JP2010502606A - カルシウムチャンネル遮断薬としてのインドロキノリン化合物 - Google Patents
カルシウムチャンネル遮断薬としてのインドロキノリン化合物 Download PDFInfo
- Publication number
- JP2010502606A JP2010502606A JP2009526607A JP2009526607A JP2010502606A JP 2010502606 A JP2010502606 A JP 2010502606A JP 2009526607 A JP2009526607 A JP 2009526607A JP 2009526607 A JP2009526607 A JP 2009526607A JP 2010502606 A JP2010502606 A JP 2010502606A
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- JP
- Japan
- Prior art keywords
- tetrahydroindolo
- quinolin
- group
- trimethyl
- lower alkyl
- 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.)
- Pending
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- 229940127291 Calcium channel antagonist Drugs 0.000 title abstract description 30
- 239000000480 calcium channel blocker Substances 0.000 title abstract description 26
- MZXDPTWGJXNUMW-UHFFFAOYSA-N 7h-pyrido[3,2-c]carbazole Chemical class C1=CC=NC2=C3C4=CC=CC=C4NC3=CC=C21 MZXDPTWGJXNUMW-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 93
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- 102000003922 Calcium Channels Human genes 0.000 claims abstract description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 48
- -1 tetrafluoroborate Chemical compound 0.000 claims description 31
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 17
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- QHFWYXXAYQEDCO-UHFFFAOYSA-N 10-fluoro-3,3,6-trimethyl-4,7-dihydro-2h-indolo[2,3-c]quinolin-1-one Chemical compound C12=CC(F)=CC=C2NC2=C1C(C(=O)CC(C)(C)C1)=C1N=C2C QHFWYXXAYQEDCO-UHFFFAOYSA-N 0.000 claims description 5
- WWSUIJPRKWPKDL-UHFFFAOYSA-N 10-methoxy-3,3-dimethyl-4,7-dihydro-2h-indolo[2,3-c]quinolin-1-one Chemical compound C1C(C)(C)CC(=O)C2=C(C=3C(=CC=C(C=3)OC)N3)C3=CN=C21 WWSUIJPRKWPKDL-UHFFFAOYSA-N 0.000 claims description 5
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- DVKIWQCKLANAGR-UHFFFAOYSA-N 2,3,4,7-tetrahydroindolo[2,3-c]quinolin-1-one Chemical class C1=CC=C2C3=C4C(=O)CCCC4=NC=C3NC2=C1 DVKIWQCKLANAGR-UHFFFAOYSA-N 0.000 claims description 4
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- OGITWMCELVAMET-UHFFFAOYSA-N 9-chloro-3,3,6-trimethyl-4,7-dihydro-2h-indolo[2,3-c]quinolin-1-one Chemical compound C12=CC=C(Cl)C=C2NC2=C1C(C(=O)CC(C)(C)C1)=C1N=C2C OGITWMCELVAMET-UHFFFAOYSA-N 0.000 claims description 4
- ZDJDKZMJTJMYFL-UHFFFAOYSA-N 9-fluoro-3,3-dimethyl-4,7-dihydro-2h-indolo[2,3-c]quinolin-1-one Chemical compound N1C2=CC(F)=CC=C2C2=C1C=NC1=C2C(=O)CC(C)(C)C1 ZDJDKZMJTJMYFL-UHFFFAOYSA-N 0.000 claims description 4
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- SVGKIVDCRYSXIV-UHFFFAOYSA-N N-(3,3,6-trimethyl-4,7-dihydro-2H-indolo[2,3-c]quinolin-1-ylidene)hydroxylamine Chemical compound C12=CC=CC=C2NC2=C1C(C(=NO)CC(C)(C)C1)=C1N=C2C SVGKIVDCRYSXIV-UHFFFAOYSA-N 0.000 claims description 4
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- KPNUHXSBIPHPLV-UHFFFAOYSA-N 3,3-dimethyl-1,2,4,7-tetrahydroindolo[2,3-c]quinoline Chemical compound N1C2=CC=CC=C2C2=C1C=NC1=C2CCC(C)(C)C1 KPNUHXSBIPHPLV-UHFFFAOYSA-N 0.000 claims description 3
- UZVVRCOBTVFFGE-UHFFFAOYSA-N 3,3-dimethyl-6-propan-2-yl-4,7-dihydro-2h-indolo[2,3-c]quinolin-1-one Chemical compound C12=CC=CC=C2NC2=C1C(C(=O)CC(C)(C)C1)=C1N=C2C(C)C UZVVRCOBTVFFGE-UHFFFAOYSA-N 0.000 claims description 3
- ZZLJCXPQRULBAZ-UHFFFAOYSA-N 7-ethyl-3,3,6-trimethyl-2,4-dihydroindolo[2,3-c]quinolin-1-one Chemical compound O=C1CC(C)(C)CC2=NC(C)=C3N(CC)C4=CC=CC=C4C3=C21 ZZLJCXPQRULBAZ-UHFFFAOYSA-N 0.000 claims description 3
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- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical group CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- ZHNFLHYOFXQIOW-LPYZJUEESA-N quinine sulfate dihydrate Chemical compound [H+].[H+].O.O.[O-]S([O-])(=O)=O.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 ZHNFLHYOFXQIOW-LPYZJUEESA-N 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000002336 repolarization Effects 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 230000003248 secreting effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000018448 secretion by cell Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000003625 skull Anatomy 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 206010041823 squamous cell carcinoma Diseases 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 230000025033 vasoconstriction Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000012178 vegetable wax Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- A61K31/33—Heterocyclic compounds
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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Abstract
Description
9−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
10−メトキシ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
11−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
6−メチル−3‘H−スピロシクロへキサン−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンとがある。
9−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
10−メトキシ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
11−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
6−メチル−3‘H−スピロシクロヘキサン−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
10−クロロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
6−エチル−3,3−ジメチル−2,3,4,7−テトラヒドロ−インドロ[2,3−c]キノリン−1−オンとがある。
3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
9−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
10−メトキシ−3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
10−メトキシ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
3−イソプロピル−6−メチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
6−メチル−3‘H−スピロシクロヘキサン−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
10−クロロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
9,10−ジフルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
6−エチル−3,3−ジメチル−2,3,4,7−テトラヒドロ−インドロ[2,3−c]キノリン−1−オンと、
10−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
3,3,6−トリメチル−2,3,4,7−テトラヒドロ−1H−インドロ[2,3−c]キノリンとがある。
3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリンと、
9−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
9−フルオロ−3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
10−メトキシ−3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
10−メトキシ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
9−クロロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
9−メトキシ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
11−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
3,6−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
3−イソプロピル−6−メチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
6−メチル−3‘H−スピロシクロヘキサン−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
10−クロロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
6−メチル−3−フェニル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンオキシムと、
3,6−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンオキシムと、
9,10−ジフルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
6−エチル−3,3−ジメチル−2,3,4,7−テトラヒドロ−インドロ[2,3−c]キノリン−1−オンと、
10−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
3,3,6−トリメチル−2,3,4,7−テトラヒドロ−1H−インドロ[2,3−c]キノリンと、
7−N−エチル−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンとがある。
3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリンと、
9−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
9−フルオロ−3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
10−メトキシ−3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
10−メトキシ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
9−クロロ−3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
9−クロロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
9−メトキシ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
11−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
3,6−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
3−イソプロピル−6−メチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
6−メチル−3‘H−スピロシクロヘキサン−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
10−クロロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
6−メチル−3−フェニル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンオキシムと、
3,6−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンオキシムと、
9,10−ジフルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
6−エチル−3,3−ジメチル−2,3,4,7−テトラヒドロ−インドロ[2,3−c]キノリン−1−オンと、
6−イソプロピル−3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
10−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
3,3,6−トリメチル−2,3,4,7−テトラヒドロ−1H−インドロ[2,3−c]キノリンと、
7−N−エチル−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンと、
7−N−プロピル−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンとがある。
3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリンの製造
9−フルオロ−3,3,6−トリメチルー2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
a)2−(6−フルオロ−1H−インド−ル−3−イル)−5,5−ジメチルシクロヘキサン−1,3−ジノン
3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
9−フルオロ−3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
10−メトキシ−3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
10−メトキシ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
9−クロロ−3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
9−クロロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
9−メトキシ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
11−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
3,6−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
3−イソプロピル−6−メチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
6−メチル−3‘H−スピロシクロヘキサン−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
10−クロロ−3,6,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
6−メチル−3−フェニル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
工程3aで2−(1H−インドール−3−イル)−5−フェニル−シクロヘキサン−1,3−ジオンを2−(6−フルオロ−1H−インド−ル−3−イル)−5,5−ジメチルシクロヘキサン−1,3−ジオンに置換し、実施例1の工程1eで5−フェニルシクロヘキサン−1,3−ジオンを5,5−ジメチルシクロヘキサン−1,3−ジオンに置換する以外、実施例3a〜cに記述した手順を用いて、上掲の化合物を製造し、トルエンから結晶化した。融点246〜248℃
3,6−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンオキシムの製造
9,10−ジフルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
工程3aで2−(5,6−ジフルオロ−1H−インド−ル−3−イル)−5,5−ジメチル−シクロヘキサン−1,3−ジオンを2−(6−フルオロ−1H−インド−ル−3−イル)−5,5−ジメチルシクロヘキサン−1,3−ジオンに置換し、実施例1の工程1aで2−アミノ−4,5−ジフルオロ安息香酸をアントラニル酸に置換する以外、実施例3a〜cに記述した手順を用いて、上掲の化合物を製造し、トルエンから結晶化した。融点260〜262℃
6−エチル−3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
6−イソプロピル−3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
10−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
3,3,6−トリメチル−2,3,4,7−テトラヒドロ−1H−インドロ[2,3−c]キノリンの製造
7−N−エチル−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
7−N−プロピル−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造
(I)カルシウムチャンネル、タイプL(ジヒドロピリジン部位)[ 3 H]ニトレンジピン放射性リガンド結合検定法
(II)カルシウムチャンネル、タイプL(ベンゾチアゼピン部位)[ 3 H]ジルチアゼム放射性リガンド結合検定法
(III)GABA A 、塩素チャンネル(tert-ブチルビシクロオルト安息香酸エステル(TBOB)部位)[ 3 H]TBOB放射性リガンド結合検定法
Claims (20)
- 下記の構造式(I)で表わされた化学式:
R2およびR3は、それぞれ独立してH、低級アルキル基、シクロalk基、アリール基、アリールアルキル基の一つから選択されるか、又はR2およびR3が一緒に(CH2)n−で、nが6,5もしくは4であるか、またはR2およびR3が一緒にCH(低級アルキル)(CH2)n−で、nが5,4もしくは3であり、
R4およびR5は、それぞれ独立してH,NH2,OHもしくは低級alk基の一つから選択されるか、またはR4およびR5が一緒にO,SもしくはNOHであり、
R6,R7,R8およびR9は、それぞれ独立してH、ハロゲン、CN,CF3,OCF3,低級アルキル基、シクロalk基,低級アルコキシ基,NH−低級アルキル基、NH−アルキルアリール基、N(低級アルキル)2,C(O)OH,C(O)O−低級アルキル基、OH、OC(O)−低級アルキル基からなる群から選択され、
R10は、H、低級アルキル基、シクロalk基、アリールアルキル基、アリール基の一つである。)を有する化合物、又はその薬学的に許容し得る塩、水和物、互変異性体、溶媒和物および複合体。 - 構造式IにおけるR1が水素または低級アルキル基である請求項1に記載の化合物。
- 前記低級アルキル基がメチル基またはエチル基である請求項2に記載の化合物。
- 構造式IにおけるR2およびR3が、それぞれ独立して水素、低級アルキル基またはアリール基の一つから選択される請求項1に記載の化合物。
- 前記低級アルキル基がメチル基又はイソプロピル基である請求項4に記載の化合物。
- 前記アリール基がフェニル基である請求項4に記載の化合物。
- 構造式IにおけるR2およびR3が一緒に(CH2)n−であり、nが5である請求項1に記載の化合物。
- 構造式IにおけるR4およびR5がそれぞれ水素である請求項1に記載の化合物。
- 構造式IにおけるR4およびR5が一緒に酸素またはNOHである請求項1に記載の化合物。
- 構造式(I)におけるR6,R7,R8,およびR9が、それぞれ独立して水素、ハロゲンまたは低級アルコキシ基から選択される請求項1に記載の化合物。
- 前記ハロゲンがフッ素または塩素である請求項10に記載の化合物。
- 前記低級アルコキシ基がメトキシ基である請求項10に記載の化合物。
- 構造式IにおけるR10が水素または低級アルキル基である請求項1に記載の化合物。
- 前記低級アルキル基がエチル基およびプロピル基のうち一つである請求項13に記載の化合物。
- 前記構造式Iによって表される化合物が3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン、9−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、9−フルオロ−3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、10−メトキシ−3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、10−メトキシ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、9−クロロ−3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、9−クロロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、9−メトキシ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、11−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、3,6−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、3−イソプロピル−6−メチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、6−メチル−3‘H−スピロシクロヘキサン−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、10−クロロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、6−メチル−3−フェニル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンオキシム、3,6−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンオキシム、9,10−ジフルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、6−エチル−3,3−ジメチル−2,3,4,7−テトラヒドロ−インドロ[2,3−c]キノリン−1−オン、6−イソプロピル−3,3−ジメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、10−フルオロ−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オン、3,3,6−トリメチル−2,3,4,7−テトラヒドロ−1H−インドロ[2,3−c]キノリン、7−N−エチル−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンおよび7−N−プロピル−3,3,6−トリメチル−2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの少なくとも一つである請求項1に記載の化合物。
- 請求項1に記載の構造式(I)によって表される化合物と、薬学的に許容し得る希釈剤もしくは賦形剤とを備える医薬組成物。
- 置換1−オキソ−2,3,4,7−テトラヒドロ−1H−5−オキソニア−7−アザベンゾ[c]フルオレン過塩素酸塩、ジヒドロリン酸塩またはテトラフルオロホウ酸塩を水酸化アンモニウムまたは酢酸アンモニウムと反応させることを備える置換2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造方法。
- 請求項17に記載の置換2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンをヒドラジン水和物と反応させることを備える置換2,3,4,7−テトラヒドロインドロ[2,3−c]キノリン−1−オンの製造方法。
- カルシウムチャンネルによって媒介された中枢神経系病気または疾患を治療するに当たり、その治療が必要な対象に請求項1に記載の構造式Iによって表される化合物の有効量を投与することを備える治療方法。
- 前記中枢神経系疾患が、脳卒中、頭部外傷、脊髄損傷、外傷性ショック、アルツハイマー病、パーキンソン病、ハンチントン病、筋萎縮側索硬化症、てんかん、発作、痙攣性疾患、低酸素誘因神経細胞損傷、疼痛、うつ病、不安神経症、パニック障害、脅迫神経症、外傷後ストレス障害、麻酔後認識衰退、オピオイド耐性、薬物乱用、アルコール依存症および統合失調症の少なくとも一つである請求項19に記載の方法。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5767129A (en) * | 1995-08-24 | 1998-06-16 | Warner-Lambert Company | Substituted quinolines and isoquinolines as calcium channel blockers, their preparation and the use thereof |
Non-Patent Citations (13)
Title |
---|
JPN5009016600; KOMISSAROV,I.V.: KHIMIKO-FARMATSEVTICHESKII ZHURNAL Vol.19, No.3, 198503, P.187 * |
JPN5009016601; KOMISSAROV,I.V.: KHIMIKO-FARMATSEVTICHESKII ZHURNAL Vol.23,No.6, 1989, p.471 * |
JPN6012066270; REGISTRY(STN)[online] , 20060313 * |
JPN6012066271; J.Org.Chem. Vol.40, No.17, 1975, p.2525-2529 * |
JPN6012066272; CHEMISTRY OF HETEROCYCLIC COMPOUNDS Vol.40, No.7, 2004, p.962-963 * |
JPN6012066273; PHARMACEUTICAL CHEMISTRY JOURNAL Vol.25, No.3, 1991, p.193-196 * |
JPN6012066274; CHEMISTRY OF HETEROCYCLIC COMPOUNDS Vol.21, No.3, 1985, p.302-305 * |
JPN6012066275; Khim Geterotsikl Soedin No.8, 1995, p.1124-1130 * |
JPN6012066276; REGISTRY(STN)[online] , 19910823 * |
JPN6012066277; REGISTRY(STN)[online] , 19850922 * |
JPN6012066278; REGISTRY(STN)[online] , 19850609 * |
JPN6012066279; REGISTRY(STN)[online] , 19850609 * |
JPN6012066280; REGISTRY(STN)[online] , 19841116 * |
Also Published As
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WO2008027182A2 (en) | 2008-03-06 |
AU2007290758A2 (en) | 2009-06-04 |
US20080051426A1 (en) | 2008-02-28 |
EP2063891A2 (en) | 2009-06-03 |
US7820691B2 (en) | 2010-10-26 |
WO2008027182A3 (en) | 2008-10-16 |
EP2063891A4 (en) | 2010-12-15 |
CA2662185A1 (en) | 2008-03-06 |
KR20090043007A (ko) | 2009-05-04 |
AU2007290758A1 (en) | 2008-03-06 |
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