PL178329B1

PL178329B1 - Nowe sulfonamidy, sposób ich wytwarzania oraz zawierająca je kompozycja farmaceutyczna

Nowe sulfonamidy, sposób ich wytwarzania oraz zawierająca je kompozycja farmaceutyczna

Info

Publication number: PL178329B1
Authority: PL; Poland
Prior art keywords: group; methoxy; butyl; chloro; benzenesulfonamide
Prior art date: 1992-12-10

Application number

PL93301394A

Other languages

English (en)

Polish (pl)

Other versions

PL301394A1 (en

Inventor

Volker Breu

Kaspar Burri

Jean-Marie Cassal

Martine Clozel

Georges Hirth

Bernd-Michael Löffler

Marcel Müller

Werner Neidhart

Henri Ramuz

Original Assignee

Hoffmann La Roche

Priority date

1992-12-10

Filing date

1993-12-09

Publication date

2000-04-28

1993-12-09 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1994-06-13 Publication of PL301394A1 publication Critical patent/PL301394A1/xx

2000-04-28 Publication of PL178329B1 publication Critical patent/PL178329B1/pl

Links

229940124530 sulfonamide Drugs 0.000 title claims abstract description 16
150000003456 sulfonamides Chemical class 0.000 title claims abstract description 12
150000001875 compounds Chemical class 0.000 title claims description 101
238000000034 method Methods 0.000 title claims description 7
239000008194 pharmaceutical composition Substances 0.000 title claims description 4
-1 methylenedioxy group Chemical group 0.000 claims abstract description 97
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 30
125000003545 alkoxy group Chemical group 0.000 claims abstract description 25
229910052736 halogen Inorganic materials 0.000 claims abstract description 22
125000005843 halogen group Chemical group 0.000 claims abstract description 18
150000002367 halogens Chemical class 0.000 claims abstract description 18
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 17
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 14
239000001257 hydrogen Substances 0.000 claims abstract description 11
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 9
125000004414 alkyl thio group Chemical group 0.000 claims abstract description 9
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical group FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims abstract description 9
150000003839 salts Chemical class 0.000 claims abstract description 9
125000004122 cyclic group Chemical group 0.000 claims abstract description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
125000003118 aryl group Chemical group 0.000 claims abstract description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 6
125000002541 furyl group Chemical group 0.000 claims abstract description 5
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 5
229910052740 iodine Inorganic materials 0.000 claims abstract description 4
125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 4
125000001544 thienyl group Chemical group 0.000 claims abstract description 4
125000006701 (C1-C7) alkyl group Chemical group 0.000 claims abstract 7
125000004076 pyridyl group Chemical group 0.000 claims abstract 2
125000000217 alkyl group Chemical group 0.000 claims description 24
238000002360 preparation method Methods 0.000 claims description 16
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 11
229910052783 alkali metal Inorganic materials 0.000 claims description 6
150000002148 esters Chemical class 0.000 claims description 5
CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 4
239000004480 active ingredient Substances 0.000 claims description 4
239000000654 additive Substances 0.000 claims description 4
150000001340 alkali metals Chemical class 0.000 claims description 4
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 4
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
IHCCAYCGZOLTEU-UHFFFAOYSA-N Furane-3-carboxylic acid Natural products OC(=O)C=1C=COC=1 IHCCAYCGZOLTEU-UHFFFAOYSA-N 0.000 claims description 3
150000001768 cations Chemical class 0.000 claims description 3
YNVOMSDITJMNET-UHFFFAOYSA-N thiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 claims description 3
125000000229 (C1-C4)alkoxy group Chemical group 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
150000002431 hydrogen Chemical class 0.000 claims 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
PAEXAIBDCHBNDC-UHFFFAOYSA-N 2-pyridin-4-ylacetic acid Chemical compound OC(=O)CC1=CC=NC=C1 PAEXAIBDCHBNDC-UHFFFAOYSA-N 0.000 claims 1
KUGKCBHYBZOJDP-UHFFFAOYSA-N 4-tert-butyl-n-[2-formyl-6-methoxy-5-(2-methoxyphenyl)sulfanylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=CC=C1SC(C(=NC(C=O)=N1)OC)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 KUGKCBHYBZOJDP-UHFFFAOYSA-N 0.000 claims 1
OKRXZGIWGKFMGX-FQEVSTJZSA-N 4-tert-butyl-n-[5-(2-chloro-4-methoxyphenoxy)-6-[[(2s)-2,3-dihydroxypropoxy]methyl]-2-morpholin-4-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound ClC1=CC(OC)=CC=C1OC1=C(COC[C@@H](O)CO)N=C(N2CCOCC2)N=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 OKRXZGIWGKFMGX-FQEVSTJZSA-N 0.000 claims 1
BKPGYJBAWIADLW-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-2-(chloromethyl)-6-methoxypyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC(CCl)=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)OC)=C1 BKPGYJBAWIADLW-UHFFFAOYSA-N 0.000 claims 1
BKRUAPWYLGMLSG-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-2-formyl-6-methoxypyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC(C=O)=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)OC)=C1 BKRUAPWYLGMLSG-UHFFFAOYSA-N 0.000 claims 1
QZGVJJGVQZEPKV-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-2-methyl-4-oxo-1h-pyrimidin-6-yl]benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(N=C(C)NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)=O)=C1 QZGVJJGVQZEPKV-UHFFFAOYSA-N 0.000 claims 1
LUQGFYZOMJBYGC-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-6-(2,3-dihydroxypropoxymethyl)-2-morpholin-4-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC(=NC=2COCC(O)CO)N2CCOCC2)NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)=C1 LUQGFYZOMJBYGC-UHFFFAOYSA-N 0.000 claims 1
USXXYJBMYGYYGJ-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-6-(2-hydroxyethoxymethyl)pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC=NC=2COCCO)NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)=C1 USXXYJBMYGYYGJ-UHFFFAOYSA-N 0.000 claims 1
JIYHYXIBFLNJSK-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-6-(chloromethyl)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC(=NC=2CCl)C=2N=CC=CN=2)NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)=C1 JIYHYXIBFLNJSK-UHFFFAOYSA-N 0.000 claims 1
QYMJVEOQDDDIQV-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-6-(hydroxymethyl)-2-pyrimidin-2-ylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC(=NC=2CO)C=2N=CC=CN=2)NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)=C1 QYMJVEOQDDDIQV-UHFFFAOYSA-N 0.000 claims 1
XJVWOIPAJCYJEK-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-6-[(2,3-dihydroxypropylamino)methyl]pyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC=NC=2CNCC(O)CO)NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)=C1 XJVWOIPAJCYJEK-UHFFFAOYSA-N 0.000 claims 1
VKFZJTKODAYTIP-UHFFFAOYSA-N 4-tert-butyl-n-[5-(2-chloro-5-methoxyphenoxy)-6-methoxy-2-methylpyrimidin-4-yl]benzenesulfonamide Chemical compound COC1=CC=C(Cl)C(OC=2C(=NC(C)=NC=2NS(=O)(=O)C=2C=CC(=CC=2)C(C)(C)C)OC)=C1 VKFZJTKODAYTIP-UHFFFAOYSA-N 0.000 claims 1
KYDZEZNYRFJCSA-UHFFFAOYSA-N 4-tert-butylbenzenesulfonamide Chemical compound CC(C)(C)C1=CC=C(S(N)(=O)=O)C=C1 KYDZEZNYRFJCSA-UHFFFAOYSA-N 0.000 claims 1
KTAZPNLOPIXDGP-UHFFFAOYSA-N C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=C(C=CC(=C1)OC)Cl)C(N)CCO Chemical compound C(C)(C)(C)C1=CC=C(C=C1)S(=O)(=O)NC1=NC=NC(=C1OC1=C(C=CC(=C1)OC)Cl)C(N)CCO KTAZPNLOPIXDGP-UHFFFAOYSA-N 0.000 claims 1
125000002757 morpholinyl group Chemical group 0.000 claims 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
WBLIXGSTEMXDSM-UHFFFAOYSA-N chloromethane Chemical compound Cl[CH2] WBLIXGSTEMXDSM-UHFFFAOYSA-N 0.000 abstract 1
125000001145 hydrido group Chemical group *[H] 0.000 abstract 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
239000000243 solution Substances 0.000 description 20
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
239000000460 chlorine Substances 0.000 description 15
238000006243 chemical reaction Methods 0.000 description 13
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
239000000741 silica gel Substances 0.000 description 11
229910002027 silica gel Inorganic materials 0.000 description 11
239000000126 substance Substances 0.000 description 11
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
239000012074 organic phase Substances 0.000 description 10
239000011734 sodium Substances 0.000 description 10
239000002904 solvent Substances 0.000 description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
239000011541 reaction mixture Substances 0.000 description 9
229910052708 sodium Inorganic materials 0.000 description 9
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 8
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 8
239000002253 acid Substances 0.000 description 8
125000001424 substituent group Chemical group 0.000 description 8
102000002045 Endothelin Human genes 0.000 description 7
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VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 7
239000007858 starting material Substances 0.000 description 7
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
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229910052786 argon Inorganic materials 0.000 description 5
229910052801 chlorine Inorganic materials 0.000 description 5
125000004494 ethyl ester group Chemical group 0.000 description 5
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 5
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
239000007983 Tris buffer Substances 0.000 description 4
239000002775 capsule Substances 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
FHHZOYXKOICLGH-UHFFFAOYSA-N dichloromethane;ethanol Chemical compound CCO.ClCCl FHHZOYXKOICLGH-UHFFFAOYSA-N 0.000 description 4
201000010099 disease Diseases 0.000 description 4
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
230000000694 effects Effects 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 4
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 4
KQIGMPWTAHJUMN-UHFFFAOYSA-N 3-aminopropane-1,2-diol Chemical compound NCC(O)CO KQIGMPWTAHJUMN-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
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125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 3
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125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
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TWBYWOBDOCUKOW-UHFFFAOYSA-N isonicotinic acid Chemical compound OC(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-N 0.000 description 2
239000008101 lactose Substances 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
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VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 2
125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
229910052938 sodium sulfate Inorganic materials 0.000 description 2
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