NO309605B1 - Nye piperazinforbindelser, farmasöytiske preparater inneholdende slike forbindelser, og deres anvendelse - Google Patents

Info

Publication number

NO309605B1

NO309605B1 NO971305A NO971305A NO309605B1 NO 309605 B1 NO309605 B1 NO 309605B1 NO 971305 A NO971305 A NO 971305A NO 971305 A NO971305 A NO 971305A NO 309605 B1 NO309605 B1 NO 309605B1

Authority

NO

Norway

Prior art keywords

cis

piperazinecarboxylate

bis

cyclooctylene

trans

Prior art date

1994-09-23

Links

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• 150000001875 compounds Chemical class 0.000 title claims description 177
• 239000000825 pharmaceutical preparation Substances 0.000 title claims description 15
• 150000004885 piperazines Chemical class 0.000 title description 2
• 239000000203 mixture Substances 0.000 claims description 52
• 125000002947 alkylene group Chemical group 0.000 claims description 45
• -1 amino, guanidino Chemical group 0.000 claims description 44
• 238000011282 treatment Methods 0.000 claims description 35
• 150000003839 salts Chemical class 0.000 claims description 31
• 208000006673 asthma Diseases 0.000 claims description 30
• 238000002360 preparation method Methods 0.000 claims description 25
• 208000027866 inflammatory disease Diseases 0.000 claims description 22
• 239000000443 aerosol Substances 0.000 claims description 21
• 230000001404 mediated effect Effects 0.000 claims description 19
• 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 15
• KWKAKUADMBZCLK-UHFFFAOYSA-N 1-octene Chemical group CCCCCCC=C KWKAKUADMBZCLK-UHFFFAOYSA-N 0.000 claims description 15
• KNOCWIRLLNOGLX-UHFFFAOYSA-N C1=CC(=CC=C1CNC(=O)CNC(=O)O)N=C(N)N Chemical compound C1=CC(=CC=C1CNC(=O)CNC(=O)O)N=C(N)N KNOCWIRLLNOGLX-UHFFFAOYSA-N 0.000 claims description 14
• 239000000651 prodrug Substances 0.000 claims description 12
• 229940002612 prodrug Drugs 0.000 claims description 12
• 125000000217 alkyl group Chemical group 0.000 claims description 11
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 11
• 239000003937 drug carrier Substances 0.000 claims description 10
• 125000005407 trans-1,4-cyclohexylene group Chemical group [H]C1([H])C([H])([H])[C@]([H])([*:2])C([H])([H])C([H])([H])[C@@]1([H])[*:1] 0.000 claims description 10
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 8
• 125000005842 heteroatom Chemical group 0.000 claims description 8
• 239000001257 hydrogen Substances 0.000 claims description 8
• 229910052739 hydrogen Inorganic materials 0.000 claims description 8
• 230000001225 therapeutic effect Effects 0.000 claims description 7
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• 125000004978 cyclooctylene group Chemical group 0.000 claims description 6
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• ZGEGCLOFRBLKSE-UHFFFAOYSA-N 1-Heptene Chemical group CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 claims description 5
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• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 4
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• 206010010741 Conjunctivitis Diseases 0.000 claims description 3
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 3
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• XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 claims description 2
• LSLYOANBFKQKPT-DIFFPNOSSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]benzene-1,3-diol Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(O)C=C(O)C=1)C1=CC=C(O)C=C1 LSLYOANBFKQKPT-DIFFPNOSSA-N 0.000 claims description 2
• 241000124008 Mammalia Species 0.000 claims description 2
• DBCJCAUXOLQIFH-UHFFFAOYSA-N NC(=N)Nc1ccc(CNC(=O)N2CCN(CC2)C(=O)OC2CCCCCCC2)cc1 Chemical compound NC(=N)Nc1ccc(CNC(=O)N2CCN(CC2)C(=O)OC2CCCCCCC2)cc1 DBCJCAUXOLQIFH-UHFFFAOYSA-N 0.000 claims description 2
• NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 claims description 2
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• BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 claims description 2
• 229960002052 salbutamol Drugs 0.000 claims description 2
• 229960000195 terbutaline Drugs 0.000 claims description 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 4
• AFFLGGQVNFXPEV-UHFFFAOYSA-N 1-decene Chemical group CCCCCCCCC=C AFFLGGQVNFXPEV-UHFFFAOYSA-N 0.000 claims 3
• 150000007942 carboxylates Chemical class 0.000 claims 1
• 125000006639 cyclohexyl carbonyl group Chemical group 0.000 claims 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
• RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 claims 1
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• 239000000243 solution Substances 0.000 description 55
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• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 48
• 238000000034 method Methods 0.000 description 44
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• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
• 238000001914 filtration Methods 0.000 description 26
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
• 229940126214 compound 3 Drugs 0.000 description 22
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 19
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 19
• 241001494479 Pecora Species 0.000 description 18
• 238000001035 drying Methods 0.000 description 18
• 238000006243 chemical reaction Methods 0.000 description 16
• 210000003630 histaminocyte Anatomy 0.000 description 16
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 15
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• 239000012044 organic layer Substances 0.000 description 15
• 239000000725 suspension Substances 0.000 description 15
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
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