IE56201B1 - Substituted 1-pyridyloxy-3-indolylalkylamino-2-propanols,preparation and use thereof - Google Patents

Substituted 1-pyridyloxy-3-indolylalkylamino-2-propanols,preparation and use thereof

Info

Publication number: IE56201B1
Authority: IE; Ireland
Prior art keywords: compound; hydrogen; alkyl; formula; hydroxy
Prior art date: 1982-09-03

Application number

IE2063/83A

Other languages

English (en)

Other versions

IE832063L (en

Original Assignee

Bristol Myers Squibb Co

Priority date (The priority date 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 date listed.)

1982-09-03

Filing date

1983-09-02

Publication date

1991-05-22

1983-09-02 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

1983-09-02 Priority to IE654/87A priority Critical patent/IE56202B1/en

1984-03-03 Publication of IE832063L publication Critical patent/IE832063L/en

1991-05-22 Publication of IE56201B1 publication Critical patent/IE56201B1/en

Links

238000002360 preparation method Methods 0.000 title description 10
150000001875 compounds Chemical class 0.000 claims abstract description 56
JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 21
230000008878 coupling Effects 0.000 claims abstract description 8
238000010168 coupling process Methods 0.000 claims abstract description 8
238000005859 coupling reaction Methods 0.000 claims abstract description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 8
125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 5
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims abstract description 5
150000003222 pyridines Chemical class 0.000 claims abstract description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 34
238000000034 method Methods 0.000 claims description 33
239000001257 hydrogen Substances 0.000 claims description 30
125000000217 alkyl group Chemical group 0.000 claims description 28
238000006243 chemical reaction Methods 0.000 claims description 25
239000000047 product Substances 0.000 claims description 24
150000003839 salts Chemical class 0.000 claims description 24
239000002253 acid Substances 0.000 claims description 22
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
229910052736 halogen Inorganic materials 0.000 claims description 17
150000002367 halogens Chemical class 0.000 claims description 17
239000000203 mixture Substances 0.000 claims description 17
230000008569 process Effects 0.000 claims description 16
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 13
125000003118 aryl group Chemical group 0.000 claims description 11
125000003545 alkoxy group Chemical group 0.000 claims description 10
239000002585 base Substances 0.000 claims description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
206010020772 Hypertension Diseases 0.000 claims description 8
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 8
150000002431 hydrogen Chemical class 0.000 claims description 8
230000007062 hydrolysis Effects 0.000 claims description 8
238000006460 hydrolysis reaction Methods 0.000 claims description 8
231100000252 nontoxic Toxicity 0.000 claims description 8
230000003000 nontoxic effect Effects 0.000 claims description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
125000003710 aryl alkyl group Chemical group 0.000 claims description 6
125000001041 indolyl group Chemical group 0.000 claims description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 6
230000000304 vasodilatating effect Effects 0.000 claims description 6
HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 claims description 5
238000010438 heat treatment Methods 0.000 claims description 5
239000007788 liquid Substances 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 4
230000002378 acidificating effect Effects 0.000 claims description 4
230000003276 anti-hypertensive effect Effects 0.000 claims description 4
239000000625 cyclamic acid and its Na and Ca salt Substances 0.000 claims description 4
239000012458 free base Substances 0.000 claims description 4
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 4
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 4
239000002244 precipitate Substances 0.000 claims description 4
125000003107 substituted aryl group Chemical group 0.000 claims description 4
239000004593 Epoxy Substances 0.000 claims description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 3
125000004423 acyloxy group Chemical group 0.000 claims description 3
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 3
125000004104 aryloxy group Chemical group 0.000 claims description 3
239000002243 precursor Substances 0.000 claims description 3
230000001225 therapeutic effect Effects 0.000 claims description 3
125000003368 amide group Chemical group 0.000 claims description 2
150000001412 amines Chemical class 0.000 claims description 2
125000005605 benzo group Chemical group 0.000 claims description 2
230000037396 body weight Effects 0.000 claims description 2
238000001704 evaporation Methods 0.000 claims description 2
229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
239000011707 mineral Substances 0.000 claims description 2
238000006386 neutralization reaction Methods 0.000 claims description 2
239000003960 organic solvent Substances 0.000 claims description 2
238000007910 systemic administration Methods 0.000 claims description 2
FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims 3
206010047141 Vasodilatation Diseases 0.000 claims 2
230000024883 vasodilation Effects 0.000 claims 2
PLNKBMZCVFBVSU-UHFFFAOYSA-N 2-[2-hydroxy-3-[[1-(1H-indol-3-yl)-2-methylpropan-2-yl]amino]propoxy]pyridine-3-carbonitrile Chemical compound OC(COC1=NC=CC=C1C#N)CNC(CC1=CNC2=CC=CC=C12)(C)C PLNKBMZCVFBVSU-UHFFFAOYSA-N 0.000 claims 1
BLXXOSYJVJJZMC-UHFFFAOYSA-N 2-[2-hydroxy-3-[[1-(1H-indol-3-yl)-2-methylpropan-2-yl]amino]propoxy]pyridine-3-carboxamide Chemical compound OC(COC1=NC=CC=C1C(=O)N)CNC(CC1=CNC2=CC=CC=C12)(C)C BLXXOSYJVJJZMC-UHFFFAOYSA-N 0.000 claims 1
239000003937 drug carrier Substances 0.000 claims 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
-1 hydroxyl-substituted propanol Chemical class 0.000 abstract description 19
239000003071 vasodilator agent Substances 0.000 abstract description 6
102000012740 beta Adrenergic Receptors Human genes 0.000 abstract description 5
108010079452 beta Adrenergic Receptors Proteins 0.000 abstract description 5
230000000903 blocking effect Effects 0.000 abstract description 5
230000000694 effects Effects 0.000 abstract description 5
230000008570 general process Effects 0.000 abstract description 5
229940124549 vasodilator Drugs 0.000 abstract description 5
150000001408 amides Chemical class 0.000 abstract description 2
239000002327 cardiovascular agent Substances 0.000 abstract 1
229940125692 cardiovascular agent Drugs 0.000 abstract 1
IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 20
239000000543 intermediate Substances 0.000 description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
239000007787 solid Substances 0.000 description 13
239000000243 solution Substances 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
235000019439 ethyl acetate Nutrition 0.000 description 10
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
238000001953 recrystallisation Methods 0.000 description 7
238000012360 testing method Methods 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
238000005481 NMR spectroscopy Methods 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
239000000463 material Substances 0.000 description 6
239000012299 nitrogen atmosphere Substances 0.000 description 6
IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 6
AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 6
238000010992 reflux Methods 0.000 description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
239000002220 antihypertensive agent Substances 0.000 description 5
229940030600 antihypertensive agent Drugs 0.000 description 5
230000036772 blood pressure Effects 0.000 description 5
238000001816 cooling Methods 0.000 description 5
239000012312 sodium hydride Substances 0.000 description 5
229910000104 sodium hydride Inorganic materials 0.000 description 5
238000003756 stirring Methods 0.000 description 5
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
239000003814 drug Substances 0.000 description 4
230000000144 pharmacologic effect Effects 0.000 description 4
239000000725 suspension Substances 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 3
XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 3
KVTGTAZVDSYIPY-NSHDSACASA-N 2-[(2s)-3-(tert-butylamino)-2-hydroxypropoxy]pyridine-3-carbonitrile Chemical compound CC(C)(C)NC[C@H](O)COC1=NC=CC=C1C#N KVTGTAZVDSYIPY-NSHDSACASA-N 0.000 description 3
FBMYKMYQHCBIGU-UHFFFAOYSA-N 2-[2-hydroxy-3-[[1-(1h-indol-3-yl)-2-methylpropan-2-yl]amino]propoxy]benzonitrile Chemical compound C=1NC2=CC=CC=C2C=1CC(C)(C)NCC(O)COC1=CC=CC=C1C#N FBMYKMYQHCBIGU-UHFFFAOYSA-N 0.000 description 3
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
241000282472 Canis lupus familiaris Species 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
241000700159 Rattus Species 0.000 description 3
230000009471 action Effects 0.000 description 3
239000004480 active ingredient Substances 0.000 description 3
239000000908 ammonium hydroxide Substances 0.000 description 3
239000007900 aqueous suspension Substances 0.000 description 3
239000002876 beta blocker Substances 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
230000001631 hypertensive effect Effects 0.000 description 3
229940039009 isoproterenol Drugs 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
229960003712 propranolol Drugs 0.000 description 3
239000000377 silicon dioxide Substances 0.000 description 3
230000003595 spectral effect Effects 0.000 description 3
MGXIQKFKOYJROW-UHFFFAOYSA-N 1-(6-methoxy-1h-indol-3-yl)-n,n-dimethylmethanamine Chemical compound COC1=CC=C2C(CN(C)C)=CNC2=C1 MGXIQKFKOYJROW-UHFFFAOYSA-N 0.000 description 2
DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 2
FGLBSLMDCBOPQK-UHFFFAOYSA-N 2-nitropropane Chemical compound CC(C)[N+]([O-])=O FGLBSLMDCBOPQK-UHFFFAOYSA-N 0.000 description 2
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
208000003098 Ganglion Cysts Diseases 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 2
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
208000005400 Synovial Cyst Diseases 0.000 description 2
238000010521 absorption reaction Methods 0.000 description 2
229940030611 beta-adrenergic blocking agent Drugs 0.000 description 2
ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
230000007423 decrease Effects 0.000 description 2
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
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230000002526 effect on cardiovascular system Effects 0.000 description 2
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125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
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238000001914 filtration Methods 0.000 description 2
150000005748 halopyridines Chemical class 0.000 description 2
BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 2
238000011552 rat model Methods 0.000 description 2
239000000376 reactant Substances 0.000 description 2
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FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
239000000080 wetting agent Substances 0.000 description 2
LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
IHWDSEPNZDYMNF-UHFFFAOYSA-N 1H-indol-2-amine Chemical compound C1=CC=C2NC(N)=CC2=C1 IHWDSEPNZDYMNF-UHFFFAOYSA-N 0.000 description 1
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IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
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239000000741 silica gel Substances 0.000 description 1
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239000011734 sodium Substances 0.000 description 1
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235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
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239000011780 sodium chloride Substances 0.000 description 1
229960001462 sodium cyclamate Drugs 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
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239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
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239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
231100000378 teratogenic Toxicity 0.000 description 1
230000003390 teratogenic effect Effects 0.000 description 1
231100000211 teratogenicity Toxicity 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
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QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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JUKPJGZUFHCZQI-UHFFFAOYSA-N undecanoyl chloride Chemical compound CCCCCCCCCCC(Cl)=O JUKPJGZUFHCZQI-UHFFFAOYSA-N 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—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
- C07D401/02—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 two hetero rings
- C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
- 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
- C07D209/14—Radicals substituted by nitrogen atoms, not forming part of a nitro radical
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (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)
Public Health (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

IE2063/83A 1982-09-03 1983-09-02 Substituted 1-pyridyloxy-3-indolylalkylamino-2-propanols,preparation and use thereof IE56201B1 (en)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
IE654/87A IE56202B1 (en)	1982-09-03	1983-09-02	Intermediates for syntheses of indole derivatives

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US41474882A	1982-09-03	1982-09-03

Publications (2)

Publication Number	Publication Date
IE832063L IE832063L (en)	1984-03-03
IE56201B1 true IE56201B1 (en)	1991-05-22

Family

ID=23642783

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IE2063/83A IE56201B1 (en)	1982-09-03	1983-09-02	Substituted 1-pyridyloxy-3-indolylalkylamino-2-propanols,preparation and use thereof

Country Status (28)

Country	Link
JP (1)	JPS5965087A (de)
KR (1)	KR870001019B1 (de)
AT (1)	AT387385B (de)
AU (4)	AU567112B2 (de)
BE (1)	BE897671A (de)
CA (1)	CA1236834A (de)
CH (2)	CH668593A5 (de)
CY (1)	CY1521A (de)
DE (1)	DE3331612A1 (de)
DK (1)	DK399783A (de)
ES (4)	ES525243A0 (de)
FI (1)	FI79709C (de)
FR (1)	FR2543952B1 (de)
GB (1)	GB2126230B (de)
GR (1)	GR79061B (de)
HK (1)	HK17490A (de)
HU (2)	HU194164B (de)
IE (1)	IE56201B1 (de)
IL (1)	IL69618A (de)
IT (1)	IT1169459B (de)
LU (1)	LU84986A1 (de)
NL (1)	NL8303038A (de)
NO (1)	NO161258C (de)
NZ (1)	NZ205466A (de)
PT (1)	PT77282B (de)
SE (2)	SE460419B (de)
YU (2)	YU45150B (de)
ZA (1)	ZA836469B (de)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2543952B1 (fr) *	1982-09-03	1986-02-21	Bristol Myers Co	Composes hydrocarbones heterocycliques appartenant aux series indoliques et leur application pharmacologique
DE3721260A1 (de) *	1987-06-27	1989-01-12	Beiersdorf Ag	Neue indolylpropanole, verfahren zu ihrer herstellung und ihre verwendung sowie die verbindungen enthaltende zubereitungen
US5030640A (en) *	1989-01-05	1991-07-09	Merck & Co., Inc.	Novel β-adrenergic agonists and pharmaceutical compositions thereof
BR0114884A (pt) *	2000-10-25	2004-07-06	Smithkline Beecham Corp	Compostos calcilìticos
KR100457857B1 (ko) *	2002-05-23	2004-11-18	(주) 비엔씨바이오팜	2-[2-(3-인돌릴)에틸아미노]피리딘 유도체, 그 제조방법및 이를 포함하는 항바이러스용 약학적 조성물

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4144343A (en) *	1978-01-04	1979-03-13	Merck & Co., Inc.	Heterocycle substituted (3-loweralkylamino-2-R1 O-propoxy)pyridines
FR2463765A1 (fr) *	1979-08-17	1981-02-27	Clin Midy	Nouveaux derives de l'indole actifs sur le systeme cardiovasculaire
FR2543952B1 (fr) *	1982-09-03	1986-02-21	Bristol Myers Co	Composes hydrocarbones heterocycliques appartenant aux series indoliques et leur application pharmacologique
CA1241660A (en) *	1984-06-25	1988-09-06	Yvan Guindon	Indole-2-alkanoic acids

1983
- 1983-08-26 FR FR8313793A patent/FR2543952B1/fr not_active Expired
- 1983-08-30 GR GR72336A patent/GR79061B/el unknown
- 1983-08-30 ES ES525243A patent/ES525243A0/es active Granted
- 1983-08-31 NL NL8303038A patent/NL8303038A/nl not_active Application Discontinuation
- 1983-08-31 AU AU18592/83A patent/AU567112B2/en not_active Ceased
- 1983-08-31 FI FI833102A patent/FI79709C/fi not_active IP Right Cessation
- 1983-08-31 ZA ZA836469A patent/ZA836469B/xx unknown
- 1983-09-01 IL IL69618A patent/IL69618A/xx unknown
- 1983-09-01 NO NO833128A patent/NO161258C/no unknown
- 1983-09-01 PT PT77282A patent/PT77282B/pt not_active IP Right Cessation
- 1983-09-01 DE DE19833331612 patent/DE3331612A1/de not_active Withdrawn
- 1983-09-01 DK DK399783A patent/DK399783A/da not_active Application Discontinuation
- 1983-09-01 CA CA000435880A patent/CA1236834A/en not_active Expired
- 1983-09-02 IT IT22765/83A patent/IT1169459B/it active
- 1983-09-02 HU HU864311A patent/HU194164B/hu not_active IP Right Cessation
- 1983-09-02 IE IE2063/83A patent/IE56201B1/en unknown
- 1983-09-02 GB GB08323641A patent/GB2126230B/en not_active Expired
- 1983-09-02 JP JP58160596A patent/JPS5965087A/ja active Pending
- 1983-09-02 AT AT0315583A patent/AT387385B/de not_active IP Right Cessation
- 1983-09-02 NZ NZ205466A patent/NZ205466A/en unknown
- 1983-09-02 KR KR1019830004140A patent/KR870001019B1/ko not_active IP Right Cessation
- 1983-09-02 BE BE211466A patent/BE897671A/fr unknown
- 1983-09-02 HU HU833064A patent/HU192862B/hu not_active IP Right Cessation
- 1983-09-02 SE SE8304751A patent/SE460419B/sv not_active IP Right Cessation
- 1983-09-02 LU LU84986A patent/LU84986A1/fr unknown
- 1983-09-05 YU YU1803/83A patent/YU45150B/xx unknown
- 1983-09-05 CH CH4390/86A patent/CH668593A5/fr not_active IP Right Cessation
- 1983-09-05 CH CH4855/83A patent/CH661512A5/fr not_active IP Right Cessation
1984
- 1984-04-25 ES ES531872A patent/ES531872A0/es active Granted
1985
- 1985-09-19 ES ES547111A patent/ES8604931A1/es not_active Expired
- 1985-09-19 ES ES547110A patent/ES8604930A1/es not_active Expired
1986
- 1986-12-25 YU YU2247/86A patent/YU44940B/xx unknown
1987
- 1987-10-30 AU AU80559/87A patent/AU613589B2/en not_active Ceased
- 1987-10-30 AU AU80558/87A patent/AU609068B2/en not_active Ceased
- 1987-10-30 AU AU80557/87A patent/AU609067B2/en not_active Ceased
1988
- 1988-06-16 SE SE8802265A patent/SE8802265D0/xx not_active Application Discontinuation
1990
- 1990-03-08 HK HK174/90A patent/HK17490A/xx unknown
- 1990-11-16 CY CY1521A patent/CY1521A/xx unknown

Also Published As

Publication number	Publication date
DE3331612A1 (de)	1984-03-08
AU567112B2 (en)	1987-11-12
AU1859283A (en)	1984-03-08
YU224786A (en)	1987-10-31
CY1521A (en)	1990-11-16
YU44940B (en)	1991-04-30
ES8604930A1 (es)	1986-02-16
KR840006235A (ko)	1984-11-22
CA1236834A (en)	1988-05-17
SE460419B (sv)	1989-10-09
IE832063L (en)	1984-03-03
FI833102A (fi)	1984-03-04
GB2126230A (en)	1984-03-21
AU613589B2 (en)	1991-08-08
AU8055887A (en)	1988-02-18
AU8055787A (en)	1988-02-18
HK17490A (en)	1990-03-16
NL8303038A (nl)	1984-04-02
NZ205466A (en)	1986-12-05
NO833128L (no)	1984-03-05
SE8802265L (sv)	1988-06-16
FI833102A0 (fi)	1983-08-31
SE8304751L (sv)	1984-03-04
ES547111A0 (es)	1986-02-16
YU45150B (en)	1992-03-10
DK399783A (da)	1984-03-04
FR2543952B1 (fr)	1986-02-21
KR870001019B1 (ko)	1987-05-23
NO161258B (no)	1989-04-17
IT1169459B (it)	1987-05-27
PT77282B (en)	1986-04-28
HU192862B (en)	1987-07-28
ES547110A0 (es)	1986-02-16
SE8802265D0 (sv)	1988-06-16
IL69618A0 (en)	1983-12-30
ZA836469B (en)	1984-04-25
IL69618A (en)	1987-02-27
IT8322765A0 (it)	1983-09-02
AU609067B2 (en)	1991-04-26
PT77282A (en)	1983-10-01
SE8304751D0 (sv)	1983-09-02
BE897671A (fr)	1984-03-02
GB8323641D0 (en)	1983-10-05
JPS5965087A (ja)	1984-04-13
ES8507537A1 (es)	1985-09-01
ES8505200A1 (es)	1985-05-16
LU84986A1 (fr)	1984-04-24
AU8055987A (en)	1988-02-18
CH668593A5 (fr)	1989-01-13
FI79709B (fi)	1989-10-31
HU194164B (en)	1988-01-28
FI79709C (fi)	1990-02-12
YU180383A (en)	1988-06-30
ES531872A0 (es)	1985-05-16
FR2543952A1 (fr)	1984-10-12
NO161258C (no)	1989-07-26
CH661512A5 (fr)	1987-07-31
AU609068B2 (en)	1991-04-26
DK399783D0 (da)	1983-09-01
GB2126230B (en)	1987-01-14
ES8604931A1 (es)	1986-02-16
ATA315583A (de)	1988-06-15
ES525243A0 (es)	1985-09-01
AT387385B (de)	1989-01-10
GR79061B (de)	1984-10-02

Publication	Publication Date	Title
US5637593A (en)	1997-06-10	Tryptamine analogues as 5-ht1-like agonists
JPH04145079A (ja)	1992-05-19	インドール誘導体およびその用途
US4517188A (en)	1985-05-14	1-Pyrimidinyloxy-3-hetaryl-alkylamino-2-propanols
GB2177393A (en)	1987-01-21	Benzimidazole derivatives
CA1332835C (en)	1994-11-01	Aliphatic carboxamides
IE56201B1 (en)	1991-05-22	Substituted 1-pyridyloxy-3-indolylalkylamino-2-propanols,preparation and use thereof
GB2162523A (en)	1986-02-05	Intermediates for syntheses of indole derivatives
US4436740A (en)	1984-03-13	3-Cycloalkylamino-2-OR-propoxycyanopyridines
NZ253881A (en)	1996-01-26	N-(1-substituted indolylalkyl)urea and c2-5 alkanoic acid amide derivatives; pharmaceutical compositions
KR900005021B1 (ko)	1990-07-18	1-펜옥시-3-히드록시 인돌릴 알킬아미노-3-프로판올류 및 그 제조방법
JPS63233972A (ja)	1988-09-29	新規なインドールカルボキサミド誘導体及びその塩類、それらの製造法及び中間体、これら誘導体の医薬品への使用並びにそれらを含有する組成物
US5512566A (en)	1996-04-30	Tricyclic compounds having affinity for the 5-HT1A receptor
JPS60109567A (ja)	1985-06-15	ビス（置換メチル）―メチル―イソキノリン誘導体
IE56202B1 (en)	1991-05-22	Intermediates for syntheses of indole derivatives
JPH0415224B2 (de)	1992-03-17
JPS6222769A (ja)	1987-01-30	テトラヒドロイソキノリン誘導体