IL92291A - Quarterly ammonium salts and the history of the alkyl alkyl of H 2 1- Benzofirans, their preparation and pharmaceutical preparations that protect the lava containing - Google Patents

Quarterly ammonium salts and the history of the alkyl alkyl of H 2 1- Benzofirans, their preparation and pharmaceutical preparations that protect the lava containing

Info

Publication number: IL92291A
Authority: IL; Israel
Prior art keywords: compound; alkyl; methyl; dihydro; benzopyran
Prior art date: 1988-11-14

Application number

IL9229189A

Other languages

English (en)

Hebrew (he)

Other versions

IL92291A0 (en

Original Assignee

Merrell Dow Pharma

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.)

1988-11-14

Filing date

1989-11-13

Publication date

1994-10-07

1988-11-14 Priority claimed from EP88402853A external-priority patent/EP0369082A1/de

1988-11-14 Priority claimed from EP88402854A external-priority patent/EP0369083A1/de

1989-11-13 Application filed by Merrell Dow Pharma filed Critical Merrell Dow Pharma

1990-07-26 Publication of IL92291A0 publication Critical patent/IL92291A0/xx

1994-10-07 Publication of IL92291A publication Critical patent/IL92291A/en

Links

239000000203 mixture Substances 0.000 title claims description 20
238000002360 preparation method Methods 0.000 title description 16
230000003293 cardioprotective effect Effects 0.000 title description 6
150000003242 quaternary ammonium salts Chemical class 0.000 title description 3
150000000463 2H-chromenes Chemical class 0.000 title description 2
125000003282 alkyl amino group Chemical group 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 86
125000000217 alkyl group Chemical group 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 13
238000006243 chemical reaction Methods 0.000 claims description 9
238000005576 amination reaction Methods 0.000 claims description 8
239000004480 active ingredient Substances 0.000 claims description 7
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
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 claims description 4
239000003963 antioxidant agent Substances 0.000 claims description 4
125000003710 aryl alkyl group Chemical group 0.000 claims description 4
230000003078 antioxidant effect Effects 0.000 claims description 3
125000003118 aryl group Chemical group 0.000 claims description 3
125000004663 dialkyl amino group Chemical group 0.000 claims description 3
230000007760 free radical scavenging Effects 0.000 claims description 3
230000001225 therapeutic effect Effects 0.000 claims description 3
125000006545 (C1-C9) alkyl group Chemical group 0.000 claims description 2
229910052739 hydrogen Inorganic materials 0.000 claims description 2
230000000069 prophylactic effect Effects 0.000 claims description 2
125000005270 trialkylamine group Chemical group 0.000 claims description 2
125000001246 bromo group Chemical group Br* 0.000 claims 3
125000001309 chloro group Chemical group Cl* 0.000 claims 3
239000008194 pharmaceutical composition Substances 0.000 claims 3
125000005843 halogen group Chemical group 0.000 claims 2
125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 claims 2
238000004519 manufacturing process Methods 0.000 claims 1
238000000034 method Methods 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
239000000243 solution Substances 0.000 description 18
-1 methylene, ethylene, propylene Chemical group 0.000 description 17
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
210000001519 tissue Anatomy 0.000 description 12
239000002253 acid Substances 0.000 description 11
239000007858 starting material Substances 0.000 description 11
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
150000005208 1,4-dihydroxybenzenes Chemical class 0.000 description 8
239000007788 liquid Substances 0.000 description 8
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
239000003826 tablet Substances 0.000 description 8
241000700159 Rattus Species 0.000 description 7
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
239000002585 base Substances 0.000 description 7
239000001301 oxygen Substances 0.000 description 7
229910052760 oxygen Inorganic materials 0.000 description 7
150000003254 radicals Chemical class 0.000 description 7
230000010410 reperfusion Effects 0.000 description 7
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 6
229940123457 Free radical scavenger Drugs 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
150000001298 alcohols Chemical class 0.000 description 6
239000003814 drug Substances 0.000 description 6
210000005003 heart tissue Anatomy 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
230000008569 process Effects 0.000 description 6
125000001453 quaternary ammonium group Chemical group 0.000 description 6
239000002516 radical scavenger Substances 0.000 description 6
238000010561 standard procedure Methods 0.000 description 6
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 6
ODWFNKAXBDDVMD-UHFFFAOYSA-N 2-(2-bromoethyl)-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound O1C(C)(CCBr)CCC2=C1C(C)=C(C)C(O)=C2C ODWFNKAXBDDVMD-UHFFFAOYSA-N 0.000 description 5
206010061216 Infarction Diseases 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
230000036770 blood supply Effects 0.000 description 5
150000004820 halides Chemical group 0.000 description 5
230000007574 infarction Effects 0.000 description 5
239000000546 pharmaceutical excipient Substances 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
239000002904 solvent Substances 0.000 description 5
GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical class OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 5
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 4
RUYZTDOMKYWHFC-UHFFFAOYSA-N 2-(2-hydroxyethyl)-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound O1C(C)(CCO)CCC2=C1C(C)=C(C)C(O)=C2C RUYZTDOMKYWHFC-UHFFFAOYSA-N 0.000 description 4
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
206010063837 Reperfusion injury Diseases 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
VXMLCAVRCWKVJZ-UHFFFAOYSA-N [2-(2-bromoethyl)-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-yl] acetate Chemical compound O1C(C)(CCBr)CCC2=C(C)C(OC(=O)C)=C(C)C(C)=C21 VXMLCAVRCWKVJZ-UHFFFAOYSA-N 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
IMNFDUFMRHMDMM-UHFFFAOYSA-N anhydrous n-heptane Natural products CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
239000008280 blood Substances 0.000 description 4
238000009833 condensation Methods 0.000 description 4
230000005494 condensation Effects 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
230000000144 pharmacologic effect Effects 0.000 description 4
239000000047 product Substances 0.000 description 4
239000004094 surface-active agent Substances 0.000 description 4
150000003512 tertiary amines Chemical class 0.000 description 4
238000012360 testing method Methods 0.000 description 4
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
MOIVCWDOASUQCZ-UHFFFAOYSA-M 2-(6-acetyloxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)ethyl-trimethylazanium;bromide Chemical compound [Br-].O1C(C)(CC[N+](C)(C)C)CCC2=C(C)C(OC(=O)C)=C(C)C(C)=C21 MOIVCWDOASUQCZ-UHFFFAOYSA-M 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
206010061218 Inflammation Diseases 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
230000010933 acylation Effects 0.000 description 3
238000005917 acylation reaction Methods 0.000 description 3
235000006708 antioxidants Nutrition 0.000 description 3
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
229910052794 bromium Inorganic materials 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
210000004351 coronary vessel Anatomy 0.000 description 3
229940079593 drug Drugs 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
210000002216 heart Anatomy 0.000 description 3
230000004054 inflammatory process Effects 0.000 description 3
208000028867 ischemia Diseases 0.000 description 3
239000000463 material Substances 0.000 description 3
208000010125 myocardial infarction Diseases 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
239000007787 solid Substances 0.000 description 3
238000011477 surgical intervention Methods 0.000 description 3
229940124597 therapeutic agent Drugs 0.000 description 3
230000002537 thrombolytic effect Effects 0.000 description 3
230000001052 transient effect Effects 0.000 description 3
ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 2
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 2
PKDBCJSWQUOKDO-UHFFFAOYSA-M 2,3,5-triphenyltetrazolium chloride Chemical compound [Cl-].C1=CC=CC=C1C(N=[N+]1C=2C=CC=CC=2)=NN1C1=CC=CC=C1 PKDBCJSWQUOKDO-UHFFFAOYSA-M 0.000 description 2
RFODZFMPLDRYFK-UHFFFAOYSA-N 2-(2-hydroxyethyl)-2,5,7-trimethyl-3,4-dihydrochromen-6-ol Chemical compound O1C(C)(CCO)CCC2=C1C=C(C)C(O)=C2C RFODZFMPLDRYFK-UHFFFAOYSA-N 0.000 description 2
GBDMZFNPKFKLCD-UHFFFAOYSA-N 2-(3-hydroxypropyl)-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound O1C(C)(CCCO)CCC2=C1C(C)=C(C)C(O)=C2C GBDMZFNPKFKLCD-UHFFFAOYSA-N 0.000 description 2
DMJBVWXZFUWUKC-UHFFFAOYSA-N 3-(2-hydroxyethyl)-2,5,7,8-tetramethyl-3,4-dihydro-2h-chromen-6-ol Chemical compound CC1=C(O)C(C)=C2CC(CCO)C(C)OC2=C1C DMJBVWXZFUWUKC-UHFFFAOYSA-N 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 2
102000019197 Superoxide Dismutase Human genes 0.000 description 2
108010012715 Superoxide dismutase Proteins 0.000 description 2
DNRCGFUTOSMVEM-UHFFFAOYSA-N [2-[2-(dimethylamino)ethyl]-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-yl] acetate Chemical compound CC(=O)OC1=C(C)C(C)=C2OC(CCN(C)C)(C)CCC2=C1C DNRCGFUTOSMVEM-UHFFFAOYSA-N 0.000 description 2
JMEHNOZNAWODKF-UHFFFAOYSA-N [2-[2-(dimethylamino)ethyl]-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-yl] acetate;hydron;chloride Chemical compound Cl.CC(=O)OC1=C(C)C(C)=C2OC(CCN(C)C)(C)CCC2=C1C JMEHNOZNAWODKF-UHFFFAOYSA-N 0.000 description 2
125000002947 alkylene group Chemical group 0.000 description 2
238000000540 analysis of variance Methods 0.000 description 2
238000003556 assay Methods 0.000 description 2
238000006701 autoxidation reaction Methods 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
239000002775 capsule Substances 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
230000030833 cell death Effects 0.000 description 2
230000001413 cellular effect Effects 0.000 description 2
238000001311 chemical methods and process Methods 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical class C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 2
230000006378 damage Effects 0.000 description 2
125000005265 dialkylamine group Chemical group 0.000 description 2
HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 2
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
239000003937 drug carrier Substances 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
238000009472 formulation Methods 0.000 description 2
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
239000012458 free base Substances 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
230000005764 inhibitory process Effects 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
239000000314 lubricant Substances 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
238000005259 measurement Methods 0.000 description 2
239000012528 membrane Substances 0.000 description 2
VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical group COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 2
125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
210000004165 myocardium Anatomy 0.000 description 2
210000000056 organ Anatomy 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
239000000843 powder Substances 0.000 description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
125000004673 propylcarbonyl group Chemical group 0.000 description 2
230000001681 protective effect Effects 0.000 description 2
239000000376 reactant Substances 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
230000009467 reduction Effects 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
241000894007 species Species 0.000 description 2
229910001220 stainless steel Inorganic materials 0.000 description 2
239000010935 stainless steel Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
125000006253 t-butylcarbonyl group Chemical group [H]C([H])([H])C(C(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
230000000699 topical effect Effects 0.000 description 2
125000005490 tosylate group Chemical group 0.000 description 2
PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
GLEVLJDDWXEYCO-AWEZNQCLSA-N (2s)-6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromene-2-carboxylic acid Chemical compound O1[C@](C)(C(O)=O)CCC2=C1C(C)=C(C)C(O)=C2C GLEVLJDDWXEYCO-AWEZNQCLSA-N 0.000 description 1
UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
NQAWQSVOOHTLEY-UHFFFAOYSA-N 1-chlorobutane-1-sulfonic acid Chemical compound CCCC(Cl)S(O)(=O)=O NQAWQSVOOHTLEY-UHFFFAOYSA-N 0.000 description 1
GJBUJQVUDIPYFS-UHFFFAOYSA-N 2,5,7,8-tetramethyl-3,4-dihydrochromen-2-ol Chemical class C1CC(C)(O)OC2=C(C)C(C)=CC(C)=C21 GJBUJQVUDIPYFS-UHFFFAOYSA-N 0.000 description 1
OKJNZYICKKQLIC-UHFFFAOYSA-N 2-(2-hydroxyethyl)-2,5,8-trimethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(CCO)OC2=C1C(C)=C(O)C=C2C OKJNZYICKKQLIC-UHFFFAOYSA-N 0.000 description 1
ATHLDZBNADHMCS-UHFFFAOYSA-N 2-(2-hydroxyethyl)-2,7,8-trimethyl-3,4-dihydrochromen-6-ol Chemical compound O1C(C)(CCO)CCC2=C1C(C)=C(C)C(O)=C2 ATHLDZBNADHMCS-UHFFFAOYSA-N 0.000 description 1
FSCGLKWYHHSLST-UHFFFAOYSA-N 2-(3-sulfanylpropanoylamino)acetic acid Chemical compound OC(=O)CNC(=O)CCS FSCGLKWYHHSLST-UHFFFAOYSA-N 0.000 description 1
RNKIPVYVFKGZEG-UHFFFAOYSA-N 2-(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)ethyl-trimethylazanium;bromide Chemical compound [Br-].O1C(C)(CC[N+](C)(C)C)CCC2=C1C(C)=C(C)C(O)=C2C RNKIPVYVFKGZEG-UHFFFAOYSA-N 0.000 description 1
PFYKITIFGZARLJ-UHFFFAOYSA-N 2-(6-hydroxy-2,7,8-trimethyl-3,4-dihydrochromen-2-yl)ethyl-trimethylazanium;bromide Chemical compound [Br-].C1CC(C)(CC[N+](C)(C)C)OC2=C(C)C(C)=C(O)C=C21 PFYKITIFGZARLJ-UHFFFAOYSA-N 0.000 description 1
QUVUREVUGMARII-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-ol;hydrochloride Chemical compound Cl.OC1=C(C)C(C)=C2OC(CCN(C)C)(C)CCC2=C1C QUVUREVUGMARII-UHFFFAOYSA-N 0.000 description 1
XWMXMPOPGYEXLH-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]-2,5,7-trimethyl-3,4-dihydrochromen-6-ol Chemical compound OC1=C(C)C=C2OC(CCN(C)C)(C)CCC2=C1C XWMXMPOPGYEXLH-UHFFFAOYSA-N 0.000 description 1
NKZRBFJFSNLQAI-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]-2,5,8-trimethyl-3,4-dihydrochromen-6-ol Chemical compound OC1=CC(C)=C2OC(CCN(C)C)(C)CCC2=C1C NKZRBFJFSNLQAI-UHFFFAOYSA-N 0.000 description 1
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HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 1
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CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
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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
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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XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/70—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with two hydrocarbon radicals attached in position 2 and elements other than carbon and hydrogen in position 6
- C07D311/72—3,4-Dihydro derivatives having in position 2 at least one methyl radical and in position 6 one oxygen atom, e.g. tocopherols
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
- 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
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Heart & Thoracic Surgery (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Cardiology (AREA)
General Chemical & Material Sciences (AREA)
Urology & Nephrology (AREA)
Vascular Medicine (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Pyrane Compounds (AREA)

IL9229189A 1988-11-14 1989-11-13 Quarterly ammonium salts and the history of the alkyl alkyl of H 2 1- Benzofirans, their preparation and pharmaceutical preparations that protect the lava containing IL92291A (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
EP88402853A EP0369082A1 (de)	1988-11-14	1988-11-14	Herzschutz-Tocopherolanaloge
EP88402854A EP0369083A1 (de)	1988-11-14	1988-11-14	Herzschutz-Tocopherolanaloge

Publications (2)

Publication Number	Publication Date
IL92291A0 IL92291A0 (en)	1990-07-26
IL92291A true IL92291A (en)	1994-10-07

Family

ID=26118102

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL9229189A IL92291A (en)	1988-11-14	1989-11-13	Quarterly ammonium salts and the history of the alkyl alkyl of H 2 1- Benzofirans, their preparation and pharmaceutical preparations that protect the lava containing

Country Status (18)

Country	Link
EP (1)	EP0369874B1 (de)
JP (1)	JP3066901B2 (de)
KR (1)	KR0160112B1 (de)
CN (1)	CN1033972C (de)
AR (1)	AR246962A1 (de)
AT (1)	ATE118771T1 (de)
AU (1)	AU620660B2 (de)
CA (1)	CA2002649C (de)
DE (1)	DE68921298T2 (de)
DK (1)	DK568189A (de)
ES (1)	ES2071674T3 (de)
FI (1)	FI91404C (de)
HU (2)	HU204807B (de)
IE (1)	IE65584B1 (de)
IL (1)	IL92291A (de)
NO (1)	NO173334C (de)
NZ (1)	NZ231367A (de)
PT (1)	PT92299B (de)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FR2676056B1 (fr) *	1991-05-03	1993-07-16	Adir	Nouveaux derives du benzopyranne leur procede de preparation et les compositions pharmaceutiques qui les contiennent.
US5135945A (en) *	1991-06-05	1992-08-04	Merrell Dow Pharmaceuticals Inc.	Cholesterol-lowering tocopherol analogs
EP0535283A1 (de) *	1991-10-02	1993-04-07	Merrell Dow Pharmaceuticals Inc.	Tocopherol Analoge mit kardioprotektiver Wirkung
DE4135474A1 (de) *	1991-10-28	1993-04-29	Bayer Ag	2-aminomethyl-chromane
CA2082004A1 (en) *	1991-11-20	1993-05-21	David Laffan	Substituted pentaalkylchromans
EP0550292A1 (de) *	1992-01-02	1993-07-07	Merrell Dow Pharmaceuticals Inc.	Tocopherol-Analog zum Gewebeschutz
ATE146175T1 (de) *	1992-04-06	1996-12-15	Merrell Pharma Inc	Neue kardioprotektive wirkstoffe
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1989
- 1989-11-09 CA CA002002649A patent/CA2002649C/en not_active Expired - Lifetime
- 1989-11-10 AR AR89315417A patent/AR246962A1/es active
- 1989-11-13 HU HU895879A patent/HU204807B/hu not_active IP Right Cessation
- 1989-11-13 IL IL9229189A patent/IL92291A/en not_active IP Right Cessation
- 1989-11-13 NZ NZ231367A patent/NZ231367A/xx unknown
- 1989-11-13 PT PT92299A patent/PT92299B/pt not_active IP Right Cessation
- 1989-11-13 FI FI895393A patent/FI91404C/fi not_active IP Right Cessation
- 1989-11-13 DK DK568189A patent/DK568189A/da not_active Application Discontinuation
- 1989-11-13 IE IE364089A patent/IE65584B1/en not_active IP Right Cessation
- 1989-11-13 KR KR1019890016464A patent/KR0160112B1/ko not_active Expired - Fee Related
- 1989-11-13 NO NO894521A patent/NO173334C/no not_active IP Right Cessation
- 1989-11-14 CN CN89109257A patent/CN1033972C/zh not_active Expired - Fee Related
- 1989-11-14 AU AU44682/89A patent/AU620660B2/en not_active Ceased
- 1989-11-14 AT AT89403125T patent/ATE118771T1/de not_active IP Right Cessation
- 1989-11-14 DE DE68921298T patent/DE68921298T2/de not_active Expired - Lifetime
- 1989-11-14 ES ES89403125T patent/ES2071674T3/es not_active Expired - Lifetime
- 1989-11-14 EP EP89403125A patent/EP0369874B1/de not_active Expired - Lifetime
- 1989-11-14 JP JP1294094A patent/JP3066901B2/ja not_active Expired - Lifetime
1995
- 1995-06-16 HU HU95P/P00237P patent/HU211877A9/hu unknown

Also Published As

Publication number	Publication date
NO894521L (no)	1990-05-15
ATE118771T1 (de)	1995-03-15
PT92299A (pt)	1990-05-31
DK568189D0 (da)	1989-11-13
FI895393A0 (fi)	1989-11-13
JPH02178278A (ja)	1990-07-11
EP0369874A2 (de)	1990-05-23
IE893640L (en)	1990-05-14
NO894521D0 (no)	1989-11-13
NZ231367A (en)	1992-12-23
KR900007827A (ko)	1990-06-02
DE68921298D1 (de)	1995-03-30
ES2071674T3 (es)	1995-07-01
CA2002649C (en)	2000-06-06
IL92291A0 (en)	1990-07-26
AU4468289A (en)	1990-05-17
FI91404C (fi)	1994-06-27
IE65584B1 (en)	1995-11-01
CA2002649A1 (en)	1990-05-14
HU211877A9 (en)	1995-12-28
EP0369874B1 (de)	1995-02-22
PT92299B (pt)	1996-07-31
CN1033972C (zh)	1997-02-05
KR0160112B1 (ko)	1998-12-01
NO173334B (no)	1993-08-23
HUT51610A (en)	1990-05-28
FI91404B (fi)	1994-03-15
AR246962A1 (es)	1994-10-31
EP0369874A3 (en)	1990-12-27
HU204807B (en)	1992-02-28
AU620660B2 (en)	1992-02-20
CN1042911A (zh)	1990-06-13
DK568189A (da)	1990-05-15
JP3066901B2 (ja)	2000-07-17
DE68921298T2 (de)	1995-07-06
HU895879D0 (en)	1990-02-28
NO173334C (no)	1993-12-01

Legal Events

Date	Code	Title	Description
2000-08-31	RH	Patent void
2002-02-10	NE	Application for restoration - patent lapsed through non-payment of renewal fees (section 60, patents law, 5727-1967)
2004-07-25	RH1	Patent not in force
2006-09-05	HC	Change of name of proprietor(s)	Owner name: AVENTIS INC. Free format text: FORMER NAME:MERRELL PHARMACEUTICALS INC.

Publication	Publication Date	Title
CA2002649C (en)	2000-06-06	Cardioprotective tocopherol analogs
EP0536036B1 (de)	1998-02-25	Tocopherol-Analoge mit cardioprotectiver Wirkung
US5135945A (en)	1992-08-04	Cholesterol-lowering tocopherol analogs
EP0550337B1 (de)	1997-02-12	Tocopherol-Analoge zum Gewebeschutz
EP0369083A1 (de)	1990-05-23	Herzschutz-Tocopherolanaloge
US5500444A (en)	1996-03-19	Cardioprotective tocopherol analogs
EP0369082A1 (de)	1990-05-23	Herzschutz-Tocopherolanaloge
EP0447325B1 (de)	1996-04-24	Ascorbinsäure Derivate
US5270336A (en)	1993-12-14	Ascorbic acid derivatives
IL105319A (en)	1998-02-22	Hydrazide derivatives of 3, 4-dihydro-2h-1-benzopyrans and pharmaceutical compositions containing them