CA1234809A - Oxazepinones aromatiques condensees et leurs analogues sulfures, utiles comme antihistaminiques - Google Patents

Oxazepinones aromatiques condensees et leurs analogues sulfures, utiles comme antihistaminiques

Info

Publication number: CA1234809A
Authority: CA; Canada
Prior art keywords: dihydro; compound; acceptable salt; ethyl; methyl
Prior art date: 1982-09-30
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.): Expired

Application number

CA000438362A

Other languages

English (en)

Inventor

Charles A. Leonard

Bernard V. Franko

Albert D. Cale, Jr.

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.)

Wyeth LLC

Original Assignee

AH Robins Co Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1982-09-30

Filing date

1983-09-30

Publication date

1988-04-05

1983-09-30 Application filed by AH Robins Co Inc filed Critical AH Robins Co Inc

1988-04-05 Application granted granted Critical

1988-04-05 Publication of CA1234809A publication Critical patent/CA1234809A/fr

Status Expired legal-status Critical Current

Links

-1 aromatic oxazepinones Chemical class 0.000 title claims abstract description 170
238000000034 method Methods 0.000 title claims abstract description 147
150000003463 sulfur Chemical class 0.000 title abstract description 4
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 title 2
229960001340 histamine Drugs 0.000 title 1
230000008569 process Effects 0.000 claims abstract description 105
238000002360 preparation method Methods 0.000 claims abstract description 72
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 28
229910052760 oxygen Inorganic materials 0.000 claims abstract description 23
239000001301 oxygen Substances 0.000 claims abstract description 23
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 22
229910052717 sulfur Inorganic materials 0.000 claims abstract description 17
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 16
239000011593 sulfur Substances 0.000 claims abstract description 16
230000001387 anti-histamine Effects 0.000 claims abstract description 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 267
150000001875 compounds Chemical class 0.000 claims description 229
150000003839 salts Chemical class 0.000 claims description 167
239000000460 chlorine Substances 0.000 claims description 153
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 130
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 98
ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 89
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 78
239000002253 acid Chemical group 0.000 claims description 70
UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 67
238000006243 chemical reaction Methods 0.000 claims description 63
239000000047 product Substances 0.000 claims description 63
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 61
229910052739 hydrogen Inorganic materials 0.000 claims description 52
239000001257 hydrogen Substances 0.000 claims description 52
239000011734 sodium Substances 0.000 claims description 52
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 claims description 51
229910052708 sodium Inorganic materials 0.000 claims description 51
125000005843 halogen group Chemical group 0.000 claims description 50
150000003254 radicals Chemical class 0.000 claims description 46
239000002904 solvent Substances 0.000 claims description 42
150000002500 ions Chemical class 0.000 claims description 41
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 41
125000001309 chloro group Chemical group Cl* 0.000 claims description 40
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 39
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 35
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 33
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 32
150000002431 hydrogen Chemical group 0.000 claims description 29
SFJGCXYXEFWEBK-UHFFFAOYSA-N oxazepine Chemical compound O1C=CC=CC=N1 SFJGCXYXEFWEBK-UHFFFAOYSA-N 0.000 claims description 28
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 27
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical group C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 26
125000003118 aryl group Chemical group 0.000 claims description 24
125000004093 cyano group Chemical group *C#N 0.000 claims description 23
229910052757 nitrogen Inorganic materials 0.000 claims description 23
125000000623 heterocyclic group Chemical group 0.000 claims description 22
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 20
239000003795 chemical substances by application Substances 0.000 claims description 20
NYERMPLPURRVGM-UHFFFAOYSA-N thiazepine Chemical compound S1C=CC=CC=N1 NYERMPLPURRVGM-UHFFFAOYSA-N 0.000 claims description 20
229910000104 sodium hydride Inorganic materials 0.000 claims description 19
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 18
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 18
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 18
150000003141 primary amines Chemical class 0.000 claims description 18
239000012312 sodium hydride Substances 0.000 claims description 18
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 17
229910052801 chlorine Inorganic materials 0.000 claims description 17
239000012458 free base Substances 0.000 claims description 17
229910021529 ammonia Inorganic materials 0.000 claims description 16
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
238000010438 heat treatment Methods 0.000 claims description 15
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical group C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 claims description 14
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 14
229910052794 bromium Chemical group 0.000 claims description 14
239000007858 starting material Substances 0.000 claims description 14
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 13
241001061127 Thione Species 0.000 claims description 13
150000001412 amines Chemical class 0.000 claims description 13
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 13
150000003335 secondary amines Chemical class 0.000 claims description 13
AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methylaniline Chemical compound CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 claims description 12
125000004432 carbon atom Chemical group C* 0.000 claims description 12
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 12
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 10
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 10
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 10
230000002140 halogenating effect Effects 0.000 claims description 10
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 10
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 10
CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 claims description 10
JKCJXAVMBWFTTC-UHFFFAOYSA-N thiazepine 1-oxide Chemical compound O=S1C=CC=CC=N1 JKCJXAVMBWFTTC-UHFFFAOYSA-N 0.000 claims description 10
IBRSSZOHCGUTHI-UHFFFAOYSA-N 2-chloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=C1Cl IBRSSZOHCGUTHI-UHFFFAOYSA-N 0.000 claims description 9
150000001299 aldehydes Chemical class 0.000 claims description 9
230000003472 neutralizing effect Effects 0.000 claims description 9
239000000376 reactant Substances 0.000 claims description 9
150000004820 halides Chemical class 0.000 claims description 8
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 claims description 8
229910000105 potassium hydride Inorganic materials 0.000 claims description 8
238000007363 ring formation reaction Methods 0.000 claims description 8
229910052783 alkali metal Inorganic materials 0.000 claims description 7
150000003512 tertiary amines Chemical class 0.000 claims description 7
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 claims description 6
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 5
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 5
125000004122 cyclic group Chemical group 0.000 claims description 5
235000019253 formic acid Nutrition 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
LKZKGRRDUWVNSR-UHFFFAOYSA-N oxazepin-3-one Chemical compound O=C1NOC=CC=C1 LKZKGRRDUWVNSR-UHFFFAOYSA-N 0.000 claims description 5
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 claims description 4
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 claims description 4
VULDZQDXUMXSFD-UHFFFAOYSA-N 1-sulfanylidenethiazepine Chemical compound S=S1C=CC=CC=N1 VULDZQDXUMXSFD-UHFFFAOYSA-N 0.000 claims description 3
RGHPCLZJAFCTIK-UHFFFAOYSA-N 2-methylpyrrolidine Chemical compound CC1CCCN1 RGHPCLZJAFCTIK-UHFFFAOYSA-N 0.000 claims description 3
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 3
239000011737 fluorine Chemical group 0.000 claims description 3
229910052731 fluorine Chemical group 0.000 claims description 3
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
LWXRDBXEIVCNSZ-UHFFFAOYSA-N oxazepine-3-thione Chemical compound S=C1NOC=CC=C1 LWXRDBXEIVCNSZ-UHFFFAOYSA-N 0.000 claims description 3
TVCXVUHHCUYLGX-UHFFFAOYSA-N 2-Methylpyrrole Chemical compound CC1=CC=CN1 TVCXVUHHCUYLGX-UHFFFAOYSA-N 0.000 claims description 2
RGNZODVGZCOGII-UHFFFAOYSA-N 4h-oxazepine-5-thione Chemical compound S=C1CC=NOC=C1 RGNZODVGZCOGII-UHFFFAOYSA-N 0.000 claims description 2
238000007112 amidation reaction Methods 0.000 claims description 2
DXZDEAJXVCLRLE-UHFFFAOYSA-N azepin-2-one Chemical compound O=C1C=CC=CC=N1 DXZDEAJXVCLRLE-UHFFFAOYSA-N 0.000 claims description 2
150000001768 cations Chemical class 0.000 claims description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 2
125000003884 phenylalkyl group Chemical group 0.000 claims description 2
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 2
239000007795 chemical reaction product Substances 0.000 claims 25
125000004433 nitrogen atom Chemical group N* 0.000 claims 9
WVSHDPAFBXVZGC-UHFFFAOYSA-N 2-(2-chloroethyl)-4-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepine-5-thione Chemical compound S=C1N(C)CC(CCCl)OC2=NC=CC=C21 WVSHDPAFBXVZGC-UHFFFAOYSA-N 0.000 claims 5
DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
230000009467 reduction Effects 0.000 claims 4
238000006722 reduction reaction Methods 0.000 claims 4
VSABEHKRJMWYNR-UHFFFAOYSA-N 2-(2-aminoethyl)-4-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one Chemical compound O=C1N(C)CC(CCN)OC2=NC=CC=C21 VSABEHKRJMWYNR-UHFFFAOYSA-N 0.000 claims 3
STSZUFICUXVPMD-UHFFFAOYSA-N 2-(2-aminoethyl)-4-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepine-5-thione Chemical compound S=C1N(C)CC(CCN)OC2=NC=CC=C21 STSZUFICUXVPMD-UHFFFAOYSA-N 0.000 claims 3
AMGSWNMQLPCPOH-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-4-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one Chemical compound O1C(CN(C)C)CN(C)C(=O)C2=CC=CN=C21 AMGSWNMQLPCPOH-UHFFFAOYSA-N 0.000 claims 3
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims 3
PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 claims 3
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 2
ALCFXZOCRYTXCW-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-4-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepine-5-thione Chemical compound O1C(CN(C)C)CN(C)C(=S)C2=CC=CN=C21 ALCFXZOCRYTXCW-UHFFFAOYSA-N 0.000 claims 2
JLVOGZVGPHLBHD-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]-3,4-dihydro-2h-pyrido[3,2-f][1,4]oxazepin-5-one Chemical compound O1C(CCN(C)C)CNC(=O)C2=CC=CN=C21 JLVOGZVGPHLBHD-UHFFFAOYSA-N 0.000 claims 2
YZGOSPARCZPUNX-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]-3,4-dihydro-2h-pyrido[3,2-f][1,4]oxazepine-5-thione Chemical compound O1C(CCN(C)C)CN=C(S)C2=CC=CN=C21 YZGOSPARCZPUNX-UHFFFAOYSA-N 0.000 claims 2
OHGAIBSIEJHPIF-UHFFFAOYSA-N 2-[2-(dimethylamino)ethyl]-4-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one Chemical compound O1C(CCN(C)C)CN(C)C(=O)C2=CC=CN=C21 OHGAIBSIEJHPIF-UHFFFAOYSA-N 0.000 claims 2
LMARXFGQYAYYQT-UHFFFAOYSA-N 4-methyl-2-(2-piperidin-1-ylethyl)-2,3-dihydropyrido[3,2-f][1,4]oxazepine-5-thione Chemical compound O1C2=NC=CC=C2C(=S)N(C)CC1CCN1CCCCC1 LMARXFGQYAYYQT-UHFFFAOYSA-N 0.000 claims 2
OJYGUYLOVRXCQY-UHFFFAOYSA-N 4-methyl-2-[2-(2-methylpyrrolidin-1-yl)ethyl]-2,3-dihydropyrido[3,2-f][1,4]oxazepine-5-thione Chemical compound CC1CCCN1CCC1OC2=NC=CC=C2C(=S)N(C)C1 OJYGUYLOVRXCQY-UHFFFAOYSA-N 0.000 claims 2
KVHXXPXXRSVKJC-UHFFFAOYSA-N 4-methyl-2-[2-(4-methylpiperazin-1-yl)ethyl]-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one Chemical compound C1CN(C)CCN1CCC1OC2=NC=CC=C2C(=O)N(C)C1 KVHXXPXXRSVKJC-UHFFFAOYSA-N 0.000 claims 2
WWZOSYINDDDDHF-UHFFFAOYSA-N 4-methyl-2-[2-(4-methylpiperazin-1-yl)ethyl]-2,3-dihydropyrido[3,2-f][1,4]oxazepine-5-thione Chemical compound C1CN(C)CCN1CCC1OC2=NC=CC=C2C(=S)N(C)C1 WWZOSYINDDDDHF-UHFFFAOYSA-N 0.000 claims 2
ZTKITZJVKQFLCV-UHFFFAOYSA-N 4-methyl-2-[2-(methylamino)ethyl]-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one Chemical compound O1C(CCNC)CN(C)C(=O)C2=CC=CN=C21 ZTKITZJVKQFLCV-UHFFFAOYSA-N 0.000 claims 2
ZXQCFUSIQJIRGN-UHFFFAOYSA-N 4-methyl-2-[2-(n-methylanilino)ethyl]-2,3-dihydropyrido[3,2-f][1,4]oxazepine-5-thione Chemical compound C1N(C)C(=S)C2=CC=CN=C2OC1CCN(C)C1=CC=CC=C1 ZXQCFUSIQJIRGN-UHFFFAOYSA-N 0.000 claims 2
BTQQLYFLQGFYBV-UHFFFAOYSA-N 6-chloro-2-(2-chloroethyl)-4-methyl-2,3-dihydropyrido[4,3-f][1,4]oxazepin-5-one Chemical compound O=C1N(C)CC(CCCl)OC2=CN=CC(Cl)=C21 BTQQLYFLQGFYBV-UHFFFAOYSA-N 0.000 claims 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical group [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims 2
125000003277 amino group Chemical group 0.000 claims 2
JWALPKATZIMQNG-UHFFFAOYSA-N azepine-2-thione Chemical compound S=C1C=CC=CC=N1 JWALPKATZIMQNG-UHFFFAOYSA-N 0.000 claims 2
150000002366 halogen compounds Chemical class 0.000 claims 2
125000004957 naphthylene group Chemical group 0.000 claims 2
229960003966 nicotinamide Drugs 0.000 claims 2
239000011570 nicotinamide Substances 0.000 claims 2
235000005152 nicotinamide Nutrition 0.000 claims 2
125000004430 oxygen atom Chemical group O* 0.000 claims 2
125000006239 protecting group Chemical group 0.000 claims 2
125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims 2
XNMHCMQTWIAATP-UHFFFAOYSA-N 2-(2-chloroethyl)-4-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one Chemical compound O=C1N(C)CC(CCCl)OC2=NC=CC=C21 XNMHCMQTWIAATP-UHFFFAOYSA-N 0.000 claims 1
GVEWVPHTXSJGSP-UHFFFAOYSA-N 2-(2-chloropropyl)-4-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one Chemical compound O1C(CC(Cl)C)CN(C)C(=O)C2=CC=CN=C21 GVEWVPHTXSJGSP-UHFFFAOYSA-N 0.000 claims 1
QEVAXSTVHNVMTB-UHFFFAOYSA-N 2-(2-imidazol-1-ylethyl)-4-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one Chemical compound O1C2=NC=CC=C2C(=O)N(C)CC1CCN1C=CN=C1 QEVAXSTVHNVMTB-UHFFFAOYSA-N 0.000 claims 1
IEPJTALWQNKZFL-UHFFFAOYSA-N 2-(2-imidazol-1-ylethyl)-4-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepine-5-thione Chemical compound O1C2=NC=CC=C2C(=S)N(C)CC1CCN1C=CN=C1 IEPJTALWQNKZFL-UHFFFAOYSA-N 0.000 claims 1
YWNFNHUTYHWVRS-UHFFFAOYSA-N 2-(3-aminopropyl)-4-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepin-5-one Chemical compound O=C1N(C)CC(CCCN)OC2=NC=CC=C21 YWNFNHUTYHWVRS-UHFFFAOYSA-N 0.000 claims 1
ITUNNRRXOXDPEW-UHFFFAOYSA-N 2-(3-aminopropyl)-4-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepine-5-thione Chemical compound S=C1N(C)CC(CCCN)OC2=NC=CC=C21 ITUNNRRXOXDPEW-UHFFFAOYSA-N 0.000 claims 1
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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
239000003960 organic solvent Substances 0.000 description 1
239000002245 particle Substances 0.000 description 1
239000008188 pellet Substances 0.000 description 1
RLZZZVKAURTHCP-UHFFFAOYSA-N phenanthrene-3,4-diol Chemical compound C1=CC=C2C3=C(O)C(O)=CC=C3C=CC2=C1 RLZZZVKAURTHCP-UHFFFAOYSA-N 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
238000002953 preparative HPLC Methods 0.000 description 1
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
125000006308 propyl amino group Chemical group 0.000 description 1
230000002633 protecting effect Effects 0.000 description 1
239000003586 protic polar solvent Substances 0.000 description 1
238000000746 purification Methods 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 description 1
238000010791 quenching Methods 0.000 description 1
ZEXKKIXCRDTKBF-UHFFFAOYSA-N quinoline-2-carboxamide Chemical compound C1=CC=CC2=NC(C(=O)N)=CC=C21 ZEXKKIXCRDTKBF-UHFFFAOYSA-N 0.000 description 1
102220044643 rs587781450 Human genes 0.000 description 1
JZWFDVDETGFGFC-UHFFFAOYSA-N salacetamide Chemical group CC(=O)NC(=O)C1=CC=CC=C1O JZWFDVDETGFGFC-UHFFFAOYSA-N 0.000 description 1
230000007017 scission Effects 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
239000007921 spray Substances 0.000 description 1
229910001220 stainless steel Inorganic materials 0.000 description 1
239000010935 stainless steel Substances 0.000 description 1
125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
150000008054 sulfonate salts Chemical class 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012976 tarts Nutrition 0.000 description 1
125000001302 tertiary amino group Chemical group 0.000 description 1
238000010998 test method Methods 0.000 description 1
238000012360 testing method Methods 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000012546 transfer Methods 0.000 description 1
238000011282 treatment Methods 0.000 description 1
VLPFTAMPNXLGLX-UHFFFAOYSA-N trioctanoin Chemical compound CCCCCCCC(=O)OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC VLPFTAMPNXLGLX-UHFFFAOYSA-N 0.000 description 1
FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
229940116269 uric acid Drugs 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
238000005406 washing Methods 0.000 description 1
238000005303 weighing Methods 0.000 description 1

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Plural Heterocyclic Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000438362A 1982-09-30 1983-09-30 Oxazepinones aromatiques condensees et leurs analogues sulfures, utiles comme antihistaminiques Expired CA1234809A (fr)

Applications Claiming Priority (10)

Application Number	Priority Date	Filing Date
US43199882A	1982-09-30	1982-09-30
US43150082A	1982-09-30	1982-09-30
US431,500		1982-09-30
US431,998		1982-09-30
US52755983A	1983-08-29	1983-08-29
US52755883A	1983-08-29	1983-08-29
US527,558		1983-08-29
US527,559		1983-08-29
US65205884A	1984-09-19	1984-09-19
US652,058		1984-09-19

Publications (1)

Publication Number	Publication Date
CA1234809A true CA1234809A (fr)	1988-04-05

Family

ID=27541589

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000438362A Expired CA1234809A (fr)	1982-09-30	1983-09-30	Oxazepinones aromatiques condensees et leurs analogues sulfures, utiles comme antihistaminiques

Country Status (1)

Country	Link
CA (1)	CA1234809A (fr)

1983
- 1983-09-30 CA CA000438362A patent/CA1234809A/fr not_active Expired

Legal Events

Date	Code	Title	Description
2005-04-05	MKEX	Expiry

Publication	Publication Date	Title
AU643337B2 (en)	1993-11-11	Condensed heterocyclic compounds, their production and use
FI93012B (fi)	1994-10-31	Menetelmä terapeuttisesti käyttökelpoisten (1-hydroksi-2-piperidinoalkyyli)-2-indoloni-, 2-kinoloni-, 2-bentso/b/-atsepinoni-, bentsimidatsoloni- ja 2-kinatsolinonijohdannaisten valmistamiseksi
US4933336A (en)	1990-06-12	Thiadiazinone, oxadiazinone and triazinone derivatives, and their use for treating acute or chronic heart disease
SK282476B6 (sk)	2002-02-05	Derivát benzylpiperidínu, spôsob jeho prípravy, jeho použitie a farmaceutický prostriedok, ktorý ho obsahuje
CS201040B2 (en)	1980-10-31	Method of producing etherified hydroxy-benzo-diheterocyclic compounds
CH672126A5 (fr)	1989-10-31
HU206709B (en)	1992-12-28	Process for producing new 3-/4-/1-substituted-4-piperazinyl/-butyl/-4-thiazolidinone derivatives and pharmaceutical compositions containing them
NZ230068A (en)	1991-07-26	Indazole-3-carboxylic acid esters and amides of diaza compounds having 6,7, or 8 ring members: preparatory processes and pharmaceutical compositions
FI78103C (fi)	1989-06-12	Foerfarande foer framstaellning av terapeutiskt anvaendbara 11-substituerade 5h,11h-pyrrolo/2,1-c//1,4/ bensoxazepiner.
EP0107930B1 (fr)	1990-11-28	Oxazépinones aromatiques condensées et analogues du soufre, leur préparation et utilisation comme antagonistes de l'histamine
KR870001362B1 (ko)	1987-07-20	테트라하이드로 이미다조퀴나졸리논 유도체의 제조방법
CA1234809A (fr)	1988-04-05	Oxazepinones aromatiques condensees et leurs analogues sulfures, utiles comme antihistaminiques
EP0670313A1 (fr)	1995-09-06	Composés spiranniques, leur préparation et leur utilisation
US4748280A (en)	1988-05-31	Certain chlorination process for preparing 2-chloro-1,1,1-(C1 -C6)
KR100382998B1 (ko)	2003-08-27	6-메톡시-1h-벤조트리아졸-5-카르복사미드유도체,그제조방법및그것을함유하는의약조성물
US5917047A (en)	1999-06-29	Heterocyclic compounds
DE68910593T2 (de)	1994-04-14	Chinolinoncarbonsäuren.
CA1253145A (fr)	1989-04-25	Oxazepinones, diazepinones et thiazepinones aromatique condensees et leurs analogues sulfures
EP0197318B1 (fr)	1990-05-09	Benzo[c]-1,5-naphtyridines, un procédé et des produits intermédiaires pour leur préparation et leur utilisation comme médicaments
US4604388A (en)	1986-08-05	Fused aromatic oxazepinones, thiazepinones, diazepinones and sulfur analogs thereof in a method of counteracting histamine
KR100254106B1 (ko)	2000-05-01	4-퀴놀리논 유도체 또는 그의 염
JPH0753715B2 (ja)	1995-06-07	ベンゾヘテロ環化合物
KR890001184B1 (ko)	1989-04-26	융합된 방향족 디아제피논 및 이의 황동족체
US4975427A (en)	1990-12-04	17-sulfur-20,21-dinor-eburnamenines
FI78290C (fi)	1989-07-10	3-(pyridyloxi)pyrrolidin- och 3-(pyridyloxi)-azedinderivat, som aer anvaendbara som mellanprodukter.