UA67724C2 - Benzo[c]quinolizine derivatives, a method for the preparation thereof, a pharmaceutical composition and a method for the treatment of pathologies connected with 5 alpha-reductases - Google Patents

Benzo[c]quinolizine derivatives, a method for the preparation thereof, a pharmaceutical composition and a method for the treatment of pathologies connected with 5 alpha-reductases Download PDF

Info

Publication number: UA67724C2
Authority: UA; Ukraine
Prior art keywords: benzo; alkyl; quinolisin; phenyl; group
Prior art date: 1996-02-09

Application number

UA98094739A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Applied Research Systems

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.)

1996-02-09

Filing date

1997-07-02

Publication date

2004-07-15

1997-07-02 Application filed by Applied Research Systems filed Critical Applied Research Systems

2004-07-15 Publication of UA67724C2 publication Critical patent/UA67724C2/uk

Links

238000000034 method Methods 0.000 title claims abstract description 11
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 11
230000007170 pathology Effects 0.000 title claims description 9
238000002360 preparation method Methods 0.000 title abstract description 9
UOGFZJRMCBHRQU-UHFFFAOYSA-N 10ah-benzo[c]quinolizine Chemical class N12C=CC=CC2=CC=C2C1C=CC=C2 UOGFZJRMCBHRQU-UHFFFAOYSA-N 0.000 title abstract 2
108010066551 Cholestenone 5 alpha-Reductase Proteins 0.000 title 1
150000003839 salts Chemical class 0.000 claims abstract description 7
150000002148 esters Chemical class 0.000 claims abstract description 6
150000001875 compounds Chemical class 0.000 claims description 47
125000000217 alkyl group Chemical group 0.000 claims description 40
DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 33
125000005605 benzo group Chemical group 0.000 claims description 24
RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 22
ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 claims description 22
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
239000000203 mixture Substances 0.000 claims description 16
-1 phenylamino, naphthylamino Chemical group 0.000 claims description 16
229920006395 saturated elastomer Polymers 0.000 claims description 14
229910052739 hydrogen Inorganic materials 0.000 claims description 13
125000001624 naphthyl group Chemical group 0.000 claims description 13
108010044467 Isoenzymes Proteins 0.000 claims description 12
229910052799 carbon Inorganic materials 0.000 claims description 12
PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical compound C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 claims description 11
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 11
LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical compound C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims description 11
125000003342 alkenyl group Chemical group 0.000 claims description 11
WJTCGQSWYFHTAC-UHFFFAOYSA-N cyclooctane Chemical compound C1CCCCCCC1 WJTCGQSWYFHTAC-UHFFFAOYSA-N 0.000 claims description 11
239000004914 cyclooctane Substances 0.000 claims description 11
125000000304 alkynyl group Chemical group 0.000 claims description 10
UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
WZCXJNBOOQLKKD-UHFFFAOYSA-N 2,4-dihydroquinolizin-3-one Chemical compound C1=CC=CN2CC(=O)CC=C21 WZCXJNBOOQLKKD-UHFFFAOYSA-N 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 5
125000003282 alkyl amino group Chemical group 0.000 claims description 5
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
229910052796 boron Inorganic materials 0.000 claims description 5
238000006243 chemical reaction Methods 0.000 claims description 5
210000002307 prostate Anatomy 0.000 claims description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
201000004384 Alopecia Diseases 0.000 claims description 4
206010020112 Hirsutism Diseases 0.000 claims description 4
125000003368 amide group Chemical group 0.000 claims description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
230000003676 hair loss Effects 0.000 claims description 4
125000006239 protecting group Chemical group 0.000 claims description 4
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 4
208000002874 Acne Vulgaris Diseases 0.000 claims description 3
206010060862 Prostate cancer Diseases 0.000 claims description 3
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
206010000496 acne Diseases 0.000 claims description 3
239000003795 chemical substances by application Substances 0.000 claims description 3
KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
UCUUFSAXZMGPGH-UHFFFAOYSA-N penta-1,4-dien-3-one Chemical compound C=CC(=O)C=C UCUUFSAXZMGPGH-UHFFFAOYSA-N 0.000 claims description 3
HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 claims description 2
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
102000004316 Oxidoreductases Human genes 0.000 claims description 2
108090000854 Oxidoreductases Proteins 0.000 claims description 2
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
150000008064 anhydrides Chemical class 0.000 claims description 2
150000001540 azides Chemical class 0.000 claims description 2
230000006315 carbonylation Effects 0.000 claims description 2
238000005810 carbonylation reaction Methods 0.000 claims description 2
150000002170 ethers Chemical class 0.000 claims description 2
230000007062 hydrolysis Effects 0.000 claims description 2
238000006460 hydrolysis reaction Methods 0.000 claims description 2
230000005764 inhibitory process Effects 0.000 claims description 2
BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 claims description 2
239000012434 nucleophilic reagent Substances 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 claims description 2
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 claims description 2
229910000033 sodium borohydride Inorganic materials 0.000 claims description 2
239000012279 sodium borohydride Substances 0.000 claims description 2
230000009466 transformation Effects 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims 10
206010020880 Hypertrophy Diseases 0.000 claims 2
239000004480 active ingredient Substances 0.000 claims 2
125000005843 halogen group Chemical group 0.000 claims 2
239000004615 ingredient Substances 0.000 claims 2
125000005185 naphthylcarbonyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims 2
108091007187 Reductases Proteins 0.000 claims 1
125000002619 bicyclic group Chemical group 0.000 claims 1
JFNLZVQOOSMTJK-KNVOCYPGSA-N norbornene Chemical compound C1[C@@H]2CC[C@H]1C=C2 JFNLZVQOOSMTJK-KNVOCYPGSA-N 0.000 claims 1
230000001590 oxidative effect Effects 0.000 claims 1
239000000546 pharmaceutical excipient Substances 0.000 claims 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
125000003118 aryl group Chemical group 0.000 description 8
239000012047 saturated solution Substances 0.000 description 8
239000000243 solution Substances 0.000 description 8
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
125000000623 heterocyclic group Chemical group 0.000 description 7
239000000047 product Substances 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
125000000753 cycloalkyl group Chemical group 0.000 description 6
239000002904 solvent Substances 0.000 description 6
108090000790 Enzymes Proteins 0.000 description 5
102000004190 Enzymes Human genes 0.000 description 5
239000013078 crystal Substances 0.000 description 5
230000002401 inhibitory effect Effects 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 4
238000002844 melting Methods 0.000 description 4
230000008018 melting Effects 0.000 description 4
239000011541 reaction mixture Substances 0.000 description 4
NVKAWKQGWWIWPM-ABEVXSGRSA-N 17-β-hydroxy-5-α-Androstan-3-one Chemical compound C1C(=O)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@H]21 NVKAWKQGWWIWPM-ABEVXSGRSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
229960003473 androstanolone Drugs 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
239000012043 crude product Substances 0.000 description 3
238000004821 distillation Methods 0.000 description 3
238000001914 filtration Methods 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
239000003112 inhibitor Substances 0.000 description 3
239000007787 solid Substances 0.000 description 3
JLIDVCMBCGBIEY-UHFFFAOYSA-N 1-penten-3-one Chemical compound CCC(=O)C=C JLIDVCMBCGBIEY-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical compound CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
208000004403 Prostatic Hyperplasia Diseases 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
125000001769 aryl amino group Chemical group 0.000 description 2
125000004104 aryloxy group Chemical group 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
229940125782 compound 2 Drugs 0.000 description 2
230000000694 effects Effects 0.000 description 2
239000007788 liquid Substances 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
239000003208 petroleum Substances 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
150000003431 steroids Chemical class 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
229960003604 testosterone Drugs 0.000 description 2
FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 2
VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical compound CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
TZOYXRMEFDYWDQ-UHFFFAOYSA-N 3,4-dihydro-1h-quinolin-2-one Chemical compound C1=CC=C2NC(=O)CCC2=C1 TZOYXRMEFDYWDQ-UHFFFAOYSA-N 0.000 description 1
SHALBPKEGDBVKK-UHFFFAOYSA-N 4-methoxybuta-1,3-dien-2-yloxy(trimethyl)silane Chemical compound COC=CC(=C)O[Si](C)(C)C SHALBPKEGDBVKK-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
MJBPUQUGJNAPAZ-UHFFFAOYSA-N Butine Natural products O1C2=CC(O)=CC=C2C(=O)CC1C1=CC=C(O)C(O)=C1 MJBPUQUGJNAPAZ-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
229910008484 TiSi Inorganic materials 0.000 description 1
229960000583 acetic acid Drugs 0.000 description 1
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
239000003098 androgen Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
239000012300 argon atmosphere Substances 0.000 description 1
125000005129 aryl carbonyl group Chemical group 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
239000002585 base Substances 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
239000000872 buffer Substances 0.000 description 1
IAQRGUVFOMOMEM-UHFFFAOYSA-N butene Natural products CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 1
YAGCIXJCAUGCGI-UHFFFAOYSA-N butoxycarbonyl butyl carbonate Chemical compound CCCCOC(=O)OC(=O)OCCCC YAGCIXJCAUGCGI-UHFFFAOYSA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
210000004027 cell Anatomy 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000006071 cream Substances 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
239000003480 eluent Substances 0.000 description 1
238000010828 elution Methods 0.000 description 1
230000013020 embryo development Effects 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 1
229960004039 finasteride Drugs 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
210000004392 genitalia Anatomy 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
210000005260 human cell Anatomy 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
239000011256 inorganic filler Substances 0.000 description 1
229910003475 inorganic filler Inorganic materials 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
239000011630 iodine Substances 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
210000004185 liver Anatomy 0.000 description 1
238000012423 maintenance Methods 0.000 description 1
210000000260 male genitalia Anatomy 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000002674 ointment Substances 0.000 description 1
239000012766 organic filler Substances 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
MWWATHDPGQKSAR-UHFFFAOYSA-N propyne Chemical compound CC#C MWWATHDPGQKSAR-UHFFFAOYSA-N 0.000 description 1
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
238000010992 reflux Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000003756 stirring Methods 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/04—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing a quinolizine ring system condensed with only one six-membered carbocyclic ring, e.g. julolidine
- C07D455/06—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing a quinolizine ring system condensed with only one six-membered carbocyclic ring, e.g. julolidine containing benzo [a] quinolizine ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/10—Anti-acne agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/28—Antiandrogens
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Reproductive Health (AREA)
Dermatology (AREA)
Endocrinology (AREA)
Diabetes (AREA)
Gynecology & Obstetrics (AREA)
Pregnancy & Childbirth (AREA)
Urology & Nephrology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Plural Heterocyclic Compounds (AREA)

UA98094739A 1996-02-09 1997-07-02 Benzo[c]quinolizine derivatives, a method for the preparation thereof, a pharmaceutical composition and a method for the treatment of pathologies connected with 5 alpha-reductases UA67724C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
IT96FI000019A IT1286545B1 (it)	1996-02-09	1996-02-09	Derivati benzo(c) chinolizinici,loro preparazione ed uso come inibitori delle 5-alfa-riduttasi
PCT/EP1997/000552 WO1997029107A1 (en)	1996-02-09	1997-02-07	BENZO[C]QUINOLIZINE DERIVATIVES, THEIR PREPARATION AND USE AS 5α-REDUCTASES INHIBITORS

Publications (1)

Publication Number	Publication Date
UA67724C2 true UA67724C2 (en)	2004-07-15

Family

ID=11351478

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA98094739A UA67724C2 (en)	1996-02-09	1997-07-02	Benzo[c]quinolizine derivatives, a method for the preparation thereof, a pharmaceutical composition and a method for the treatment of pathologies connected with 5 alpha-reductases

Country Status (25)

Country	Link
US (3)	US6303622B1 (de)
EP (1)	EP0880520B1 (de)
JP (1)	JP2000504680A (de)
KR (1)	KR100480448B1 (de)
CN (1)	CN1116296C (de)
AT (1)	ATE237614T1 (de)
AU (1)	AU711886C (de)
BG (1)	BG64596B1 (de)
CZ (1)	CZ298061B6 (de)
DE (1)	DE69720966T2 (de)
DK (1)	DK0880520T3 (de)
EA (1)	EA000975B1 (de)
EE (1)	EE04058B1 (de)
ES (1)	ES2192263T3 (de)
HU (1)	HUP9900509A3 (de)
IL (2)	IL125628A0 (de)
IT (1)	IT1286545B1 (de)
MX (1)	MX9806229A (de)
NO (2)	NO320155B1 (de)
NZ (1)	NZ331256A (de)
PL (1)	PL187618B1 (de)
PT (1)	PT880520E (de)
SK (1)	SK283299B6 (de)
UA (1)	UA67724C2 (de)
WO (1)	WO1997029107A1 (de)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ITFI970193A1 (it) *	1997-08-01	1999-02-01	Applied Research Systems	Uso di derivati benzo(c) chinolizinici come regolatori della crescita delle piante e composizioni ad uso agricolo che contengono tali
EP0926148A1 (de) *	1997-12-23	1999-06-30	Applied Research Systems Ars Holding N.V.	Benzo (c)quinolizine-derivate,deren herstellung und verwendung als 5-alpha-reduktase-hemmer
US6723850B1 (en) *	1998-08-03	2004-04-20	Applied Research Systems Ars Holding N.V.	Process for the synthesis of (1-H)-benzo[c]quinolizin-3-ones derivatives
AP2007004244A0 (en)	2005-05-10	2007-12-31	Intermune Inc	Method of modulating stress-activated protein kinase system
JP5463034B2 (ja) *	2005-05-20	2014-04-09	アラントス・フアーマシユーテイカルズ・ホールデイング・インコーポレイテツド	ピリミジン若しくはトリアジン縮合二環式メタロプロテアーゼ阻害薬
US20070155738A1 (en)	2005-05-20	2007-07-05	Alantos Pharmaceuticals, Inc.	Heterobicyclic metalloprotease inhibitors
EP2296653B1 (de)	2008-06-03	2016-01-27	Intermune, Inc.	Verbindungen und verfahren zur behandlung von entzündungserkrankungen und fibrotischen erkrankungen
AR092742A1 (es)	2012-10-02	2015-04-29	Intermune Inc	Piridinonas antifibroticas
RU2692485C2 (ru)	2014-04-02	2019-06-25	Интермьюн, Инк.	Противофиброзные пиридиноны
CN105001216B (zh) *	2015-07-08	2017-03-01	中国科学院兰州化学物理研究所	一种喹嗪酮的制备方法
CN107089980B (zh) *	2017-05-11	2019-08-30	合肥工业大学	一种手性苯并[a]喹嗪-2-酮类化合物及其不对称催化合成方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3455929A (en) *	1966-08-15	1969-07-15	Bristol Myers Co	Esters of 1,4-dihydroquinoline-n-carboxylic acids and thione acids
FR1534278A (fr) *	1966-08-15	1968-07-26	Bristol Myers Co	Procédé de fabrication de 1, 4-dihydroquinoléine-n-carboxylates d'alcoyle
US3625877A (en) *	1968-01-08	1971-12-07	Eastman Kodak Co	High-modulus polycarbonate compositions
SU1027166A1 (ru)	1981-09-11	1983-07-07	Киевский Ордена Ленина Государственный Университет Им.Т.Г.Шевченко	Способ получени 1,2-полиметиленкетоцианоазагетероциклов
IE57014B1 (en)	1983-03-25	1992-03-11	Wyeth John & Brother Ltd	Benzoquinolizines

1996
- 1996-02-09 IT IT96FI000019A patent/IT1286545B1/it active IP Right Grant
1997
- 1997-02-07 EE EE9800233A patent/EE04058B1/xx not_active IP Right Cessation
- 1997-02-07 DE DE69720966T patent/DE69720966T2/de not_active Expired - Fee Related
- 1997-02-07 WO PCT/EP1997/000552 patent/WO1997029107A1/en not_active Ceased
- 1997-02-07 PL PL97328123A patent/PL187618B1/pl not_active IP Right Cessation
- 1997-02-07 SK SK1044-98A patent/SK283299B6/sk not_active IP Right Cessation
- 1997-02-07 NZ NZ331256A patent/NZ331256A/xx unknown
- 1997-02-07 EP EP97903230A patent/EP0880520B1/de not_active Expired - Lifetime
- 1997-02-07 EA EA199800701A patent/EA000975B1/ru unknown
- 1997-02-07 HU HU9900509A patent/HUP9900509A3/hu unknown
- 1997-02-07 KR KR10-1998-0705848A patent/KR100480448B1/ko not_active Expired - Fee Related
- 1997-02-07 CZ CZ0228998A patent/CZ298061B6/cs not_active IP Right Cessation
- 1997-02-07 US US09/117,583 patent/US6303622B1/en not_active Expired - Fee Related
- 1997-02-07 IL IL12562897A patent/IL125628A0/xx active IP Right Grant
- 1997-02-07 PT PT97903230T patent/PT880520E/pt unknown
- 1997-02-07 DK DK97903230T patent/DK0880520T3/da active
- 1997-02-07 AT AT97903230T patent/ATE237614T1/de not_active IP Right Cessation
- 1997-02-07 AU AU17672/97A patent/AU711886C/en not_active Ceased
- 1997-02-07 JP JP9528158A patent/JP2000504680A/ja not_active Ceased
- 1997-02-07 CN CN97192097A patent/CN1116296C/zh not_active Expired - Fee Related
- 1997-02-07 ES ES97903230T patent/ES2192263T3/es not_active Expired - Lifetime
- 1997-07-02 UA UA98094739A patent/UA67724C2/uk unknown
1998
- 1998-07-24 NO NO19983444A patent/NO320155B1/no not_active IP Right Cessation
- 1998-07-30 BG BG102661A patent/BG64596B1/bg unknown
- 1998-08-03 IL IL125628A patent/IL125628A/en not_active IP Right Cessation
- 1998-08-03 MX MX9806229A patent/MX9806229A/es unknown
2001
- 2001-06-25 US US09/891,088 patent/US6552034B2/en not_active Expired - Fee Related
- 2001-06-25 US US09/888,952 patent/US6555549B2/en not_active Expired - Fee Related
2004
- 2004-11-24 NO NO20045132A patent/NO20045132L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
CN1116296C (zh)	2003-07-30
US6303622B1 (en)	2001-10-16
EE04058B1 (et)	2003-06-16
EP0880520A1 (de)	1998-12-02
AU711886C (en)	2002-10-17
CZ298061B6 (cs)	2007-06-06
US20010047098A1 (en)	2001-11-29
CZ228998A3 (cs)	1998-10-14
HUP9900509A2 (hu)	1999-06-28
PL187618B1 (pl)	2004-08-31
EE9800233A (et)	1998-12-15
ES2192263T3 (es)	2003-10-01
NO983444D0 (no)	1998-07-24
SK283299B6 (sk)	2003-05-02
EA000975B1 (ru)	2000-08-28
JP2000504680A (ja)	2000-04-18
ITFI960019A0 (de)	1996-02-09
ITFI960019A1 (it)	1997-08-09
KR19990082126A (ko)	1999-11-15
KR100480448B1 (ko)	2005-08-31
DE69720966T2 (de)	2004-05-19
IT1286545B1 (it)	1998-07-15
BG64596B1 (bg)	2005-08-31
EP0880520B1 (de)	2003-04-16
US6555549B2 (en)	2003-04-29
MX9806229A (es)	1998-11-30
EA199800701A1 (ru)	1999-02-25
BG102661A (en)	1999-04-30
US6552034B2 (en)	2003-04-22
NO320155B1 (no)	2005-11-07
WO1997029107A1 (en)	1997-08-14
NO20045132L (no)	1998-07-24
HK1018783A1 (en)	2000-01-07
US20010044542A1 (en)	2001-11-22
NO983444L (no)	1998-07-24
PT880520E (pt)	2003-07-31
DK0880520T3 (da)	2003-08-11
IL125628A0 (en)	1999-04-11
AU1767297A (en)	1997-08-28
ATE237614T1 (de)	2003-05-15
HUP9900509A3 (en)	1999-11-29
PL328123A1 (en)	1999-01-18
SK104498A3 (en)	1998-12-02
DE69720966D1 (de)	2003-05-22
CN1210536A (zh)	1999-03-10
NZ331256A (en)	1999-06-29
AU711886B2 (en)	1999-10-21
IL125628A (en)	2006-10-31

Publication	Publication Date	Title
US4929731A (en)	1990-05-29	Method for the synthesis of huperzine A and analogs thereof and compounds useful therein
US6303622B1 (en)	2001-10-16	Benzo[c]quinolizine derivatives, their preparation and use as 5α-reductases inhibitors
KR100624239B1 (ko)	2006-09-13	(1ｈ)-벤조〔ｃ〕퀴놀리진-3-온 유도체의 합성방법
EP0334695A1 (de)	1989-09-27	Verfahren zur Herstellung von Isochinolinderivaten
KR100580742B1 (ko)	2006-05-15	벤조[ｃ]퀴놀리진 유도체 및 5 알파-리덕타제억제제로서의 용도
MXPA00011238A (es)	2002-05-23	Nuevos compuestos analogos de camptotecina, un proceso para su preparacion y composiciones farmaceuticas que los contienen.
Fernandez et al.	1994	Synthesis of 5-methoxy-2 (1H)-quinolinone
KR0153530B1 (ko)	1998-11-16	락탐 유도체의 제조 방법
CA2493090C (fr)	2012-04-24	Nouveaux derives de benzo[b]chromeno-naphthyridin-7-one et de pyrano[2'3':7,8]quino[2,3-b]quinoxalin-7-one, leur procede de preparation et les compositions pharmaceutiques qui lescontiennent
Tao et al.	1996	SYNTHESIS OF 2H-4, 8-DIMETHYLTHIENO [2′, 3′: 5, 6] NAPHTHO [1, 2-b] PYRAN-2-ONE WITH POTENTIAL PHOTOBIOLOGICAL ACTIVITY TO DNA
CA2245758C (en)	2006-04-11	Benzo[c]quinolizine derivatives, their preparation and use as 5.alpha.-reductases inhibitors
US4624955A (en)	1986-11-25	6H-isoxazolo[3,4-d]pyrazolo[3,4-b]pyridines, method for their preparation and use as anxiolytic agents
ATE238989T1 (de)	2003-05-15	Verfahren zur herstellung von spiro((4- cyclohexanon)-(3h)indol)-2'(1'h)-on derivaten
HK1018783B (en)	2003-11-28	BENZO[C]QUINOLIZINE DERIVATIVES, THEIR PREPARATION AND USE AS 5α-REDUCTASES INHIBITORS
MXPA01000869A (en)	2001-12-13	Process for the synthesis of (1h