化钯(II)等钯类、二氯〔1、3、-双(二苯膦基)丙烷〕镍(II)、四(三对磷酸三苯酯)镍(0)等镍类、二氯三(三苯膦)钌等钌类、氯三(三苯膦)铑等铑类。
此反应可以在与反应式(6)一样的条件下进行。又、脱保护条件亦与上述相同。反应式(9)
(式中R1，R2，R3，R4，R5，R6，R7，A，D，E，G，X，Y，Z及V是与上述相同、M是表示锂、铜等金属原子、氯化锌、溴化镁等卤化金属、三甲基锡、三丁基锡等烷基金属或硼酸)。
反应式(9)是在无催化剂或催化剂存在下，使式〔1e〕化合物与有机卤化物反应，合成式〔1a〕化合物，视其需要进行脱保护，来制造式〔1〕的化合物的方法。
有机卤化物可以使用甲基碘、丙基碘等烷基卤、苯基碘、2-溴苯甲腈等芳基卤、乙烯基溴等卤化烯类等。
可视其需要使用作为催化剂的四(三苯膦)钯(0)、氯化钯(II)等钯类、二氯〔1、3、-双(二苯膦基)丙烷〕镍(II)、四(三对磷酸三苯酯)镍(0)等镍类、二氯三(三苯膦)钌等钌类、氯三(三苯膦)铑等铑类。
此反应可以在与反应式(6)一样的条件下进行。又、脱保护条件亦与上述相同。反应式(10)(式中R1，R2，R3，R4，R5，R6，R7，A，D，E，G，X，Y，Z及V是与上述相同)。
反应式(10)是在无催化剂或催化剂存在下使式〔1f〕化合物与烷基卤或酰基卤化物反应，合成式〔1a〕化合物后视其需要施予脱保护，以制造式〔1〕的化合物的方法。
此反应可在碳酸钾、碳酸钠、碳酸锂、碳酸氢钾、碳酸氢钠、氢氧化锂等无机碱存在下进行。又、除上述无机碱之外还可以使用氢化钠、氢化钾、正丁氧基锂等金属氢化物、甲醇钠、乙醇钠、叔丁醇钠等醇金属，氨基钠、二异丙氨基锂、六甲基二硅叠氮锂、2，2，6，6-四甲基哌啶锂等金属酰胺及三甲胺、三乙胺、吡啶、二异丙乙胺等有机碱。
此反应可视其需要使用如Adogen 464〔氯化甲基三烷基(C8-10)铵(Ashland Chemical Co.公司商标)〕类的四级卤化铵作为催化剂，与反应式(6)一样进行，又，脱保护条件亦与上述相同。反应式(11)(式中R1，R2，R3，R4，R5，R6，R7，A，D，E，G，X，Y，Z及V与上述相同)。
反应式(11)是使式〔1c〕化合物与一级或二级胺相反应，生成为式〔1a〕的化合物后，视其需要进行脱保护，以制造式〔1〕的化合物的方法。
此反应可在碳酸钾、碳酸钠、碳酸锂、碳酸氢钾、碳酸氢钠、氢氧化锂等无机碱存在下进行。
作为催化剂可以单独或组合使用铜、氧化铜(I)、氧化铜(II)等铜类。
作为胺使用正丙胺、正丁胺、二乙胺等烷基胺、苯胺等芳基胺等。
此反应可以在与反应式(1)一样的条件下进行反应。脱保护的条件亦与上述相同。
作为上述制造方法中的原料的式〔6〕化合物及式〔7〕化合物可以依以下方法制造。反应式(12)(式中R1，R4，R5，R6，R7，E，G，X，Y，Z及V是与上述相同)。
反应式(12)是使反应式〔2b〕化合物与式〔4a〕化合物反应，以制造式〔6〕化合物的方法。此反应可以在与反应式(3)一样的条件下进行。反应式(13)
(式中R1，R4，R5，R6，R7，E，G，X，Y，Z及V是与上述相同)。
反应式(13)是使反应式〔4a〕化合物与式〔4a〕化合物反应，以制造式〔6〕化合物的方法。此反应可以在与反应式(1)一样的条件下进行。反应式(14)
(式中R1，R2，R3，A，D，X，及V是与上述相同)。
反应式(14)是使式〔3b〕化合物与式〔4a〕化合物反应，以制造式〔7〕化合物的方法。此反应可以在与反应式(2)一样的条件下进行。反应式(15)
(式中R1，R2，R3，A，D，X，及V是与上述相同)。
反应式(15)是使式〔4b〕化合物与式〔3a〕化合物反应，以制造式〔7〕化合物的方法。此反应可以在反应式(1)一样的条件下进行。
其次说明作为原料的式〔3a〕化合物与式〔3b〕化合物的制法。
式〔3b〕的化合物中X为氮原子的式〔11〕化合物可依Z.Chem.8,420(1969)，Aust.J.Chem.36,135(1983)，Org.Prep.Proced.Int.17,70(1985)，J.Heterocycl.Chem.19,1265(1782)，J.Heterocycl.Chem.19,1267(1782)，J.Med.Chem.7,259(1964)，J.Heterocycl.Chem.17.73(1980)，Monatsh.Chem.112，875(1981)，TetrahedronLett.2991(1979)，Chem.Ber.98,2576(1965)，Helv.Chim.Acta 42,763(1959)中所记载的方法制造。〔式中R2、R3、A、D及V是与上述相同，V1是表示卤素原子(氯、溴等)、羟基、烷氧基(甲氧基、乙氧基等)、氨基(NH2、NMe2、NHPh等)〕。
即，使式〔8〕化合物与式〔9〕化合物或式〔10〕化合物反应，或使式〔11a〕化合物在均一或二层反应条件下与化合物V-A-D反应，来合成式〔11〕化合物。
作为式〔3b〕的化合物中X为氮原子的式〔4〕化合物的制法可用J.Amer.Chem.Soc.78,784(1956)，J.Org.Chem.21,1240(1956)，EP-320765，J.Prakt.Chem.331,552(1989)，DD-248587，J.Hterocycl.Chem.23,1035(1986)，J.Heterocycl.Chem.22,1093(1985)，Synthes is 794(1985)，Syn thesis 3,276(1984)，EP-53698，EP-53699，EP-53678，Chem，Ber.114,2834(1981)，DD-149517，J Gen.Chem.USSR 50,2116(1980)，J.Heterocycl.Chem.17,1527(1980)，J.Heterocycl.Chem.11,423(1974)，J.Chem.Soc.C 1501(1971)，J.Chem.Soc.C 1610(1971)，Helv.Chim.Acta36,986(1956)，Liebigs Ann.Chem.339,117(1905)等中所记载的方法。反应式(17)
〔式中R2、R3、A、D及V与上述相同〕
即，使肼与式〔12〕化合物反应，或使氨与式〔13〕的化合物反应，即可合成为式〔14〕化合物。
式〔3a〕化合物中X为氮原子的式〔17〕化合物的制法可用J.Chem.Soc.C 1507(1968)，J.Org.Chem.25,1259(1960)，J.Amer.Chem.Soc.73,4664(1951)，Gazz.Chim.Ital.78,332(1948)，Liebigs Ann.Chem.338,183(1905)，Liebigs Ann.Chem.338,267(1905)等中所记载方法。反应式(18)
(式中R2、R3、A、D及V与上述相同)
即，使氧代卤化磷与式〔15〕化合物反应，或使重氮化合物与式〔16〕化合物反应，或重氮化式〔11〕的化合物与卤化铜反应，即可合成为式〔17〕化合物。
作为式〔3a〕化合物中X为氮原子的式〔22〕化合物的制法可用J.Chem.SOC.2769(1961)，Bull.Chem.Soc.Jpn.46,1572(1973)，J.Amer.Chem.Soc.73,4664(1951)，J.Amer.Chem.Soc.76,3686(154)，J.Heterocycl.Chem.26,241(1989)，JP-1100570，Acta Chem.Scand.33,483(1979)，J.Org.Chem.36,2542(1971)，Bull.Soc.Chim.Fr.1974(1970)，J.chem.Soc.C 1507(1968)，J.Gen.Chem.USSR 30,3251(1960)，J.Pharm.Soc.Japan 61，26(1941)，J.Chem.Soc.1739(1934)，J.Chem.Soc.475(1933)，Liebigs Ann.Chem.338,183(1905)，Chem.Ber.33,2595(1900)，J.Heterocycl.Chem.，1545(1991)等中所记载的方法。反应式(19)
(式中R2、R3、A、D及V是与上述相同)
即、使氧代卤化磷与式〔18〕化合物，或使式〔19〕化合物与卤素(氯、溴)反应或使重氮化合物与式〔20〕化合物反应，使式〔21〕的化合物重氮化，使其与卤化铜反应，即可合成为式〔22〕化合物。
作为式〔3a〕化合物中X为氮原子的式〔24〕化合物的制法可用J.Med.Chem.32,2573(1989)等中所记载方法。反应式(20)
(式中R2、R3、A、D及V是与上述相同)
即，在Adogen 464、碳酸钾、氢氧化钠水溶液存在下，于甲苯中使式〔23〕化合物与烷基卤反应、即可合成为〔24〕的化合物。
下列为本发明优选的化合物组：
式〔1〕中的R1表示C1-C10烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’可分别独立表示氢原子、C1-C10的烷基及C6-C10的芳香族基)、SR9(R9与R8相同)所取代}、C2-C10链烯基{该链烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’可分别独立表示与上述相同)、SR9(R9与上述相同)所取代}、C3-C10环烷基{该环烷基可任意被卤素原子、羟基、C1-C10烷氧基、NR8R8’(R8及R8’可分别独立表示与上述相同)、SR9(R9与上述相同)所取代}的吡唑化合物、其互变异构体及其盐类，为本发明优选的化合物组A的化合物。
式〔1〕中的R2表示卤素原子、硝基、氰基、甲酰基、磺酸基、磺酰氨基、PO2H2、PO3H2，5-四唑基、C1-C10烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示氢原子、C1-C10的烷基及C6-C10的芳香族基)、SR11(R11与R10相同)、C6-C10的芳香族基或杂环基所取代}、以及(CH2)m1COX1R12[m1表示0、1、或2、R12表示氢原子或C1-C10的烷基(该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、X1表示氧原子、硫原子或NR13(R13与R10相同)1、R4、R5及R6为氢原子、E为CH2、G为共价键、CO-NR57(R57为氢原子、C1-C10的烷基或C6-C10的芳香族基)、或NR58-CO(R58为氢原子、C1-C10的烷基或C6-C10的芳香族基)的吡唑化合物、其互变异构体及其盐类，为本发明的优选化合物；
上述化合物组A的化合物中，式〔1〕中与此被同样定义的化合物、其互变异构体及其盐类，也是本发明的另外的优选化合物组B的化合物。
式中，R1为C1-C10的烷基、R7为5-四唑基、Y及Z分别为CH的式〔1〕及化合物组A的吡唑化合物、其互变异构体及其盐类，也是本发明的另外的优选化合物；
上述化合物组B的化合物中，式〔1〕中与此被同样定义的化合物、其互变异构体及其盐类，也是本发明的另外的优选化合物组C的化合物。
式中，D为苯基(该苯基也可被R3所示的取代基任意取代)的式[1]以及化合物组A或B的吡唑化合物、其互变异构体及其盐类，也是本发明的其他优选化合物；
上述化合物组C的化合物中，式〔1〕中与此被同样定义的化合物、其互变异构体及其盐类，也是本发明的另外的优选化合物组D的化合物。
式中，R2为羧基的式[1]以及化合物组A、B或C的吡唑化合物、其互变异构体及其盐类，也是本发明的其他优选化合物；
上述化合物组D的化合物中，式〔1〕中与此被同样定义的化合物、其互变异构体及其盐类，也是本发明的另外的优选化合物组E的化合物。
本发明的其他目的在于提供一种抗高血压药、缺血性心功能不全治疗药以及慢性肾病的治疗药，该治疗药的特征在于含有上述式〔1〕或优选化合物组A、B、C、D、E或上述本发明其他优选的吡唑化合物、其互变异构体及/或它们的盐类中的任意一种以上。
本发明的式〔1〕吡唑化合物，其互变异构体及盐的投予形态可为注射剂(皮下、静脉内、肌肉内、腹腔内注射)、软膏剂、栓剂、喷雾剂等非经口投予、或片剂、胶囊剂、颗粒剂、丸剂、糖浆剂、液剂、乳剂、悬浊剂等经口投予。
含有本发明化合物的上述药学组合物是对全部组合物的重量而言，含有约0.1～99.5％的式(1)化合物，优选约含有0.5～95％式〔1〕化合物。式〔1〕所示化合物或含有式〔1〕化合物的组合物中还可以再含有其他药学活性化合物。又，这些组合物还可以含有多数的式〔1〕化合物。
临床上式〔1〕化合物的投予量是因年龄、体重、病人的感受性、症状轻重等而不同。通常有效的投予量是成人每日0.003～1.5g，优选0.1～0.6左右。但视其需要还可使用上述范围以外的量。
式〔1〕的化合物可以通过一般制药的惯用方法，制剂为给药用剂型。
即，经口投予用的片剂、胶囊剂、颗粒剂、丸剂可以使用赋形剂，例如白糖、乳糖、葡萄糖、淀粉、甘露糖醇；粘合剂，例如糖浆、阿拉伯胶、明胶、山梨糖醇、黄耆胶、甲基纤维素、聚乙烯吡咯烷酮；崩解剂，例如淀粉、羧甲基纤维素或其钙盐、微晶纤维素、聚乙二醇；润滑剂，例如滑石粉、硬脂酸镁或钙、二氧化硅；滑润剂，例如月桂酸钠、甘油等予以调制。
注射剂、液剂、乳剂、悬浊剂、糖浆剂及喷雾剂可以使用活性成分的溶剂，例如水、乙醇、异丙醇、丙二醇、1、3-丁二醇、聚乙二醇；表面活性剂，例如山梨糖醇酐脂肪酸酯、聚氧化乙烯山梨糖醇酐脂肪酸酯、聚氧化乙烯脂肪酸酯、氢化蓖麻油的聚氧乙烯醚、卵磷脂；悬浊剂，例如羧甲基纤维素钠盐、甲基纤维素等纤维素衍生物、黄耆胶、阿拉伯胶等天然橡胶类；防腐剂，例如对羟基苯甲酸的酯类、氯化苄烷铵、山梨酸盐等予以调制。栓剂是使用聚乙二醇、羊毛脂、可可椰子油等予以调制。
作为本发明化合物除可为与后述制法有关的实施例中所述化合物，还可为第1表～第5表中所记载的化合物及其药理学上可容许的盐。
又，表中n是代表‘正’，i代表‘异’，e代表‘环’，sec代表‘仲’，t代表‘叔’，Me代表甲基，Et代表乙基，Pr代表丙基，Bu代表丁基，Pen代表戊基，Hex代表己基，Ph代表苯基，Bz代表苄基，又，表中J1＝NHCOEt，J2＝N(n-Pen)COPh及U＝COOH，T代表以下取代基。
第1表
R1 R2 R3 R7 An-Pr U F T -n-Pr U Cl T -n-Pr U Br T -n-Pr U I T -n-Pr U Me T -n-Pr U CF3 T -n-Pr U Et T -n-Pr U n-Pr T -n-Pr U NO2 T -n-Pr U NH2 T -n-Pr U NHCOPh T -n-Pr U CHO T -n-Pr U CN T -n-Pr U Ph T -n-Pr U F T CH2n-Pr U Cl T CH2n-Pr U Br T CH2n-Pr U I T CH2n-Pr U Me T CH2n-Pr U CF3 T CH2n-Pr U Et T CH2n-Pr U n-Pr T CH2n-Pr U NO2 T CH2n-Pr U NH2 T CH2n-Pr U NHCOPh T CH2n-Pr U CHO T CH2n-Pr U CN T CH2n-Pr U Ph T CH2Et U F T CH2Et U Cl T CH2Et U Br T CH2Et U I T CH2R1 R2 R3 R7 AEt U Me T CH2Et U CF3 T CH2Et U Et T CH2Et U n-Pr T CH2Et U NO2 T CH2Et U NH2 T CH2Et U NHCOPh T CH2Et U CHO T CH2Et U CN T CH2Et U Ph T CH2n-Bu U F T CH2n-Bu U Cl T CH2n-Bu U Br T CH2n-Bu U I T CH2n-Bu U Me T CH2n-Bu U CF3 T CH2n-Bu U EL T CH2n-Bu U n-Pr T CH2n-Bu U NO2 T CH2n-Bu U NH2 T CH2n-Bu U NHCOPh T CH2n-Bu U CHO T CH2n-Bu U CN T CH2n-Bu U Ph T CH2c-Pr U F T CH2c-Pr U Cl T CH2c-Pr U Br T CH2c-Pr U I T CH2c-Pr U Me T CH2c-Pr U CF3 T CH2c-Pr U Et T CH2c-Pr U n-Pr T CH2c-Pr U NO2 T CH2c-Pr U NH2 T CH2c-Pr U NHCOPh T CH2c-Pr U CHO T CH2c-Pr U CN T CH2c-Pr U Ph T CH2n-Pr U F T (CH2)3 R1 R2 R3 R7 An-Pr U Cl T (CH2)3n-Pr U Br T (CH2)3n-Pr U I T (CH2)3n-Pr U Me T (CH2)3n-Pr U CF3 T (CH2)3n-Pr U Et T (CH2)3n-Pr U n-Pr T (CH2)3n-Pr U NO2 T (CH2)3n-Pr U NH2 T (CH2)3n-Pr U NHCOPh T (CH2)3n-Pr U CHO T (CH2)3n-Pr U CN T (CH2)3n-Pr U Ph T (CH2)3Et U F T (CH2)3Et U Cl T (CH2)3Et U Br T (CH2)3Et U I T (CH2)3Et U Me T (CH2)3Et U CF3 T (CH2)3Et U Et T (CH2)3Et U n-Pr T (CH2)3Et U NO2 T (CH2)3Et U NH2 T (CH2)3Et U NHCOPh T (CH2)3Et U CHO T (CH2)3Et U CN T (CH2)3Et U Ph T (CH2)3n-Bu U F T (CH2)3n-Bu U Cl T (CH2)3n-Bu U Br T (CH2)3n-Bu U I T (CH2)3n-Bu U Me T (CH2)3n-Bu U CF3 T (CH2)3n-Bu U Et T (CH2)3n-Bu U n-Pr T (CH2)3n-Bu U NO2 T (CH2)3n-Bu U NH2 T (CH2)3n-Bu U NHCOPh T (CH2)3n-Bu U CHO T (CH2)3R1 R2 R3 R7 An-Bu U CN T (CH2)3n-Bu U Ph T (CH2)3c-Pr U F T (CH2)3c-Pr U Cl T (CH2)3c-Pr U Br T (CH2)3c-Pr U I T (CH2)3c-Pr U Me T (CH2)3c-Pr U CF3 T (CH2)3c-Pr U Et T (CH2)3c-Pr U n-Pr T (CH2)3c-Pr U NO2 T (CH2)3c-Pr U NH2 T (CH2)3c-Pr U NHCOPh T (CH2)3c-Pr U CHO T (CH2)3c-Pr U CN T (CH2)3c-Pr U Ph T (CH2)3n-Pr U F T (CH2)4n-Pr U Cl T (CH2)4n-Pr U Br T (CH2)4n-Pr U I T (CH2)4n-Pr U Me T (CH2)4n-Pr U CF3 T (CH2)4n-Pr U Et T (CH2)4n-Pr U n-Pr T (CH2)4n-Pr U NO2 T (CH2)4n-Pr U NH2 T (CH2)4n-Pr U NHCOPh T (CH2)4n-Pr U CHO T (CH2)4n-Pr U CN T (CH2)4n-Pr U Ph T (CH2)4Et U F T (CH2)4Et U Cl T (CH2)4Et U Hr T (CH2)4Et U I T (CH2)4Et U Me T (CH2)4Et U CF3 T (CH2)4Et U Et T (CH2)4Et U n-Pr T (CH2)4Et U NO2 T (CH2)4R1 R2 R3 R7 AEt U NH2 T (CH2)4Et U NHCOPh T (CH2)4Et U CHO T (CH2)4Et U CN T (CH2)4Et U Ph T (CH2)4n-Bu U F T (CH2)4n-Bu U Cl T (CH2)4n-Bu U Br T (CH2)4n-Bu U I T (CH2)4n-Bu U Me T (CH2)4n-Bu U CF3 T (CH2)4n-Bu U Et T (CH2)4n-Bu U n-Pr T (CH2)4n-Bu U NO2 T (CH2)4n-Bu U NH2 T (CH2)4n-Bu U NHCOPh T (CH2)4n-Bu U CHO T (CH2)4n-Bu U CN T (CH2)4n-Bu U Ph T (CH2)4c-Pr U F T (CH2)4c-Pr U Cl T (CH2)4c-Pr U Br T (CH2)4c-Pr U I T (CH2)4c-Pr U Me T (CH2)4c-Pr U CF3 T (CH2)4c-Pr U Et T (CH2)4c-Pr U n-Pr T (CH2)4c-Pr U NO2 T (CH2)4c-Pr U NH2 T (CH2)4c-Pr U NHCOPh T (CH2)4c-Pr U CHO T (CH2)4c-Pr U CN T (CH2)4c-Pr U Ph T (CH2)4n-Pr U F T C(＝O)n-Pr U Cl T C(＝O)n-Pr U Br T C(＝O)n-Pr U I T C(＝O)n-Pr U Me T C(＝O)n-Pr U CF3 T C(＝O) R1 R2 R3 R7 An-Pr U Et T C(＝O)n-Pr U n-Pr T C(＝O)n-Pr U NO2 T C(＝O)n-Pr U NH2 T C(＝O)n-Pr U NHCOPh T C(＝O)n-Pr U CHO T C(＝O)n-Pr U CN T C(＝O)n-Pr U Ph T C(＝O)n-Pr U F T (CH2)2COn-Pr U Cl T (CH2)2COn-Pr U Br T (CH2)2COn-Pr U I T (CH2)2COn-Pr U Me T (CH2)2COn-Pr U CF3 T (CH2)2COn-Pr U Et T (CH2)2COn-Pr U n-Pr T (CH2)2COn-Pr U NO2 T (CH2)2COn-Pr U NH2 T (CH2)2COn-Pr U NHCOPh T (CH2)2COn-Pr U CHO T (CH2)2COn-Pr U CN T (CH2)2COn-Pr U Ph T (CH2)2COEt U F T (CH2)2COEt U Cl T (CH2)2COEt U Br T (CH2)2COEt U I T (CH2)2COEt U Me T (CH2)2COEt U CF3 T (CH2)2COEt U Et T (CH2)2COEt U n-Pr T (CH2)2COEt U NO2 T (CH2)2COEt U NH2 T (CH2)2COEt U NHCOPh T (CH2)2COEt U CHO T (CH2)2COEt U CN T (CH2)2COEt U Ph T (CH2)2COn-Bu U F T (CH2)2COn-Bu U Cl T (CH2)2COn-Bu U Br T (CH2)2COR1 R2 R3 R7 An-Bu U I T (CH2)2COn-Bu U Me T (CH2)2COn-Bu U CF3 T (CH2)2COn-Bu U Et T (CH2)2COn-Bu U n-Pr T (CH2)2COn-Bu U NO2 T (CH2)2COn-Bu U NH2 T (CH2)2COn-Bu U NHCOPh T (CH2)2COn-Bu U CHO T (CH2)2COn-Bu U CN T (CH2)2COn-Bu U Ph T (CH2)2COc-Pr U F T (CH2)2COc-Pr U Cl T (CH2)2COc-Pr U Br T (CH2)2COc-Pr U I T (CH2)2COc-Pr U Me T (CH2)2COc-Pr U CF3 T (CH2)2COc-Pr U Et T (CH2)2COc-Pr U n-Pr T (CH2)2COc-Pr U NO2 T (CH2)2COc-Pr U NH2 T (CH2)2COc-Pr U NHCOPh T (CH2)2COc-Pr U CHO T (CH2)2COc-Pr U CN T (CH2)2COc-Pr U Ph T (CH2)2COn-Pr U F T CH2COCH2n-Pr U Cl T CH2COCH2n-Pr U Br T CH2COCH2n-Pr U I T CH2COCH2n-Pr U Me T CH2COCH2n-Pr U CF3 T CH2COCH2n-Pr U Et T CH2COCH2n-Pr U n-Pr T CH2COCH2n-Pr U NO2 T CH2COCH2n-Pr U NH2 T CH2COCH2n-Pr U NHCOPh T CH2COCH2n-Pr U CHO T CH2COCH2n-Pr U CN T CH2COCH2n-Pr U Ph T CH2COCH2R1 R2 R3 R7 AEt U F T CH2COCH2Et U Cl T CH2COCH2Et U Br T CH2COCH2Et U I T CH2COCH2Et U Me T CH2COCH2Et U CF3 T CH2COCH2Et U Et T CH2COCH2Et U n-Pr T CH2COCH2Et U NO2 T CH2COCH2Et U NH2 T CH2COCH2Et U NHCOPh T CH2COCH2Et U CHO T CH2COCH2Et U CN T CH2COCH2Et U Ph T CH2COCH2n-Bu U F T CH2COCH2n-Bu U Cl T CH2COCH2n-Bu U Br T CH2COCH2n-Bu U I T CH2COCH2n-Bu U Me T CH2COCH2n-Bu U CF3 T CH2COCH2n-Bu U Et T CH2COCH2n-Bu U n-Pr T CH2COCH2n-Bu U NO2 T CH2COCH2n-Bu U NH2 T CH2COCH2n-Bu U NHCOPh T CH2COCH2n-Bu U CHO T CH2COCH2n-Bu U CN T CH2COCH2n-Bu U Ph T CH2COCH2c-Pr U F T CH2COCH2c-Pr U Cl T CH2COCH2c-Pr U Br T CH2COCH2c-Pr U I T CH2COCH2c-Pr U Me T CH2COCH2c-Pr U CF3 T CH2COCH2c-Pr U Et T CH2COCH2c-Pr U n-Pr T CH2COCH2c-Pr U NO2 T CH2COCH2c-Pr U NH2 T CH2COCH2c-Pr U NHCOPh T CH2COCH2 R1 R2 R3 R7 Ac-Pr U CHO T CH2COCH2c-Pr U CN T CH2COCH2c-Pr U Ph T CH2COCH2n-Pr U F T CH2CH(Ph)n-Pr U Cl T CH2CH(Ph)n-Pr U Br T CH2CH(Ph)n-Pr U I T CH2CH(Ph)n-Pr U Me T CH2CH(Ph)n-Pr U CF3 T CH2CH(Ph)n-Pr U Et T CH2CH(Ph)n-Pr U n-Pr T CH2CH(Ph)n-Pr U c-Pr T CH2CH(Ph)n-Pr U NO2 T CH2CH(Ph)n-Pr U NH2 T CH2CH(Ph)n-Pr U N(Me)H T CH2CH(Ph)n-Pr U N(Me)2 T CH2CH(Ph)n-Pr U N(Me)n-Bu T CH2CH(Ph)n-Pr U N(nPen)H T CH2CH(Ph)n-Pr U NHCOPh T CH2CH(Ph)n-Pr U N(Me)CO-c-Hex T CH2CH(Ph)n-Pr U NHCONHMe T CH2CH(Ph)n-Pr U N(Me)CONHPh T CH2CH(Ph)n-Pr U NHCONH-c-Hex T CH2CH(Ph)n-Pr U NHCOBz T CH2CH(Ph)n-Pr U J1 T CH2CH(Ph)n-Pr U NBzCO-n-Bu T CH2CH(Ph)n-Pr U NBzCOO-i-Bu T CH2CH(Ph)n-Pr U NHCO-n-Bu T CH2CH(Ph)n-Pr U NHCOO-i-Bu T CH2CH(Ph)n-Pr U NHCOCF3 T CH2CH(Ph)n-Pr U NHSO2CF3 T CH2CH(Ph)n-Pr U N(Me)Ph T CH2CH(Ph)n-Pr U NHC(＝NH)NH2 T CH2CH(Ph)n-Pr U C(＝NH)NH2 T CH2CH(Ph)n-Pr U CHO T CH2CH(Ph)n-Pr U CN T CH2CH(Ph)n-Pr U U T CH2CH(Ph)n-Pr U COOMe T CH2CH(Ph)n-Pr U CONH2 T CH2CH(Ph) R1 R2 R3 R7 An-Pr U CONHCOMe T CH2CH(Ph)n-Pr U CH2NH2 T CH2CH(Ph)n-Pr U CH2OH T CH2CH(Ph)n-Pr U CH2NHCOPh T CH2CH(Ph)n-Pr U CH2N(nPen)COPh T CH2CH(Ph)n-Pr U CH2NHCONHMe T CH2CH(Ph)n-Pr U CH2CONHPh T CH2CH(Ph)n-Pr U CH2COOH T CH2CH(Ph)n-Pr U Ph T CH2CH(Ph)n-Pr U Bz T CH2CH(Ph)n-Pr U CH2CH2Ph T CH2CH(Ph)n-Pr U 2-thienyl T CH2CH(Ph)n-Pr U 3-furyl T CH2CH(Ph)n-Pr U 1-pyrrolyl T CH2CH(Ph)n-Pr U 1-imidazolyl T CH2CH(Ph)n-Pr U 1-pyrazolyl T CH2CH(Ph)n-Pr U 2-pyridyl T CH2CH(Ph)n-Pr U 1-pyrrolidinyl T CH2CH(Ph)n-Pr U 1-piperidyl T CH2CH(Ph)n-Pr U 1-piperazinyl T CH2CH(Ph)n-Pr U 4-morpholinyl T CH2CH(Ph)n-Pr U Ph(2-Cl) T CH2CH(Ph)n-Pr U Ph(3-Me) T CH2CH(Ph)n-Pr U Ph(4-OMe) T CH2CH(Ph)n-Pr U Ph(2-NO2) T CH2CH(Ph)n-Pr U Ph(3-NH2) T CH2CH(Ph)n-Pr U Ph(4-NMe2) T CH2CH(Ph)n-Pr U Ph(4-J2) T CH2CH(Ph)n-Pr U Ph(2-Cl，3-J1) T CH2CH(Ph)n-Pr U Ph(2-Cl，4-J1) T CH2CH(Ph)n-Pr U Ph(2-Cl，5-J1) T CH2CH(Ph)n-Pr U Ph(2-Cl，6-J1) T CH2CH(Ph)n-Pr U CH2CH2Ph(2-Cl，5-J1) T CH2CH(Ph)n-Pr U T T CH2CH(Ph)Et U F T CH2CH(Ph)Et U Cl T CH2CH(Ph)Et U Br T CH2CH(Ph)Et U I T CH2CH(Ph)Et U Me T CH2CH(Ph)R1 R2 R3 R7 AEt U CF3 T CH2CH(Ph)Et U Et T CH2CH(Ph)Et U n-Pr T CH2CH(Ph)Et U c-Pr T CH2CH(Ph)Et U NO2 T CH2CH(Ph)Et U NH2 T CH2CH(Ph)Et U N(Me)H T CH2CH(Ph)Et U N(Me)2 T CH2CH(Ph)Et U N(Me)n-Bu T CH2CH(Ph)Et U N(nPen)H T CH2CH(Ph)Et U NHCOPh T CH2CH(Ph)Et U NHC(＝NH)NH2 T CH2CH(Ph)Et U C(＝NH)NH2 T CH2CH(Ph)Et U CHO T CH2CH(Ph)Et U CN T CH2CH(Ph)Et U U T CH2CH(Ph)Et U COOMe T CH2CH(Ph)Et U CONH2 T CH2CH(Ph)Et U CONHCOMe T CH2CH(Ph)n-Bu U F T CH2CH(Ph)n-Bu U C1 T CH2CH(Ph)n-Bu U Br T CH2CH(Ph)n-Bu U I T CH2CH(Ph)n-Bu U Me T CH2CH(Ph)n-Bu U CF3 T CH2CH(Ph)n-Bu U Et T CH2CH(Ph)n-Bu U n-Pr T CH2CH(Ph)n-Bu U c-Pr T CH2CH(Ph)n-Bu U NO2 T CH2CH(Ph)n-Bu U NH2 T CH2CH(Ph)n-Bu U N(Me)H T CH2CH(Ph)n-Bu U N(Me)2 T CH2CH(Ph)n-Bu U N(Me)n-Bu T CH2CH(Ph)n-Bu U N(nPen)H T CH2CH(Ph)n-Bu U NHCOPh T CH2CH(Ph)n-Bu U NHC(＝NH)NH2 T CH2CH(Ph)n-Bu U C(＝NH)NH2 T CH2CH(Ph)n-Bu U CHO T CH2CH(Ph)n-Bu U CN T CH2CH(Ph) R1 R2 R3 R7 An-Bu U U T CH2CH(Ph)n-Bu U COOMe T CH2CH(Ph)n-Bu U CONH2 T CH2CH(Ph)n-Bu U CONHCOMe T CH2CH(Ph)c-Pr U F T CH2CH(Ph)c-Pr U Cl T CH2CH(Ph)c-Pr U Br T CH2CH(Ph)c-Pr U I T CH2CH(Ph)c-Pr U Me T CH2CH(Ph)c-Pr U CF3 T CH2CH(Ph)c-Pr U Et T CH2CH(Ph)c-Pr U n-Pr T CH2CH(Ph)c-Pr U c-Pr T CH2CH(Ph)c-Pr U NO2 T CH2CH(Ph)c-Pr U NH2 T CH2CH(Ph)c-Pr U N(Me)H T CH2CH(Ph)c-Pr U N(Me)2 T CH2CH(Ph)c-Pr U N(Me)n-Bu T CH2CH(Ph)c-Pr U N(nPen)H T CH2CH(Ph)c-Pr U NHCOPh T CH2CH(Ph)c-Pr U NHC(＝NH)NH2 T CH2CH(Ph)c-Pr U C(＝NH)NH2 T CH2CH(Ph)c-Pr U CHO T CH2CH(Ph)c-Pr U CN T CH2CH(Ph)c-Pr U U T CH2CH(Ph)c-Pr U COOMe T CH2CH(Ph)c-Pr U CONH2 T CH2CH(Ph)c-Pr U CONHCOMe T CH2CH(Ph)n-Pr U F U CH2CH(Ph)n-Pr U Cl U CH2CH(Ph)n-Pr U Br U CH2CH(Ph)n-Pr U I U CH2CH(Ph)n-Pr U Me U CH2CH(Ph)n-Pr U CF3 U CH2CH(Ph)n-Pr U Et U CH2CH(Ph)n-Pr U n-Pr U CH2CH(Ph)n-Pr U c-Pr U CH2CH(Ph)n-Pr U NO2 U CH2CH(Ph)n-Pr U NH2 U CH2CH(Ph)R1 R2 R3 R7 An-Pr U N(Me)H U CH2CH(Phn-Pr U N(Me)2 U CH2CH(Phn-Pr U N(Me)n-Bu U CH2CH(Phn-Pr U N(nPen)H U CH2CH(Phn-Pr U NHCOPh U CH2CH(Phn-Pr U NHC(＝NH)NH2 U CH2CH(Phn-Pr U C(＝NH)NH2 U CH2CH(Phn-Pr U CHO U CH2CH(Phn-Pr U CN U CH2CH(Phn-Pr U U U CH2CH(Ph)n-Pr U COOMe U CH2CH(Ph)n-Pr U CONH2 U CH2CH(Ph)n-Pr U CONHCOMe U CH2CH(Ph)n-Pr U F T CH2C(＝O)n-Pr U Cl T CH2C(＝O)n-Pr U Br T CH2C(＝O)n-Pr U I T CH2C(＝O)n-Pr U Me T CH2C(＝O)n-Pr U CF3 T CH2C(＝O)n-Pr U Et T CH2C(＝O)n-Pr U n-Pr T CH2C(＝O)n-Pr U c-Pr T CH2C(＝O)n-Pr U NO2 T CH2C(＝O)n-Pr U NH2 T CH2C(＝O)n-Pr U N(Me)H T CH2C(＝O)n-Pr U N(Me)2 T CH2C(＝O)n-Pr U N(Me)n-Bu T CH2C(＝O)n-Pr U N(nPen)H T CH2C(＝O)n-Pr U NHCOPh T CH2C(＝O)n-Pr U N(Me)CO-c-Hex T CH2C(＝O)n-Pr U NHCONHMe T CH2C(＝O)n-Pr U N(Me)CONHPh T CH2C(＝O)n-Pr U NHCONH-c-Hex T CH2C(＝O)n-Pr U NHCOBz T CH2C(＝O)n-Pr U J1 T CH2C(＝O)n-Pr U NBzCO-n-Bu T CH2C(＝O)n-Pr U NBzCOO-i-Bu T CH2C(＝O)n-Pr U NHCO-n-Bu T CH2C(＝O)n-Pr U NHCOO-i-Bu T CH2C(＝O) R1 R2 R3 R7 An-Pr U NHCOCF3 T CH2C(＝O)n-Pr U NHSO2CF3 T CH2C(＝O)n-Pr U N(Me)Ph T CH2C(＝O)n-Pr U NHC(＝NH)NH2 T CH2C(＝O)n-Pr U C(＝NH)NH2 T CH2C(＝O)n-Pr U CHO T CH2C(＝O)n-Pr U CN T CH2C(＝O)n-Pr U U T CH2C(＝O)n-Pr U COOMe T CH2C(＝O)n-Pr U CONH2 T CH2C(＝O)n-Pr U CONHCOMe T CH2C(＝O)n-Pr U CH2NH2 T CH2C(＝O)n-Pr U CH2OH T CH2C(＝O)n-Pr U CH2NHCOPh T CH2C(＝O)n-Pr U CH2N(nPen)COPh T CH2C(＝O)n-Pr U CH2NHCONHMe T CH2C(＝O)n-Pr U CH2CONHPh T CH2C(＝O)n-Pr U CH2COOH T CH2C(＝O)n-Pr U Ph T CH2C(＝O)n-Pr U Bz T CH2C(＝O)n-Pr U CH2CH2Ph T CH2C(＝O)n-Pr U 2-thienyl T CH2C(＝O)n-Pr U 3-furyl T CH2C(＝O)n-Pr U 1-pyrrolyl T CH2C(＝O)n-Pr U 1-imidazolyl T CH2C(＝O)n-Pr U 1-pyrazolyl T CH2C(＝O)n-Pr U 2-pyridyl T CH2C(＝O)n-Pr U 1-pyrrolidinyl T CH2C(＝O)n-Pr U 1-piperidyl T CH2C(＝O)n-Pr U 1-piperazinyl T CH2C(＝O)n-Pr U 4-morpholinyl T CH2C(＝O)n-Pr U Ph(2-Cl) T CH2C(＝O)n-Pr U Ph(3-Me) T CH2C(＝O)n-Pr U Ph(4-OMe) T CH2C(＝O)n-Pr U Ph(2-NO2) T CH2C(＝O)n-Pr U Ph(3-NH2) T CH2C(＝O)n-Pr U Ph(4-NMe2) T CH2C(＝O)n-Pr U Ph(4-J2) T CH2C(＝O)n-Pr U Ph(2-Cl，3-J1) T CH2C(＝O) R1 R2 R3 R7 An-Pr U Ph(2-Cl，4-J1) T CH2C(＝O)n-Pr U Ph(2-Cl，5-J1) T CH2C(＝O)n-Pr U Ph(2-Cl，6-J1) T CH2C(＝O)n-Pr U CH2CH2Ph(2-Cl，5-J1)T CH2C(＝O)n-Pr U T T CH2C(＝O)Et U F T CH2C(＝O)Et U Cl T CH2C(＝O)Et U Br T CH2C(＝O)Et U I T CH2C(＝O)Et U Me T CH2C(＝O)Et U CF3 T CH2C(＝O)Et U Et T CH2C(＝O)Et U n-Pr T CH2C(＝O)Et U c-Pr T CH2C(＝O)Et U NO2 T CH2C(＝O)Et U NH2 T CH2C(＝O)Et U N(Me)H T CH2C(＝O)Et U N(Me)2 T CH2C(＝O)Et U N(Me)n-Bu T CH2C(＝O)Et U N(nPen)H T CH2C(＝O)Et U NHCOPh T CH2C(＝O)Et U N(Me)CO-c-Hex T CH2C(＝O)Et U NHCONHMe T CH2C(＝O)Et U N(Me)CONHPh T CH2C(＝O)Et U NHC(＝NH)NH2 T CH2C(＝O)Et U C(＝NH)NH2 T CH2C(＝O)Et U CHO T CH2C(＝O)Et U CN T CH2C(＝O)Et U U T CH2C(＝O)Et U COOMe T CH2C(＝O)Et U CONH2 T CH2C(＝O)Et U CONHCOMe T CH2C(＝O)n-Bu U F T CH2C(＝O)n-Bu U Cl T CH2C(＝O)n-Bu U Br T CH2C(＝O)n-Bu U I T CH2C(＝O)n-Bu U Me T CH2C(＝O)n-Bu U CF3 T CH2C(＝O)n-Bu U Et T CH2C(＝O)R1 R2 R3 R7 An-Bu U n-Pr T CH2C(＝O)n-Bu U c-Pr T CH2C(＝O)n-Bu U NO2 T CH2C(＝O)n-Bu U NH2 T CH2C(＝O)n-Bu U N(Me)H T CH2C(＝O)n-Bu U N(Me)2 T CH2C(＝O)n-Bu U N(Me)n-Bu T CH2C(＝O)n-Bu U N(nPen)H T CH2C(-＝O)n-Bu U NHCOPh T CH2C(＝O)n-Bu U NHC(＝NH)NH2 T CH2C(＝O)n-Bu U C(＝NH)NH2 T CH2C(＝O)n-Bu U CHO T CH2C(＝O)n-Bu U CN T CH2C(＝O)n-Bu U U T CH2C(＝O)n-Bu U COOMe T CH2C(＝O)n-Bu U CONH2 T CH2C(＝O)n-Bu U CONHCOMe T CH2C(＝O)c-Pr U F T CH2C(＝O)c-Pr U Cl T CH2C(＝O)c-Pr U Br T CH2C(＝O)c-Pr U I T CH2C(＝O)c-Pr U Me T CH2C(＝O)c-Pr U CF3 T CH2C(＝O)c-Pr U Et T CH2C(＝O)c-Pr U n-Pr T CH2C(＝O)c-Pr U c-Pr T CH2C(＝O)c-Pr U NO2 T CH2C(＝O)c-Pr U NH2 T CH2C(-＝O)c-Pr U N(Me)H T CH2C(＝O)c-Pr U N(Me)2 T CH2C(-＝O)c-Pr U N(Me)n-Bu T CH2C(＝O)c-Pr U N(nPen)H T CH2C(＝O)c-Pr U NHCOPh T CH2C(＝O)c-Pr U NHC(＝NH)NH2 T CH2C(＝O)c-Pr U C(＝NH)NH2 T CH2C(＝O)c-Pr U CHO T CH2C(＝O)c-Pr U CN T CH2C(＝O)c-Pr U U T CH2C(＝O)c-Pr U COOMe T CH2C(＝O) R1 R2 R3 R7 Ac-Pr U CONH2 T CH2C(＝O)c-Pr U CONHCOMe T CH2C(＝O)n-Pr U F T (CH2)2n-Pr U Cl T (CH2)2n-Pr U Br T (CH2)2n-Pr U I T (CH2)2n-Pr U Me T (CH2)2n-Pr U CF3 T (CH2)2n-Pr U Et T (CH2)2n-Pr U n-Pr T (CH2)2n-Pr U c-Pr T (CH2)2n-Pr U NO2 T (CH2)2n-Pr U NH2 T (CH2)2n-Pr U N(Me)H T (CH2)2n-Pr U N(Me)2 T (CH2)2n-Pr U N(Me)n-Bu T (CH2)2n-Pr U N(nPen)H T (CH2)2n-Pr U NHCOPh T (CH2)2n-Pr U N(Me)CO-c-Hex T (CH2)2n-Pr U NHCONHMe T (CH2)2n-Pr U N(Me)CONHPh T (CH2)2n-Pr U NHCONH-c-Hex T (CH2)2n-Pr U NHCOBz T (CH2)2n-Pr U J1 T (CH2)2n-Pr U NBzCO-n-Bu T (CH2)2n-Pr U NBzCOO-i-Bu T (CH2)2n-Pr U NHCO-n-Bu T (CH2)2n-Pr U NHCOO-i-Bu T (CH2)2n-Pr U NHCOCF3 T (CH2)2n-Pr U NHSO2CF3 T (CH2)2n-Pr U N(Me)Ph T (CH2)2n-Pr U NHC(＝NH)NH2 T (CH2)2n-Pr U C(＝NH)NH2 T (CH2)2n-Pr U CHO T (CH2)2n-Pr U CN T (CH2)2n-Pr U U T (CH2)2n-Pr U COOMe T (CH2)2n-Pr U CONH2 T (CH2)2n-Pr U CONHCOMe T (CH2)2 R1 R2 R3 R7 An-Pr U CH2NH2 T (CH2)2n-Pr U CH2OH T (CH2)2n-Pr U CH2NHCOPh T (CH2)2n-Pr U CH2N(nPen)COPh T (CH2)2n-Pr U CH2NHCONHMe T (CH2)2n-Pr U CH2CONHPh T (CH2)2n-Pr U CH2COOH T (CH2)2n-Pr U Ph T (CH2)2n-Pr U Bz T (CH2)2n-Pr U CH2CH2Ph T (CH2)2n-Pr U 2-thienyl T (CH2)2n-Pr U 3-furyl T (CH2)2n-Pr U 1-pyrrolyl T (CH2)2n-Pr U 1-imidazolyl T (CH2)2n-Pr U 1-pyrazolyl T (CH2)2n-Pr U 2-pyridyl T (CH2)2n-Pr U 1-pyrrolidinyl T (CH2)2n-Pr U 1-piperidyl T (CH2)2n-Pr U 1-piperazinyl T (CH2)2n-Pr U 4-morpholinyl T (CH2)2n-Pr U Ph(2-Cl) T (CH2)2n-Pr U Ph(3-Me) T (CH2)2n-Pr U Ph(4-OMe) T (CH2)2n-Pr U Ph(2-NO2) T (CH2)2n-Pr U Ph(3-NH2) T (CH2)2n-Pr U Ph(4-NMe2) T (CH2)2n-Pr U Ph(4-J2) T (CH2)2n-Pr U Ph(2-Cl，3-J1) T (CH2)2n-Pr U Ph(2-Cl，4-J1) T (CH2)2n-Pr U Ph(2-Cl，5-J1) T (CH2)2n-Pr U Ph(2-Cl，6-J1) T (CH2)2n-Pr U Ph(3-NHCOPh) T (CH2)2n-Pr U Ph(4-NHCO-c-Hex) T (CH2)2n-Pr U Ph(3-NHCONHMe) T (CH2)2n-Pr U Ph(4-NMeCONHPh) T (CH2)2n-Pr U Ph(3-NHCONH-c-Hex) T (CH2)2n-Pr U Ph(4-NHCOBz) T (CH2)2n-Pr U Ph(4-N(nPen)COPh) T (CH2)2n-Pr U Ph(3-NHCOnBu) T (CH2)2 R1 R2 R3 R7 An-Pr U Ph(4-NHCOCF3) T (CH2)2n-Pr U Ph(3-NHSO2CF3) T (CH2)2n-Pr U Ph(4-NMePh) T (CH2)2n-Pr U Ph(3-NHC(＝NH)NH2) T (CH2)2n-Pr U Ph(4-C(＝NH)NH2) T (CH2)2n-Pr U Ph(3-COOH) T (CH2)2n-Pr U Ph(4-CONH2) T (CH2)2n-Pr U Ph(3-CH2NH2) T (CH2)2n-Pr U Ph(4-CH2OH) T (CH2)2n-Pr U Ph(4-CH2J2) T (CH2)2n-Pr U Ph(4-CH2NHCONHMe) T (CH2)2n-Pr U Ph(4-CH2CONHPh) T (CH2)2n-Pr U Ph(4-CH2COOH) T (CH2)2n-Pr U Ph(4-Ph) T (CH2)2n-Pr U CH2CH2Ph(2-Cl，5-J1) T (CH2)2n-Pr U OH T (CH2)2n-Pr U OMe T (CH2)2n-Pr U OPh T (CH2)2n-Pr U SH T (CH2)2n-Pr U SPh T (CH2)2n-Pr U SO2Ph T (CH2)2n-Pr U S-n-Bu T (CH2)2n-Pr U 2-pyrazinyl T (CH2)2n-Pr U 2-pyrimidinyl T (CH2)2n-Pr U 3-pyridyl T (CH2)2n-Pr U 4-pyridyl T (CH2)2n-Pr U T T (CH2)2Me U F T (CH2)2Me U Cl T (CH2)2Me U Br T (CH2)2Me U I T (CH2)2Me U Me T (CH2)2Me U CF3 T (CH2)2Me U Et T (CH2)2Me U n-Pr T (CH2)2Me U c-Pr T (CH2)2Me U NO2 T (CH2)2Me U NH2 T (CH2)2Me U N(Me)H T (CH2)2 R1 R2 R3 R7 AMe U N(Me)2 T (CH2)2Me U N(Me)n-Bu T (CH2)2Me U N(nPen)H T (CH2)2Me U NHCOPh T (CH2)2Me U J1 T (CH2)2Me U NHC(＝NH)NH2 T (CH2)2Me U C(＝NH)NH2 T (CH2)2Me U CHO T (CH2)2Me U CN T (CH2)2Me U U T (CH2)2Me U COOMe T (CH2)2Me U CONH2 T (CH2)2Me U CONHCOMe T (CH2)2Me U CH2COOH T (CH2)2Me U Ph T (CH2)2Me U Bz T (CH2)2Me U CH2CH2Ph T (CH2)2Me U T T (CH2)2Et U F T (CH2)2Et U Cl T (CH2)2Et U Br T (CH2)2Et U I T (CH2)2Et U Me T (CH2)2Et U CF3 T (CH2)2Et U Et T (CH2)2Et U n-Pr T (CH2)2Et U c-Pr T (CH2)2Et U NO2 T (CH2)2Et U NH2 T (CH2)2Et U N(Me)H T (CH2)2Et U N(Me)2 T (CH2)2Et U N(Me)n-Bu T (CH2)2Et U N(nPen)H T (CH2)2Et U NHCOPh T (CH2)2Et U N(Me)CO-c-Hex T (CH2)2Et U NHCONHMe T (CH2)2Et U N(Me)CONHPh T (CH2)2Et U NHCONH-c-Hex T (CH2)2Et U NHCOBz T (CH2)2 R1 R2 R3 R7 AEt U J1 T (CH2)2Et U NBzCO-n-Bu T (CH2)2Et U NBzCOO-i-Bu T (CH2)2Et U NHCO-n-Bu T (CH2)2Et U NHCOO-i-Bu T (CH2)2Et U NHCOCF3 T (CH2)2Et U NHSO2CF3 T (CH2)2Et U N(Me)Ph T (CH2)2Et U NHC(＝NH)NH2 T (CH2)2Et U C(＝NH)NH2 T (CH2)2Et U CHO T (CH2)2Et U CN T (CH2)2Et U U T (CH2)2Et U COOMe T (CH2)2Et U CONH2 T (CH2)2Et U CONHCOMe T (CH2)2Et U CH2NH2 T (CH2)2Et U CH2OH T (CH2)2Et U CH2NHCOPh T (CH2)2Et U CH2N(nPen)COPh T (CH2)2Et U CH2NHCONHMe T (CH2)2Et U CH2CONHPh T (CH2)2Et U CH2COOH T (CH2)2Et U Ph T (CH2)2Et U Bz T (CH2)2Et U CH2CH2Ph T (CH2)2Et U 2-thienyl T (CH2)2Et U 3-furyl T (CH2)2Et U 1-pyrrolyl T (CH2)2Et U 1-imidazolyl T (CH2)2Et U 1-pyrazolyl T (CH2)2Et U 2-pyridyl T (CH2)2Et U 1-pyrrolidinyl T (CH2)2Et U 1-piperidyl T (CH2)2Et U 1-piperazinyl T (CH2)2Et U 4-morpholinyl T (CH2)2Et U Ph(2-Cl) T (CH2)2Et U Ph(3-Me) T (CH2)2Et U Ph(4-OMe) T (CH2)2 R1 R2 R3 R7 AEt U Ph(2-NO2) T (CH2)2Et U Ph(3-NH2) T (CH2)2Et U Ph(4-NMe2) T (CH2)2Et U Ph(4-J2) T (CH2)2Et U Ph(2-Cl，3-J1) T (CH2)2Et U Ph(2-Cl，4-J1) T (CH2)2Et U Ph(2-C1，5-J1) T (CH2)2Et U Ph(2-Cl，6-J1) T (CH2)2Et U Ph(3-NHCOPh) T (CH2)2Et U Ph(4-NHCO-c-Hex) T (CH2)2Et U Ph(3-NHCONHMe) T (CH2)2Et U Ph(4-NMeCONHPh) T (CH2)2Et U Ph(3-NHCONH-c-Hex) T (CH2)2Et U Ph(4-NHCOBz) T (CH2)2Et U Ph(4-N(nPen)COPh) T (CH2)2Et U Ph(3-NHCOnBu) T (CH2)2Et U Ph(4-NHCOCF3) T (CH2)2Et U Ph(3-NHSO2CF3) T (CH2)2Et U Ph(4-NMePh) T (CH2)2Et U Ph(3-NHC(＝NH)NH2) T (CH2)2Et U Ph(4-C(＝NH)NH2) T (CH2)2Et U Ph(3-COOH) T (CH2)2Et U Ph(4-CONH2) T (CH2)2Et U Ph(3-CH2NH2) T (CH2)2Et U Ph(4-CH2OH) T (CH2)2Et U Ph(4-CH2J2) T (CH2)2Et U Ph(4-CH2NHCONHMe) T (CH2)2Et U Ph(4-CH2CONHPh) T (CH2)2Et U Ph(4-CH2COOH) T (CH2)2Et U Ph(4-Ph) T (CH2)2Et U CH2CH2Ph(2-Cl，5-J1) T (CH2)2Et U OH T (CH2)2Et U OMe T (CH2)2Et U OPh T (CH2)2Et U SH T (CH2)2Et U SPh T (CH2)2Et U SO2Ph T (CH2)2Et U S-n-Bu T (CH2)2Et U 2-pyrazinyl T (CH2)2 R1 R2 R3 R7 AEt U 2-pyrimidinyl T (CH2)2Et U 3-pyridyl T (CH2)2Et U 4-pyridyl T (CH2)2Et U T T (CH2)2n-Bu U F T (CH2)2n-Bu U Cl T (CH2)2n-Bu U Br T (CH2)2n-Bu U I T (CH2)2n-Bu U Me T (CH2)2n-Bu U CF3 T (CH2)2n-Bu U Et T (CH2)2n-Bu U n-Pr T (CH2)2n-Bu U c-Pr T (CH2)2n-Bu U NO2 T (CH2)2n-Bu U NH2 T (CH2)2n-Bu U N(Me)H T (CH2)2n-Bu U N(Me)2 T (CH2)2n-Bu U N(Me)n-Bu T (CH2)2n-Bu U N(nPen)H T (CH2)2n-Bu U NHCOPh T (CH2)2n-Bu U N(Me)CO-c-Hex T (CH2)2n-Bu U NHCONHMe T (CH2)2n-Bu U N(Me)CONHPh T (CH2)2n-Bu U NHCONH-c-Hex T (CH2)2n-Bu U NHCOBz T (CH2)2n-Bu U J1 T (CH2)2n-Bu U NBzCO-n-Bu T (CH2)2n-Bu U NBzCOO-i-Bu T (CH2)2n-Bu U NHCO-n-Bu T (CH2)2n-Bu U NHCOO-i-Bu T (CH2)2n-Bu U NHCOCF3 T (CH2)2n-Bu U NHSO2CF3 T (CH2)2n-Bu U N(Me)Ph T (CH2)2n-Bu U NHC(＝NH)NH2 T (CH2)2n-Bu U C(＝NH)NH2 T (CH2)2n-Bu U CHO T (CH2)2n-Bu U CN T (CH2)2n-Bu U U T (CH2)2n-Bu U COOMe T (CH2)2 R1 R2 R3 R7 An-Bu U CONH2 T (CH2)2n-Bu U CONHCOMe T (CH2)2n-Bu U CH2NH2 T (CH2)2n-Bu U CH2OH T (CH2)2n-Bu U CH2NHCOPh T (CH2)2n-Bu U CH2N(nPen)COPh T (CH2)2n-Bu U CH2NHCONHMe T (CH2)2n-Bu U CH2CONHPh T (CH2)2n-Bu U CH2COOH T (CH2)2n-Bu U Ph T (CH2)2n-Bu U Bz T (CH2)2n-Bu U CH2CH2Ph T (CH2)2n-Bu U 2-thienyl T (CH2)2n-Bu U 3-furyl T (CH2)2n-Bu U 1-pyrrolyl T (CH2)2n-Bu U 1-imidazolyl T (CH2)2n-Bu U 1-pyrazolyl T (CH2)2n-Bu U 2-pyridyl T (CH2)2n-Bu U 1-pyrrolidinyl T (CH2)2n-Bu U 1-piperidyl T (CH2)2n-Bu U 1-piperazinyl T (CH2)2n-Bu U 4-morpholinyl T (CH2)2n-Bu U Ph(2-Cl) T (CH2)2n-Bu U Ph(3-Me) T (CH2)2n-Bu U Ph(4-OMe) T (CH2)2n-Bu U Ph(2-NO2) T (CH2)2n-Bu U Ph(3-NH2) T (CH2)2n-Bu U Ph(4-NMe2) T (CH2)2n-Bu U Ph(4-J2) T (CH2)2n-Bu U Ph(2-Cl，3-J1) T (CH2)2n-Bu U Ph(2-Cl，4-J1) T (CH2)2n-Bu U Ph(2-Cl，5-J1) T (CH2)2n-Bu U Ph(2-Cl，6-J1) T (CH2)2n-Bu U Ph(3-NHCOPh) T (CH2)2n-Bu U Ph(4-NHCO-c-Hex) T (CH2)2n-Bu U Ph(3-NHCONHMe) T (CH2)2n-Bu U Ph(4-NMeCONHPh) T (CH2)2n-Bu U Ph(3-NHCONH-c-Hex) T (CH2)2n-Bu U Ph(4-NHCOBz) T (CH2)2 R1 R2 R3 R7 An-Bu U Ph(4-N(nPen)COPh) T (CH2)2n-Bu U Ph(3-NHCOnBu) T (CH2)2n-Bu U Ph(4-NHCOCF3) T (CH2)2n-Bu U Ph(3-NHSO2CF3) T (CH2)2n-Bu U Ph(4-NMePh) T (CH2)2n-Bu U Ph(3-NHC(＝NH)NH2) T (CH2)2n-Bu U Ph(4-C(＝NH)NH2) T (CH2)2n-Bu U Ph(3-COOH) T (CH2)2n-Bu U Ph(4-CONH2) T (CH2)2n-Bu U Ph(3-CH2NH2) T (CH2)2n-Bu U Ph(4-CH2OH) T (CH2)2n-Bu U Ph(4-CH2J2) T (CH2)2n-Bu U Ph(4-CH2NHCONHMe) T (CH2)2n-Bu U Ph(4-CH2CONHPh) T (CH2)2n-Bu U Ph(4-CH2COOH) T (CH2)2n-Bu U Ph(4-Ph) T (CH2)2n-Bu U CH2CH2Ph(2-C1，5-J1) T (CH2)2n-Bu U OH T (CH2)2n-Bu U OMe T (CH2)2n-Bu U OPh T (CH2)2n-Bu U SH T (CH2)2n-Bu U SPh T (CH2)2n-Bu U SO2Ph T (CH2)2n-Bu U S-n-Bu T (CH2)2n-Bu U 2-pyrazinyl T (CH2)2n-Bu U 2-pyrimidinyl T (CH2)2n-Bu U 3-pyridyl T (CH2)2n-Bu U 4-pyridyl T (CH2)2n-Bu U T T (CH2)2c-Pr U F T (CH2)2c-Pr U Cl T (CH2)2c-Pr U Br T (CH2)2c-Pr U I T (CH2)2c-Pr U Me T (CH2)2c-Pr U CF3 T (CH2)2c-Pr U Et T (CH2)2c-Pr U n-Pr T (CH2)2c-Pr U c-Pr T (CH2)2c-Pr U NO2 T (CH2)2 R1 R2 R3 R7 Ac-Pr U NH2 T (CH2)2c-Pr U N(Me)H T (CH2)2c-Pr U N(Me)2 T (CH2)2c-Pr U N(Me)n-Bu T (CH2)2c-Pr U N(nPen)H T (CH2)2c-Pr U NHCOPh T (CH2)2c-Pr U N(Me)CO-c-Hex T (CH2)2c-Pr U NHCONHMe T (CH2)2c-Pr U N(Me)CONHPh T (CH2)2c-Pr U NHCONH-c-Hex T (CH2)2c-Pr U NHCOBz T (CH2)2c-Pr U J1 T (CH2)2c-Pr U NBzCO-n-Bu T (CH2)2c-Pr U NBzCOO-i-Bu T (CH2)2c-Pr U NHCO-n-Bu T (CH2)2c-Pr U NHCOO-i-Bu T (CH2)2c-Pr U NHCOCF3 T (CH2)2c-Pr U NHSO2CF3 T (CH2)2c-Pr U N(Me)Ph T (CH2)2c-Pr U NHC(＝NH)NH2 T (CH2)2c-Pr U C(＝NH)NH2 T (CH2)2c-Pr U CHO T (CH2)2c-Pr U CN T (CH2)2c-Pr U U T (CH2)2c-Pr U COOMe T (CH2)2c-Pr U CONH2 T (CH2)2c-Pr U CONHCOMe T (CH2)2c-Pr U CH2NH2 T (CH2)2c-Pr U CH2OH T (CH2)2c-Pr U CH2NHCOPh T (CH2)2c-Pr U CH2N(nPen)COPh T (CH2)2c-Pr U CH2NHCONHMe T (CH2)2c-Pr U CH2CONHPh T (CH2)2c-Pr U CH2COOH T (CH2)2c-Pr U Ph T (CH2)2c-Pr U Bz T (CH2)2c-Pr U CH2CH2Ph T (CH2)2c-Pr U 2-thienyl T (CH2)2c-Pr U 3-furyl T (CH2)2R1 R2 R3 R7 Ac-Pr U 1 -pyrrolyl T (CH2)2c-Pr U 1-imidazolyl T (CH2)2c-Pr U 1-pyrazolyl T (CH2)2c-Pr U 2-pyridyl T (CH2)2c-Pr U 1-pyrrolidinyl T (CH2)2c-Pr U 1-piperidyl T (CH2)2c-Pr U 1-piperazinyl T (CH2)2c-Pr U 4-morpholinyl T (CH2)2c-Pr U Ph(2-Cl) T (CH2)2c-Pr U Ph(3-Me) T (CH2)2c-Pr U Ph(4-OMe) T (CH2)2c-Pr U Ph(2-NO2) T (CH2)2c-Pr U Ph(3-NH2) T (CH2)2c-Pr U Ph(4-NMe2) T (CH2)2c-Pr U Ph(4-J2) T (CH2)2c-Pr U Ph(2-Cl，3-J1) T (CH2)2c-Pr U Ph(2-Cl，4-J1) T (CH2)2c-Pr U Ph(2-Cl，5-J1) T (CH2)2c-Pr U Ph(2-C1，6-J1) T (CH2)2c-Pr U Ph(3-NHCOPh) T (CH2)2c-Pr U Ph(4-NHCO-c-Hex) T (CH2)2c-Pr U Ph(3-NHCONHMe) T (CH2)2c-Pr U Ph(4-NMeCONHPh) T (CH2)2c-Pr U Ph(3-NHCONH-c-Hex) T (CH2)2c-Pr U Ph(4-NHCOBz) T (CH2)2c-Pr U Ph(4-N(nPen)COPh) T (CH2)2c-Pr U Ph(3-NHCOnBu) T (CH2)2c-Pr U Ph(4-NHCOCF3) T (CH2)2c-Pr U Ph(3-NHSO2CF3) T (CH2)2c-Pr U Ph(4-NMePh) T (CH2)2c-Pr U Ph(3-NHC(＝NH)NH2) T (CH2)2c-Pr U Ph(4-C(＝NH)NH2) T (CH2)2c-Pr U Ph(3-COOH) T (CH2)2c-Pr U Ph(4-CONH2) T (CH2)2c-Pr U Ph(3-CH2NH2) T (CH2)2c-Pr U Ph(4-CH2OH) T (CH2)2c-Pr U Ph(4-CH2J2) T (CH2)2c-Pr U Ph(4-CH2NHCONHMe) T (CH2)2c-Pr U Ph(4-CH2CONHPh) T (CH2)2R1 R2 R3 R7 Ac-Pr U Ph(4-CH2COOH) T (CH2)2c-Pr U Ph(4-Ph) T (CH2)2c-Pr U CH2CH2Ph(2-Cl，5-J1)T (CH2)2c-Pr U OH T (CH2)2c-Pr U OMe T (CH2)2c-Pr U OPh T (CH2)2c-Pr U SH T (CH2)2c-Pr U SPh T (CH2)2c-Pr U SO2Ph T (CH2)2c-Pr U S-n-Bu T (CH2)2c-Pr U 2-pyrazinyl T (CH2)2c-Pr U 2-pyrimidiny T (CH2)2c-Pr U 3-pyridyl T (CH2)2c-Pr U 4-pyridyl T (CH2)2c-Pr U T T (CH2)2i-Pr U F T (CH2)2i-Pr U Cl T (CH2)2i-Pr U Br T (CH2)2i-Pr U I T (CH2)2i-Pr U Me T (CH2)2i-Pr U CF3 T (CH2)2i-Pr U Et T (CH2)2i-Pr U n-Pr T (CH2)2i-Pr U c-Pr T (CH2)2i-Pr U NO2 T (CH2)2i-Pr U NH2 T (CH2)2i-Pr U N(Me)H T (CH2)2i-Pr U N(Me)2 T (CH2)2i-Pr U N(Me)n-Bu T (CH2)2i-Pr U N(nPen)H T (CH2)2i-Pr U NHCOPh T (CH2)2i-Pr U J1 T (CH2)2i-Pr U NHC(＝NH)NH2 T (CH2)2i-Pr U C(＝NH)NH2 T (CH2)2i-Pr U CHO T (CH2)2i-Pr U CN T (CH2)2i-Pr U U T (CH2)2i-Pr U COOMe T (CH2)2i-Pr U CONH2 T (CH2)2 R1 R2 R3 R7 Ai-Pr U CONHCOMe T (CH2)2i-Pr U CH2COOH T (CH2)2i-Pr U Ph T (CH2)2i-Pr U Bz T (CH2)2i-Pr U CH2CH2Ph T (CH2)2n-Pr T F T (CH2)2n-Pr T Cl T (CH2)2n-Pr T Br T (CH2)2n-Pr T I T (CH2)2n-Pr T Me T (CH2)2n-Pr T CF3 T (CH2)2n-Pr T Et T (CH2)2n-Pr T n-Pr T (CH2)2n-Pr T c-Pr T (CH2)2n-Pr T NO2 T (CH2)2n-Pr T NH2 T (CH2)2n-Pr T N(Me)H T (CH2)2n-Pr T N(Me)2 T (CH2)2n-Pr T N(Me)n-Bu T (CH2)2n-Pr T N(nPen)H T (CH2)2n-Pr T NHCOPh T (CH2)2n-Pr T J1 T (CH2)2n-Pr T NHC(＝NH)NH2 T (CH2)2n-Pr T C(＝NH)NH2 T (CH2)2n-Pr T CHO T (CH2)2n-Pr T CN T (CH2)2n-Pr T U T (CH2)2n-Pr T COOMe T (CH2)2n-Pr T CONH2 T (CH2)2n-Pr T CONHCOMe T (CH2)2n-Pr T CH2COOH T (CH2)2n-Pr T Ph T (CH2)2n-Pr T Bz T (CH2)2n-Pr T CH2CH2Ph T (CH2)2n-Pr T T T (CH2)21-Propenyl U F T (CH2)21-Propenyl U Cl T (CH2)21-Propenyl U Br T (CH2)21-Propenyl U I T (CH2)2R1 R2 R3 R7 A1-Propenyl U Me T (CH2)21-Propenyl U CF3 T (CH2)21-Propenyl U Et T (CH2)21-Propenyl U n-Pr T (CH2)21-Propenyl U c-Pr T (CH2)21-Propenyl U NO2 T (CH2)21-Propenyl U NH2 T (CH2)21-Propenyl U N(Me)H T (CH2)21-Propenyl U N(Me)2 T (CH2)21-Propenyl U N(Me)n-Bu T (CH2)21-Propenyl U N(nPen)H T (CH2)21-Propenyl U NHCOPh T (CH2)21-Propenyl U N(Me)CO-c-Hex T (CH2)21-Propenyl U NHCONHMe T (CH2)21-Propenyl U N(Me)CONHPh T (CH2)21-Propenyl U NHCONH-c-Hex T (CH2)21-Propenyl U NHCOBz T (CH2)21-Propenyl U J1 T (CH2)21-Propenyl U NBzCO-n-Bu T (CH2)21-Propenyl U NBzCOO-i-Bu T (CH2)21-Propenyl U NHCO-n-Bu T (CH2)21-Propenyl U NHCOO-i-Bu T (CH2)21-Propenyl U NHCOCF3 T (CH2)21-Propenyl U NHSO2CF3 T (CH2)21-Propenyl U N(Me)Ph T (CH2)21-Propenyl U NHC(＝NH)NH2 T (CH2)21-Propenyl U C(＝NH)NH2 T (CH2)21-Propenyl U CHO T (CH2)21-Propenyl U CN T (CH2)21-Propenyl U U T (CH2)21-Propenyl U COOMe T (CH2)21-Propenyl U CONH2 T (CH2)21-Propenyl U CONHCOMe T (CH2)21-Propenyl U CH2NH2 T (CH2)21-Propenyl U CH2OH T (CH2)21-Propenyl U CH2NHCOPh T (CH2)21-Propenyl U CH2N(nPen)COPh T (CH2)21-Propenyl U CH2NHCONHMe T (CH2)21-Propenyl U CH2CONHPh T (CH2)2R1 R2 R3 R7 A1-Propenyl U CH2COOH T (CH2)21-Propenyl U Ph T (CH2)21-Propenyl U Bz T (CH2)21-Propenyl U CH2CH2Ph T (CH2)21-Propenyl U 2-thienyl T (CH2)21-Propenyl U 3-furyl T (CH2)21-Propenyl U 1-pyrrolyl T (CH2)21-Propenyl U 1-imidazolyl T (CH2)21-Propenyl U 1-pyrazolyl T (CH2)21-Propenyl U 2-pyridyl T (CH2)21-Propenyl U 1-pyrrolidinyl T (CH2)21-Propenyl U 1-piperidyl T (CH2)21-Propenyl U 1-piperazinyl T (CH2)21-Propenyl U 4-morpholinyl T (CH2)21-Propenyl U Ph(2-C1) T (CH2)21-Propenyl U Ph(3-Me) T (CH2)21-Propenyl U Ph(4-OMe) T (CH2)21-Propenyl U Ph(2-NO2) T (CH2)21-Propenyl U Ph(3-NH2) T (CH2)21-Propenyl U Ph(4-NMe2) T (CH2)21-Propenyl U Ph(4-J2) T (CH2)21-Propenyl U Ph(2-C1，3-J1) T (CH2)21-Propenyl U Ph(2-Cl，4-J1) T (CH2)21-Propenyl U Ph(2-Cl，5-J1) T (CH2)21-Propenyl U Ph(2-Cl，6-J1) T (CH2)21-Propenyl U Ph(3-NHCOPh) T (CH2)21-Propenyl U Ph(4-NHCO-c-Hex) T (CH2)21-Propenyl U Ph(3-NHCONHMe) T (CH2)21-Propenyl U Ph(4-NMeCONHPh) T (CH2)21-Propenyl U Ph(3-NHCONH-c-Hex) T (CH2)21-Propenyl U Ph(4-NHCOBz) T (CH2)21-Propenyl U Ph(4-N(nPen)COPh) T (CH2)21-Propenyl U Ph(3-NHCOnBu) T (CH2)21-Propenyl U Ph(4-NHCOCF3) T (CH2)21-Propenyl U Ph(3-NHSO2CF3) T (CH2)21-Propenyl U Ph(4-NMePh) T (CH2)21-Propenyl U Ph(3-NHC(＝NH)NH2) T (CH2)21-Propenyl U Ph(4-C(＝NH)NH2) T (CH2)21-Propenyl U Ph(3-COOH) T (CH2)2R1 R2 R3 R7 A1-Propenyl U Ph(4-CONH2) T (CH2)21-Propenyl U Ph(3-CH2NH2) T (CH2)21-Propenyl U Ph(4-CH2OH) T (CH2)21-Propenyl U Ph(4-CH2J2) T (CH2)21-Propenyl U Ph(4-CH2NHCONHMe) T (CH2)21-Propenyl U Ph(4-CH2CONHPh) T (CH2)21-Propenyl U Ph(4-CH2COOH) T (CH2)21-Propenyl U Ph(4-Ph) T (CH2)21-Propenyl U CH2CH2Ph(2-Cl，5-J1)T (CH2)21-Propenyl U OH T (CH2)21-Propenyl U OMe T (CH2)21-Propenyl U OPh T (CH2)21-Propenyl U SH T (CH2)21-Propenyl U SPh T (CH2)21-Propenyl U SO2Ph T (CH2)21-Propenyl U S-n-Bu T (CH2)21-Propenyl U 2-pyrazinyl T (CH2)21-Propenyl U 2-pyrimidinyl T (CH2)21-Propenyl U 3-pyridyl T (CH2)21-Propenyl U 4-pyridyl T (CH2)21-Propenyl U T T (CH2)22-Propenyl U F T (CH2)22-Propenyl U Cl T (CH2)22-Propenyl U Br T (CH2)22-Propenyl U I T (CH2)22-Propenyl U Me T (CH2)22-Propenyl U CF3 T (CH2)22-Propenyl U Et T (CH2)22-Propenyl U n-Pr T (CH2)22-Propenyl U c-Pr T (CH2)22-Propenyl U NO2 T (CH2)22-Propenyl U NH2 T (CH2)22-Propenyl U N(Me)H T (CH2)22-Propenyl U N(Me)2 T (CH2)22-Propenyl U N(Me)n-Bu T (CH2)22-Propenyl U N(nPen)H T (CH2)22-Propenyl U NHCOPh T (CH2)22-Propenyl U N(Me)CO-c-Hex T (CH2)22-Propenyl U NHCONHMe T (CH2)2 R1 R2 R3 R7 A2-Propenyl U N(Me)CONHPh T (CH2)22-Propenyl U NHCONH-c-Hex T (CH2)22-Propenyl U NHCOBz T (CH2)22-Propenyl U J1 T (CH2)22-Propenyl U NBzCO-n-Bu T (CH2)22-Propenyl U NBzCOO-i-Bu T (CH2)22-Propenyl U NHCO-n-Bu T (CH2)22-Propenyl U NHCOO-i-Bu T (CH2)22-Propenyl U NHCOCF3 T (CH2)22-Propenyl U NHSO2CF3 T (CH2)22-Propenyl U N(Me)Ph T (CH2)22-Propenyl U NHC(＝NH)NH2 T (CH2)22-Propenyl U C(＝NH)NH2 T (CH2)22-Propenyl U CHO T (CH2)22-Propenyl U CN T (CH2)22-Propenyl U U T (CH2)22-Propenyl U COOMe T (CH2)22-Propenyl U CONH2 T (CH2)22-Propenyl U CONHCOMe T (CH2)22-Propenyl U CH2NH2 T (CH2)22-Propenyl U CH2OH T (CH2)22-Propenyl U CH2NHCOPh T (CH2)22-Propenyl U CH2N(nPen)COPh T (CH2)22-Propenyl U CH2NHCONHMe T (CH2)22-Propenyl U CH2CONHPh T (CH2)22-Propenyl U CH2COOH T (CH2)22-Propenyl U Ph T (CH2)22-Propenyl U Bz T (CH2)22-Propenyl U CH2CH2Ph T (CH2)22-Propenyl U 2-thienyl T (CH2)22-Propenyl U 3-furyl T (CH2)22-Propenyl U 1-pyrrolyl T (CH2)22-Propenyl U 1-imidazolyl T (CH2)22-Propenyl U 1-pyrazolyl T (CH2)22-Propenyl U 2-pyridyl T (CH2)22-Propenyl U 1-pyrrolidinyl T (CH2)22-Propenyl U 1-piperidyl T (CH2)22-Propenyl U 1-piperazinyl T (CH2)22-Propenyl U 4-morpholinyl T (CH2)2R1 R2 R3 R7 A2-Propenyl U Ph(2-Cl) T (CH2)22-Propenyl U Ph(3-Me) T (CH2)22-Propenyl U Ph(4-OMe) T (CH2)22-Propenyl U Ph(2-NO2) T (CH2)22-Propenyl U Ph(3-NH2) T (CH2)22-Propenyl U Ph(4-NMe2) T (CH2)22-Propenyl U Ph(4-J2) T (CH2)22-Propenyl U Ph(2-Cl，3-J1) T (CH2)22-Propenyl U Ph(2-Cl，4-J1) T (CH2)22-Propenyl U Ph(2-Cl，5-J1) T (CH2)22-Propenyl U Ph(2-Cl，6-J1) T (CH2)22-Propenyl U Ph(3-NHCOPh) T (CH2)22-Propenyl U Ph(4-NHCO-c-Hex) T (CH2)22-Propenyl U Ph(3-NHCONHMe) T (CH2)22-Propenyl U Ph(4-NMeCONHPh) T (CH2)22-Propenyl U Ph(3-NHCONH-c-Hex) T (CH2)22-Propenyl U Ph(4-NHCOBz) T (CH2)22-Propenyl U Ph(4-N(nPen)COPh) T (CH2)22-Propenyl U Ph(3-NHCOnBu) T (CH2)22-Propenyl U Ph(4-NHCOCF3) T (CH2)22-Propenyl U Ph(3-NHSO2CF3 T (CH2)22-Propenyl U Ph(4-NMePh) T (CH2)22-Propenyl U Ph(3-NHC(＝NH)NH2) T (CH2)22-Propenyl U Ph(4-C(＝NH)NH2) T (CH2)22-Propenyl U Ph(3-COOH) T (CH2)22-Propenyl U Ph(4-CONH2) T (CH2)22-Propenyl U Ph(3-CH2NH2) T (CH2)22-Propenyl U Ph(4-CH2OH) T (CH2)22-Propenyl U Ph(4-CH2J2) T (CH2)22-Propenyl U Ph(4-CH2NHCONHMe) T (CH2)22-Propenyl U Ph(4-CH2CONHPh) T (CH2)22-Propenyl U Ph(4-CH2COOH) T (CH2)22-Propenyl U Ph(4-Ph) T (CH2)22-Propenyl U CH2CH2Ph(2-Cl，5-J1) T (CH2)22-Propenyl U OH T (CH2)22-Propenyl U OMe T (CH2)22-Propenyl U OPh T (CH2)22-Propenyl U SH T (CH2)22-Propenyl U SPh T (CH2)2R1 R2 R3 R7 A2-Propenyl U SO2Ph T (CH2)22-Propenyl U S-n-Bu T (CH2)22-Propeny1 U 2-pyrazinyl T (CH2)22-Propenyl U 2-pyrimidinyl T (CH2)22-Propenyl U 3-pyridyl T (CH2)22-Propenyl U 4-pyridyl T (CH2)22-Propenyl U T T (CH2)21-Butenyl U F T (CH2)21-Butenyl U Cl T (CH2)21-Butenyl U Br T (CH2)21-Butenyl U I T (CH2)21-Butenyl U Me T (CH2)21-Butenyl U CF3 T (CH2)21-Butenyl U Et T (CH2)21 -Butenyl U n-Pr T (CH2)21-Butenyl U c-Pr T (CH2)2l-Butenyl U NO2 T (CH2)21-Butenyl U NH2 T (CH2)21-Butenyl U N(Me)H T (CH2)21-Butenyl U N(Me)2 T (CH2)21-Butenyl U N(Me)n-Bu T (CH2)21-Butenyl U N(nPen)H T (CH2)21-Butenyl U NHCOPh T (CH2)21-Butenyl U Jl T (CH2)21-Butenyl U NHC(＝NH)NH2 T (CH2)21-Butenyl U C(＝NH)NH2 T (CH2)2l-Butenyl U CHO T (CH2)21-Butenyl U CN T (CH2)21-Butenyl U U T (CH2)21-Butenyl U COOMe T (CH2)21-Butenyl U CONH2 T (CH2)21-Butenyl U CONHCOMe T (CH2)21-Butenyl U CH2COOH T (CH2)21-Butenyl U Ph T (CH2)21-Butenyl U Bz T (CH2)21-Butenyl U CH2CH2Ph T (CH2)21-Butenyl U 2-thienyl T (CH2)21-Butenyl U 3-furyl T (CH2)21-Butenyl U Ph(4-J2) T (CH2)2 R1 R2 R3 R7 A1-Butenyl U Ph(2-Cl，3-J1) T (CH2)21-Butenyl U Ph(2-Cl，4-J1) T (CH2)21-Butenyl U Ph(2-C1，5-J1) T (CH2)21-Butenyl U Ph(2-Cl，6-J1) T (CH2)21-Butenyl U Ph(3-NHCOPh) T (CH2)21-Butenyl U Ph(4-NHCO-c-Hex) T (CH2)21-Butenyl U Ph(3-NHCONHMe) T (CH2)21-Butenyl U Ph(4-NMeCONHPh) T (CH2)21-Butenyl U Ph(3-NHCONH-c-Hex) T (CH2)21-Butenyl U Ph(4-NHCOBz) T (CH2)21-Butenyl U Ph(4-N(nPen)COPh) T (CH2)21-Butenyl U Ph(3-NHCOnBu) T (CH2)21-Butenyl U Ph(4-N H COCF3) T (CH2)21-Butenyl U Ph(3-NHSO2CF3) T (CH2)21-Butenyl U Ph(4-NMePh) T (CH2)21-Butenyl U Ph(3-NHC(＝NH)NH2) T (CH2)21-Butenyl U Ph(4-C(＝NH)NH2) T (CH2)21-Butenyl U Ph(3-COOH) T (CH2)21-Butenyl U Ph(4-CONH2) T (CH2)21-Butenyl U Ph(3-CH2NH2) T (CH2)21-Butenyl U Ph(4-CH2OH) T (CH2)21-Butenyl U Ph(4-CH2J2) T (CH2)21-Butenyl U Ph(4-CH2NHCONHMe) T (CH2)21-Butenyl U Ph(4-CH2CONHPh) T (CH2)21-Butenyl U Ph(4-CH2COOH) T (CH2)21-Butenyl U Ph(4-Ph) T (CH2)21-Butenyl U CH2CH2Ph(2-Cl，5-J1)T (CH2)21-Butenyl U OH T (CH2)21-Butenyl U T T (CH2)22-Butenyl U F T (CH2)22-Butenyl U Cl T (CH2)22-Butenyl U Br T (CH2)22-Butenyl U l T (CH2)22-Butenyl U Me T (CH2)22-Butenyl U CF3 T (CH2)22-Butenyl U Et T (CH2)22-Butenyl U n-Pr T (CH2)22-Butenyl U c-Pr T (CH2)22-Butenyl U NO2 T (CH2)2 R1 R2 R3 R7 A2-Butenyl U NH2 T (CH2)22-Butenyl U N(Me)H T (CH2)22-Butenyl U N(Me)2 T (CH2)22-Butenyl U N(Me)n-Bu T (CH2)22-Butenyl U N(nPen)H T (CH2)22-Butenyl U NHCOPh T (CH2)22-Butenyl U N(Me)CO-c-Hex T (CH2)22-Butenyl U NHCONHMe T (CH2)22-Butenyl U N(Me)CONHPh T (CH2)22-Butenyl U J1 T (CH2)22-Butenyl U NHC(＝NH)NH2 T (CH2)22-Butenyl U C(＝NH)NH2 T (CH2)22-Butenyl U CHO T (CH2)22-Butenyl U CN T (CH2)22-Butenyl U U T (CH2)22-Butenyl U COOMe T (CH2)22-Butenyl U CONH2 T (CH2)22-Butenyl U CONHCOMe T (CH2)22-Butenyl U CH2COOH T (CH2)22-Butenyl U Ph T (CH2)22-Butenyl U Bz T (CH2)22-Butenyl U CH2CH2Ph T (CH2)22-Butenyl U 2-thienyl T (CH2)22-Butenyl U 3-furyl T (CH2)22-Butenyl U Ph(4-J2) T (CH2)22-Butenyl U Ph(2-Cl，3-J1) T (CH2)22-Butenyl U Ph(2-Cl，4-J1) T (CH2)22-Butenyl U Ph(2-Cl，5-J1) T (CH2)22-Butenyl U Ph(2-Cl，6-J1) T (CH2)22-Butenyl U Ph(3-NHCOPh) T (CH2)22-Butenyl U Ph(4-NHCO-c-Hex) T (CH2)22-Butenyl U Ph(3-NHCONHMe) T (CH2)22-Butenyl U Ph(4-NMeCONHPh) T (CH2)22-Butenyl U Ph(3-NHCONH-c-Hex) T (CH2)22-Butenyl U Ph(4-NHCOBz) T (CH2)22-Butenyl U Ph(4-N(nPen)COPh) T (CH2)22-Butenyl U Ph(3-NHCOnBu) T (CH2)22-Butenyl U Ph(4-NHCOCF3) T (CH2)22-Butenyl U Ph(3-NHSO2CF3) T (CH2)2 R1 R2 R3 R7 A2-Butenyl U Ph(4-NMePh) T (CH2)22-Butenyl U Ph(3-NHC(＝NH)NH2) T (CH2)22-Butenyl U Ph(4-C(＝NH)NH2) T (CH2)22-Butenyl U Ph(3-COOH) T (CH2)22-Butenyl U Ph(4-CONH2) T (CH2)22-Butenyl U Ph(3-CH2NH2) T (CH2)22-Butenyl U Ph(4-CH2OH) T (CH2)22-Butenyl U Ph(4-CH2J2) T (CH2)22-Butenyl U Ph(4-CH2NHCONHMe) T (CH2)22-Butenyl U Ph(4-CH2CONHPh) T (CH2)22-Butenyl U Ph(4-CH2COOH) T (CH2)22-Butenyl U Ph(4-Ph) T (CH2)22-Butenyl U CH2CH2Ph(2-Cl，5-J1) T (CH2)22-Butenyl U T T (CH2)23-Butenyl U F T (CH2)23-Butenyl U Cl T (CH2)23-Butenyl U Br T (CH2)23-Butenyl U I T (CH2)23-Butenyl U Me T (CH2)23-Butenyl U CF3 T (CH2)23-Butenyl U Et T (CH2)23-Butenyl U n-Pr T (CH2)23-Butenyl U c-Pr T (CH2)23-Butenyl U NO2 T (CH2)23-Butenyl U NH2 T (CH2)23-Butenyl U N(Me)H T (CH2)23-Butenyl U N(Me)2 T (CH2)23-Butenyl U N(Me)n-Bu T (CH2)23-Butenyl U N(nPen)H T (CH2)23-Butenyl U NHCOPh T (CH2)23-Butenyl U J1 T (CH2)23-Butenyl U NHC(＝NH)NH2 T (CH2)23-Butenyl U C(＝NH)NH2 T (CH2)23-Butenyl U CHO T (CH2)23-Butenyl U CN T (CH2)23-Butenyl U U T (CH2)23-Butenyl U COOMe T (CH2)23-Butenyl U CONH2 T (CH2)23-Butenyl U CONHCOMe T (CH2)2 R1 R2 R3 R7 A3-Butenyl U CH2COOH T (CH2)23-Butenyl U Ph T (CH2)23-Butenyl U Bz T (CH2)23-Butenyl U CH2CH2Ph T (CH2)23-Butenyl U 2-thienyl T (CH2)23-Butenyl U 3-furyl T (CH2)23-Butenyl U Ph(4-J2) T (CH2)23-Butenyl U Ph(2-Cl，3-J1) T (CH2)23-Butenyl U Ph(2-Cl，4-J1) T (CH2)23-Butenyl U Ph(2-Cl，5-J1) T (CH2)23-Butenyl U Ph(2-Cl，6-J1) T (CH2)23-Butenyl U Ph(3-NHCOPh) T (CH2)23-Butenyl U Ph(4-NHCO-c-Hex) T (CH2)23-Butenyl U Ph(3-NHCONHMe) T (CH2)23-Butenyl U Ph(4-NMeCONHPh) T (CH2)23-Butenyl U Ph(3-NHCONH-c-Hex) T (CH2)23-Butenyl U Ph(4-NHCOBz) T (CH2)23-Butenyl U Ph(4-N(nPen)COPh) T (CH2)23-Butenyl U Ph(3-NHCOnBu) T (CH2)23-Butenyl U Ph(4-NHCOCF3) T (CH2)23-Butenyl U Ph(3-NHSO2CF3) T (CH2)23-Butenyl U Ph(4-NMePh) T (CH2)23-Butenyl U Ph(3-NHC(＝NH)NH2) T (CH2)23-Butenyl U Ph(4-C(＝NH)NH2) T (CH2)23-Butenyl U Ph(3-COOH) T (CH2)23-Butenyl U Ph(4-CONH2) T (CH2)23-Butenyl U Ph(3-CH2NH2) T (CH2)23-Butenyl U Ph(4-CH2OH) T (CH2)23-Butenyl U Ph(4-CH2J2) T (CH2)23-Butenyl U Ph(4-CH2NHCONHMe) T (CH2)23-Butenyl U Ph(4-CH2CONHPh) T (CH2)23-Butenyl U Ph(4-CH2COOH) T (CH2)23-Butenyl U Ph(4-Ph) T (CH2)23-Butenyl U CH2CH2Ph(2-Cl，5-J1) T (CH2)23-Butenyl U T T (CH2)2C2H5CH(OH) U F T (CH2)2C2H5CH(OH) U CI T (CH2)2C2H5CH(OH) U Br T (CH2)2C2H5CH(OH) U I T (CH2)2R1 R2 R3 R7 AC2H5CH(OH) U Me T (CH2)2C2H5CH(OH) U CF3 T (CH2)2C2H5CH(OH) U Et T (CH2)2C2H5CH(OH) U n-Pr T (CH2)2C2H5CH(OH) U c-Pr T (CH2)2C2H5CH(OH) U NO2 T (CH2)2C2H5CH(OH) U NH2 T (CH2)2C2H5CH(OH) U N(Me)H T (CH2)2C2H5CH(OH) U N(Me)2 T (CH2)2C2H5CH(OH) U N(Me)n-Bu T (CH2)2C2H5CH(OH) U N(nPen)H T (CH2)2C2H5CH(OH) U NHCOPh T (CH2)2C2H5CH(OH) U N(Me)CO-c-Hex T (CH2)2C2H5CH(OH) U NHCONHMe T (CH2)2C2H5CH(OH) U N(Me)CONHPh T (CH2)2C2H5CH(OH) U NHCONH-c-Hex T (CH2)2C2H5CH(OH) U NHCOBz T (CH2)2C2H5CH(OH) U J1 T (CH2)2C2H5CH(OH) U NBzCO-n-Bu T (CH2)2C2H5CH(OH) U NBzCOO-i-Bu T (CH2)2C2H5CH(OH) U NHCO-n-Bu T (CH2)2C2H5CH(OH) U NHCOO-i-Bu T (CH2)2C2H5CH(OH) U NHCOCF3 T (CH2)2C2H5CH(OH) U NHSO2CF3 T (CH2)2C2H5CH(OH) U N(Me)Ph T (CH2)2C2H5CH(OH) U NHC(＝NH)NH2 T (CH2)2C2H5CH(OH) U C(＝NH)NH2 T (CH2)2C2H5CH(OH) U CHO T (CH2)2C2H5CH(OH) U CN T (CH2)2C2H5CH(OH) U U T (CH2)2C2H5CH(OH) U COOMe T (CH2)2C2H5CH(OH) U CONH2 T (CH2)2C2H5CH(OH) U CONHCOMe T (CH2)2C2H5CH(OH) U CH2NH2 T (CH2)2C2H5CH(OH) U CH2OH T (CH2)2C2H5CH(OH) U CH2NHCOPh T (CH2)2C2H5CH(OH) U CH2N(nPen)COPh T (CH2)2C2H5CH(OH) U CH2NHCONHMe T (CH2)2C2H5CH(OH) U CH2CONHPh T (CH2)2R1 R2 R3 R7 AC2H5CH(OH) U CH2COOH T (CH2)2C2H5CH(OH) U Ph T (CH2)2C2H5CH(OH) U Bz T (CH2)2C2H5CH(CH) U CH2CH2ph T (CH2)2C2H5CH(OH) U 2-thienyl T (CH2)2C2H5CH(OH) U 3-furyl T (CH2)2C2H5CH(OH) U 1-pyrrolyl T (CH2)2C2H5CH(OH) U 1-imidazolyl T (CH2)2C2H5CH(OH) U 1-pyrazolyl T (CH2)2C2H5CH(OH) U 2-pyridyl T (CH2)2C2H5CH(OH) U 1-pyrrolidinyl T (CH2)2C2H5CH(OH) U 1-piperidyl T (CH2)2C2H5CH(OH) U 1-piperazinyl T (CH2)2C2H5CH(OH) U 4-morpholinyl T (CH2)2C2H5CH(OH) U Ph(2-C1) T (CH2)2C2H5CH(OH) U Ph(3-Me) T (CH2)2C2H5CH(OH) U Ph(4-OMe) T (CH2)2C2H5CH(OH) U ph(2-NO2) T (CH2)2C2H5CH(OH) U Ph(3-NH2) T (CH2)2C2H5CH(OH) U Ph(4-NMe2) T (CH2)2C2H5CH(OH) U Ph(4-J2) T (CH2)2C2H5CH(OH) U Ph(2-Cl，3-J1) T (CH2)2C2H5CH(OH) U Ph(2-Cl，4-J1) T (CH2)2C2H5CH(OH) U Ph(2-Cl，5-J1) T (CH2)2C2H5CH(OH) U Ph(2-Cl，6-J1) T (CH2)2C2H5CH(OH) U Ph(3-NHCOPh) T (CH2)2C2H5CH(OH) U Ph(4-NHCO-c-Hex) T (CH2)2C2H5CH(OH) U Ph(3-NHCONHMe) T (CH2)2C2H5CH(OH) U Ph(4-NMeCONHPh) T (CH2)2C2H5CH(OH) U Ph(3-NHCONH-c-Hex) T (CH2)2C2H5CH(OH) U Ph(4-NHCOBz) T (CH2)2C2H5CH(OH) U Ph(4-N(nPen)COPh) T (CH2)2C2H5CH(OH) U Ph(3-NHCOnBu) T (CH2)2C2H5CH(OH) U Ph(4-NHCOCF3) T (CH2)2C2H5CH(OH) U Ph(3-NHSO2CF3) T (CH2)2C2H5CH(OH) U Ph(4-NMePh) T (CH2)2C2H5CH(OH) U Ph(3-NHC(＝NH)NH2) T (CH2)2C2H5CH(OH) U Ph(4-C(＝NH)NH2) T (CH2)2C2H5CH(OH) U Ph(3-COOH) T (CH2)2R1 R2 R3 R7 AC2H5CH(OH) U Ph(4-CONH2) T (CH2)2C2H5CH(OH) U Ph(3-CH2NH2) T (CH2)2C2H5CH(OH) U Ph(4-CH2OH) T (CH2)2C2H5CH(OH) U Ph(4-CH2J2) T (CH2)2C2H5CH(OH) U Ph(4-CH2NHCONHMe) T (CH2)2C2H5CH(OH) U Ph(4-CH2CONHPh) T (CH2)2C2H5CH(OH) U Ph(4-CH2COOH) T (CH2)2C2H5CH(OH) U Ph(4-Ph) T (CH2)2C2H5CH(OH) U CH2CH2Ph(2-Cl，5-J1) T (CH2)2C2H5CH(OH) U OH T (CH2)2C2H5CH(OH) U OMe T (CH2)2C2H5CH(OH) U OPh T (CH2)2C2H5CH(OH) U SH T (CH2)2C2H5CH(OH) U SPh T (CH2)2C2H5CH(OH) U SO2Ph T (CH2)2C2H5CH(OH) U S-n-Bu T (CH2)2C2H5CH(OH) U 2-pyrazinyl T (CH2)2C2H5CH(OH) U 2-pyrimidinyl T (CH2)2C2H5CH(OH) U 3-pyridyl T (CH2)2C2H5CH(OH) U 4-pyridyl T (CH2)2C2H5CH(OH) U T T (CH2)2n-Pr CH2OH F T (CH2)2n-Pr CH2OH Cl T (CH2)2n-Pr CH2OH Br T (CH2)2n-Pr CH2OH I T (CH2)2n-Pr CH2OH Me T (CH2)2n-Pr CH2OH CF3 T (CH2)2n-Pr CH2OH Et T (CH2)2n-Pr CH2OH n-Pr T (CH2)2n-Pr CH2OH c-Pr T (CH2)2n-Pr CH2OH NO2 T (CH2)2n-Pr CH2OH NH2 T (CH2)2n-Pr CH2OH N(Me)H T (CH2)2n-Pr CH2OH N(Me)2 T (CH2)2n-Pr CH2OH N(Me)n-Bu T (CH2)2n-Pr CH2OH N(nPen)H T (CH2)2n-Pr CH2OH NHCOPh T (CH2)2n-Pr CH2OH NHC(＝NH)NH2 T (CH2)2n-Pr CH2OH C(＝NH)NH2 T (CH2)2R1 R2 R3 R7 An-Pr CH2OH CHO T (CH2)2n-Pr CH2OH CN T (CH2)2n-Pr CH2OH U T (CH2)2n-Pr CH2OH COOMe T (CH2)2n-Pr CH2OH CONH2 T (CH2)2n-Pr CH2OH CONHCOMe T (CH2)2n-Pr CH2OH CH2COOH T (CH2)2n-Pr CH2OH Ph T (CH2)2n-Pr CH2OH Bz T (CH2)2n-Pr CH2OH CH2CH2Ph T (CH2)2n-Pr CH2OH 2-thienyl T (CH2)2n-Pr CH2OH 3-furyl T (CH2)2n-Pr CH2OH T T (CH2)2n-Pr CHO F T (CH2)2n-Pr CHO Cl T (CH2)2n-Pr CHO Br T (CH2)2n-Pr CHO I T (CH2)2n-Pr CHO Me T (CH2)2n-Pr CHO CF3 T (CH2)2n-Pr CHO Et T (CH2)2n-Pr CHO n-Pr T (CH2)2n-Pr CHO c-Pr T (CH2)2n-Pr CHO NO2 T (CH2)2n-Pr CHO NH2 T (CH2)2n-Pr CHO N(Me)H T (CH2)2n-Pr CHO N(Me)2 T (CH2)2n-Pr CHO N(Me)n-Bu T (CH2)2n-Pr CHO N(nPen)H T (CH2)2n-Pr CHO NHCOPh T (CH2)2n-Pr CHO NHC(＝NH)NH2 T (CH2)2n-Pr CHO C(＝NH)NH2 T (CH2)2n-Pr CHO CHO T (CH2)2n-Pr CHO CN T (CH2)2n-Pr CHO U T (CH2)2n-Pr CHO COOMe T (CH2)2n-Pr CHO CONH2 T (CH2)2n-Pr CHO CONHCOMe T (CH2)2n-Pr CHO CH2NH2 T (CH2)2n-Pr CHO CH2OH T (CH2)2R1 R2 R3 R7 An-Pr CHO CH2NHCOPh T (CH2)2n-Pr CHO CH2N(nPen)COPh T (CH2)2n-Pr CHO CH2NHCONHMe T (CH2)2n-Pr CHO CH2CONHPh T (CH2)2n-Pr CHO CH2COOH T (CH2)2n-Pr CHO Ph T (CH2)2n-Pr CHO Bz T (CH2)2n-Pr CHO CH2CH2Ph T (CH2)2n-Pr CHO 2-thienyl T (CH2)2n-Pr CHO 3-furyl T (CH2)2n-Pr CHO T T (CH2)2n-Pr NHCOCF3 F T (CH2)2n-Pr NHCOCF3 Cl T (CH2)2n-Pr NHCOCF3 Br T (CH2)2n-Pr NHCOCF3 I T (CH2)2n-Pr NHCOCF3 Me T (CH2)2n-Pr NHCOCF3 CF3 T (CH2)2n-Pr NHCOCF3 Et T (CH2)2n-Pr NHCOCF3 n-Pr T (CH2)2n-Pr NHCOCF3 c-Pr T (CH2)2n-Pr NHCOCF3 NO2 T (CH2)2n-Pr NHCOCF3 NH2 T (CH2)2n-Pr NHCOCF3 N(Me)H T (CH2)2n-Pr NHCOCF3 N(Me)2 T (CH2)2n-Pr NHCOCF3 N(Me)n-Bu T (CH2)2n-Pr NHCOCF3 N(nPen)H T (CH2)2n-Pr NHCOCF3 NHCOPh T (CH2)2n-Pr NHCOCF3 NHC(＝NH)NH2 T (CH2)2n-Pr NHCOCF3 C(＝NH)NH2 T (CH2)2n-Pr NHCOCF3 CHO T (CH2)2n-Pr NHCOCF3 CN T (CH2)2n-Pr NHCOCF3 U T (CH2)2n-Pr NHCOCF3 COOMe T (CH2)2n-Pr NHCOCF3 CONH2 T (CH2)2n-Pr NHCOCF3 CONHCOMe T (CH2)2n-Pr NHCOCF3 CH2COOH T (CH2)2n-Pr NHCOCF3 Ph T (CH2)2n-Pr NHCOCF3 Bz T (CH2)2n-Pr NHCOCF3 CH2CH2Ph T (CH2)2 R1 R2 R3 R7 An-Pr NHCOCF3 2-thienyl T (CH2)2n-Pr NHCOCF3 3-furyl T (CH2)2n-Pr NHCOCF3 T T (CH2)2n-Pr NH2 F T (CH2)2n-Pr NH2 Cl T (CH2)2n-Pr NH2 Br T (CH2)2n-Pr NH2 I T (CH2)2n-Pr NH2 Me T (CH2)2n-Pr NH2 CF3 T (CH2)2n-Pr NH2 Et T (CH2)2n-Pr NH2 n-Pr T (CH2)2n-Pr NH2 c-Pr T (CH2)2n-Pr NH2 NO2 T (CH2)2n-Pr NH2 NH2 T (CH2)2n-Pr NH2 N(Me)H T (CH2)2n-Pr NH2 N(Me)2 T (CH2)2n-Pr NH2 N(Me)n-Bu T (CH2)2n-Pr NH2 N(nPen)H T (CH2)2n-Pr NH2 NHCOPh T (CH2)2n-Pr NH2 NHC(＝NH)NH2 T (CH2)2n-Pr NH2 C(＝NH)NH2 T (CH2)2n-Pr NH2 CHO T (CH2)2n-Pr NH2 CN T (CH2)2n-Pr NH2 U T (CH2)2n-Pr NH2 COOMe T (CH2)2n-Pr NH2 CONH2 T (CH2)2n-Pr NH2 CONHCOMe T (CH2)2n-Pr NH2 CH2COOH T (CH2)2n-Pr NH2 Ph T (CH2)2n-Pr NH2 Bz T (CH2)2n-Pr NH2 CH2CH2Ph T (CH2)2n-Pr NH2 2-thienyl T (CH2)2n-Pr NH2 3-furyl T (CH2)2n-Pr NH2 T T (CH2)2n-Pr CH2COOH F T (CH2)2n-Pr CH2COOH Cl T (CH2)2n-Pr CH2COOH Br T (CH2)2n-Pr CH2COOH I T (CH2)2n-Pr CH2COOH Me T (CH2)2R1 R2 R3 R7 An-Pr CH2COOH CF3 T (CH2)2n-Pr CH2COOH Et T (CH2)2n-Pr CH2COOH n-Pr T (CH2)2n-Pr CH2COOH c-Pr T (CH2)2n-Pr CH2COOH NO2 T (CH2)2n-Pr CH2COOH NH2 T (CH2)2n-Pr CH2COOH N(Me)H T (CH2)2n-Pr CH2COOH N(Me)2 T (CH2)2n-Pr CH2COOH N(Me)n-Bu T (CH2)2n-Pr CH2COOH N(nPen)H T (CH2)2n-Pr CH2COOH NHCOPh T (CH2)2n-Pr CH2COOH NHC(＝NH)NH2 T (CH2)2n-Pr CH2COOH C(＝NH)NH2 T (CH2)2n-Pr CH2COOH CHO T (CH2)2n-Pr CH2COOH CN T (CH2)2n-Pr CH2COOH U T (CH2)2n-Pr CH2COOH COOMe T (CH2)2n-Pr CH2COOH CONH2 T (CH2)2n-Pr CH2COOH CONHCOMe T (CH2)2n-Pr CH2COOH CH2COOH T (CH2)2n-Pr CH2COOH Ph T (CH2)2n-Pr CH2COOH Bz T (CH2)2n-Pr CH2COOH CH2CH2Ph T (CH2)2n-Pr CH2COOH 2-thienyl T (CH2)2n-Pr CH2COOH 3-furyl T (CH2)2n-Pr CH2COOH T T (CH2)2n-Pr OH F T (CH2)2n-Pr OH Cl T (CH2)2n-Pr OH Br T (CH2)2n-Pr OH I T (CH2)2n-Pr OH Me T (CH2)2n-Pr OH CF3 T (CH2)2n-Pr OH Et T (CH2)2n-Pr OH n-Pr T (CH2)2n-Pr OH c-Pr T (CH2)2n-Pr OH NO2 T (CH2)2n-Pr OH NH2 T (CH2)2n-Pr OH N(Me)H T (CH2)2n-Pr OH N(Me)2 T (CH2)2 R1 R2 R3 R7 An-Pr OH N(Me)n-Bu T (CH2)2n-Pr OH N(nPen)H T (CH2)2n-Pr OH NHCOPh T (CH2)2n-Pr OH NHC(＝NH)NH2 T (CH2)2n-Pr OH C(＝NH)NH2 T (CH2)2n-Pr OH CHO T (CH2)2n-Pr OH CN T (CH2)2n-Pr OH U T (CH2)2n-Pr OH COOMe T (CH2)2n-Pr OH CONH2 T (CH2)2n-Pr OH CONHCOMe T (CH2)2n-Pr OH CH2COOH T (CH2)2n-Pr OH Ph T (CH2)2n-Pr OH Bz T (CH2)2n-Pr OH CH2CH2Ph T (CH2)2n-Pr OH 2-thienyl T (CH2)2n-Pr OH 3-furyl T (CH2)2n-Pr OH T T (CH2)2n-Pr NHSO2CF3 F T (CH2)2n-Pr NHSO2CF3 Cl T (CH2)2n-Pr NHSO2CF3 Br T (CH2)2n-Pr NHSO2CF3 I T (CH2)2n-Pr NHSO2CF3 Me T (CH2)2n-Pr NHSO2CF3 CF3 T (CH2)2n-Pr NHSO2CF3 Et T (CH2)2n-Pr NHSO2CF3 n-Pr T (CH2)2n-Pr NHSO2CF3 c-Pr T (CH2)2n-Pr NHSO2CF3 NO2 T (CH2)2n-Pr NHSO2CF3 NH2 T (CH2)2n-Pr NHSO2CF3 N(Me)H T (CH2)2n-Pr NHSO2CF3 N(Me)2 T (CH2)2n-Pr NHSO2CF3 N(Me)n-Bu T (CH2)2n-Pr NHSO2CF3 N(nPen)H T (CH2)2n-Pr NHSO2CF3 NHCOPh T (CH2)2n-Pr NHSO2CF3NHC(＝NH)NH2 T (CH2)2n-Pr NHSO2CF3 C(＝NH)NH2 T (CH2)2n-Pr NHSO2CF3 CHO T (CH2)2n-Pr NHSO2CF3 CN T (CH2)2n-Pr NHSO2CF3 U T (CH2)2R1 R2 R3 R7 An-Pr NHSO2CF3 COOMe T (CH2)2n-Pr NHSO2CF3 CONH2 T (CH2)2n-Pr NHSO2CF3 CONHCOMe T (CH2)2n-Pr NHSO2CF3 CH2COOH T (CH2)2n-Pr NHSO2CF3 Ph T (CH2)2n-Pr NHSO2CF3 Bz T (CH2)2n-Pr NHSO2CF3 CH2CH2Ph T (CH2)2n-Pr NHSO2CF3 2-thienyl T (CH2)2n-Pr NHSO2CF3 3-furyl T (CH2)2n-Pr NHSO2CF3 T T (CH2)2n-Pr U F U (CH2)2n-Pr U Cl U (CH2)2n-Pr U Br U (CH2)2n-Pr U I U (CH2)2n-Pr U Me U (CH2)2n-Pr U CF3 U (CH2)2n-Pr U Et U (CH2)2n-Pr U n-Pr U (CH2)2n-Pr U c-Pr U (CH2)2n-Pr U NO2 U (CH2)2n-Pr U NH2 U (CH2)2n-Pr U N(Me)H U (CH2)2n-Pr U N(Me)2 U (CH2)2n-Pr U N(Me)n-Bu U (CH2)2n-Pr U N(nPen)H U (CH2)2n-Pr U NHCOPh U (CH2)2n-Pr U NHC(＝NH)NH2 U (CH2)2n-Pr U C(＝NH)NH2 U (CH2)2n-Pr U CHO U (CH2)2n-Pr U CN U (CH2)2n-Pr U U U (CH2)2n-Pr U COOMe U (CH2)2n-Pr U CONH2 U (CH2)2n-Pr U CONHCOMe U (CH2)2n-Pr U CH2COOH U (CH2)2n-Pr U Ph U (CH2)2n-Pr U Bz U (CH2)2n-Pr U CH2CH2Ph U (CH2)2n-Pr U 2-thienyl U (CH2)2R1 R2 R3 R7 An-Pr U 3-furyl U (CH2)2n-Pr U 1-pyrrolyl U (CH2)2n-Pr U 1-imidazolyl U (CH2)2n-Pr U Ph(4-J2) U (CH2)2n-Pr U Ph(2-Cl，5-J1) U (CH2)2n-Pr U Ph(2-Cl，6-J1) U (CH2)2n-Pr U Ph(3-NHCOPh) U (CH2)2n-Pr U Ph(4-NHCO-c-Hex) U (CH2)2n-Pr U Ph(3-NHCONHMe) U (CH2)2n-Pr U Ph(4-NMeCONHPh) U (CH2)2n-Pr U Ph(3-NHC(＝NH)NH2) U (CH2)2n-Pr U Ph(4-C(＝NH)NH2) U (CH2)2n-Pr U Ph(3-COOH) U (CH2)2n-Pr U Ph(4-CONH2) U (CH2)2n-Pr U Ph(3-CH2NH2) U (CH2)2n-Pr U Ph(4-CH2OH) U (CH2)2n-Pr U Ph(4-CH2J2) U (CH2)2n-Pr U Ph(4-CH2NHCONHMe) U (CH2)2n-Pr U Ph(4-CH2CONHPh) U (CH2)2n-Pr U Ph(4-CH2COOH) U (CH2)2n-Pr U Ph(4-Ph) U (CH2)2n-Pr U CH2CH2Ph(2-Cl，5-J1)U (CH2)2n-Pr U OH U (CH2)2n-Pr U T U (CH2)2n-Pr U F NHSO2CF3 (CH2)2n-Pr U Cl NHSO2CF3 (CH2)2n-Pr U Br NHSO2CF3 (CH2)2n-Pr U I NHSO2CF3 (CH2)2n-Pr U Me NHSO2CF3 (CH2)2n-Pr U CF3 NHSO2CF3 (CH2)2n-Pr U Et NHSO2CF3 (CH2)2n-Pr U n-Pr NHSO2CF3 (CH2)2n-Pr U c-Pr NHSO2CF3 (CH2)2n-Pr U NO2 NHSO2CF3 (CH2)2n-Pr U NH2 NHSO2CF3 (CH2)2n-Pr U N(Me)H NHSO2CF3 (CH2)2n-Pr U N(Me)2 NHSO2CF3 (CH2)2n-Pr U N(Me)n-Bu NHSO2CF3 (CH2)2n-Pr U N(nPen)H NHSO2CF3 (CH2)2R1 R2 R3 R7 An-Pr U NHCOPh NHSO2CF3 (CH2)2n-Pr U NHCONH-c-Hex NHSO2CF3 (CH2)2n-Pr U NHCOBz NHSO2CF3 (CH2)2n-Pr U J1 NHSO2CF3 (CH2)2n-Pr U NBzCO-n-Bu NHSO2CF3 (CH2)2n-Pr U NBzCOO-i-Bu NHSO2CF3 (CH2)2n-Pr U NHCO-n-Bu NHSO2CF3 (CH2)2n-Pr U NHCOO-i-Bu NHSO2CF3 (CH2)2n-Pr U NHCOCF3 NHSO2CF3 (CH2)2n-Pr U NHSO2CF3 NHSO2CF3 (CH2)2n-Pr U N(Me)Ph NHSO2CF3 (CH2)2n-Pr U NHC(＝NH)NH2 NHSO2CF3 (CH2)2n-Pr U C(＝NH)NH2 NHSO2CF3 (CH2)2n-Pr U CHO NHSO2CF3 (CH2)2n-Pr U CN NHSO2CF3 (CH2)2n-Pr U U NHSO2CF3 (CH2)2n-Pr U COOMe NHSO2CF3 (CH2)2n-Pr U CONH2 NHSO2CF3 (CH2)2n-Pr U CONHCOMe NHSO2CF3 (CH2)2n-Pr U CH2COOH NHSO2CF3 (CH2)2n-Pr U Ph NHSO2CF3 (CH2)2n-Pr U Bz NHSO2CF3 (CH2)2n-Pr U CH2CH2Ph NHSO2CF3 (CH2)2n-Pr U 2-thienyl NHSO2CF3 (CH2)2n-Pr U 3-furyl NHSO2CF3 (CH2)2n-Pr U Ph(4-J2) NHSO2CF3 (CH2)2n-Pr U Ph(2-Cl，3-J1) NHSO2CF3 (CH2)2n-Pr U Ph(2-Cl，4-J1) NHSO2CF3 (CH2)2n-Pr U Ph(2-Cl，5-J1) NHSO2CF3 (CH2)2n-Pr U Ph(2-Cl，6-J1) NHSO2CF3 (CH2)2n-Pr U Ph(3-NHCOPh) NHSO2CF3 (CH2)2n-Pr U Ph(4-NHCO-c-Hex) NHSO2CF3 (CH2)2n-Pr U Ph(3-NHCONHMe) NHSO2CF3 (CH2)2n-Pr U Ph(4-NMeCONHPh) NHSO2CF3 (CH2)2n-Pr U Ph(3-NHCONH-c-Hex)NHSO2CF3 (CH2)2n-Pr U Ph(4-NHCOBz) NHSO2CF3 (CH2)2n-Pr U Ph(4-N(nPen)COPh) NHSO2CF3 (CH2)2n-Pr U Ph(3-NHCOnBu) NHSO2CF3 (CH2)2n-Pr U Ph(4-NHCOCF3) NHSO2CF3 (CH2)2R1 R2 R3 R7 An-Pr U Ph(3-NHSO2CF3) NHSO2CF3 (CH2)2n-Pr U Ph(4-NMePh) NHSO2CF3 (CH2)2n-Pr U Ph(3-NHC(＝NH)NH2)NHSO2CF3 (CH2)2n-Pr U Ph(4-C(＝NH)NH2) NHSO2CF3 (CH2)2n-Pr U Ph(3-COOH) NHSO2CF3 (CH2)2n-Pr U Ph(4-CONH2) NHSO2CF3 (CH2)2n-Pr U Ph(3-CH2NH2) NHSO2CF3 (CH2)2n-Pr U Ph(4-CH2OH) NHSO2CF3 (CH2)2n-Pr U Ph(4-CH2J2) NHSO2CF3 (CH2)2n-Pr U Ph(4-CH2NHCONHMe)NHSO2CF3 (CH2)2n-Pr U Ph(4-CH2CONHPh) NHSO2CF3 (CH2)2n-Pr U Ph(4-CH2COOH) NHSO2CF3 (CH2)2n-Pr U Ph(4-Ph) NHSO2CF3 (CH2)2n-Pr U OH NHSO2CF3 (CH2)2n-Pr U OMe NHSO2CF3 (CH2)2n-Pr U OPh NHSO2CF3 (CH2)2n-Pr U SH NHSO2CF3 (CH2)2n-Pr U SPh NHSO2CF3 (CH2)2n-Pr U SO2Ph NHSO2CF3 (CH2)2n-Pr U S-n-Bu NHSO2CF3 (CH2)2n-Pr U 2-pyrazinyl NHSO2CF3 (CH2)2n-Pr U 2-pyrimidinyl NHSO2CF3 (CH2)2n-Pr U 3-pyridyl NHSO2CF3 (CH2)2n-Pr U 4-pyridyl NHSO2CF3 (CH2)2n-Pr U T NHSO2CF3 (CH2)2n-Pr U F NHCOCF3 (CH2)2n-Pr U Cl NHCOCF3 (CH2)2n-Pr U Br NHCOCF3 (CH2)2n-Pr U I NHCOCF3 (CH2)2n-Pr U Me NHCOCF3 (CH2)2n-Pr U CF3 NHCOCF3 (CH2)2n-Pr U Et NHCOCF3 (CH2)2n-Pr U n-Pr NHCOCF3 (CH2)2n-Pr U c-Pr NHCOCF3 (CH2)2n-Pr U NO2 NHCOCF3 (CH2)2n-Pr U NH2 NHCOCF3 (CH2)2n-Pr U N(Me)H NHCOCF3 (CH2)2n-Pr U N(Me)2 NHCOCF3 (CH2)2n-Pr U N(Me)n-Bu NHCOCF3 (CH2)2 R1 R2 R3 R7 An-Pr U N(nPen)H NHCOCF3 (CH2)2n-Pr U NHCOPh NHCOCF3 (CH2)2n-Pr U N(Me)CO-c-Hex NHCOCF3 (CH2)2n-Pr U J1 NHCOCF3 (CH2)2n-Pr U NBzCO-n-Bu NHCOCF3 (CH2)2n-Pr U NBzCOO-i-Bu NHCOCF3 (CH2)2n-Pr U NHCO-n-Bu NHCOCF3 (CH2)2n-Pr U NHCOO-i-Bu NHCOCF3 (CH2)2n-Pr U NHCOCF3 NHCOCF3 (CH2)2n-Pr U NHSO2CF3 NHCOCF3 (CH2)2n-Pr U N(Me)Ph NHCOCF3 (CH2)2n-Pr U NHC(＝NH)NH2 NHCOCF3 (CH2)2n-Pr U C(＝NH)NH2 NHCOCF3 (CH2)2n-Pr U CHO NHCOCF3 (CH2)2n-Pr U CN NHCOCF3 (CH2)2n-Pr U U NHCOCF3 (CH2)2n-Pr U COOMe NHCOCF3 (CH2)2n-Pr U CONH2 NHCOCF3 (CH2)2n-Pr U CONHCOMe NHCOCF3 (CH2)2n-Pr U CH2COOH NHCOCF3 (CH2)2n-Pr U Ph NHCOCF3 (CH2)2n-Pr U Bz NHCOCF3 (CH2)2n-Pr U CH2CH2Ph NHCOCF3 (CH2)2n-Pr U 2-thienyl NHCOCF3 (CH2)2n-Pr U 3-furyl NHCOCF3 (CH2)2n-Pr U Ph(4-J2) NHCOCF3 (CH2)2n-Pr U Ph(2-Cl，3-J1) NHCOCF3 (CH2)2n-Pr U Ph(2-Cl，4-J1) NHCOCF3 (CH2)2n-Pr U Ph(2-Cl， 5-J1)NHCOCF3 (CH2)2n-Pr U Ph(2-Cl， 6-J1)NHCOCF3 (CH2)2n-Pr U Ph(3-NHCOPh) NHCOCF3 (CH2)2n-Pr U Ph(4-NHCO-c-Hex) NHCOCF3 (CH2)2n-Pr U Ph(3-NHCONHMe) NHCOCF3 (CH2)2n-Pr U Ph(4-NMeCONHPh) NHCOCF3 (CH2)2n-Pr U Ph(3-NHCONH-c-Hex)NHCOCF3 (CH2)2n-Pr U Ph(4-NHCOBz) NHCOCF3 (CH2)2n-Pr U Ph(4-N(nPen)COPh) NHCOCF3 (CH2)2n-Pr U Ph(3-NHCOnBu) NHCOCF3 (CH2)2n-Pr U Ph(4-NHCOCF3) NHCOCF3 (CH2)2R1 R2 R3 R7 An-Pr U Ph(3-NHSO2CF3) NHCOCF3 (CH2)2n-Pr U Ph(4-NMePh) NHCOCF3 (CH2)2n-Pr U Ph(3-NHC(＝NH)NH2) NHCOCF3 (CH2)2n-Pr U Ph(4-C(＝NH)NH2) NHCOCF3 (CH2)2n-Pr U Ph(3-COOH) NHCOCF3 (CH2)2n-Pr U Ph(4-CONH2) NHCOCF3 (CH2)2n-Pr U Ph(3-CH2NH2) NHCOCF3 (CH2)2n-Pr U Ph(4-CH2OH) NHCOCF3 (CH2)2n-Pr U Ph(4-CH2J2) NHCOCF3 (CH2)2n-Pr U Ph(4-CH2NHCONHMe) NHCOCF3 (CH2)2n-Pr U Ph(4-CH2CONHPh) NHCOCF3 (CH2)2n-Pr U Ph(4-CH2COOH) NHCOCF3 (CH2)2n-Pr U Ph(4-Ph) NHCOCF3 (CH2)2n-Pr U OH NHCOCF3 (CH2)2n-Pr U OMe NHCOCF3 (CH2)2n-Pr U OPh NHCOCF3 (CH2)2n-Pr U SH NHCOCF3 (CH2)2n-Pr U SPh NHCOCF3 (CH2)2n-Pr U SO2Ph NHCOCF3 (CH2)2n-Pr U S-n-Bu NHCOCF3 (CH2)2n-Pr U 2-pyrazinyl NHCOCF3 (CH2)2n-Pr U 2-pyrimidinyl NHCOCF3 (CH2)2n-Pr U 3-pyridyl NHCOCF3 (CH2)2n-Pr U 4-pyridyl NHCOCF3 (CH2)2n-Pr U T NHCOCF3 (CH2)2
第2表R3 R4 R5 R6 R7Y ZF Me H H T CH CHCl Me H H T CH CHBr Me H H T CH CHI Me H H T CH CHMe Me H H T CH CHCF3 Me H H T CH CHEt Me H H T CH CHn-Pr Me H H T CH CHc-Pr Me H H T CH CHNO2 Me H H T CH CHNH2 Me H H T CH CHN(Me)H Me H H T CH CHN(Me)2 Me H H T CH CHN(Me)n-Bu Me H H T CH CHN(nPen)H Me H H T CH CHNHCOPh Me H H T CH CHNHC(＝NH)NH2 Me H H T CH CHC(＝NH)NH2 Me H H T CH CHCHO Me H H T CH CHCN Me H H T CH CHU Me H H T CH CHCOOMe Me H H T CH CHCONH2 Me H H T CH CHCONHCOMe Me H H T CH CHPh Me H H T CH CHBz Me H H T CH CHCH2CH2Ph Me H H T CH CH2-thienyl Me H H T CH CH3-furyl Me H H T CH CHPh(4-J2) Me H H T CH CHPh(2-Cl，5-J1) Me H H T CH CHR3 R4 R5 R6 R7Y ZT Me H H T CH CHF F H H T CH CHCl F H H T CH CHBr F H H T CH CHI F H H T CH CHMe F H H T CH CHCF3 F H H T CH CHEt F H H T CH CHn-Pr F H H T CH CHc-Pr F H H T CH CHNO2 F H H T CH CHNH2 F H H T CH CHN(Me)H F H H T CH CHN(Me)2 F H H T CH CHN(Me)n-Bu F H H T CH CHN(nPen)H F H H T CH CHNHCOPh F H H T CH CHJ1 F H H T CH CHNHC(＝NH)NH2 F H H T CH CHC(＝NH)NH2 F H H T CH CHCHO F H H T CH CHCN F H H T CH CHU F H H T CH CHCOOMe F H H T CH CHCONH2 F H H T CH CHCONHCOMe F H H T CH CHCH2N(nPen)COPh F H H T CH CHPh F H H T CH CHBz F H H T CH CHCH2CH2Ph F H H T CH CH2-thienyl F H H T CH CH3-furyl F H H T CH CHPh(4-J2) F H H T CH CHPh(2-CI，5-J1) F H H T CH CHT F H H T CH CHF Cl H H T CH CHCl Cl H H T CH CHBr Cl H H T CH CHR3 R4 R5 R6 R7Y ZI Cl H H T CH CHMe Cl H H T CH CHCF3 Cl H H T CH CHEt Cl H H T CH CHn-Pr Cl H H T CH CHc-Pr Cl H H T CH CHNO2 Cl H H T CH CHNH2 Cl H H T CH CHN(Me)H Cl H H T CH CHN(Me)2 Cl H H T CH CHN(Me)n-Bu Cl H H T CH CHN(nPen)H Cl H H T CH CHNHCOPh Cl H H T CH CHJ1 Cl H H T CH CHNHC(＝NH)NH2 Cl H H T CH CHC(＝NH)NH2 Cl H H T CH CHCHO Cl H H T CH CHCN Cl H H T CH CHU Cl H H T CH CHCOOMe Cl H H T CH CHCONH2 Cl H H T CH CHCONHCOMe Cl H H T CH CHCH2N(nPen)COPh Cl H H T CH CHPh Cl H H T CH CHBz Cl H H T CH CHCH2CH2Ph Cl H H T CH CH2-thienyl Cl H H T CH CH3-furyl Cl H H T CH CHPh(4-J2) Cl H H T CH CHPh(2-Cl，5-J1) Cl H H T CH CHT Cl H H T CH CHF Br H H T CH CHCl Br H H T CH CHBr Br H H T CH CHI Br H H T CH CHMe Br H H T CH CHCF3 Br H H T CH CHEt Br H H T CH CHR3 R4 R5 R6 R7Y Zn-Pr Br H H T CH CHc-Pr Br H H T CH CHNO2 Br H H T CH CHNH2 Br H H T CH CHN(Me)H Br H H T CH CHN(Me)2 Br H H T CH CHN(Me)n-Bu Br H H T CH CHN(nPen)H Br H H T CH CHNHCOPh Br H H T CH CHJ1 Br H H T CH CHNHC(＝NH)NH2 Br H H T CH CHC(＝NH)NH2 Br H H T CH CHCHO Br H H T CH CHCN Br H H T CH CHU Br H H T CH CHCOOMe Br H H T CH CHCONH2 Br H H T CH CHCONHCOMe Br H H T CH CHCH2N(nPen)COPh Br H H T CH CHPh Br H H T CH CHBz Br H H T CH CHCH2CH2Ph Br H H T CH CH2-thienyl Br H H T CH CH3-furyl Br H H T CH CHPh(4-J2) Br H H T CH CHPh(2-Cl，5-J1) Br H H T CH CHT Br H H T CH CHF OH H H T CH CHCl OH H H T CH CHBr OH H H T CH CHI OH H H T CH CHMe OH H H T CH CHCF3 OH H H T CH CHEt OH H H T CH CHn-Pr OH H H T CH CHc-Pr OH H H T CH CHNO2 OH H H T CH CHNH2 OH H H T CH CHR3 R4 R5 R6 R7 Y ZN(Me)H OH H H T CH CHN(Me)2 OH H H T CH CHN(Me)n-Bu OH H H T CH CHN(nPen)H OH H H T CH CHNHCOPh OH H H T CH CHJ1 OH H H T CH CHNHC(＝NH)NH2 OH H H T CH CHC(＝NH)NH2 OH H H T CH CHCHO OH H H T CH CHCN OH H H T CH CHU OH H H T CH CHCOOMe OH H H T CH CHCH2N(nPen)COPh OH H H T CH CHPh OH H H T CH CHBz OH H H T CH CHCH2CH2Ph OH H H T CH CH2-thienyl OH H H T CH CH3-furyl OH H H T CH CHPh(4-J2) OH H H T CH CHPh(2-Cl，5-J1) OH H H T CH CHT OH H H T CH CHF H H H T CMe CHCl H H H T CMe CHBr H H H T CMe CHI H H H T CMe CHMe H H H T CMe CHCF3 H H H T CMe CHEt H H H T CMe CHn-Pr H H H T CMe CHc-Pr H H H T CMe CHNO2 H H H T CMe CHNH2 H H H T CMe CHN(Me)H H H H T CMe CHN(Me)2 H H H T CMe CHN(Me)n-Bu H H H T CMe CHN(nPen)H H H H T CMe CHNHCOPh H H H T CMe CHJ1 H H H T CMe CHR3 R4 R5 R6 R7Y ZNHC(＝NH)NH2 H H H T CMe CHC(＝NH)NH2 H H H T CMe CHCHO H H H T CMe CHCN H H H T CMe CHU H H H T CMe CHCOOMe H H H T CMe CHCONH2 H H H T CMe CHCONHCOMe H H H T CMe CHCH2N(nPen)COPh H H H T CMe CHPh H H H T CMe CHBz H H H T CMe CHCH2CH2Ph H H H T CMe CH2-thienyl H H H T CMe CH3-furyl H H H T CMe CHPh(4-J2) H H H T CMe CHPh(2-Cl，5-J1) H H H T CMe CHT H H H T CMe CHF H H H T CF CHCl H H H T CF CHBr H H H T CF CHI H H H T CF CHMe H H H T CF CHCF3 H H H T CF CHEt H H H T CF CHn-Pr H H H T CF CHc-Pr H H H T CF CHNO2 H H H T CF CHNH2 H H H T CF CHN(Me)H H H H T CF CHN(Me)2 H H H T CF CHN(Me)n-Bu H H H T CF CHN(nPen)H H H H T CF CHNHCOPh H H H T CF CHJ1 H H H T CF CHNHC(＝NH)NH2 H H H T CF CHC(＝NH)NH2 H H H T CF CHCHO H H H T CF CHCN H H H T CF CHR3 R4 R5 R6 R7Y ZU H H H T CF CHCOOMe H H H T CF CHCONH2 H H H T CF CHCONHCOMe H H H T CF CHCH2N(nPen)COPh H H H T CF CHPh H H H T CF CHBz H H H T CF CHCH2CH2Ph H H H T CF CH2-thienyl H H H T CF CH3-furyl H H H T CF CHPh(4-J2) H H H T CF CHPh(2-Cl，5-J1) H H H T CF CHT H H H T CF CHF H H H T CCl CHCl H H H T CCl CHBr H H H T CCl CHI H H H T CCl CHMe H H H T CCl CHCF3 H H H T CCl CHEt H H H T CCl CHn-Pr H H H T CCl CHc-Pr H H H T CCl CHNO2 H H H T CCl CHNH2 H H H T CCl CHN(Me)H H H H T CCl CHN(Me)2 H H H T CCl CHN(Me)n-Bu H H H T CCl CHN(nPen)H H H H T CCl CHNHCOPh H H H T CCl CHJ1 H H H T CCl CHNHC(＝NH)NH2 H H H T CCl CHC(＝NH)NH2 H H H T CCl CHCHO H H H T CCl CHCN H H H T CCl CHU H H H T CCl CHCOOMe H H H T CCl CHCONH2 H H H T CCl CHCONHCOMe H H H T CCl CHR3 R4 R5 R6 R7Y ZCH2N(nPen)COPh H H H T CCl CHPh H H H T CCl CHBz H H H T CCl CHCH2CH2Ph H H H T CCl CH2-thienyl H H H T CCl CH3-furyl H H H T CCl CHPh(4-J2) H H H T CCl CHPh(2-Cl，5-J1) H H H T CCl CHT H H H T CCl CHF H H H T CBr CHCl H H H T CBr CHBr H H H T CBr CHI H H H T CBr CHMe H H H T CBr CHCF3 H H H T CBr CHEt H H H T CBr CHn-Pr H H H T CBr CHc-Pr H H H T CBr CHNO2 H H H T CBr CHNH2 H H H T CBr CHN(Me)H H H H T CBr CHN(Me)2 H H H T CBr CHN(Me)n-Bu H H H T CBr CHN(nPen)H H H H T CBr CHNHCOPh H H H T CBr CHJl H H H T CBr CHNHC(＝NH)NH2 H H H T CBr CHC(＝NH)NH2 H H H T CBr CHCHO H H H T CBr CHCN H H H T CBr CHU H H H T CBr CHCOOMe H H H T CBr CHCONH2 H H H T CBr CHCONHCOMe H H H T CBr CHCH2N(nPen)COPh H H H T CBr CHPh H H H T CBr CHBz H H H T CBr CHCH2CH2Ph H H H T CBr CHR3 R4 R5 R6 R7 Y Z2-thienyl H H H T CBr CH3-furyl H H H T CBr CHPh(4-J2) H H H T CBr CHPh(2-Cl，5-J1) H H H T CBr CHT H H H T CBr CHF H H H T COH CHCl H H H T COH CHBr H H H T COH CHI H H H T COH CHMe H H H T COH CHCF3 H H H T COH CHEt H H H T COH CHn-Pr H H H T COH CHc-Pr H H H T COH CHNO2 H H H T COH CHNH2 H H H T COH CHN(Me)H H H H T COH CHN(Me)2 H H H T COH CHN(Me)n-Bu H H H T COH CHN(nPen)H H H H T COH CHNHCOPh H H H T COH CHJ1 H H H T COH CHNHC(＝NH)NH2 H H H T COH CHC(＝NH)NH2 H H H T COH CHCHO H H H T COH CHCN H H H T COH CHU H H H T COH CHCOOMe H H H T COH CHCONH2 H H H T COH CHCONHCOMe H H H T COH CHPh H H H T COH CHBz H H H T COH CHCH2CH2Ph H H H T COH CH2-thienyl H H H T COH CHPh(4-J2) H H H T COH CHPh(2-Cl，5-J1) H H H T COH CHT H H H T COH CHF H H H T N CHR3 R4 R5 R6 R7 Y ZCl H H H T N CHBr H H H T N CHI H H H T N CHMe H H H T N CHCF3 H H H T N CHEt H H H T N CHn-Pr H H H T N CHc-Pr H H H T N CHNO2 H H H T N CHNH2 H H H T N CHN(Me)H H H H T N CHN(Me)2 H H H T N CHN(Me)n-Bu H H H T N CHN(nPen)H H H H T N CHNHCOPh H H H T N CHJ1 H H H T N CHNHC(＝NH)NH2 H H H T N CHC(＝NH)NH2 H H H T N CHCHO H H H T N CHCN H H H T N CHU H H H T N CHCOOMe H H H T N CHCONH2 H H H T N CHCONHCOMe H H H T N CHCH2N(nPen)COPh H H H T N CHPh H H H T N CHBz H H H T N CHCH2CH2Ph H H H T N CH2-thienyl H H H T N CH3-furyl H H H T N CHPh(4-J2) H H H T N CHPh(2-Cl，5-J1) H H H T N CHT H H H T N CHF H Me H T CH CHCl H Me H T CH CHBr H Me H T CH CHI H Me H T CH CHMe H Me H T CH CHR3 R4 R5 R6 R7Y ZCF3 H Me H T CH CHEt H Me H T CH CHn-Pr H Me H T CH CHc-Pr H Me H T CH CHNO2 H Me H T CH CHNH2 H Me H T CH CHN(Me)H H Me H T CH CHN(Me)2 H Me H T CH CHN(Me)n-Bu H Me H T CH CHN(nPen)H H Me H T CH CHNHCOPh H Me H T CH CHJ1 H Me H T CH CHNHC(＝NH)NH2 H Me H T CH CHC(＝NH)NH2 H Me H T CH CHCHO H Me H T CH CHCN H Me H T CH CHU H Me H T CH CHCOOMe H Me H T CH CHCONH2 H Me H T CH CHCONHCOMe H Me H T CH CHCH2N(nPen)COPhH Me H T CH CHPh H Me H T CH CHBz H Me H T CH CHCH2CH2Ph H Me H T CH CH2-thienyl H Me H T CH CH3-furyl H Me H T CH CHPh(4-J2) H Me H T CH CHPh(2-Cl，5-J1)H Me H T CH CHT H Me H T CH CHF H F H T CH CHCl H F H T CH CHBr H F H T CH CHI H F H T CH CHMe H F H T CH CHCF3 H F H T CH CHEt H F H T CH CHn-Pr H F H T CH CHc-Pr H F H T CH CHR3 R4 R5 R6R7 Y ZNO2 H F H T CH CHNH2 H F H T CH CHN(Me)H H F H T CH CHN(Me)2 H F H T CH CHN(Me)n-Bu H F H T CH CHN(nPen)H H F H T CH CHNHCOPh H F H T CH CHJ1 H F H T CH CHNHC(＝NH)NH2 H F H T CH CHC(＝NH)NH2 H F H T CH CHCHO H F H T CH CHCN H F H T CH CHU H F H T CH CHCOOMe H F H T CH CHCONH2 H F H T CH CHCONHCOMe H F H T CH CHCH2N(nPen)COPh H F H T CH CHPh H F H T CH CHBz H F H T CH CHCH2CH2Ph H F H T CH CH2-thienyl H F H T CH CH3-furyl H F H T CH CHPh(4-J2) H F H T CH CHPh(2-CI，5-J1) H F H T CH CHT H F H T CH CHF H Cl H T CH CHCl H Cl H T CH CHBr H Cl H T CH CHI H Cl H T CH CHMe H Cl H T CH CHCF3 H Cl H T CH CHEt H Cl H T CH CHn-Pr H Cl H T CH CHc-Pr H Cl H T CH CHNO2 H Cl H T CH CHNH2 H Cl H T CH CHN(Me)H H Cl H T CH CHN(Me)2 H Cl H T CH CHR3 R4 R5 R6 R7Y ZN(Me)n-Bu H Cl H T CH CHN(nPen)H H Cl H T CH CHNHCOPh H Cl H T CH CHJ1 H Cl H T CH CHNHC(＝NH)NH2 H Cl H T CH CHC(＝NH)NH2 H Cl H T CH CHCHO H Cl H T CH CHCN H Cl H T CH CHU H Cl H T CH CHCOOMe H Cl H T CH CHCONH2 H Cl H T CH CHCONHCOMe H Cl H T CH CHCH2N(nPen)COPh H Cl H T CH CHPh H Cl H T CH CHBz H Cl H T CH CHCH2CH2Ph H Cl H T CH CH2-thienyl H Cl H T CH CH3-furyl H Cl H T CH CHPh(4-J2) H Cl H T CH CHPh(2-Cl，5-J1) H Cl H T CH CHT H Cl H T CH CHF H Br H T CH CHCl H Br H T CH CHBr H Br H T CH CHI H Br H T CH CHMe H Br H T CH CHCF3 H Br H T CH CHEt H Br H T CH CHn-Pr H Br H T CH CHc-Pr H Br H T CH CHNO2 H Br H T CH CHNH2 H Br H T CH CHN(Me)H H Br H T CH CHN(Me)2 H Br H T CH CHN(Me)n-Bu H Br H T CH CHN(nPen)H H Br H T CH CHNHCOPh H Br H T CH CHJ1 H Br H T CH CHR3 R4 R5 R6R7 Y ZNHC(＝NH)NH2 H Br H T CH CHC(＝NH)NH2 H Br H T CH CHCHO H Br H T CH CHCN H Br H T CH CHU H Br H T CH CHCOOMe H Br H T CH CHCONH2 H Br H T CH CHCONHCOMe H Br H T CH CHCH2N(nPen)COPh H Br H T CH CHPh H Br H T CH CHBz H Br H T CH CHCH2CH2Ph H Br H T CH CH2-thienyl H Br H T CH CH3-furyl H Br H T CH CHPh(4-J2) H Br H T CH CHPh(2-Cl，5-J1) H Br H T CH CHT H Br H T CH CHF H OH H T CH CHCl H OH H T CH CHBr H OH H T CH CHI H OH H T CH CHMe H OH H T CH CHCF3 H OH H T CH CHEt H OH H T CH CHn-Pr H OH H T CH CHc-Pr H OH H T CH CHNO2 H OH H T CH CHNH2 H OH H T CH CHN(Me)H H OH H T CH CHN(Me)2 H OH H T CH CHN(Me)n-Bu H OH H T CH CHN(nPen)H H OH H T CH CHNHCOPh H OH H T CH CHJ1 H OH H T CH CHNHC(＝NH)NH2 H OH H T CH CHC(＝NH)NH2 H OH H T CH CHCHO H OH H T CH CHCN H OH H T CH CHR3 R4 R5 R6R7Y ZU H OH H T CH CHCOOMe H OH H T CH CHCONH2 H OH H T CH CHCONHCOMe H OH H T CH CHCH2N(nPen)COPh H OH H T CH CHPh H OH H T CH CHBz H OH H T CH CHCH2CH2Ph H OH H T CH CH2-thienyl H OH H T CH CH3-furyl H OH H T CH CH1 -pyrrolyl H OH H T CH CHPh(4-J2) H OH H T CH CHPh(2-Cl，5-J1) H OH H T CH CHT H OH H T CH CHF H H Me T CH CHCl H H Me T CH CHBr H H Me T CH CHI H H Me T CH CHMe H H Me T CH CHCF3 H H Me T CH CHEt H H Me T CH CHn-Pr H H Me T CH CHc-Pr H H Me T CH CHNO2 H H Me T CH CHNH2 H H Me T CH CHN(Me)H H H Me T CH CHN(Me)2 H H Me T CH CHN(Me)n-Bu H H Me T CH CHN(nPen)H H H Me T CH CHNHCOPh H H Me T CH CHJ1 H H Me T CH CHNHC(＝NH)NH2 H H Me T CH CHC(＝NH)NH2 H H Me T CH CHCHO H H Me T CH CHCN H H Me T CH CHU H H Me T CH CHCOOMe H H Me T CH CHCONH2 H H Me T CH CHR3 R4 R5 R6 R7 Y ZCONHCOMe H H Me T CH CHCH2N(nPen)COPh H H Me T CH CHPh H H Me T CH CHBz H H Me T CH CHCH2CH2Ph H H Me T CH CH2-thienyl H H Me T CH CH3-furyl H H Me T CH CHPh(4-J2) H H Me T CH CHPh(2-Cl，5-J1) H H Me T CH CHT H H Me T CH CHF H H F T CH CHCl H H F T CH CHBr H H F T CH CHI H H F T CH CHMe H H F T CH CHCF3 H H F T CH CHEt H H F T CH CHn-Pr H H F T CH CHc-Pr H H F T CH CHNO2 H H F T CH CHNH2 H H F T CH CHN(Me)H H H F T CH CHN(Me)2 H H F T CH CHN(Me)n-Bu H H F T CH CHN(nPen)H H H F T CH CHNHCOPh H H F T CH CHJ1 H H F T CH CHNHC(＝NH)NH2 H H F T CH CHC(＝NH)NH2 H H F T CH CHCHO H H F T CH CHCN H H F T CH CHU H H F T CH CHCOOMe H H F T CH CHCONH2 H H F T CH CHCONHCOMe H H F T CH CHCH2N(nPen)COPh H H F T CH CHPh H H F T CH CHBz H H F T CH CHR3 R4 R5 R6 R7 Y ZCH2CH2Ph H H F T CH CH2-thienyl H H F T CH CH3-furyl H H F T CH CHPh(4-J2) H H F T CH CHPh(2-Cl，5-J1) H H F T CH CHT H H F T CH CHF H H Cl T CH CHCl H H Cl T CH CHBr H H Cl T CH CHI H H Cl T CH CHMe H H Cl T CH CHCF3 H H Cl T CH CHEt H H Cl T CH CHn-Pr H H Cl T CH CHc-Pr H H Cl T CH CHNO2 H H Cl T CH CHNH2 H H Cl T CH CHN(Me)H H H Cl T CH CHN(Me)2 H H Cl T CH CHN(Me)n-Bu H H Cl T CH CHN(nPen)H H H Cl T CH CHNHCOPh H H Cl T CH CHJ1 H H Cl T CH CHNHC(＝NH)NH2 H H Cl T CH CHC(＝NH)NH2 H H Cl T CH CHCHO H H Cl T CH CHCN H H Cl T CH CHU H H Cl T CH CHCOOMe H H Cl T CH CHCONH2 H H Cl T CH CHCONHCOMe H H Cl T CH CHCH2N(nPen)COPh H H Cl T CH CHPh H H Cl T CH CHBz H H Cl T CH CHCH2CH2Ph H H Cl T CH CH2-thienyl H H Cl T CH CH3-furyl H H Cl T CH CHPh(4-J2) H H Cl T CH CHR3 R4 R5 R6 R7 Y ZPh(2-Cl，5-J1) H H Cl T CH CHT H H Cl T CH CHF H H Br T CH CHCl H H Br T CH CHBr H H Br T CH CHI H H Br T CH CHMe H H Br T CH CHCF3 H H Br T CH CHEt H H Br T CH CHn-Pr H H Br T CH CHc-Pr H H Br T CH CHNO2 H H Br T CH CHNH2 H H Br T CH CHN(Me)H H H Br T CH CHN(Me)2 H H Br T CH CHN(Me)n-Bu H H Br T CH CHN(nPen)H H H Br T CH CHNHCOPh H H Br T CH CHJ1 H H Br T CH CHNHC(＝NH)NH2 H H Br T CH CHC(＝NH)NH2 H H Br T CH CHCHO H H Br T CH CHCN H H Br T CH CHU H H Br T CH CHCOOMe H H Br T CH CHCONH2 H H Br T CH CHCONHCOMe H H Br T CH CHCH2N(nPen)COPh H H Br T CH CHPh H H Br T CH CHBz H H Br T CH CHCH2CH2Ph H H Br T CH CH2-thienyl H H Br T CH CH3-furyl H H Br T CH CHPh(4-J2) H H Br T CH CHPh(2-Cl，5-J1) H H Br T CH CHT H H Br T CH CHF H H OH T CH CHCl H H OH T CH CHR3 R4 R5 R6 R7Y ZBr H H OH T CH CHI H H OH T CH CHMe H H OH T CH CHCF3 H H OH T CH CHEt H H OH T CH CHn-Pr H H OH T CH CHc-Pr H H OH T CH CHNO2 H H OH T CH CHNH2 H H OH T CH CHN(Me)H H H OH T CH CHN(Me)2 H H OH T CH CHN(Me)n-Bu H H OH T CH CHN(nPen)H H H OH T CH CHNHCOPh H H OH T CH CHJ1 H H OH T CH CHNHC(＝NH)NH2 H H OH T CH CHC(＝NH)NH2 H H OH T CH CHCHO H H OH T CH CHCN H H OH T CH CHU H H OH T CH CHCOOMe H H OH T CH CHCONH2 H H OH T CH CHCONHCOMe H H OH T CH CHCH2N(nPen)COPh H H OH T CH CHPh H H OH T CH CHBz H H OH T CH CHCH2CH2Ph H H OH T CH CH2-thienyl H H OH T CH CH3-furyl H H OH T CH CHPh(4-J2) H H OH T CH CHPh(2-Cl，5-J1) H H OH T CH CHT H H OH T CH CHF H H H T CH CMeCl H H H T CH CMeBr H H H T CH CMeI H H H T CH CMeMe H H H T CH CMeCF3 H H H T CH CMeR3 R4 R5 R6 R7Y ZEt H H H T CH CMen-Pr H H H T CH CMec-Pr H H H T CH CMeNO2 H H H T CH CMeNH2 H H H T CH CMeN(Me)H H H H T CH CMeN(Me)2 H H H T CH CMeN(Me)n-Bu H H H T CH CMeN(nPen)H H H H T CH CMeNHCOPh H H H T CH CMeJ1 H H H T CH CMeNHC(＝NH)NH2 H H H T CH CMeC(＝NH)NH2 H H H T CH CMeCHO H H H T CH CMeCN H H H T CH CMeU H H H T CH CMeCOOMe H H H T CH CMeCONH2 H H H T CH CMeCONHCOMe H H H T CH CMeCH2N(nPen)COPh H H H T CH CMePh H H H T CH CMeBz H H H T CH CMeCH2CH2Ph H H H T CH CMe2-thienyl H H H T CH CMe3-furyl H H H T CH CMePh(4-J2) H H H T CH CMePh(2-Cl，5-J1) H H H T CH CMeT H H H T CH CMeF H H H T CH CFCl H H H T CH CFBr H H H T CH CFI H H H T CH CFMe H H H T CH CFCF3 H H H T CH CFEt H H H T CH CFn-Pr H H H T CH CFc-Pr H H H T CH CFNO2 H H H T CH CFR3 R4 R5 R6 R7 Y ZNH2 H H H T CH CFN(Me)H H H H T CH CFN(Me)2 H H H T CH CFN(Me)n-Bu H H H T CH CFN(nPen)H H H H T CH CFNHCOPh H H H T CH CFJ1 H H H T CH CFNHC(＝NH)NH2 H H H T CH CFC(＝NH)NH2 H H H T CH CFCHO H H H T CH CFCN H H H T CH CFU H H H T CH CFCOOMe H H H T CH CFCONH2 H H H T CH CFCONHCOMe H H H T CH CFCH2N(nPen)COPh H H H T CH CFPh H H H T CH CFBz H H H T CH CFCH2CH2Ph H H H T CH CF2-thienyl H H H T CH CF3-furyl H H H T CH CFPh(4-J2) H H H T CH CFPh(2-Cl，5-J1) H H H T CH CFT H H H T CH CFF H H H T CH CClCl H H H T CH CClBr H H H T CH CClI H H H T CH CClMe H H H T CH CClCF3 H H H T CH CClEt H H H T CH CCln-Pr H H H T CH CClc-Pr H H H T CH CClNO2 H H H T CH CClNH2 H H H T CH CClN(Me)H H H H T CH CClN(Me)2 H H H T CH CClN(Me)n-Bu H H H T CH CClR3 R4 R5 R6R7 Y ZN(nPen)H H H H T CH CClNHCOPh H H H T CH CClJ1 H H H T CH CClNHC(＝NH)NH2 H H H T CH CClC(＝NH)NH2 H H H T CH CClCHO H H H T CH CClCN H H H T CH CClU H H H T CH CClCOOMe H H H T CH CClCONH2 H H H T CH CClCONHCOMe H H H T CH CClCH2N(nPen)COPh H H H T CH CClPh H H H T CH CClBz H H H T CH CClCH2CH2Ph H H H T CH CCl2-thienyl H H H T CH CCl3-furyl H H H T CH CClPh(4-J2) H H H T CH CClPh(2-Cl，5-J1) H H H T CH CClT H H H T CH CClF H H H T CH CBrCl H H H T CH CBrBr H H H T CH CBrI H H H T CH CBrMe H H H T CH CBrCF3 H H H T CH CBrEt H H H T CH CBrn-Pr H H H T CH CBrc-Pr H H H T CH CBrNO2 H H H T CH CBrNH2 H H H T CH CBrN(Me)H H H H T CH CBrN(Me)2 H H H T CH CBrN(Me)n-Bu H H H T CH CBrN(nPen)H H H H T CH CBrNHCOPh H H H T CH CBrJ1 H H H T CH CBrNHC(＝NH)NH2 H H H T CH CBrR3 R4 R5 R6 R7Y ZC(＝NH)NH2 H H H T CH CBrCHO H H H T CH CBrCN H H H T CH CBrU H H H T CH CBrCOOMe H H H T CH CBrCONH2 H H H T CH CBrCONHCOMe H H H T CH CBrCH2N(nPen)COPhH H H T CH CBrPh H H H T CH CBrBz H H H T CH CBrCH2CH2Ph H H H T CH CBr2-thienyl H H H T CH CBr3-furyl H H H T CH CBrPh(4-J2) H H H T CH CBrPh(2-Cl，5-J1)H H H T CH CBrT H H H T CH CBrF H H H T CH COHCl H H H T CH COHBr H H H T CH COHI H H H T CH COHMe H H H T CH COHCF3 H H H T CH COHEt H H H T CH COHn-Pr H H H T CH COHc-Pr H H H T CH COHNO2 H H H T CH COHNH2 H H H T CH COHN(Me)H H H H T CH COHN(Me)2 H H H T CH COHN(Me)n-Bu H H H T CH COHN(nPen)H H H H T CH COHNHCOPh H H H T CH COHJ1 H H H T CH COHNHC(＝NH)NH2 H H H T CH COHC(＝NH)NH2 H H H T CH COHCHO H H H T CH COHCN H H H T CH COHU H H H T CH COHR3 R4 R5 R6 R7 Y ZCOOMe H H H T CH COHCONH2 H H H T CH COHCONHCOMe H H H T CH COHCH2N(nPen)COPh H H H T CH COHPh H H H T CH COHBz H H H T CH COHCH2CH2Ph H H H T CH COH2-thienyl H H H T CH COH3-furyl H H H T CH COHPh(4-J2) H H H T CH COHPh(2-Cl，5-J1) H H H T CH COHT H H H T CH COHF H H H T CH NCl H H H T CH NBr H H H T CH NI H H H T CH NMe H H H T CH NCF3 H H H T CH NEt H H H T CH Nn-Pr H H H T CH Nc-Pr H H H T CH NNO2 H H H T CH NNH2 H H H T CH NN(Me)H H H H T CH NN(Me)2 H H H T CH NN(Me)n-Bu H H H T CH NN(nPen)H H H H T CH NNHCOPh H H H T CH NJ1 H H H T CH NNHC(＝NH)NH2 H H H T CH NC(＝NH)NH2 H H H T CH NCHO H H H T CH NCN H H H T CH NU H H H T CH NCOOMe H H H T CH NCONH2 H H H T CH NCONHCOMe H H H T CH NCH2N(nPen)COPh H H H T CH NR3 R4 R5 R6 R7Y ZPh H H H T CH NBz H H H T CH NCH2CH2Ph H H H T CH N2-thienyl H H H T CH N3-furyl H H H T CH NPh(4-J2) H H H T CH NPh(2-Cl，5-J1) H H H T CH NT H H H T CH N
第3表
R3 R60 R61 R62 R63 R64F Me H H H HCl Me H H H HBr Me H H H HI Me H H H HMe Me H H H HCF3 Me H H H HEt Me H H H Hn-Pr Me H H H Hc-Pr Me H H H HNO2 Me H H H HNH2 Me H H H HN(Me)n-Bu Me H H H HN(nPen)H Me H H H HNHCOPh Me H H H HJ1 Me H H H HU Me H H H HCOOMe Me H H H HCONH2 Me H H H HCONHCOMe Me H H H HCH2N(nPen)COPh Me H H H HPh Me H H H HBz Me H H H HCH2CH2Ph Me H H H H2-thienyl Me H H H H3-furyl Me H H H HPh(4-J2) Me H H H HPh(2-Cl，5-J1) Me H H H HT Me H H H HF H Me H H HCl H Me H H HR3 R60 R61 R62 R63 R64Br H Me H H HI H Me H H HMe H Me H H HCF3 H Me H H HEt H Me H H Hn-Pr H Me H H Hc-Pr H Me H H HNO2 H Me H H HNH2 H Me H H HN(Me)n-Bu H Me H H HN(nPen)H H Me H H HNHCOPh H Me H H HJ1 H Me H H HU H Me H H HCOOMe H Me H H HCONH2 H Me H H HCONHCOMe H Me H H HCH2N(nPen)COPh H Me H H HPh H Me H H HBz H Me H H HCH2CH2Ph H Me H H H2-thienyl H Me H H H3-furyl H Me H H HPh(4-J2) H Me H H HPh(2-Cl，5-J1) H Me H H HT H Me H H HF H H Me H HCl H H Me H HBr H H Me H HI H H Me H HMe H H Me H HCF3 H H Me H HEt H H Me H Hn-Pr H H Me H Hc-Pr H H Me H HNO2 H H Me H HNH2 H H Me H HN(nPen)H H H Me H HR3 R60 R61 R62 R63 R64NHCOPh H H Me H HJ1 H H Me H HU H H Me H HCOOMe H H Me H HCONH2 H H Me H HCONHCOMe H H Me H HCH2N(nPen)COPh H H Me H HPh H H Me H HBz H H Me H HCH2CH2Ph H H Me H H2-thienyl H H Me H H3-furyl H H Me H HPh(4-J2) H H Me H HPh(2-Cl，5-J1) H H Me H HT H H Me H HF F H H H HCl F H H H HBr F H H H HI F H H H HMe F H H H HCF3 F H H H HEt F H H H Hn-Pr F H H H Hc-Pr F H H H HNO2 F H H H HNH2 F H H H HN(Me)n-Bu F H H H HN(nPen)H F H H H HNHCOPh F H H H HJ1 F H H H HU F H H H HCOOMe F H H H HCONH2 F H H H HCONHCOMe F H H H HCH2N(nPen)COPh F H H H HPh F H H H HBz F H H H HCH2CH2Ph F H H H HR3 R60 R61 R62 R63 R642-thienyl F H H H H3-furyl F H H H HPh(4-J2) F H H H HPh(2-Cl，5-J1) F H H H HT F H H H HF H F H H HCl H F H H HBr H F H H HI H F H H HMe H F H H HCF3 H F H H HEt H F H H Hn-Pr H F H H Hc-Pr H F H H HNO2 H F H H HN(Me)n-Bu H F H H HN(nPen)H H F H H HNHCOPh H F H H HJ1 H F H H HU H F H H HCOOMe H F H H HCONH2 H F H H HCONHCOMe H F H H HCH2N(nPen)COPh H F H H HPh H F H H HBz H F H H HCH2CH2Ph H F H H H2-thienyl H F H H H3-furyl H F H H HPh(4-J2) H F H H HPh(2-Cl，5-J1) H F H H HT H F H H HF H H F H HCl H H F H HBr H H F H HI H H F H HMe H H F H HCF3 H H F H HR3 R60 R61 R62 R63 R64Et H H F H Hn-Pr H H F H Hc-Pr H H F H HNO2 H H F H HNH2 H H F H HN(Me)n-Bu H H F H HN(nPen)H H H F H HNHCOPh H H F H HJ1 H H F H HU H H F H HCOOMe H H F H HCONH2 H H F H HCONHCOMe H H F H HCH2N(nPen)COPh H H F H HPh H H F H HBz H H F H HCH2CH2Ph H H F H H2-thienyl H H F H H3-furyl H H F H HPh(4-J2) H H F H HPh(2-Cl，5-J1) H H F H HT H H F H HF Cl H H H HCl Cl H H H HBr Cl H H H HI Cl H H H HMe Cl H H H HCF3 Cl H H H HEt Cl H H H Hn-Pr Cl H H H Hc-Pr Cl H H H HNO2 Cl H H H HNH2 Cl H H H HN(Me)n-Bu Cl H H H HN(nPen)H Cl H H H HNHCOPh Cl H H H HJ1 Cl H H H HU Cl H H H HR3 R60 R61 R62 R63 R64COOMe Cl H H H HCONH2 Cl H H H HCONHCOMe Cl H H H HCH2N(nPen)COPh Cl H H H HPh Cl H H H HBz Cl H H H HCH2CH2Ph Cl H H H H2-thienyl Cl H H H H3-furyl Cl H H H HPh(4-J2) Cl H H H HPh(2-Cl，5-J1) Cl H H H HT Cl H H H HF H Cl H H HCl H Cl H H HBr H Cl H H HI H Cl H H HMe H Cl H H HCF3 H Cl H H HEt H Cl H H Hn-Pr H Cl H H Hc-Pr H Cl H H HNO2 H Cl H H HNH2 H Cl H H HN(Me)n-Bu H Cl H H HN(nPen)H H Cl H H HNHCOPh H Cl H H HJ1 H Cl H H HU H Cl H H HCOOMe H Cl H H HCONH2 H Cl H H HCONHCOMe H Cl H H HCH2N(nPen)COPh H Cl H H HPh H Cl H H HBz H Cl H H HCH2CH2Ph H Cl H H H2-thienyl H Cl H H H3-furyl H Cl H H HPh(4-J2) H Cl H H HR3 R60 R61 R62 R63 R64Ph(2-Cl，5-J1) H Cl H H HT H Cl H H HF H H Cl H HCl H H Cl H HBr H H Cl H HI H H Cl H HMe H H Cl H HCF3 H H Cl H HEt H H Cl H Hn-Pr H H Cl H Hc-Pr H H Cl H HNO2 H H Cl H HNH2 H H Cl H HN(Me)n-Bu H H Cl H HN(nPen)H H H Cl H HNHCOPh H H Cl H HJ1 H H Cl H HU H H Cl H HCOOMe H H Cl H HCONH2 H H Cl H HCONHCOMe H H Cl H HCH2N(nPen)COPh H H Cl H HPh H H Cl H HBz H H Cl H HCH2CH2Ph H H Cl H H2-thienyl H H Cl H H3-furyl H H Cl H HPh(4-J2) H H CI H HPh(2-Cl，5-J1) H H Cl H HT H H Cl H HF Br H H H HCl Br H H H HBr Br H H H HI Br H H H HMe Br H H H HCF3 Br H H H HEt Br H H H Hn-Pr Br H H H HR3 R60 R61 R62 R63 R64cpr Br H H H HNO2 Br H H H HNH2 Br H H H HN(Me)n-Bu Br H H H HN(nPen)H Br H H H HNHCOPh Br H H H HN(Me)CONHPh Br H H H HJ1 Br H H H HU Br H H H HCOOMe Br H H H HCONH2 Br H H H HCONHCOMe Br H H H HCH2N(nPen)COPh Br H H H HPh Br H H H HBz Br H H H HCH2CH2Ph Br H H H H2-thienyl Br H H H H3-fury1 Br H H H HPh(4-J2) Br H H H HPh(2-Cl，5-J1) Br H H H HT Br H H H HF H Br H H HCl H Br H H HBr H Br H H HI H Br H H HMe H Br H H HCF3 H Br H H HEt H Br H H Hn-Pr H Br H H Hc-Pr H Br H H HNO2 H Br H H HNH2 H Br H H HN(Me)n-Bu H Br H H HN(nPen)H H Br H H HNHCOPh H Br H H HJ1 H Br H H HU H Br H H HCOOMe H Br H H HR3 R60 R61 R62 R63 R64CONH2 H Br H H HCONHCOMe H Br H H HCH2N(nPen)COPh H Br H H HPh H Br H H HBz H Br H H HCH2CH2Ph H Br H H H2-thienyl H Br H H H3-furyl H Br H H HPh(4-J2) H Br H H HPh(2-Cl，5-J1) H Br H H HT H Br H H HF H H Br H HCl H H Br H HBr H H Br H HI H H Br H HMe H H Br H HCF3 H H Br H HEt H H Br H Hn-Pr H H Br H Hc-Pr H H Br H HNO2 H H Br H HN(Me)n-Bu H H Br H HN(nPen)H H H Br H HNHCOPh H H Br H HJ1 H H Br H HU H H Br H HCOOMe H H Br H HCONH2 H H Br H HCONHCOMe H H Br H HCH2N(nPen)COPh H H Br H HPh H H Br H HBz H H Br H HCH2CH2Ph H H Br H H2-thienyl H H Br H H3-furyl H H Br H HPh(4-J2) H H Br H Hph(2-Cl，5-J1) H H Br H HT H H Br H HR3 R60 R61 R62 R63R64F J2 H H H HCl J2 H H H HBr J2 H H H HI J2 H H H HMe J2 H H H HCF3 J2 H H H HEt J2 H H H Hn-Pr J2 H H H Hc-Pr J2 H H H HNO2 J2 H H H HNH2 J2 H H H HN(Me)n-Bu J2 H H H HN(nPen)H J2 H H H HNHCOPh J2 H H H HJ1 J2 H H H HU J2 H H H HCOOMe J2 H H H HCONH2 J2 H H H HCONHCOMe J2 H H H HCH2N(nPen)COPh J2 H H H HPh J2 H H H HBz J2 H H H HCH2CH2Ph J2 H H H H2-thienyl J2 H H H H3-furyl J2 H H H HPh(4-J2) J2 H H H HPh(2-Cl，5-J1) J2 H H H HT J2 H H H HF H J2 H H HCl H J2 H H HBr H J2 H H HI H J2 H H HMe H J2 H H HCF3 H J2 H H HEt H J2 H H Hn-Pr H J2 H H Hc-Pr H J2 H H HNO2 H J2 H H HR3 R60 R61 R62 R63 R64NH2 H J2 H H HN(Me)n-Bu H J2 H H HN(nPen)H H J2 H H HNHCOPh H J2 H H HJ1 H J2 H H HU H J2 H H HCOOMe H J2 H H HCONH2 H J2 H H HCONHCOMe H J2 H H HCH2N(nPen)COPh H J2 H H HPh H J2 H H HBz H J2 H H HCH2CH2Ph H J2 H H H2-thienyl H J2 H H H3-furyl H J2 H H HPh(4-J2) H J2 H H HPh(2-Cl，5-J1) H J2 H H HT H J2 H H HF H H J2 H HCl H H J2 H HBr H H J2 H HI H H J2 H HMe H H J2 H HCF3 H H J2 H HEt H H J2 H Hn-Pr H H J2 H Hc-Pr H H J2 H HNO2 H H J2 H HNH2 H H J2 H HN(Me)n-Bu H H J2 H HN(nPen)H H H J2 H HNHCOPh H H J2 H HJ1 H H J2 H HU H H J2 H HCOOMe H H J2 H HCONH2 H H J2 H HCONHCOMe H H J2 H HCH2N(nPen)COPh H H J2 H HR3 R60 R61 R62 R63 R64Ph H H J2 H HBz H H J2 H HCH2CH2Ph H H J2 H H2-thienyl H H J2 H H3-furyl H H J2 H HPh(4-J2) H H J2 H HPh(2-Cl，5-J1) H H J2 H HT H H J2 H HF Cl J1 H H HCl Cl J1 H H HBr Cl J1 H H HI Cl J1 H H HMe Cl J1 H H HCF3 Cl J1 H H HEt Cl J1 H H Hn-Pr Cl J1 H H Hc-Pr Cl J1 H H HNO2 Cl J1 H H HNH2 Cl J1 H H HJ1 Cl J1 H H HU Cl J1 H H HCOOMe Cl J1 H H HCONH2 Cl J1 H H HCONHCOMe Cl J1 H H HCH2N(nPen)COPh Cl J1 H H HPh Cl J1 H H HBz Cl J1 H H HCH2CH2Ph Cl J1 H H H2-thienyl Cl J1 H H H3-furyl Cl J1 H H HPh(4-J2) Cl J1 H H HPh(2-Cl，5-J1) Cl J1 H H HT Cl J1 H H HF Cl H J1 H HCl Cl H J1 H HBr Cl H J1 H HI Cl H J1 H HMe Cl H J1 H HR3 R60 R61 R62 R63 R64CF3 Cl H J1 H HEt Cl H J1 H Hn-Pr Cl H J1 H Hc-Pr Cl H J1 H HNO2 Cl H J1 H HNH2 Cl H J1 H HJ1 Cl H J1 H HU Cl H J1 H HCOOMe Cl H J1 H HCONH2 Cl H J1 H HCONHCOMe Cl H Jl H HCH2N(nPen)COPh Cl H J1 H HPh Cl H J1 H HBz Cl H J1 H HCH2CH2Ph Cl H J1 H H2-thienyl Cl H J1 H H3-furyl Cl H J1 H HPh(4-J2) Cl H J1 H HPh(2-Cl，5-J1) Cl H J1 H HT Cl H J1 H HF Cl H H J1 HCl Cl H H J1 HBr Cl H H J1 HI Cl H H J1 HMe Cl H H J1 HCF3 Cl H H J1 HEt Cl H H J1 Hn-Pr Cl H H J1 Hc-Pr Cl H H J1 HNO2 Cl H H J1 HNH2 Cl H H J1 HN(Me)H Cl H H J1 HN(Me)2 Cl H H J1 HN(Me)n-Bu Cl H H J1 HN(nPen)H Cl H H J1 HNHCOPh Cl H H J1 HN(Me)CO-c-Hex Cl H H J1 HNHCONHMe Cl H H J1 HR3 R60 R61 R62 R63 R64N(Me)CONHPh Cl H H J1 HNHCONH-c-Hex Cl H H J1 HNHCOBz Cl H H J1 HJ1 Cl H H J1 HNBzCO-n-Bu Cl H H J1 HNBzCOO-i-Bu Cl H H J1 HNHCO-n-Bu Cl H H J1 HNHCOO-i-Bu Cl H H J1 HNHCOCF3 Cl H H J1 HNHSO2CF3 Cl H H J1 HN(Me)Ph Cl H H J1 HNHC(＝NH)NH2 Cl H H J1 HC(＝NH)NH2 Cl H H J1 HCHO Cl H H J1 HCN Cl H H J1 HU Cl H H J1 HCOOMe Cl H H J1 HCONH2 Cl H H J1 HCONHCOMe Cl H H J1 HCH2NH2 Cl H H J1 HCH2OH Cl H H J1 HCH2NHCOPh Cl H H J1 HCH2N(nPen)COPh Cl H H J1 HCH2NHCONHMe Cl H H J1 HCH2CONHPh Cl H H J1 HCH2COOH Cl H H J1 HPh Cl H H J1 HBz Cl H H J1 HCH2CH2Ph Cl H H J1 H2-thienyl Cl H H J1 H3-furyl Cl H H J1 HPh(4-J2) Cl H H J1 HPh(2-Cl，3-J1) C1 H H J1 HPh(2-Cl，4-J1) Cl H H J1 HPh(2-Cl，5-J1) Cl H H J1 HPh(2-Cl，6-J1) Cl H H J1 HCH2CH2Ph(2-Cl，5-J1)Cl H H J1 HT Cl H H J1 HR3 R60 R61 R62 R63 R64F Cl H H H J1Cl Cl H H H J1Br Cl H H H J1I Cl H H H J1Me Cl H H H J1CF3 Cl H H H J1Et Cl H H H J1N(Me)n-Bu Cl H H H J1N(nPen)H Cl H H H J1NHCOPh Cl H H H J1J1 Cl H H H J1NHC(＝NH)NH2 Cl H H H J1C(＝NH)NH2 Cl H H H J1CHO Cl H H H J1CN C1 H H H J1U Cl H H H J1COOMe Cl H H H J1CONH2 Cl H H H J1CONHCOMe Cl H H H J1CH2N(nPen)COPh Cl H H H J1Ph Cl H H H J1Bz Cl H H H J1CH2CH2Ph Cl H H H J1Ph(4-J2) Cl H H H J1Ph(2-Cl，5-J1) Cl H H H J1
第4表
R1 R3 R60 R61 R62 R63 R64n-Pr F H H H H Hn-Pr Cl H H H H Hn-Pr Br H H H H Hn-Pr I H H H H Hn-Pr Me H H H H Hn-Pr CF3 H H H H Hn-Pr Et H H H H Hn-Pr n-Pr H H H H Hn-Pr c-Pr H H H H Hn-Pr NO2 H H H H Hn-Pr NH2 H H H H Hn-Pr N(Me)n-Bu H H H H Hn-Pr N(nPen)H H H H H Hn-Pr NHCOPh H H H H Hn-Pr U H H H H Hn-Pr CONH2 H H H H Hn-Pr CONHCOMe H H H H Hn-Pr CH2N(nPen)COPh H H H H Hn-Pr Ph(2-Cl，5-J1)H H H H Hn-Pr OH H H H H Hn-Pr T H H H H HEt F H H H H HEt Cl H H H H HEt Br H H H H HEt I H H H H HEt Me H H H H HEt CF3 H H H H HEt NO2 H H H H HEt NH2 H H H H HEt NHCOPh H H H H HR1 R3 R60 R64 R62 R63 R64Et OH H H H H HEt T H H H H Hn-Bu F H H H H Hn-Bu Cl H H H H Hn-Bu Br H H H H Hn-Bu I H H H H Hn-Bu Me H H H H Hn-Bu CF3 H H H H Hn-Bu NO2 H H H H Hn-Bu NH2 H H H H Hn-Bu N(M)CO-c-Hex H H H H Hn-Bu NHCONH-c-Hex H H H H Hn-Bu OH H H H H Hn-Bu T H H H H Hn-Pr F Me H H H Hn-Pr Cl Me H H H Hn-Pr Br Me H H H Hn-Pr I Me H H H Hn-Pr Me Me H H H Hn-Pr CF3 Me H H H Hn-Pr Et Me H H H Hn-Pr n-Pr Me H H H Hn-Pr c-Pr Me H H H Hn-Pr NO2 Me H H H Hn-Pr NH2 Me H H H Hn-Pr NHCOPh Me H H H Hn-Pr J1 Me H H H Hn-Pr NHC(＝NH)NH2 Me H H H Hn-Pr C(＝NH)NH2 Me H H H Hn-Pr CHO Me H H H Hn-Pr CN Me H H H Hn-Pr U Me H H H Hn-Pr CONH2 Me H H H Hn-Pr CH2N(nPen)COPh Me H H H Hn-Pr Ph Me H H H Hn-Pr Bz Me H H H Hn-Pr CH2CH2Ph Me H H H Hn-Pr 2-thienyl Me H H H Hn-Pr 3-furyl Me H H H HR1 R3 R60 R61 R62 R63 R64n-Pr Ph(4-J2) Me H H H Hn-Pr Ph(2-Cl，5-J1)Me H H H Hn-Pr T Me H H H Hn-Pr F H Me H H Hn-Pr Cl H Me H H Hn-Pr Br H Me H H Hn-Pr I H Me H H Hn-Pr Me H Me H H Hn-Pr CF3 H Me H H Hn-Pr NO2 H Me H H Hn-Pr NH2 H Me H H Hn-Pr NHCOPh H Me H H Hn-Pr J1 H Me H H Hn-Pr NHC(＝NH)NH2 H Me H H Hn-Pr C(＝NH)NH2 H Me H H Hn-Pr CHO H Me H H Hn-Pr CN H Me H H Hn-Pr U H Me H H Hn-Pr CONH2 H Me H H Hn-Pr CH2N(nPen)COPh H Me H H Hn-Pr Ph H Me H H Hn-Pr Bz H Me H H Hn-Pr CH2CH2Ph H Me H H Hn-Pr 2-thienyl H Me H H Hn-Pr 3-furyl H Me H H Hn-Pr Ph(4-J2) H Me H H Hn-Pr Ph(2-Cl，5-J1)H Me H H Hn-Pr T H Me H H Hn-Pr F H H Me H Hn-Pr Cl H H Me H Hn-Pr Br H H Me H Hn-Pr I H H Me H Hn-Pr Me H H Me H Hn-Pr CF3 H H Me H Hn-Pr NO2 H H Me H Hn-Pr NH2 H H Me H Hn-Pr NHCOPh H H Me H Hn-Pr J1 H H Me H Hn-Pr NHC(＝NH)NH2 H H Me H HR1 R3 R60 R61 R62 R63 R64n-Pr C(＝NH)NH2 H H Me H Hn-Pr CHO H H Me H Hn-Pr CN H H Me H Hn-Pr U H H Me H Hn-Pr CONH2 H H Me H Hn-Pr CH2N(nPen)COPh H H Me H Hn-Pr Ph H H Me H Hn-Pr Bz H H Me H Hn-Pr CH2CH2Ph H H Me H Hn-Pr 2-thienyl H H Me H Hn-Pr 3-furyl H H Me H Hn-Pr Ph(4-J2) H H Me H Hn-Pr Ph(2-Cl，5-J1) H H Me H Hn-Pr T H H Me H Hn-Pr F H H H Me Hn-Pr Cl H H H Me Hn-Pr Br H H H Me Hn-Pr I H H H Me Hn-Pr Me H H H Me Hn-Pr CF3 H H H Me Hn-Pr Et H H H Me Hn-Pr n-Pr H H H Me Hn-Pr c-Pr H H H Me Hn-Pr NO2 H H H Me Hn-Pr NH2 H H H Me Hn-Pr NHCOPh H H H Me Hn-Pr J1 H H H Me Hn-Pr NHC(＝NH)NH2 H H H Me Hn-Pr C(＝NH)NH2 H H H Me Hn-Pr CHO H H H Me Hn-Pr CN H H H Me Hn-Pr U H H H Me Hn-Pr CONH2 H H H Me Hn-Pr CH2N(nPen)COPh H H H Me Hn-Pr Ph H H H Me Hn-Pr Bz H H H Me Hn-Pr CH2CH2Ph H H H Me Hn-Pr 2-thienyl H H H Me Hn-Pr 3-furyl H H H Me HR1 R3 R60 R61 R62 R63 R64n-Pr Ph(4-J2) H H H Me Hn-Pr Ph(2-Cl，5-J1) H H H Me Hn-Pr T H H H Me Hn-Pr F H H H H Men-Pr Cl H H H H Men-Pr Br H H H H Men-Pr I H H H H Men-Pr Me H H H H Men-Pr CF3 H H H H Men-Pr Et H H H H Men-Pr n-Pr H H H H Men-Pr c-Pr H H H H Men-Pr NO2 H H H H Men-Pr NH2 H H H H Men-Pr NHCOPh H H H H Men-Pr J1 H H H H Men-Pr NHC(＝NH)NH2 H H H H Men-Pr C(＝NH)NH2 H H H H Men-Pr CHO H H H H Men-Pr CN H H H H Men-Pr U H H H H Men-Pr CONH2 H H H H Men-Pr CH2N(nPen)COPh H H H H Men-Pr Ph H H H H Men-Pr Bz H H H H Men-Pr CH2CH2Ph H H H H Men-Pr 2-thienyl H H H H Men-Pr 3-furyl H H H H Men-Pr Ph(4-J2) H H H H Men-Pr Ph(2-Cl，5-J1) H H H H Men-Pr T H H H H Men-Pr F F H H H Hn-Pr Cl F H H H Hn-Pr Br F H H H Hn-Pr I F H H H Hn-Pr Me F H H H Hn-Pr CF3 F H H H Hn-Pr F H Cl H H Hn-Pr Cl H Cl H H HR1 R3 R60 R61 R62 R63 R64n-Pr Br H Cl H H Hn-Pr I H Cl H H Hn-Pr Me H Cl H H Hn-Pr CF3 H Cl H H Hn-Pr F H H Br H Hn-Pr Cl H H Br H Hn-Pr Br H H Br H Hn-Pr I H H Br H Hn-Pr Me H H Br H Hn-Pr CF3 H H Br H Hn-Pr F H H H J2 Hn-Pr Cl H H H J2 Hn-Pr Br H H H J2 Hn-Pr I H H H J2 Hn-Pr Me H H H J2 Hn-Pr CF3 H H H J2 Hn-Pr Et H H H J2 Hn-Pr n-Pr H H H J2 Hn-Pr F Cl H H H J1n-Pr Cl Cl H H H J1n-Pr Br Cl H H H J1n-Pr I Cl H H H J1n-Pr Me Cl H H H J1n-Pr CF3 Cl H H H J1n-Pr Et Cl H H H J1n-Pr n-Pr Cl H H H J1
第5表R1 R3 R60 R61 R62 R63 R64n-Pr F H H H H Hn-Pr Cl H H H H Hn-Pr Br H H H H Hn-Pr I H H H H Hn-Pr Me H H H H Hn-Pr CF3 H H H H Hn-Pr Et H H H H Hn-Pr n-Pr H H H H Hn-Pr c-Pr H H H H Hn-Pr NO2 H H H H Hn-Pr NH2 H H H H Hn-Pr N(Me)n-Bu H H H H Hn-Pr N(nPen)H H H H H Hn-Pr NHCOPh H H H H Hn-Pr U H H H H Hn-Pr CONH2 H H H H Hn-Pr CONHCOMe H H H H Hn-Pr CH2N(nPen)COPhH H H H Hn-Pr Ph(2-Cl，5-J1)H H H H Hn-Pr OH H H H H Hn-Pr T H H H H HEt F H H H H HEt Cl H H H H HEt Br H H H H HEt I H H H H HEt Me H H H H HEt CF3 H H H H HEt NO2 H H H H HEt NH2 H H H H HEt NHCOPh H H H H HR1 R3 R60 R61 R62 R63 R64Et OH H H H H HEt T H H H H Hn-Bu F H H H H Hn-Bu Cl H H H H Hn-Bu Br H H H H Hn-Bu I H H H H Hn-Bu Me H H H H Hn-Bu CF3 H H H H Hn-Bu NO2 H H H H Hn-Bu NH2 H H H H Hn-Bu N(Me)CO-c-Hex H H H H Hn-Bu NHCONH-c-Hex H H H H Hn-Bu OH H H H H Hn-Bu T H H H H Hn-Pr F Me H H H Hn-Pr Cl Me H H H Hn-Pr Br Me H H H Hn-Pr I Me H H H Hn-Pr Me Me H H H Hn-Pr CF3 Me H H H Hn-Pr Et Me H H H Hn-Pr n-Pr Me H H H Hn-Pr c-Pr Me H H H Hn-Pr NO2 Me H H H Hn-Pr NH2 Me H H H Hn-Pr NHCOPh Me H H H Hn-Pr J1 Me H H H Hn-Pr NHC(＝NH)NH2 Me H H H Hn-Pr C(＝NH)NH2 Me H H H Hn-Pr CHO Me H H H Hn-Pr CN Me H H H Hn-Pr U Me H H H Hn-Pr CONH2 Me H H H Hn-Pr CH2N(nPen)COPh Me H H H Hn-Pr Ph Me H H H Hn-Pr Bz Me H H H Hn-Pr CH2CH2Ph Me H H H Hn-Pr 2-thienyl Me H H H Hn-Pr 3-furyl Me H H H HR1 R3 R60 R61 R62 R63 R64n-Pr Ph(4-J2) Me H H H Hn-Pr Ph(2-Cl，5-J1) Me H H H Hn-Pr T Me H H H Hn-Pr F H Me H H Hn-Pr Cl H Me H H Hn-Pr Br H Me H H Hn-Pr I H Me H H Hn-Pr Me H Me H H Hn-Pr CF3 H Me H H Hn-Pr NO2 H Me H H Hn-Pr NH2 H Me H H Hn-Pr NHCOPh H Me H H Hn-Pr J1 H Me H H Hn-Pr NHC(＝NH)NH2 H Me H H Hn-Pr C(＝NH)NH2 H Me H H Hn-Pr CHO H Me H H Hn-Pr CN H Me H H Hn-Pr U H Me H H Hn-Pr CONH2 H Me H H Hn-Pr CH2N(nPen)COPh H Me H H Hn-Pr Ph H Me H H Hn-Pr Bz H Me H H Hn-Pr CH2CH2Ph H Me H H Hn-Pr 2-thienyl H Me H H Hn-Pr 3-furyl H Me H H Hn-Pr Ph(4-J2) H Me H H Hn-Pr Ph(2-Cl，5-J1)H Me H H Hn-Pr T H Me H H Hn-Pr F H H Me H Hn-Pr Cl H H Me H Hn-Pr Br H H Me H Hn-Pr I H H Me H Hn-Pr Me H H Me H Hn-Pr CF3 H H Me H Hn-Pr NO2 H H Me H Hn-Pr NH2 H H Me H Hn-Pr NHCOPh H H Me H Hn-Pr J1 H H Me H Hn-Pr NHC(＝NH)NH2 H H Me H HR1 R3 R60 R61 R62 R63 R64n-Pr C(＝NH)NH2 H H Me H Hn-Pr CHO H H Me H Hn-Pr CN H H Me H Hn-Pr U H H Me H Hn-Pr CONH2 H H Me H Hn-Pr CH2N(nPen)COPh H H Me H Hn-Pr Ph H H Me H Hn-Pr Bz H H Me H Hn-Pr CH2CH2Ph H H Me H Hn-Pr 2-thienyl H H Me H Hn-Pr 3-furyl H H Me H Hn-Pr Ph(4-J2) H H Me H Hn-Pr Ph(2-Cl，5-J1) H H Me H Hn-Pr T H H Me H Hn-Pr F H H H Me Hn-Pr Cl H H H Me Hn-Pr Br H H H Me Hn-Pr I H H H Me Hn-Pr Me H H H Me Hn-Pr CF3 H H H Me Hn-Pr Et H H H Me Hn-Pr n-Pr H H H Me Hn-Pr c-Pr H H H Me Hn-Pr NO2 H H H Me Hn-Pr NH2 H H H Me Hn-Pr NHCOPh H H H Me Hn-Pr J1 H H H Me Hn-Pr NHC(＝NH)NH2 H H H Me Hn-Pr C(＝NH)NH2 H H H Me Hn-Pr CHO H H H Me Hn-Pr CN H H H Me Hn-Pr U H H H Me Hn-Pr CONH2 H H H Me Hn-Pr CH2N(nPen)COPh H H H Me Hn-Pr Ph H H H Me Hn-Pr Bz H H H Me Hn-Pr CH2CH2Ph H H H Me Hn-Pr 2-thienyl H H H Me Hn-Pr 3-furyl H H H Me HR1 R3 R60 R61 R62 R63 R64n-Pr Ph(4-J2) H H H Me Hn-Pr Ph(2-Cl，5-J1) H H H Me Hn-Pr T H H H Me Hn-Pr F H H H H Men-Pr Cl H H H H Men-Pr Br H H H H Men-Pr I H H H H Men-Pr Me H H H H Men-Pr CF3 H H H H Men-Pr Et H H H H Men-Pr n-Pr H H H H Men-Pr c-Pr H H H H Men-Pr NO2 H H H H Men-Pr NH2 H H H H Men-Pr NHCOPh H H H H Men-Pr J1 H H H H Men-Pr NHC(＝NH)NH2 H H H H Men-Pr C(＝NH)NH2 H H H H Men-Pr CHO H H H H Men-Pr CN H H H H Men-Pr U H H H H Men-Pr CONH2 H H H H Men-Pr CH2N(nPen)COPh H H H H Men-Pr Ph H H H H Men-Pr Bz H H H H Men-Pr CH2CH2Ph H H H H Men-Pr 2-thienyl H H H H Men-Pr 3-furyl H H H H Men-Pr Ph(4-J2) H H H H Men-Pr Ph(2-Cl，5-J1) H H H H Men-Pr T H H H H Men-Pr F F H H H Hn-Pr Cl F H H H Hn-Pr Br F H H H Hn-Pr I F H H H Hn-Pr Me F H H H Hn-Pr CF3 F H H H Hn-Pr F H Cl H H Hn-Pr Cl H Cl H H HR1 R3 R60 R61 R62 R63 R64n-Pr Br H Cl H H Hn-Pr I H Cl H H Hn-Pr Me H Cl H H Hn-Pr CF3 H Cl H H Hn-Pr F H H Br H Hn-Pr Cl H H Br H Hn-Pr Br H H Br H Hn-Pr I H H Br H Hn-Pr Me H H Br H Hn-Pr CF3 H H Br H Hn-Pr F H H H J2 Hn-Pr Cl H H H J2 Hn-Pr Br H H H J2 Hn-Pr I H H H J2 Hn-Pr Me H H H J2 Hn-Pr CF3 H H H J2 Hn-Pr Et H H H J2 Hn-Pr n-Pr H H H J2 Hn-Pr F Cl H H H J1n-Pr Cl Cl H H H J1n-Pr Br Cl H H H J1n-Pr I Cl H H H J1n-Pr Me Cl H H H J1n-Pr CF3 Cl H H H J1n-Pr Et Cl H H H J1n-Pr n-Pr Cl H H H J1
参考例1(2-苯乙基)-3-胺基-4-乙氧羰基吡唑制法A工序1-A-1(2-苯乙基)苄腙
在14.55g(2-苯乙基)肼硫酸盐的水溶液(50ml)中加入100ml 10％氢氧化钠水溶液后，加入2.25g氢氧化钠，于室温搅拌1小时。以250ml二氯甲烷萃取此反应溶液，以硫酸镁干燥后，减压下浓缩、干燥。溶解所得残渣于100ml乙醇中，加入5.55g苯甲醛，加热回流6小时。减压下浓缩干燥此反应溶液，得11.38g黄色油状物的标题化合物的粗生成物。工序1-A-23-〔苯亚甲基(2-苯乙基)肼基〕-2-氰丙烯酸乙酯
在11.38g(2-苯乙基)苄腙的甲苯溶液中加入6.19g乙氧亚甲基氰乙酸乙酯，加热回流9小时，减压馏去溶剂，以硅胶柱色谱法(正己烷：乙酸乙酯＝4∶1→乙酸乙酯)处理，以正己烷-乙酸乙酯重结晶，得8.94g淡黄色结晶的标题化合物。熔点128.9～132.9℃工序1-A-31-(2-苯乙基)-3-氨基-4-乙氧羰基吡唑
在8.89g3-〔苯亚甲基(2-苯乙基)肼基〕-2-氰丙烯酸乙酯中加入30ml乙醇及4.6ml浓盐酸，加热回流1小时。冷却后减压下馏去溶剂，溶解所得残渣于二氯甲烷中，以20ml10％氢氧化钠水溶液洗净。以100ml二氯甲烷萃取水相。将所得有机相合在一起，以硫酸镁干燥后减压下浓缩。以硅胶柱色谱法(正己烷：乙酸乙酯＝3∶1→2∶1→1∶1)处理，得5.61g无色结晶的标题化合物。熔点76.9～78.6℃制法B
在15.69g3-氨基-4-吡唑羧酸乙酯、及24.34g(2-溴乙基)苯、2.54g Adogen 464,27.7g碳酸钾的混合物中，加入250ml甲苯及0.1ml12.5M氢氧化钠水溶液，加热回流2.5小时。以200ml水洗净此反应溶液，以硫酸镁干燥后减压馏去溶剂。以硅胶柱色谱法(正己烷：乙酸乙酯＝2∶1→1∶1→1∶2)处理，得16.94g无色结晶的1-(2-苯乙基)-3-氨基-4-乙氧羰基吡唑。参考例2N-〔1-(2-苯乙基)-4-乙氧羰基吡唑-3-基〕-N-〔(2‘-(N-三苯甲基-(1H-四唑-5-基))联苯-4-基)甲基〕胺
在363mg1-(2-苯乙基)-3-氨基-4-乙氧羰基吡唑及0.40ml1，3-二甲基-3,4,5,6-四氢-2(1H)-嘧啶酮的THF溶液(35ml)中，于干冰-丙酮冷却下加入2.1ml1.5M二异丙基酰胺环己烷锂溶液，在室温下搅拌15分钟。再以干冰-丙酮冷却，加入877mg4-溴甲基-2’-〔N-三苯甲基-(1H-四唑-5-基)〕联苯的10mlTHF溶液，于室温搅拌5.5小时，在此反应溶液中加入10ml氯化铵水溶液，减压下馏去THF，用50ml二氯甲烷萃取。以硫酸镁干燥后，减压下浓缩。以硅胶柱色谱法(正己烷：乙酸乙酯＝3∶1→2∶1)处理，得234mg浅黄色不定形固体的标题化合物。1H NMR(CDCl3，60MHz)：δ1.22(t，J＝7Hz，6H)，3.18(t，J＝7Hz，2H)，3.8-4.1(m，6H)，5.62(t，J＝6Hz，1H)，6.3-8.0(m，28H)参考例3N-〔1-(2-苯乙基)-4-乙氧羰基吡唑-3-基〕-N-〔(2’-(N-三苯甲基-(1H-四唑-5-基))联苯-4-基)甲基〕-正丙胺
在223mgN-〔1-(2-苯乙基)-4-乙氧羰基吡唑-3-基〕N-〔(2‘-(N-三苯甲基-(1H-四唑-5-基))联苯-4-基)甲基〕胺及0.18ml1，3-二甲基-3,4,5,6-四氢-2(1H)嘧啶酮的THF溶液(20m1)中，于干冰-丙酮冷却下加入0.60ml1.5M二异丙酰胺环己烷锂溶液，搅拌15分钟。于该反应溶液中加入0.15ml1-碘化丙烷，于室温搅拌一晚、加入10ml氯化铵水溶液，减压下馏去THF，以50ml二氯甲烷萃取。以硫酸镁干燥后，减压下浓缩。以硅胶柱色谱法(正己烷：乙酸乙酯＝4∶1→3∶1)处理，得91mg浅黄色不定形固体的标题化合物。合成例1
N-〔1-(2-苯乙基)-4-乙氧羰基-5-溴吡唑-3-基〕-N-〔(2’-(N-三苯甲基-(1H-四唑-5-基))联苯-4-基)甲基〕-正丙胺
于395mg N-〔1-(2-苯乙基)-4-乙氧羰基吡唑-3-基〕-N-〔(2’-(N-三苯甲基-(1H-四唑-5-基))联苯-4-基)甲基〕-正丙胺及0.18ml1、3-二甲基-3，4，5，6-四氢-2(1H)-嘧啶酮的THF溶液(20ml)中，于室温下加入1.52ml1.0M双(三甲硅烷基)酰胺己烷锂溶液，加热回流30分钟。在其中加入0.6ml1，2-二溴-1，1，2，2-四氟乙烷，再加热回流30分钟。在此反应溶液中加入10ml氯化铵水溶液，减压馏去THF，以150ml二氯甲烷萃取。以硫酸镁干燥后，用硅胶柱色谱法(己烷∶乙酸乙酯＝2∶1)处理，得363mg微红色不定形固体的标题化合物。
1H NMR(CDCl3，60MHz)：δ0.81(t，J＝7Hz，
3H)，1.2-1.8(m，2H)，1.28(t，J＝7Hz，3H)，
2.8-3.2(m，4H)，4.0-4.5(m，4H)，4.32(s，2
H)，6.7-7.5(m，27H)，7.7-7.9(m，1H)
MS(FAB)：857(M＋H)合成例2N-〔1-(2-苯乙基)-4-乙氧羰基-5-溴吡唑-3-基〕-N-〔(2’-(1H-四唑-5-基))联苯-4-基)甲基〕-正丙胺
将356mg N-〔1-(2-苯乙基)-4-乙氧羰基-5-溴吡唑-3-基〕-N-〔(2’-(N-三苯甲基-(1H-四唑-5-基))联苯-4-基)甲基〕-正丙胺溶解于5ml乙醇，加热回流2小时后，减压下馏去溶剂。以硅胶柱色谱法(正己烷∶乙酸乙酯＝2∶1→乙酸乙酯)处理，得224mg浅黄色不定形固体的标题化合物。
1H NMR(CDCl3，60MHz)：δ0.87(t，J＝7Hz，
3H)，1.1-1.7(m，2H)，2.8-3.4(m，4H)，4.31
(s，2H)，4.0-4.5(m，4H)，6.8-7.5(m，12H)，
7.7-7.9(m，1H)合成例3N-[1-(2-苯乙基)-4-羧基-5-溴吡唑-3-基〕-N-〔(2’-(N-三苯甲基-(1H-四唑-5-基))联苯-4-基)甲基]-正丙胺
在206mg N-〔1-(2-苯乙基)-4-乙氧羰基-5-溴吡唑-3-基〕-N-〔(2’-(1H-四唑-5-基)联苯-4-基)甲基〕-正丙胺中加入5ml乙醇，5ml水，226mg氢氧化钾，加热回流5小时。减压下馏去乙醇，加入10ml水，以浓盐酸使其为酸性后，以50ml二氯甲烷萃取。以硫酸镁干燥后，减压下浓缩。经干燥得184mg浅黄色不定形固体的标题化合物。
1H NMR(CDCl3，60MHz)：δ0.91(t，J＝7Hz， 3H)，1.1-1.8(m，2H)，3.09(t，J＝7Hz，4H)，4.07(s，2H)，4.88(t，J＝7Hz，2H) 6.90(s，5H)，7.0-7.5(m，12H)，7.7-7.9(m，1H)，10.8-11.5(m，2H)MS(FAB)：586(M＋H)合成例4N-〔1-(2-苯乙基)-4-羧基-5-溴吡唑-3-基〕-N-〔(2’-(1H-四唑-5-基))联苯-4-基)甲基〕-正丙胺.二钾盐
将102mg N-〔1-(2-苯乙基)-4-羧基-5-溴吡唑-3-基〕-N-〔(2‘-(N-三苯甲基-(1H-四唑-5-基))联苯-4-基)甲基〕-正丙胺溶解于2ml甲醇中，加入3.5ml 0.1M氢氧化钾甲醇溶液，于室温搅拌1小时。减压下浓缩，干燥，得107mg黄色不定形固体的标题化合物。
MS(FAB)：662(M＋H)合成例5N-〔1-(2-苯乙基)-5-碘-4-乙氧羰基吡唑-3-基〕-N-〔(2’-(N-三苯甲基-(1H-四唑-5-基))联苯-4-基)甲基〕-正丙胺
在202mgN-〔1-(2-苯乙基)-5-溴-4-乙氧羰基吡唑-3-基〕-N-〔(2’-(N-三苯甲基-(1H-四唑-5-基))联苯-4-基)甲基〕-正丙胺的THF溶液(10ml)中，于干冰-丙酮冷却下，加入0.18ml1.6M正丁基锂乙烷溶液。搅拌2小时后加入667mgl，2-二碘乙烷。搅拌1小时后，于室温再搅拌1小时。在此反应溶液中加入10ml氯化铵水溶液，减压下馏去THF，以50ml二氯甲烷萃取。以硫酸镁干燥后，以硅胶柱色谱法(正己烷：乙酸乙酯＝5∶1)处理，得84mg微红色不定形固体的标题化合物。1H NMR(CDCl3，60MHz)：δ0.77(t，J＝7Hz，3H)，1.31(t，J＝7Hz，3H)，1.3-1.8(m，2H)，2.8-3.2(m，4H)，4.22(q，J＝7Hz，2H)，4.28(t，J＝7Hz，2H)，4.31(s，2H)，6.8-7.5(m，27H)，7.6-7.9(m，1H)MS(FAB)：904(M＋H)合成例6N-〔1-(2-苯乙基)-5-氯-4-乙氧羰基吡唑-3-基〕-N-〔(2’-(N-三苯甲基-(1H-四唑-5-基))联苯-4-基)甲基〕-正丙胺
在231mg N-〔1-(2-苯乙基)-5-溴-4-乙氧羰基吡唑-3-基〕-N-〔(2’-(N-三苯甲基-(1H-四唑-5-基))联苯-4-基)甲基〕-正丙胺的THF溶液(10ml)中，于干冰-丙酮冷却下，加入0.24ml1.6M正丁基锂己烷溶液。搅拌30分钟。在此反应溶液中加入10ml氯化铵水溶液，减压下馏去THF，以50ml二氯甲烷萃取。以硫酸镁干燥后，以硅胶柱色谱法(正己烷：乙酸乙酯＝5∶1)处理，得159mg浅黄色不定形固体的标题化合物。1H NMR(CDCl3，60MHz)：δ0.78(t，J＝7Hz，3H)，1.27(t，J＝7Hz，3H)，1.3-1.8(m，2H)，2.99(t，J＝7Hz，4H)，3.12(t，J＝7Hz，4H)，4.23(q，J＝7Hz，2H)，4.29(t，J＝7Hz，2H)，4.36(s，2H)，6.7-7.6(m，27H)，7.8-8.0(m，1H)MS(FAB)：812(M＋H)合成例7N-〔1-(2-苯乙基)-5-(正丁氨基)-4-乙氧羰基吡唑-3-基〕-N-〔(2’-(N-三苯甲基-(1H-四唑-5-基))联苯-4-基)甲基〕-正丙胺
在216mg N-〔1-(2-苯乙基)-5-溴-4-乙氧羰基吡唑-3-基〕-N-〔(2’-(N-三苯甲基-(1H-四唑-5-基))联苯-4-基)甲基〕-正丙胺中加入30mg还原铜，20mg氧化铜(II)，83mg碳酸钾，5ml正丁胺，加热回流14小时，以硅藻土过滤反应溶液。减压下浓缩滤液。以硅胶柱色谱法(正己烷：乙酸乙酯＝7∶1)处理残渣，得92mg浅黄色不定形固体的标题化合物。
1H NMR(CDCl3，60MHz)：δ0.75(t，J＝7Hz，
3H)，0.89(t，J＝7Hz，3H)，1.21(t，J＝7Hz，
3H)，1.1-1.8(m，6H)，2.99(t，J＝7Hz，6H)，
4.04(t，J＝7Hz，2H)，4.17(q，J＝7Hz，2H)，4.
31(s，2H)，5.91(t，J＝7Hz，1H)，6.7-7.5(m，
27H)，7.6-7.9(m，1H)合成例8N-〔1-(2-苯乙基)-5-(2-甲苯基)-4-乙氧羰基吡唑-3-基〕-N-(2’-(N-三苯甲基-(1H-四唑-5-基))联苯-4-基)甲基〕-正丙胺
在208mg N-〔1-(2-苯乙基)-5-溴-4-乙氧羰基吡唑-3-基〕-N-(2’-(N-三苯甲基-(1H-四唑-5-基))联苯-4-基)甲基〕-正丙胺及0.04ml13-二甲基-3，4，5，6-四氢-2(1H)-嘧啶酮的THF溶液(5ml)中，干冰-丙酮冷却下，滴下0.23ml1.6M正丁基锂己烷溶液，搅拌10分钟。其中加入0.74ml0.5M氯化锌THF溶液，于室温搅拌30分钟后，加入83ml间碘甲苯及36mg四(三苯膦)钯(0)的THF溶液(5ml)，于60℃搅拌28小时。在此反应溶液中加入10ml氯化铵水溶液，减压下馏去THF，以50ml二氯甲烷萃取。以硫酸镁干燥后，减压下镏去溶剂。以硅胶柱色谱法(正己烷：乙酸乙酯＝5∶1)处理所得残渣，得171mg浅黄色不定形固体的标题化合物。1H NMR(CDCl3，60MHz)：δ0.82(t，J＝7Hz，6H)，1.3-1.8(m，2H)，2.22(s，3H)，2.96(t，J＝7Hz，2H)，3.20(t，J＝7Hz，2H)，3.7-4.1(m，4H)，4.44(s，2H)，6.3-7.5(m，31H)，7.7-7.9(m，1H)MS(FAB)：868(M＋H)合成例9～21
用与合成例8一样的方法，合成以下化合物。合成例9～21
用与合成例8一样的方法，合成以下化合物。 
合成例22～37
用与合成例22一样的方法进行脱保护，合成以下所示化合物。 
合成例39～55
用与合成例3一样的方法进行酯的水解，合成以下所示化合物。 
合成例56～71
用与以合成例4一样的方法使其成为钾盐，合成以下所示化合物。 
试验例1血管紧张素拮抗作用试验
在戊巴比妥麻醉下放血致死兔子，立即取出胸部大动脉。大动脉是使其成为环状标本，保持于37℃，悬吊于通入95％氧、5％二氧化碳混合气体的营养液(Krebs-Henseleit液)中，测定其等尺度收缩(isometric contraction)。每隔20分钟交换营养液，使标本稳定1小时后，通过血管紧张素II(AngII：10-8M)激起其收缩。本发明化合物的评估是在AngII的第四次投予前20分钟施予本发明化合物(10-7M或10-8M)进行预处理，以第三次的AngII的收缩做为100％求出抑制率。又，本发明化合物是通过加入二甲亚砜(DMSO)予以修正。
抑制率(％)
本凳明化合物合成例 1×10-7M 1×10-5M
4 85 40
56 84 51
61 77 34
64 92 29
67 35 13
68 35 18
71 36 14
72 15 7试验例2降血压作用
溶解本发明化合物于生理食盐水，经口投予雄性自然发病的高血压症老鼠(10周龄)。通过预先自大腿动脉留置于大动脉内的导管，再用由压转换器测定血压。观察投予前与投予20小时后为止的血压变化。
下表所列为本发明化合物的投予量，最大降压率及投予后的时间。
本凳明化合物合成例 投与量(mg/kg) 最大降压率(％) 时间4 30 29.6 10试验例3血管紧张素IIAT2受体结合的阻碍试验
依据J.P.Bennett，Jr等的方法〔J.Biol.Chem.251，7423-7430(1976)〕，试验血管紧张素II(AngII)对牛脑受体的结合性发生作用的化合物阻碍作用。
在含有一定量牛脑标本与0.1nM125I-AngII的水溶液中加入10-5M本发明化合物，于37℃培养30分钟，通过玻璃纤维过滤器，停止反应。以γ-计数器测定结合于此过滤器的辐射能。
本凳明化合物合成例 抑制率(％)
4 55.1制剂例1片剂
合成例化合物4 10g
乳糖 260g
微晶纤维素 600g
玉米淀粉 350g
羟丙基纤维素 100g
CMC-Ca 150g
硬脂酸镁 30g
全量 1,500g
依常法混合上述成分，制造10,000片每片中含有1mg活性成分的糖衣片。制剂例2胶囊剂
合成例化合物4 10g
乳糖 440g
微晶纤维素 1,000g
硬脂酸镁 50g
全量 1,500g
依常法混合上述成分后填充于明胶胶囊，制得10,000个每胶囊中含1mg活性成分的胶囊剂。制剂例3软胶囊剂
合成例化合物4 10g
PEG400 479g
饱和脂肪酸甘油三酯 1,500g
薄荷油 1g
Polysorbate80 10g
全量 2,000g
依常法混合上述成分后填充于3号软明胶胶囊中，制得10,000个每胶囊中含1mg活性成分的软胶囊剂。制剂例4软膏
合成例化合物4 1.0g
液体石蜡 10.0g
鲸蜡醇 20.0g
白色凡士林 68.4g
对羟基苯甲酸乙酯 0.1g
1-薄荷醇 0.5g
全量 100.0g
依常法混合上述成分制成1％软膏。制剂例5栓剂
合成例化合物 41g
Witepsol II15 478g
Witepsol W35 520g
聚山梨酸酯(Polysorbate 80) 1g
全量 1,000g“注：Witepsol是甘油三酸酯类化合物的商标名”
依常法熔融混合上述成分，注入栓剂成型容器中冷却固化，制造1000个含1mg活性成分的1g栓剂。
本发明化合物对血管紧张素II具有拮抗作用，对于预防及治疗高血压症、缺血性心脏器质性病变、慢性肾脏器质性病变、醛固酮症、眼内压上升等极为有用。
Claims (9)
1.以式〔1〕所示的吡唑化合物，其互变异构体或其中任一个的盐，(式中R1表示氢原子、C1-C10烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基，NR8R8’(R8及R8’可分别独立表示氢原子、C1-C10的烷基及C6-C10的芳香族基)、SR9(R9与R8相同)、C6-C10的芳香族基或杂环基所取代}、C2-C10链烯基{该链烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’可分别独立表示与上述相同)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、C2-C10的炔基{该炔基可任意被卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及
分别独立表示与上述相同)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、C3-C10环烷基{该环烷基可任意被卤素原子、羟基、C1-C10烷氧基、NR8R8’(R8及R8’可分别独立表示与上述相同)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、C3-C10的环烯基{该环烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’可分别独立表示如上所述)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、C6-C10的芳香族基{该芳香族基可任意被C1-C10的烷基、卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’可分别独立表示如上所述)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、杂环基{该杂环基可任意被C1-C10的烷基、卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’可分别独立表示如上述)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、C1-C10酰基{该酰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’可分别独立表示如上所述)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、C1-C10烷氨甲酰基{该烷氨甲酰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’可分别与上述)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、C1-C10烷氧羰基{该烷氧羰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’与上述相同)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}、C6-C10芳氧羰基{该芳氧羰基可任意被C1-C10的烷基、卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’分别如上述)、SR9(R9与上述相同)、C6-C10芳香族基、或杂环基所取代}；
R2表示卤素原子、硝基、氰基、甲酰基、磺酸基、磺酰氨基、PO2H2，PO3H2，5-四唑基、5-四唑甲基、5-四唑乙基、C1-C10烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示氢原子、C1-C10的烷基及C6-C10的芳香族基)、SR11(R11与R10相同)、C6-C10的芳香族基或杂环基所取代}、C2-C10的链烯基{该链烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C2-C10的炔基{该炔基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C3-C10的环烷基{该环烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C3-C10的环烯基{该环烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C6-C10芳香基{该芳香基可任意被C1-C10的烷基、卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、杂环基{该杂环基可任意被C1-C10的烷基、卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C1-C10酰基{该酰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C1-C10烷氨甲酰基{该烷氨甲酰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C1-C10烷氧羰基{该烷氧羰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C6-C10芳氧羰基{该芳氧羰基可任意被C1-C10的烷基、卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、(CH2)m1COX1R12[m1表示0、1、或2、R12表示氢原子或C1-C10的烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、X1表示氧原子、硫原子或NR13(R13与R10相同)]，(CH2)n1X2R14[n1表示0、1或2、R14表示氢原子或C1-C10的烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、或C1-C10的酰基{该酰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR10R10’(R10及R10’分别独立表示如上所示)、SR11(R11与上述相同)、C6-C10的芳香族基、或杂环基所取代}、X2表示氧原子、S(O)n2(n2表示0、1、2或3)或NR15(R15与R12相同、或为SO2R16(R16表示C1-C10的烷基(该烷基可任意被卤素原子取代))}]或表示以下所示的噁二唑基。
(式中、R17、R17’、R17”与R10相同)
R3表示卤素原子、羟基、硝基、氰基、甲酰基、胍基、脒基、磺酸基、磺酰氨基、PO2H2，PO3H2，5-四唑基、5-四唑甲基、5-四唑乙基、C1-C10的烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示氢原子、C1-C10的烷基或C6-C10的芳香族基)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C2-C10的链烯基{该链烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C2-C10的炔基{该炔基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C3-C10的环烷基{该环烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C3-C10的环烯基{该环烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C6-C10的芳香族基〔该芳香族基可任意被卤素原子、羟基、硝基、氰基、甲酰基、胍基、脒基、磺酸基、磺酰氨基、PO2H2，PO3H2，5-四唑基、C1-C10的烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C2-C10的链烯基{该链烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C2-C10的链烯基{该链烯基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C3-C10的环烷基{该环烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、(CH2)m2COX3R20[m2为0、1或2、R20表示氢原子或C1-C10的烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、X3表示氧原子、硫原子或NR21(R21与R18相同)〕、(CH2)n3X4R22[n3表示0、1或2，R22表示氢原子、C1-C10的烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、C1-C10的酰基{该酰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所示)、SR19(R19与上述相同)、C6-C10的芳香族基、或杂环基所取代}、X4表示氧原子、S(O)n4(n4表示0、1、2或3)、或NR23(R23与R20相同、或表示SO2R24(R24表示C1-C10的烷基(该烷基可任意被卤素原子所取代))}]、C6-C10的芳香族基、杂环基、或以R2所示的噁二唑基中的任意1-5个所取代〕、杂环基{该杂环基可任意被C1-C10的烷基、卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所述)、SR19(R19与上相同)、C6-C10芳香基、或杂环基所取代}、C1-C10的酰基{该酰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所述)、SR19(R19与上相同)、C6-C10芳香基、或杂环基所取代}、C1-C10的烷氨甲酰基{该烷氨甲酰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所述)、SR19(R19与上相同)、C6-C10芳香基、或杂环基所取代}、C1-C10的烷氧羰基{该烷氧羰基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所述)、SR19(R19与上相同)、C6-C10芳香基、或杂环基所取代}、C6-C10的芳氧羰基{该芳氧羰基可任意被C1-C10的烷基、卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所述)、SR19(R19与上相同)、C6-C10芳香基、或杂环基所取代}、(CH2)m3COX5R25(m3表示0、1或2，R25与R1相同、X5表示共价键、氧原子、硫原子或NR26(R26与R18相同)}，(CH2)n5X6R27[n5表示0、1或2、R27与R1相同、或表示硝基、氰基、甲酰基、胍基、脒基、磺酸基、磺酰氨基、PO2H2，PO3H2，5-四唑基、或以R2表示的恶二唑基、X6表示共价键、氧原子、S(O)n6(n6表示0、1、2或3)、NR28{R28与R20相同或表示SO2R29(R29表示C1-C10的烷基(该烷基可任意被卤素原子取代)}]，(CH2)m4X7COR30[m4表示0、1或2、R30表示氢原子、C1-C10的烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR18R18’(R18及R18’分别独立表示如上所述)、SR19(R19与上相同)、C6-C10芳香基、或杂环基所取代}、或NR31R31’(R31及R31’是分别独立与R18相同)，X7是表示氧原子、硫原子或NR32(R32是与R18相同)〕；R4、R5及R6是分别独立表示卤素原子、羟基、硝基、氰基、甲酰基、胍基、脒基、羧基、磺酸基、磺酰氨基、PO2H2、PO3H2、5-四唑基、C1～C10烷基{该烷基是可任意地被卤素原子、羟基、C1～C10烷氧基、NR33R33’(R33及R33’分别独立表示氢原子、C1～C10烷基及C6～C10芳香族基)、SR34(R34与R33一样)、C6～C10芳香族基、或杂环基所取代}、C1～C10酰基{该酰基可任意地被卤素原子、羟基、C1～C10烷氧基、NR33R33’(R33及R33’是分别独立与上述相同)、SR35(R34与上述相同)、C6～C10芳香族基、或杂环基所取代}、C1～C10烷氧基、NR33R33’(R33及R33’分别独立与上述相同)；R7表示羧基(该羧基可以被甲基、叔丁基等所保护)、磺酸基、磺酰氨基、PO2H2、PO3H2、5-四唑基(该四唑基可被三苯甲基、甲氧甲基、甲氧.乙氧甲基、苯甲基等所保护)、以R2所示的恶二唑基、X8R35{(R35与R12相同、X8表示氧原子、硫原子或NR36(R36与R33相同)、或SO2R37(R37表示C1～C10烷基(该烷基可任意被卤素原子所取代))}、或杂环基{该杂环基可以任意地被C1～C10烷基、卤素原子、羟基、C1～C10烷氧基、NR38R38’(R38及R38’可分别独立表示氢原子、C1～C10烷基及C6-C10芳香族基)、SR39(R39与R38相同)、C6～C10芳香族基、或杂环基所取代}、或以下所示取代基。
X表示氮原子或N→O；
Y及Z分别独立表示氮原子或CR40(R40与R4和同)；
A表示(CR41R41’)m7-L-(CR42R42’)n7(m7及n7分别独立表示0、1、2或3、R41、R41’、R42及R42’分别独立与R4相同、L表示共价键、氧原子、羰基、NR43(R43表示氢原子、C1～C10烷基及C6～C10芳香族基)、NR44-CO(R44与R43一样)、CO-NR45(R45与R43相同)、S(O)m5(m5表示0、1或2)、NR46-CO-NR47”R46及R47分别独立表示与R43相同)、CR48＝CR49(R48及R49分别独立表示与R43相同)、C≡C、或NR50-NR51(R50及R51分别独立表示与R43相同)}。
D表示C6～C10芳香族基(该芳香族基可任意被1～5个R3所示取代基所取代)。
E是表示(CR52R53)m6X9(m6是表示0、1、或2、R52及R53是分别独立表示与R4相同、X9是表示共价键、氧原子、硫原子或NR54(R54是表示氢原子、C1～C10烷基及C6～C10芳香族基)}。
G是表示共价键、氧原子、S(O)m8(m8是表示0、1或2)、NR55(R55是表示氢原子、C1～C10烷基及C6～C10芳香族基)、羰基、(CR55R56)n8(n8是表示0、1、或2、R55及R56是表示氢原子、C1～C10烷基及C6～C10芳香族基)、CONR57(R57是表示氢原子、C1～C10烷基及C6～C10芳香族基)、或NR58-CO(R58是表示氢原子、C1～C10烷基及C6～C10芳香族基)]。
2.权利要求1中的吡唑化合物、其互变异构体或其中任一个的盐，其中R1表示C1-C10的烷基{该烷基可任意被卤素原子、羟基、C1-C10的烷氧基、NR8R8’(R8及R8’可分别独立表示氢原子、C1-C10的烷基及C6-C10芳香族基)、SR9(R9是与R8相同)所取代}、C2-C10链烯基{该链烯基可任意被卤素原子、羟基、C1-C10烷氧基、NR8R8’(R8及R8’分别独立表示如上所述)、SR9(R9与上述相同)所取代}、C3-C10环烷基{该环烷基可任意被卤素原子、羟基、C1-C10烷氧基、NR8R8’(R8及R8’分别独立表示如上所述)、SR9(R9与上述相同)所取代}。
3.权利要求2中的吡唑化合物，其互变异构体或其中任一个的盐，其中R2表示卤素原子、硝基、氰基、甲酰基、磺酸基、磺酰胺基、PO2H2、PO3H2、5-四唑基、C1-C10的烷基{该烷基可任意被卤素原子、羟基、C1-C10烷氧基、NR10R10’(R10及R10’分别独立表示氢原子、C1-C10烷基及C6-C10芳香族基)、SR11(R11与R10相同)、C6-C10的芳香族基、或杂环基所取代、(CH2)m1COX1R12[m1表示0、1或2，R12表示氢原子或C1-C10的直链或支链烷基{该烷基可任意被卤素原子、羟基、C1-C10烷氧基、NR10R10’(R10及R10’分别独立表示如上所述)、SR11(R11与上述相同)所取代}、X1表示氧原子、硫原子或NR13(R13与R10相同)1、R4，R5，R6为氢原子、E为CH2、G为共价键、CO-NR57(R57表示氢原子、C1-C10烷基及C6-C10芳香族基)或NR58-CO(R58表示氢原子、C1-C10的烷基及C6-C10芳香族基)。
4.权利要求3中的吡唑化合物、其互变异构体或其中任一个的盐，其中，R1为C1-C10的烷基，R7为5-四唑基，Y及Z分别为CH。
5.权利要求4中的吡唑化合物、其互变异构体或其中任一个的盐，其中D为苯基(该苯基可被R3所示的取代基任意取代)。
6.权利要求5中的吡唑化合物、其互变异构体或其中任一个的盐，其中R2为羧基。
7.一种抗高血压剂，其特征在于含有权利要求1-6中的吡唑化合物、共互变异构体及/或其中任一个的盐。
8.一种淤血性心脏器质性病变治疗药，其特征在于含有权利要求1-6中的吡唑化合物、其互变异构体及/或其中任一个的盐。
9.一种慢性肾脏器质性病变治疗药，其特征在于含有权利要求1-6中的吡唑化合物、其互变异构体及/或其中任一个的盐。
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8092293 | 1993-04-07 | ||
| JP80922/93 | 1993-04-07 | ||
| JP917/94 | 1994-01-10 | ||
| JP91794 | 1994-01-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1120837A true CN1120837A (zh) | 1996-04-17 |
Family
ID=26334032
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN94191705A Pending CN1120837A (zh) | 1993-04-07 | 1994-04-07 | 吡唑衍生物 |
Country Status (7)
| Country | Link |
|---|---|
| US (4) | US5721264A (zh) |
| EP (1) | EP0693480A4 (zh) |
| KR (1) | KR960701023A (zh) |
| CN (1) | CN1120837A (zh) |
| AU (1) | AU679735B2 (zh) |
| CA (1) | CA2158737A1 (zh) |
| WO (1) | WO1994022838A1 (zh) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3222619A1 (en) * | 1999-04-15 | 2017-09-27 | Bristol-Myers Squibb Holdings Ireland | Cyclic protein tyrosine kinase inhibitors |
| US7125875B2 (en) | 1999-04-15 | 2006-10-24 | Bristol-Myers Squibb Company | Cyclic protein tyrosine kinase inhibitors |
| FR2836999B1 (fr) * | 2002-03-08 | 2004-05-28 | Thales Sa | Dispositif audiophonique panoramique pour sonar passif |
| EP1667643A4 (en) * | 2003-08-28 | 2008-03-05 | Nitromed Inc | NITROSIS AND NITROSYL CARDIOVASCULAR COMPOUNDS, COMPOSITIONS AND METHODS OF USE THEREOF |
| WO2006093864A1 (en) * | 2005-02-28 | 2006-09-08 | Nitromed, Inc. | Cardiovascular compounds comprising nitric oxide enhancing groups, compositions and methods of use |
| WO2006099058A2 (en) * | 2005-03-09 | 2006-09-21 | Nitromed, Inc. | Organic nitric oxide enhancing salts of angiotensin ii antagonists, compositions and methods of use |
| EP1893570A4 (en) * | 2005-06-22 | 2009-12-23 | Reddy Manne Satynarayana | IMPROVED PROCESS FOR THE PREPARATION OF EZETIMIBE |
| US20070049748A1 (en) * | 2005-08-26 | 2007-03-01 | Uppala Venkata Bhaskara R | Preparation of ezetimibe |
Family Cites Families (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS54148788A (en) | 1978-05-15 | 1979-11-21 | Takeda Chem Ind Ltd | 1,2-disubstituted-4-halogenoimidazole-5-acetic acid derivative and its preparation |
| JPS5671073A (en) | 1979-11-12 | 1981-06-13 | Takeda Chem Ind Ltd | Imidazole derivative |
| JPS5671074A (en) * | 1979-11-12 | 1981-06-13 | Takeda Chem Ind Ltd | 1,2-disubstituted-4-halogenoimidazole-5-acetic acid derivative |
| DD149517A1 (de) | 1980-03-20 | 1981-07-15 | Jupp Kreutzmann | Verfahren zur herstellung von 5-amino-pyrazolen |
| DE3168194D1 (en) | 1980-12-05 | 1985-02-21 | Basf Ag | 5-amino-1-phenylpyrazole-4-carboxylic acids, process for their preparation, herbicides containing them and their use as herbicides |
| EP0053678A1 (de) | 1980-12-05 | 1982-06-16 | BASF Aktiengesellschaft | 5-Amino-1-phenyl-4-cyanpyrazole, diese enthaltende herbizide Mittel, Verfahren zu ihrer Herstellung und ihre Anwendung als Herbizide |
| JPS58157768A (ja) | 1982-03-16 | 1983-09-19 | Takeda Chem Ind Ltd | ４−クロロ−２−フエニルイミダゾ−ル−５−酢酸誘導体 |
| US4576958A (en) | 1984-01-23 | 1986-03-18 | E. I. Du Pont De Nemours And Company | Antihypertensive 4,5-diaryl-1H-imidazole-2-methanol derivatives |
| US4812462A (en) * | 1986-04-01 | 1989-03-14 | Warner-Lambert Company | 4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid analogs having antihypertensive activity |
| DD248587A1 (de) | 1986-04-24 | 1987-08-12 | Univ Berlin Humboldt | Verfahren zur herstellung von substituierten 5-aminopyrazolen |
| CA1334092C (en) | 1986-07-11 | 1995-01-24 | David John Carini | Angiotensin ii receptor blocking imidazoles |
| US4820843A (en) * | 1987-05-22 | 1989-04-11 | E. I. Du Pont De Nemours And Company | Tetrazole intermediates to antihypertensive compounds |
| JPH01100570A (ja) | 1987-10-14 | 1989-04-18 | Toshiba Corp | 画像形成装置 |
| DE3742822A1 (de) | 1987-12-17 | 1989-07-13 | Bayer Ag | Verfahren zur herstellung von 5-amino-l-phenyl-4-nitro-pyrazolen |
| US4880804A (en) * | 1988-01-07 | 1989-11-14 | E. I. Du Pont De Nemours And Company | Angiotensin II receptor blocking benzimidazoles |
| IL99246A0 (en) * | 1990-09-10 | 1992-07-15 | Abbott Lab | Angiotensin ii receptor antagonists and pharmaceutical compositions containing them |
| US5326776A (en) * | 1992-03-02 | 1994-07-05 | Abbott Laboratories | Angiotensin II receptor antagonists |
| WO1993017682A1 (en) * | 1992-03-04 | 1993-09-16 | Abbott Laboratories | Angiotensin ii receptor antagonists |
-
1994
- 1994-04-07 KR KR1019950704032A patent/KR960701023A/ko not_active Application Discontinuation
- 1994-04-07 WO PCT/JP1994/000587 patent/WO1994022838A1/ja not_active Application Discontinuation
- 1994-04-07 CA CA002158737A patent/CA2158737A1/en not_active Abandoned
- 1994-04-07 US US08/525,555 patent/US5721264A/en not_active Expired - Fee Related
- 1994-04-07 EP EP94912072A patent/EP0693480A4/en not_active Withdrawn
- 1994-04-07 CN CN94191705A patent/CN1120837A/zh active Pending
- 1994-04-07 AU AU64372/94A patent/AU679735B2/en not_active Ceased
-
1997
- 1997-12-29 US US08/999,493 patent/US5817828A/en not_active Expired - Fee Related
- 1997-12-29 US US08/998,669 patent/US5840909A/en not_active Expired - Fee Related
- 1997-12-29 US US08/998,671 patent/US5846991A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| KR960701023A (ko) | 1996-02-24 |
| AU6437294A (en) | 1994-10-24 |
| EP0693480A4 (en) | 1996-09-25 |
| EP0693480A1 (en) | 1996-01-24 |
| US5817828A (en) | 1998-10-06 |
| CA2158737A1 (en) | 1994-10-13 |
| US5846991A (en) | 1998-12-08 |
| US5721264A (en) | 1998-02-24 |
| AU679735B2 (en) | 1997-07-10 |
| US5840909A (en) | 1998-11-24 |
| WO1994022838A1 (en) | 1994-10-13 |
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