DE69504198T2 - Substituierte alkyldiaminderivate und ihre verwendung als tachykinin antagonisten - Google Patents
Substituierte alkyldiaminderivate und ihre verwendung als tachykinin antagonistenInfo
- Publication number
- DE69504198T2 DE69504198T2 DE69504198T DE69504198T DE69504198T2 DE 69504198 T2 DE69504198 T2 DE 69504198T2 DE 69504198 T DE69504198 T DE 69504198T DE 69504198 T DE69504198 T DE 69504198T DE 69504198 T2 DE69504198 T2 DE 69504198T2
- Authority
- DE
- Germany
- Prior art keywords
- ethylamino
- methyl
- compound
- compound according
- benzyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 102000003141 Tachykinin Human genes 0.000 title claims abstract description 32
- 108060008037 tachykinin Proteins 0.000 title claims abstract description 32
- 239000005557 antagonist Substances 0.000 title abstract description 17
- 150000004985 diamines Chemical class 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 42
- 201000010099 disease Diseases 0.000 claims abstract description 29
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 29
- 230000001404 mediated effect Effects 0.000 claims abstract description 19
- 238000011282 treatment Methods 0.000 claims abstract description 19
- 206010011224 Cough Diseases 0.000 claims abstract description 8
- 208000006673 asthma Diseases 0.000 claims abstract description 8
- 206010006451 bronchitis Diseases 0.000 claims abstract description 7
- 150000001875 compounds Chemical class 0.000 claims description 271
- 238000006243 chemical reaction Methods 0.000 claims description 90
- -1 benzyloxy, hydroxy Chemical group 0.000 claims description 83
- 239000001257 hydrogen Substances 0.000 claims description 37
- 229910052739 hydrogen Inorganic materials 0.000 claims description 37
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 37
- 239000002253 acid Substances 0.000 claims description 35
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 32
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 27
- 229940080818 propionamide Drugs 0.000 claims description 24
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 21
- 238000002360 preparation method Methods 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 18
- 125000006239 protecting group Chemical group 0.000 claims description 17
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 12
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical group 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 239000003937 drug carrier Substances 0.000 claims description 7
- 101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 claims description 5
- 239000012279 sodium borohydride Substances 0.000 claims description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 4
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 4
- GOLCUCWJUAVPFU-WNJJXGMVSA-N (3s)-3-[2-ethyl-2-[(2s)-1-[(2-methoxyphenyl)methyl-methylamino]-1-oxo-3-phenylpropan-2-yl]hydrazinyl]-4-(1h-indol-3-yl)butanoic acid Chemical compound C([C@H](N(N[C@H](CC(O)=O)CC=1C2=CC=CC=C2NC=1)CC)C(=O)N(C)CC=1C(=CC=CC=1)OC)C1=CC=CC=C1 GOLCUCWJUAVPFU-WNJJXGMVSA-N 0.000 claims description 3
- OKFWVJWVRWHROD-DITALETJSA-N (3s)-3-[2-ethyl-2-[(2s)-1-[(2-methoxyphenyl)methyl-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]hydrazinyl]-4-(1h-indol-3-yl)butanoic acid Chemical compound O=C([C@H](CC=1C=C2C=CC=CC2=CC=1)N(N[C@H](CC(O)=O)CC=1C2=CC=CC=C2NC=1)CC)N(C)CC1=CC=CC=C1OC OKFWVJWVRWHROD-DITALETJSA-N 0.000 claims description 3
- 101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 claims description 3
- ZHQLDZYSABXVFS-VMPREFPWSA-N O=C([C@H](CC=1C=CC=CC=1)N(CCN[C@@H](CC(O)=O)C=1C=CC=CC=1)C(=O)OC(C)(C)C)N(C)CC1=CC=CC=C1 Chemical compound O=C([C@H](CC=1C=CC=CC=1)N(CCN[C@@H](CC(O)=O)C=1C=CC=CC=1)C(=O)OC(C)(C)C)N(C)CC1=CC=CC=C1 ZHQLDZYSABXVFS-VMPREFPWSA-N 0.000 claims description 3
- NIRCCCPMKJFGQK-NYDCQLBNSA-N (2s)-4-[2-[[(2s)-1-[benzyl(methyl)amino]-1-oxo-3-phenylpropan-2-yl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethylamino]-2-(1h-indol-3-yl)butanoic acid Chemical compound O=C([C@H](CC=1C=CC=CC=1)N(CCNCC[C@H](C(O)=O)C=1C2=CC=CC=C2NC=1)C(=O)OC(C)(C)C)N(C)CC1=CC=CC=C1 NIRCCCPMKJFGQK-NYDCQLBNSA-N 0.000 claims description 2
- WXRRAEXVYBIVRI-NYDCQLBNSA-N (3s)-4-(1h-indol-3-yl)-3-[2-[[(2s)-1-[(2-methoxyphenyl)methyl-methylamino]-1-oxo-3-phenylpropan-2-yl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethylamino]butanoic acid Chemical compound COC1=CC=CC=C1CN(C)C(=O)[C@@H](N(CCN[C@H](CC(O)=O)CC=1C2=CC=CC=C2NC=1)C(=O)OC(C)(C)C)CC1=CC=CC=C1 WXRRAEXVYBIVRI-NYDCQLBNSA-N 0.000 claims description 2
- QVHDOZFUPVJIHV-HKBQPEDESA-N tert-butyl n-[(2s)-1-[benzyl(methyl)amino]-1-oxo-3-phenylpropan-2-yl]-n-[2-[2-(1h-indol-3-yl)ethylamino]ethyl]carbamate Chemical compound O=C([C@H](CC=1C=CC=CC=1)N(CCNCCC=1C2=CC=CC=C2NC=1)C(=O)OC(C)(C)C)N(C)CC1=CC=CC=C1 QVHDOZFUPVJIHV-HKBQPEDESA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 6
- FQCXEAJDUNKKEN-UHSQPCAPSA-N (2r)-4-[2-[(2s)-1-[benzyl(methyl)amino]-1-oxo-3-phenylpropan-2-yl]-2-ethylhydrazinyl]-2-(1h-indol-3-yl)butanoic acid Chemical compound C([C@H](N(NCC[C@@H](C(O)=O)C=1C2=CC=CC=C2NC=1)CC)C(=O)N(C)CC=1C=CC=CC=1)C1=CC=CC=C1 FQCXEAJDUNKKEN-UHSQPCAPSA-N 0.000 claims 1
- FQCXEAJDUNKKEN-WNJJXGMVSA-N (2s)-4-[2-[(2s)-1-[benzyl(methyl)amino]-1-oxo-3-phenylpropan-2-yl]-2-ethylhydrazinyl]-2-(1h-indol-3-yl)butanoic acid Chemical compound C([C@H](N(NCC[C@H](C(O)=O)C=1C2=CC=CC=C2NC=1)CC)C(=O)N(C)CC=1C=CC=CC=1)C1=CC=CC=C1 FQCXEAJDUNKKEN-WNJJXGMVSA-N 0.000 claims 1
- OHWKJQPSLYOJMO-NDEPHWFRSA-N (2s)-n-benzyl-2-[ethyl-[2-(1h-indol-3-yl)ethylamino]amino]-n-methyl-3-phenylpropanamide Chemical compound C([C@H](N(NCCC=1C2=CC=CC=C2NC=1)CC)C(=O)N(C)CC=1C=CC=CC=1)C1=CC=CC=C1 OHWKJQPSLYOJMO-NDEPHWFRSA-N 0.000 claims 1
- RUVPMIZETKKHBD-JUKUECOXSA-N (3S)-3-[2-[[(2S)-1-[benzyl(methyl)amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethylamino]-4-(1H-indol-3-yl)butanoic acid Chemical compound C(C1=CC=CC=C1)N(C([C@H](CC1=CC2=CC=CC=C2C=C1)N(C(=O)OC(C)(C)C)CCN[C@@H](CC1=CNC2=CC=CC=C12)CC(=O)O)=O)C RUVPMIZETKKHBD-JUKUECOXSA-N 0.000 claims 1
- JNVYDCQXWIIJSK-JUKUECOXSA-N (3S)-4-(1H-indol-3-yl)-3-[2-[[(2S)-1-[(2-methoxyphenyl)methyl-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-[(2-methylpropan-2-yl)oxycarbonyl]amino]ethylamino]butanoic acid Chemical compound COC1=C(CN(C([C@H](CC2=CC3=CC=CC=C3C=C2)N(C(=O)OC(C)(C)C)CCN[C@@H](CC2=CNC3=CC=CC=C23)CC(=O)O)=O)C)C=CC=C1 JNVYDCQXWIIJSK-JUKUECOXSA-N 0.000 claims 1
- UMVFPRDGEDZGOE-SVBPBHIXSA-N (3s)-3-[2-[(2s)-1-[benzoyl(methyl)amino]-3-phenylpropan-2-yl]-2-ethylhydrazinyl]-4-(1h-indol-3-yl)butanoic acid Chemical compound C([C@@H](N(N[C@H](CC(O)=O)CC=1C2=CC=CC=C2NC=1)CC)CC=1C=CC=CC=1)N(C)C(=O)C1=CC=CC=C1 UMVFPRDGEDZGOE-SVBPBHIXSA-N 0.000 claims 1
- VYPDROYGSRRHPU-WNJJXGMVSA-N (3s)-3-[2-ethyl-2-[(2s)-1-[methyl-[(3,4,5-trimethoxyphenyl)methyl]amino]-1-oxo-3-phenylpropan-2-yl]hydrazinyl]-4-(1h-indol-3-yl)butanoic acid Chemical compound C([C@H](N(N[C@H](CC(O)=O)CC=1C2=CC=CC=C2NC=1)CC)C(=O)N(C)CC=1C=C(OC)C(OC)=C(OC)C=1)C1=CC=CC=C1 VYPDROYGSRRHPU-WNJJXGMVSA-N 0.000 claims 1
- 125000005806 3,4,5-trimethoxybenzyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1C([H])([H])* 0.000 claims 1
- NIRCCCPMKJFGQK-PPTMTGTBSA-N O=C([C@H](CC=1C=CC=CC=1)N(CCNCC[C@@H](C(O)=O)C=1C2=CC=CC=C2NC=1)C(=O)OC(C)(C)C)N(C)CC1=CC=CC=C1 Chemical compound O=C([C@H](CC=1C=CC=CC=1)N(CCNCC[C@@H](C(O)=O)C=1C2=CC=CC=C2NC=1)C(=O)OC(C)(C)C)N(C)CC1=CC=CC=C1 NIRCCCPMKJFGQK-PPTMTGTBSA-N 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 258
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 234
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 171
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 116
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 100
- 238000000034 method Methods 0.000 description 87
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 78
- 238000004587 chromatography analysis Methods 0.000 description 65
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 61
- 239000000741 silica gel Substances 0.000 description 60
- 229910002027 silica gel Inorganic materials 0.000 description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
- 239000011541 reaction mixture Substances 0.000 description 56
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 54
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 50
- 235000019341 magnesium sulphate Nutrition 0.000 description 50
- 239000000047 product Substances 0.000 description 49
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
- 239000000243 solution Substances 0.000 description 46
- 239000012467 final product Substances 0.000 description 45
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 43
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- 150000001299 aldehydes Chemical class 0.000 description 42
- 239000012074 organic phase Substances 0.000 description 42
- 238000003756 stirring Methods 0.000 description 42
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 40
- 238000004809 thin layer chromatography Methods 0.000 description 39
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 239000002904 solvent Substances 0.000 description 35
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 30
- 150000002009 diols Chemical class 0.000 description 30
- 239000000203 mixture Substances 0.000 description 30
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- 230000008020 evaporation Effects 0.000 description 29
- 238000000605 extraction Methods 0.000 description 28
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 26
- 238000000746 purification Methods 0.000 description 26
- 239000003153 chemical reaction reagent Substances 0.000 description 25
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- 150000001412 amines Chemical class 0.000 description 24
- 239000000543 intermediate Substances 0.000 description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
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- 239000002585 base Substances 0.000 description 21
- 229920006395 saturated elastomer Polymers 0.000 description 21
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 20
- 238000010511 deprotection reaction Methods 0.000 description 20
- OCAAZRFBJBEVPS-UHFFFAOYSA-N prop-2-enyl carbamate Chemical compound NC(=O)OCC=C OCAAZRFBJBEVPS-UHFFFAOYSA-N 0.000 description 20
- 230000015572 biosynthetic process Effects 0.000 description 19
- 238000003786 synthesis reaction Methods 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
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- 238000010992 reflux Methods 0.000 description 17
- 239000007858 starting material Substances 0.000 description 17
- 125000006325 2-propenyl amino group Chemical group [H]C([H])=C([H])C([H])([H])N([H])* 0.000 description 15
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 108010040722 Neurokinin-2 Receptors Proteins 0.000 description 14
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- 102100037342 Substance-K receptor Human genes 0.000 description 13
- 239000010410 layer Substances 0.000 description 13
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
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- 239000012298 atmosphere Substances 0.000 description 12
- ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 12
- 238000005755 formation reaction Methods 0.000 description 11
- XNFNGGQRDXFYMM-PPHPATTJSA-N methyl (2s)-2-amino-3-(1h-indol-3-yl)propanoate;hydrochloride Chemical compound Cl.C1=CC=C2C(C[C@H](N)C(=O)OC)=CNC2=C1 XNFNGGQRDXFYMM-PPHPATTJSA-N 0.000 description 11
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- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 1
- 235000019254 sodium formate Nutrition 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000011343 solid material Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000002462 tachykinin receptor antagonist Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- DTBYUTGECHQUIZ-PMCHYTPCSA-N tert-butyl N-[(2S)-1-[benzyl(methyl)amino]-1-oxo-3-phenylpropan-2-yl]-N-[2-(oxan-2-yloxy)ethyl]carbamate Chemical compound CN(Cc1ccccc1)C(=O)[C@H](Cc1ccccc1)N(CCOC1CCCCO1)C(=O)OC(C)(C)C DTBYUTGECHQUIZ-PMCHYTPCSA-N 0.000 description 1
- ZKCZEPYLGPKKHN-QHCPKHFHSA-N tert-butyl n-[(2s)-1-[(2-methoxyphenyl)methyl-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]carbamate Chemical compound COC1=CC=CC=C1CN(C)C(=O)[C@@H](NC(=O)OC(C)(C)C)CC1=CC=C(C=CC=C2)C2=C1 ZKCZEPYLGPKKHN-QHCPKHFHSA-N 0.000 description 1
- MJOGAKPXTBXIBT-QHCPKHFHSA-N tert-butyl n-[(2s)-1-[(3,4-dichlorophenyl)methyl-methylamino]-3-naphthalen-2-yl-1-oxopropan-2-yl]carbamate Chemical compound O=C([C@H](CC=1C=C2C=CC=CC2=CC=1)NC(=O)OC(C)(C)C)N(C)CC1=CC=C(Cl)C(Cl)=C1 MJOGAKPXTBXIBT-QHCPKHFHSA-N 0.000 description 1
- OXAOFVLCGAEKSK-NRFANRHFSA-N tert-butyl n-[(2s)-1-[benzyl(methyl)amino]-1-oxo-3-phenylpropan-2-yl]-n-(2-hydroxyethyl)carbamate Chemical compound O=C([C@H](CC=1C=CC=CC=1)N(CCO)C(=O)OC(C)(C)C)N(C)CC1=CC=CC=C1 OXAOFVLCGAEKSK-NRFANRHFSA-N 0.000 description 1
- ZRPMNXGORBDRFR-QFIPXVFZSA-N tert-butyl n-[(2s)-1-[benzyl(methyl)amino]-1-oxo-3-phenylpropan-2-yl]-n-(3-oxopropyl)carbamate Chemical compound O=C([C@H](CC=1C=CC=CC=1)N(CCC=O)C(=O)OC(C)(C)C)N(C)CC1=CC=CC=C1 ZRPMNXGORBDRFR-QFIPXVFZSA-N 0.000 description 1
- GWUTYIPUZSDWPQ-VWLOTQADSA-N tert-butyl n-[(2s)-1-[benzyl(methyl)amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]-n-(2-oxoethyl)carbamate Chemical compound O=C([C@H](CC=1C=C2C=CC=CC2=CC=1)N(CC=O)C(=O)OC(C)(C)C)N(C)CC1=CC=CC=C1 GWUTYIPUZSDWPQ-VWLOTQADSA-N 0.000 description 1
- WEBFEHZEJUFFNZ-NRFANRHFSA-N tert-butyl n-[(2s)-1-[methyl-[(3,4,5-trimethoxyphenyl)methyl]amino]-1-oxo-3-phenylpropan-2-yl]-n-(2-oxoethyl)carbamate Chemical compound COC1=C(OC)C(OC)=CC(CN(C)C(=O)[C@H](CC=2C=CC=CC=2)N(CC=O)C(=O)OC(C)(C)C)=C1 WEBFEHZEJUFFNZ-NRFANRHFSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000012049 topical pharmaceutical composition Substances 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 150000003628 tricarboxylic acids Chemical class 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000000264 venule Anatomy 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 235000012431 wafers Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- JPZXHKDZASGCLU-LBPRGKRZSA-N β-(2-naphthyl)-alanine Chemical compound C1=CC=CC2=CC(C[C@H](N)C(O)=O)=CC=C21 JPZXHKDZASGCLU-LBPRGKRZSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/64—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings
- C07C233/77—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
- C07C233/78—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/20—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/52—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the nitrogen atom of at least one of the carboxamide groups further acylated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/20—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals substituted additionally by nitrogen atoms, e.g. tryptophane
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Indole Compounds (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/262,209 US5597845A (en) | 1994-06-20 | 1994-06-20 | Substituted alkyldiamine derivatives |
| PCT/US1995/006317 WO1995035279A1 (en) | 1994-06-20 | 1995-05-19 | Substituted alkyldiamine derivatives and their use as tachykinin antagonists |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69504198D1 DE69504198D1 (de) | 1998-09-24 |
| DE69504198T2 true DE69504198T2 (de) | 1999-04-29 |
Family
ID=22996631
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69504198T Expired - Fee Related DE69504198T2 (de) | 1994-06-20 | 1995-05-19 | Substituierte alkyldiaminderivate und ihre verwendung als tachykinin antagonisten |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US5597845A (enExample) |
| EP (1) | EP0767783B1 (enExample) |
| JP (1) | JP3920916B2 (enExample) |
| KR (1) | KR100371981B1 (enExample) |
| CN (1) | CN1083429C (enExample) |
| AT (1) | ATE169905T1 (enExample) |
| AU (1) | AU691619B2 (enExample) |
| CA (1) | CA2193348C (enExample) |
| DE (1) | DE69504198T2 (enExample) |
| DK (1) | DK0767783T3 (enExample) |
| ES (1) | ES2121389T3 (enExample) |
| FI (1) | FI115135B (enExample) |
| HU (1) | HUT75965A (enExample) |
| IL (1) | IL114185A (enExample) |
| MX (1) | MX9606654A (enExample) |
| NO (1) | NO307458B1 (enExample) |
| NZ (1) | NZ287291A (enExample) |
| TW (1) | TW442451B (enExample) |
| WO (1) | WO1995035279A1 (enExample) |
| ZA (1) | ZA954947B (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW541295B (en) * | 1999-01-05 | 2003-07-11 | Nippon Zoki Pharmaceutical Co | A novel substituted alkylteraamine derivative for use as tachykinin antagonist |
| US6613801B2 (en) * | 2000-05-30 | 2003-09-02 | Transtech Pharma, Inc. | Method for the synthesis of compounds of formula I and their uses thereof |
| US7361678B2 (en) | 2002-03-05 | 2008-04-22 | Transtech Pharma, Inc. | Azole derivatives and fused bicyclic azole derivatives as therapeutic agents |
| WO2002070473A2 (en) | 2001-03-05 | 2002-09-12 | Transtech Pharma, Inc. | Carboxamide derivatives as therapeutic agents |
| EP1387680A4 (en) | 2001-03-05 | 2010-01-13 | Transtech Pharma Inc | AGENTS TH RAPEUTICES D RIV S BENZIMIDAZOLE BASE |
| US20090263370A1 (en) * | 2006-11-30 | 2009-10-22 | Guoliang Tao | Methods for treating tachykinin-mediated diseases with cholinesterase |
| JP5805646B2 (ja) | 2009-09-30 | 2015-11-04 | ブイティーブイ・セラピューティクス・エルエルシー | アルツハイマー病の治療のための置換イミダゾール誘導体 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5164372A (en) * | 1989-04-28 | 1992-11-17 | Fujisawa Pharmaceutical Company, Ltd. | Peptide compounds having substance p antagonism, processes for preparation thereof and pharmaceutical composition comprising the same |
| JPH06509087A (ja) * | 1991-07-05 | 1994-10-13 | メルク シヤープ エンド ドーム リミテツド | 芳香族化合物、それらを含む医薬組成物、及び治療におけるそれらの使用 |
| EP0655055B1 (en) * | 1992-08-13 | 2000-11-29 | Warner-Lambert Company | Tachykinin antagonists |
-
1994
- 1994-06-20 US US08/262,209 patent/US5597845A/en not_active Expired - Fee Related
-
1995
- 1995-05-19 AU AU25961/95A patent/AU691619B2/en not_active Ceased
- 1995-05-19 AT AT95920539T patent/ATE169905T1/de not_active IP Right Cessation
- 1995-05-19 CN CN95193680A patent/CN1083429C/zh not_active Expired - Fee Related
- 1995-05-19 HU HU9603540A patent/HUT75965A/hu not_active Application Discontinuation
- 1995-05-19 MX MX9606654A patent/MX9606654A/es not_active IP Right Cessation
- 1995-05-19 NZ NZ287291A patent/NZ287291A/xx unknown
- 1995-05-19 EP EP95920539A patent/EP0767783B1/en not_active Expired - Lifetime
- 1995-05-19 JP JP50217396A patent/JP3920916B2/ja not_active Expired - Fee Related
- 1995-05-19 ES ES95920539T patent/ES2121389T3/es not_active Expired - Lifetime
- 1995-05-19 CA CA002193348A patent/CA2193348C/en not_active Expired - Fee Related
- 1995-05-19 WO PCT/US1995/006317 patent/WO1995035279A1/en not_active Ceased
- 1995-05-19 KR KR1019960707303A patent/KR100371981B1/ko not_active Expired - Fee Related
- 1995-05-19 DK DK95920539T patent/DK0767783T3/da active
- 1995-05-19 DE DE69504198T patent/DE69504198T2/de not_active Expired - Fee Related
- 1995-06-14 ZA ZA954947A patent/ZA954947B/xx unknown
- 1995-06-15 TW TW084106131A patent/TW442451B/zh not_active IP Right Cessation
- 1995-06-16 IL IL11418595A patent/IL114185A/xx not_active IP Right Cessation
-
1996
- 1996-12-18 FI FI965097A patent/FI115135B/fi not_active IP Right Cessation
- 1996-12-19 NO NO965469A patent/NO307458B1/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| DE69504198D1 (de) | 1998-09-24 |
| TW442451B (en) | 2001-06-23 |
| CA2193348C (en) | 1999-08-24 |
| EP0767783A1 (en) | 1997-04-16 |
| FI965097L (fi) | 1996-12-18 |
| NO965469L (no) | 1997-02-19 |
| ZA954947B (en) | 1996-01-31 |
| KR100371981B1 (ko) | 2003-06-12 |
| NO307458B1 (no) | 2000-04-10 |
| IL114185A0 (enExample) | 1995-10-31 |
| ES2121389T3 (es) | 1998-11-16 |
| JP3920916B2 (ja) | 2007-05-30 |
| EP0767783B1 (en) | 1998-08-19 |
| CN1083429C (zh) | 2002-04-24 |
| WO1995035279A1 (en) | 1995-12-28 |
| US5597845A (en) | 1997-01-28 |
| HU9603540D0 (en) | 1997-02-28 |
| FI115135B (fi) | 2005-03-15 |
| NO965469D0 (no) | 1996-12-19 |
| FI965097A0 (fi) | 1996-12-18 |
| JPH10501551A (ja) | 1998-02-10 |
| ATE169905T1 (de) | 1998-09-15 |
| AU2596195A (en) | 1996-01-15 |
| HUT75965A (en) | 1997-05-28 |
| DK0767783T3 (da) | 1999-05-25 |
| NZ287291A (en) | 1998-10-28 |
| IL114185A (en) | 1999-07-14 |
| MX9606654A (es) | 1997-12-31 |
| CA2193348A1 (en) | 1995-12-28 |
| AU691619B2 (en) | 1998-05-21 |
| CN1155883A (zh) | 1997-07-30 |
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|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8327 | Change in the person/name/address of the patent owner |
Owner name: AVENTIS INC. (N.D.GES.D. STAATES PENNSYLVANIA), GR |
|
| 8339 | Ceased/non-payment of the annual fee |