CN1071916A - 在1-位含有醚基或硫醚基的新2，3-二氮杂萘及其制备方法 - Google Patents

在1-位含有醚基或硫醚基的新2，3-二氮杂萘及其制备方法 Download PDF

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Publication number: CN1071916A
Authority: CN; China
Prior art keywords: alkyl; phenyl; group; naphthyridine; general formula
Prior art date: 1991-10-31
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Withdrawn

Application number

CN92112607A

Other languages

English (en)

Chinese (zh)

Inventor

G·舍尔福勒

I·弗莱彻赫尔

B·库茨彻

J·恩格尔

S·兹伦依

U·沃纳

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Asta Medica GmbH

Original Assignee

Asta Pharma AG

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.)

1991-10-31

Filing date

1992-10-30

Publication date

1993-05-12

1992-10-30 Application filed by Asta Pharma AG filed Critical Asta Pharma AG

1993-05-12 Publication of CN1071916A publication Critical patent/CN1071916A/zh

Status Withdrawn legal-status Critical Current

Links

238000002360 preparation method Methods 0.000 title claims description 9
125000000101 thioether group Chemical group 0.000 title description 2
125000001033 ether group Chemical group 0.000 title 1
LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 34
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 20
125000004076 pyridyl group Chemical group 0.000 claims abstract description 13
239000001301 oxygen Substances 0.000 claims abstract description 10
229910052760 oxygen Inorganic materials 0.000 claims abstract description 10
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 8
125000006383 alkylpyridyl group Chemical group 0.000 claims abstract description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 5
125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims abstract 4
238000006243 chemical reaction Methods 0.000 claims description 18
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 17
-1 C 1 -C 6 -alkyl Chemical group 0.000 claims description 15
239000003814 drug Substances 0.000 claims description 15
125000000217 alkyl group Chemical group 0.000 claims description 13
239000013543 active substance Substances 0.000 claims description 10
239000000126 substance Substances 0.000 claims description 10
150000003839 salts Chemical class 0.000 claims description 9
239000002253 acid Substances 0.000 claims description 8
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 8
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 4
125000005947 C1-C6 alkylsulfonyloxy group Chemical group 0.000 claims description 2
239000012059 conventional drug carrier Substances 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims 3
125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims 3
GESPRUVYTLDFDD-UHFFFAOYSA-N 1-methoxyphthalazine Chemical compound C1=CC=C2C(OC)=NN=CC2=C1 GESPRUVYTLDFDD-UHFFFAOYSA-N 0.000 claims 3
CSHSXUZQMJVDJY-UHFFFAOYSA-N 1-phenoxyphthalazine Chemical compound N=1N=CC2=CC=CC=C2C=1OC1=CC=CC=C1 CSHSXUZQMJVDJY-UHFFFAOYSA-N 0.000 claims 3
125000003277 amino group Chemical group 0.000 claims 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 3
229910052739 hydrogen Inorganic materials 0.000 claims 3
150000002431 hydrogen Chemical class 0.000 claims 3
239000001257 hydrogen Substances 0.000 claims 3
229910052717 sulfur Chemical group 0.000 claims 3
239000011593 sulfur Chemical group 0.000 claims 3
125000004953 trihalomethyl group Chemical group 0.000 claims 3
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims 2
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 1
FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical compound N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 claims 1
NLWWKQYRAIGRKY-UHFFFAOYSA-N 1-ethoxyphthalazine Chemical compound C1=CC=C2C(OCC)=NN=CC2=C1 NLWWKQYRAIGRKY-UHFFFAOYSA-N 0.000 claims 1
125000002252 acyl group Chemical group 0.000 claims 1
125000005279 aryl sulfonyloxy group Chemical group 0.000 claims 1
239000008024 pharmaceutical diluent Substances 0.000 claims 1
238000006467 substitution reaction Methods 0.000 claims 1
239000005864 Sulphur Chemical group 0.000 abstract description 2
150000003254 radicals Chemical group 0.000 abstract 1
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 15
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
229910052799 carbon Inorganic materials 0.000 description 11
239000003795 chemical substances by application Substances 0.000 description 11
238000000034 method Methods 0.000 description 11
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
239000003513 alkali Substances 0.000 description 10
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
230000000694 effects Effects 0.000 description 8
238000005917 acylation reaction Methods 0.000 description 7
150000001721 carbon Chemical group 0.000 description 7
239000002904 solvent Substances 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
150000001408 amides Chemical class 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
208000005392 Spasm Diseases 0.000 description 5
229910052783 alkali metal Inorganic materials 0.000 description 5
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
230000010933 acylation Effects 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
239000006185 dispersion Substances 0.000 description 4
239000000839 emulsion Substances 0.000 description 4
230000003203 everyday effect Effects 0.000 description 4
239000007788 liquid Substances 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000011734 sodium Substances 0.000 description 4
APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
229910000102 alkali metal hydride Inorganic materials 0.000 description 3
150000008046 alkali metal hydrides Chemical class 0.000 description 3
230000002152 alkylating effect Effects 0.000 description 3
239000000010 aprotic solvent Substances 0.000 description 3
150000004945 aromatic hydrocarbons Chemical class 0.000 description 3
239000002585 base Substances 0.000 description 3
150000003818 basic metals Chemical class 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
239000000460 chlorine Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
239000012442 inert solvent Substances 0.000 description 3
239000011630 iodine Substances 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
239000007921 spray Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
239000003826 tablet Substances 0.000 description 3
150000003512 tertiary amines Chemical class 0.000 description 3
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
206010037660 Pyrexia Diseases 0.000 description 2
241000700159 Rattus Species 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
229960000583 acetic acid Drugs 0.000 description 2
150000008065 acid anhydrides Chemical class 0.000 description 2
125000001931 aliphatic group Chemical group 0.000 description 2
229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
150000008041 alkali metal carbonates Chemical class 0.000 description 2
150000001339 alkali metal compounds Chemical class 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
229910052784 alkaline earth metal Inorganic materials 0.000 description 2
150000001342 alkaline earth metals Chemical class 0.000 description 2
239000002168 alkylating agent Substances 0.000 description 2
229940100198 alkylating agent Drugs 0.000 description 2
230000003110 anti-inflammatory effect Effects 0.000 description 2
239000007900 aqueous suspension Substances 0.000 description 2
125000003118 aryl group Chemical class 0.000 description 2
229910052728 basic metal Inorganic materials 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
239000002775 capsule Substances 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
150000004292 cyclic ethers Chemical class 0.000 description 2
239000008298 dragée Substances 0.000 description 2
229940079593 drug Drugs 0.000 description 2
239000012467 final product Substances 0.000 description 2
150000005826 halohydrocarbons Chemical class 0.000 description 2
238000010253 intravenous injection Methods 0.000 description 2
125000001624 naphthyl group Chemical group 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
239000006072 paste Substances 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
239000006187 pill Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
239000000047 product Substances 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
230000004044 response Effects 0.000 description 2
229910000029 sodium carbonate Inorganic materials 0.000 description 2
235000017550 sodium carbonate Nutrition 0.000 description 2
239000000243 solution Substances 0.000 description 2
239000007940 sugar coated tablet Substances 0.000 description 2
239000000829 suppository Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 description 1
AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 1
DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical group CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
BSYNRYMUTXBXSQ-FOQJRBATSA-N 59096-14-9 Chemical compound CC(=O)OC1=CC=CC=C1[14C](O)=O BSYNRYMUTXBXSQ-FOQJRBATSA-N 0.000 description 1
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
101000623895 Bos taurus Mucin-15 Proteins 0.000 description 1
239000004215 Carbon black (E152) Substances 0.000 description 1
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 1
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
206010061218 Inflammation Diseases 0.000 description 1
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 1
235000003140 Panax quinquefolius Nutrition 0.000 description 1
240000005373 Panax quinquefolius Species 0.000 description 1
240000004808 Saccharomyces cerevisiae Species 0.000 description 1
244000000231 Sesamum indicum Species 0.000 description 1
235000003434 Sesamum indicum Nutrition 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
230000009471 action Effects 0.000 description 1
230000007059 acute toxicity Effects 0.000 description 1
231100000403 acute toxicity Toxicity 0.000 description 1
150000001266 acyl halides Chemical class 0.000 description 1
238000013019 agitation Methods 0.000 description 1
239000003905 agrochemical Substances 0.000 description 1
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
125000003368 amide group Chemical group 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
230000006229 amino acid addition Effects 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
125000004391 aryl sulfonyl group Chemical group 0.000 description 1
229910001038 basic metal oxide Inorganic materials 0.000 description 1
USFRYJRPHFMVBZ-UHFFFAOYSA-M benzyl(triphenyl)phosphanium;chloride Chemical class [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)CC1=CC=CC=C1 USFRYJRPHFMVBZ-UHFFFAOYSA-M 0.000 description 1
230000037396 body weight Effects 0.000 description 1
238000009835 boiling Methods 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
238000001311 chemical methods and process Methods 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
235000009508 confectionery Nutrition 0.000 description 1
239000000470 constituent Substances 0.000 description 1
238000001816 cooling Methods 0.000 description 1
238000000354 decomposition reaction Methods 0.000 description 1
RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 1
239000013583 drug formulation Substances 0.000 description 1
238000010410 dusting Methods 0.000 description 1
206010015037 epilepsy Diseases 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
150000002191 fatty alcohols Chemical class 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000010255 intramuscular injection Methods 0.000 description 1
239000007927 intramuscular injection Substances 0.000 description 1
229910003002 lithium salt Inorganic materials 0.000 description 1
159000000002 lithium salts Chemical class 0.000 description 1
239000006210 lotion Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
229910052976 metal sulfide Inorganic materials 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
239000000203 mixture Substances 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
210000004400 mucous membrane Anatomy 0.000 description 1
230000003387 muscular Effects 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
239000002674 ointment Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
229960005489 paracetamol Drugs 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
239000003186 pharmaceutical solution Substances 0.000 description 1
CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 description 1
239000002504 physiological saline solution Substances 0.000 description 1
150000003053 piperidines Chemical class 0.000 description 1
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
235000015320 potassium carbonate Nutrition 0.000 description 1
150000003112 potassium compounds Chemical class 0.000 description 1
230000008569 process Effects 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
210000000664 rectum Anatomy 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
238000007614 solvation Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000000967 suction filtration Methods 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
150000003462 sulfoxides Chemical class 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
150000005621 tetraalkylammonium salts Chemical class 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
230000007704 transition Effects 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
125000004954 trialkylamino group Chemical group 0.000 description 1
DQWPFSLDHJDLRL-UHFFFAOYSA-N triethyl phosphate Chemical compound CCOP(=O)(OCC)OCC DQWPFSLDHJDLRL-UHFFFAOYSA-N 0.000 description 1
239000000273 veterinary drug 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
- C07D237/32—Phthalazines with oxygen atoms directly attached to carbon atoms of the nitrogen-containing ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Life Sciences & Earth Sciences (AREA)
Pain & Pain Management (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Neurology (AREA)
Biomedical Technology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Rheumatology (AREA)
Neurosurgery (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Cosmetics (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Investigating Or Analysing Biological Materials (AREA)

CN92112607A 1991-10-31 1992-10-30 在1-位含有醚基或硫醚基的新2，3-二氮杂萘及其制备方法 Withdrawn CN1071916A (zh)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DE4135910		1991-10-31
DEP4135910.0		1991-10-31

Publications (1)

Publication Number	Publication Date
CN1071916A true CN1071916A (zh)	1993-05-12

Family

ID=6443832

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CN92112607A Withdrawn CN1071916A (zh)	1991-10-31	1992-10-30	在1-位含有醚基或硫醚基的新2，3-二氮杂萘及其制备方法

Country Status (20)

Country	Link
US (1)	US5354750A (2)
EP (1)	EP0539805B1 (2)
JP (1)	JPH05222002A (2)
KR (1)	KR930007914A (2)
CN (1)	CN1071916A (2)
AT (1)	ATE157656T1 (2)
AU (1)	AU660726B2 (2)
BR (1)	BR9204187A (2)
CA (1)	CA2081819A1 (2)
DE (2)	DE59208852D1 (2)
DK (1)	DK0539805T3 (2)
ES (1)	ES2108066T3 (2)
FI (1)	FI924934A7 (2)
GR (1)	GR3025141T3 (2)
HU (2)	HUT62866A (2)
IL (1)	IL103601A0 (2)
MX (1)	MX9206245A (2)
NO (1)	NO924166L (2)
TW (1)	TW211563B (2)
ZA (1)	ZA928420B (2)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9226573D0 (en) *	1992-12-21	1993-02-17	Ici Plc	Heterocyclic compounds
US6635642B1 (en)	1997-09-03	2003-10-21	Guilford Pharmaceuticals Inc.	PARP inhibitors, pharmaceutical compositions comprising same, and methods of using same
US20020028813A1 (en) *	1997-09-03	2002-03-07	Paul F. Jackson	Thioalkyl compounds, methods, and compositions for inhibiting parp activity
US6291425B1 (en)	1999-09-01	2001-09-18	Guilford Pharmaceuticals Inc.	Compounds, methods and pharmaceutical compositions for treating cellular damage, such as neural or cardiovascular tissue damage
US6197785B1 (en)	1997-09-03	2001-03-06	Guilford Pharmaceuticals Inc.	Alkoxy-substituted compounds, methods, and compositions for inhibiting PARP activity
US6426415B1 (en)	1997-09-03	2002-07-30	Guilford Pharmaceuticals Inc.	Alkoxy-substituted compounds, methods and compositions for inhibiting parp activity
US6514983B1 (en)	1997-09-03	2003-02-04	Guilford Pharmaceuticals Inc.	Compounds, methods and pharmaceutical compositions for treating neural or cardiovascular tissue damage
US6346536B1 (en)	1997-09-03	2002-02-12	Guilford Pharmaceuticals Inc.	Poly(ADP-ribose) polymerase inhibitors and method for treating neural or cardiovascular tissue damage using the same
US6395749B1 (en)	1998-05-15	2002-05-28	Guilford Pharmaceuticals Inc.	Carboxamide compounds, methods, and compositions for inhibiting PARP activity
US6387902B1 (en)	1998-12-31	2002-05-14	Guilford Pharmaceuticals, Inc.	Phenazine compounds, methods and pharmaceutical compositions for inhibiting PARP
US6723733B2 (en)	2000-05-19	2004-04-20	Guilford Pharmaceuticals, Inc.	Sulfonamide and carbamide derivatives of 6(5H)phenanthridinones and their uses
AU2002220241A1 (en) *	2000-12-01	2002-06-11	Iconix Pharmaceuticals, Inc.	Parb inhibitors
GB0507298D0 (en)	2005-04-11	2005-05-18	Novartis Ag	Organic compounds

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2484029A (en) *	1945-12-21	1949-10-11	Ciba Pharm Prod Inc	Hydrazine derivatives of pyridazine compounds
US3882119A (en) *	1970-01-27	1975-05-06	Lepetit Spa	Tetracyclic substituted phthalazine compounds
IL48319A0 (en) *	1974-10-26	1975-12-31	Merck Patent Gmbh	Araliphatic nitrogen compounds and a process for their preparation
JPH01261386A (ja) *	1988-04-11	1989-10-18	Nisshin Flour Milling Co Ltd	新規な２―ピリジルメチルチオ誘導体及びそれを含有する抗潰瘍剤

1992
- 1992-10-16 DE DE59208852T patent/DE59208852D1/de not_active Expired - Fee Related
- 1992-10-16 DK DK92117672.3T patent/DK0539805T3/da active
- 1992-10-16 AT AT92117672T patent/ATE157656T1/de not_active IP Right Cessation
- 1992-10-16 ES ES92117672T patent/ES2108066T3/es not_active Expired - Lifetime
- 1992-10-16 EP EP92117672A patent/EP0539805B1/de not_active Expired - Lifetime
- 1992-10-16 DE DE4234933A patent/DE4234933A1/de not_active Withdrawn
- 1992-10-20 US US07/963,631 patent/US5354750A/en not_active Expired - Fee Related
- 1992-10-28 BR BR929204187A patent/BR9204187A/pt not_active Application Discontinuation
- 1992-10-28 JP JP4290058A patent/JPH05222002A/ja active Pending
- 1992-10-29 MX MX9206245A patent/MX9206245A/es unknown
- 1992-10-29 NO NO92924166A patent/NO924166L/no unknown
- 1992-10-30 KR KR1019920020137A patent/KR930007914A/ko not_active Withdrawn
- 1992-10-30 ZA ZA928420A patent/ZA928420B/xx unknown
- 1992-10-30 AU AU27471/92A patent/AU660726B2/en not_active Ceased
- 1992-10-30 IL IL103601A patent/IL103601A0/xx unknown
- 1992-10-30 FI FI924934A patent/FI924934A7/fi not_active Application Discontinuation
- 1992-10-30 CA CA002081819A patent/CA2081819A1/en not_active Abandoned
- 1992-10-30 CN CN92112607A patent/CN1071916A/zh not_active Withdrawn
- 1992-10-30 HU HU9203431A patent/HUT62866A/hu unknown
- 1992-12-02 TW TW081109717A patent/TW211563B/zh active
1995
- 1995-06-29 HU HU95P/P00584P patent/HU211863A9/hu unknown
1997
- 1997-10-22 GR GR970402773T patent/GR3025141T3/el unknown

Also Published As

Publication number	Publication date
AU2747192A (en)	1993-05-06
NO924166D0 (no)	1992-10-29
FI924934L (fi)	1993-05-01
FI924934A7 (fi)	1993-05-01
DE59208852D1 (de)	1997-10-09
HUT62866A (en)	1993-06-28
TW211563B (2)	1993-08-21
AU660726B2 (en)	1995-07-06
DK0539805T3 (da)	1998-03-23
MX9206245A (es)	1993-05-01
US5354750A (en)	1994-10-11
GR3025141T3 (en)	1998-02-27
BR9204187A (pt)	1993-05-04
ZA928420B (en)	1993-05-14
DE4234933A1 (de)	1993-05-06
JPH05222002A (ja)	1993-08-31
NO924166L (no)	1993-05-03
HU9203431D0 (en)	1993-01-28
HU211863A9 (en)	1995-12-28
ES2108066T3 (es)	1997-12-16
EP0539805B1 (de)	1997-09-03
EP0539805A1 (de)	1993-05-05
KR930007914A (ko)	1993-05-20
FI924934A0 (fi)	1992-10-30
ATE157656T1 (de)	1997-09-15
CA2081819A1 (en)	1993-05-01
IL103601A0 (en)	1993-03-15

Legal Events

Date	Code	Title
1993-05-12	C06	Publication
1993-05-12	PB01	Publication
1995-02-01	C10	Entry into substantive examination
1995-02-01	SE01	Entry into force of request for substantive examination
1997-05-21	C03	Withdrawal of patent application (patent law 1993)
1997-05-21	WW01	Invention patent application withdrawn after publication

Publication	Publication Date	Title
IE47798B1 (en)	1984-06-27	Substituted ortho-anisamides,methods of preparing them,compositions containing them and their application as psychotropic agents
JPH01226818A (ja)	1989-09-11	アリールアミドアザビシクロアルカン類およびアリールチオアミドアザビシクロアルカン類からなる記憶力増進剤または記憶障害治療剤
EP0149088A1 (de)	1985-07-24	Neue Pyridin-2-ether beziehungsweise Pyridin-2-thioether mit einem stickstoffhaltigen cycloaliphatischen Ring sowie deren Sulforide, Sulfone und Pyridin-N-oxide
JPH0729922B2 (ja)	1995-04-05	２‐アルコキシ‐ｎ‐（１‐アザビシクロ［２，２，２オクト‐３‐イル）ベンズアミド類およびチオベンズアミド類
DE2910942A1 (de)	1979-10-04	2-(m-benzoyl-phenoxy)-propionsaeurederivate und sie enthaltende arzneimittel
JPH0211579B2 (2)	1990-03-14
JPH0899882A (ja)	1996-04-16	気管支拡張組成物
JPS62155246A (ja)	1987-07-10	安息香酸および安息香酸エステル誘導体およびそれらの製法
KR850000609B1 (ko)	1985-05-01	5-벤조일-6-클로로(또는 브로모)-1,2-디히드로-3H-피롤로[1,2-a]피롤-1-카르복실산 유도체의 제조방법
US4328344A (en)	1982-05-04	Meta-amino sulfonamido-benzamides
US20020049328A1 (en)	2002-04-25	Processes for producing 7-isoindoline-quinolonecarboxylic acid derivative and its intermediate, as well as salt of 7-isoindoline-quinolonecarboxylic acid derivative, its hydrate and composition comprising the same as active ingredient
US5354750A (en)	1994-10-11	Phthalazines containing an aromatic ether or thioether group in the 1-position
US5206246A (en)	1993-04-27	Anxiolytic-R-n(1-azabicyclo[2.2.2]oct-3-yl) benzamides and thiobenzamides
CA1318595C (en)	1993-06-01	2-alkoxy-n-(1-azabicyclo[2.2.2]oct-3-yl) benzamides and thiobenzamides
JPS61215388A (ja)	1986-09-25	置換ベンズイミダゾール誘導体
CA1132585A (en)	1982-09-28	Phenylaminothiophenacetic acids, processes for their preparation and medicaments containing them
CN117682950A (zh)	2024-03-12	芳（杂）环取代的树豆酮酸a衍生物，药物组合物及其制备方法和应用
ITFI20100001A1 (it)	2011-07-05	Composti ad efficacia sia analgesica che antiperalgesica.
PT1756111E (pt)	2010-06-01	Indoloquinoxalinas com radicais alquilo como substituintes
CN1103762C (zh)	2003-03-26	新的具有抗惊厥活性且4－位上含有二取代氨基的1－芳(烷)基咪唑啉－2－酮类化合物,以及它们的制备方法
EP0894794A1 (en)	1999-02-03	Optical isomers of cloperastine
IL33530A (en)	1973-04-30	Benzylidene amino-oxyalkyl carboxylic acids and carboxylic acid derivatives,their preparation and pharmaceutical compositions containing them
CA1322552C (en)	1993-09-28	Anxiolytic-r-n(1-azabicyclo[2.2.2)oct-3-yl) benzamides and thiobenzamides
JPS5951260A (ja)	1984-03-24	Ｎ−フエニルアミジンの製法
JPH02279660A (ja)	1990-11-15	テトラヒドロナフタレン誘導体