ZA200203942B - Isoxazolecarboxamide derivatives. - Google Patents

Isoxazolecarboxamide derivatives. Download PDF

Info

Publication number: ZA200203942B
Authority: ZA; South Africa
Prior art keywords: phenyl; carboxamide; piperazinyl; propyl; trifluoroethoxy
Prior art date: 1999-10-18

Application number

ZA200203942A

Other languages

English (en)

Inventor

Amedeo Leonardi

Gianni Motta

Elena Poggesi

Carlo Riva

Original Assignee

Recordati Chem Pharm

Chemical & Pharmaceutical Co

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.)

1999-10-18

Filing date

2002-05-17

Publication date

2003-01-02

2002-05-17 Application filed by Recordati Chem Pharm, Chemical & Pharmaceutical Co filed Critical Recordati Chem Pharm

2003-01-02 Publication of ZA200203942B publication Critical patent/ZA200203942B/en

Links

LKYNGTHMKCTTQC-UHFFFAOYSA-N 1,2-oxazole-3-carboxamide Chemical class NC(=O)C=1C=CON=1 LKYNGTHMKCTTQC-UHFFFAOYSA-N 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims description 108
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 36
238000000034 method Methods 0.000 claims description 29
-1 polyfluoroalkoxy Chemical group 0.000 claims description 29
239000002904 solvent Substances 0.000 claims description 29
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 21
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
125000003545 alkoxy group Chemical group 0.000 claims description 14
125000000217 alkyl group Chemical group 0.000 claims description 14
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 12
238000009833 condensation Methods 0.000 claims description 11
230000005494 condensation Effects 0.000 claims description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
125000005843 halogen group Chemical group 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 10
239000003795 chemical substances by application Substances 0.000 claims description 9
150000001204 N-oxides Chemical class 0.000 claims description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 6
150000001408 amides Chemical class 0.000 claims description 6
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical class C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 claims description 6
229910000027 potassium carbonate Inorganic materials 0.000 claims description 6
238000002360 preparation method Methods 0.000 claims description 6
125000004093 cyano group Chemical group *C#N 0.000 claims description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
150000003839 salts Chemical class 0.000 claims description 5
125000004442 acylamino group Chemical group 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
125000003710 aryl alkyl group Chemical group 0.000 claims description 4
125000005518 carboxamido group Chemical group 0.000 claims description 4
150000002148 esters Chemical class 0.000 claims description 4
230000001737 promoting effect Effects 0.000 claims description 4
125000001424 substituent group Chemical group 0.000 claims description 4
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 3
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 claims description 3
150000001412 amines Chemical class 0.000 claims description 3
150000008064 anhydrides Chemical class 0.000 claims description 3
239000000010 aprotic solvent Substances 0.000 claims description 3
ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 claims description 3
125000004193 piperazinyl group Chemical group 0.000 claims description 3
239000002798 polar solvent Substances 0.000 claims description 3
125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims description 2
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
VBQXLSIMJIAZOB-UHFFFAOYSA-N n-[3-[4-(5-chloro-2-hydroxyphenyl)piperazin-1-yl]propyl]-5-methyl-3-phenyl-1,2-oxazole-4-carboxamide Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C(=O)NCCCN(CC1)CCN1C1=CC(Cl)=CC=C1O VBQXLSIMJIAZOB-UHFFFAOYSA-N 0.000 claims description 2
BXGFKBLMXSXOFE-UHFFFAOYSA-N n-[3-[4-[5-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl]propyl]-5-methyl-3-phenyl-1,2-oxazole-4-carboxamide Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C(=O)NCCCN(CC1)CCN1C1=CC(F)=CC=C1OCC(F)(F)F BXGFKBLMXSXOFE-UHFFFAOYSA-N 0.000 claims description 2
229910052801 chlorine Inorganic materials 0.000 claims 5
229910052731 fluorine Inorganic materials 0.000 claims 4
LYPXTDXYEQEIIN-UHFFFAOYSA-N 1,2-oxazole-4-carboxylic acid Chemical class OC(=O)C=1C=NOC=1 LYPXTDXYEQEIIN-UHFFFAOYSA-N 0.000 claims 3
125000001309 chloro group Chemical group Cl* 0.000 claims 3
QYQWBSNRTSANPD-UHFFFAOYSA-N 3-(3-fluorophenyl)-5-methyl-n-[3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl]propyl]-1,2-oxazole-4-carboxamide Chemical compound CC=1ON=C(C=2C=C(F)C=CC=2)C=1C(=O)NCCCN(CC1)CCN1C1=CC=CC=C1OCC(F)(F)F QYQWBSNRTSANPD-UHFFFAOYSA-N 0.000 claims 2
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims 2
239000000460 chlorine Substances 0.000 claims 2
125000001153 fluoro group Chemical group F* 0.000 claims 2
125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
LTMKIBSJYYJZHM-UHFFFAOYSA-N 3-(2,6-dichlorophenyl)-5-methyl-n-[3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl]propyl]-1,2-oxazole-4-carboxamide Chemical compound CC=1ON=C(C=2C(=CC=CC=2Cl)Cl)C=1C(=O)NCCCN(CC1)CCN1C1=CC=CC=C1OCC(F)(F)F LTMKIBSJYYJZHM-UHFFFAOYSA-N 0.000 claims 1
CVQNKARALCHNAS-UHFFFAOYSA-N 3-(2-chloro-6-fluorophenyl)-5-methyl-n-[3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl]propyl]-1,2-oxazole-4-carboxamide Chemical compound CC=1ON=C(C=2C(=CC=CC=2F)Cl)C=1C(=O)NCCCN(CC1)CCN1C1=CC=CC=C1OCC(F)(F)F CVQNKARALCHNAS-UHFFFAOYSA-N 0.000 claims 1
CIXALRUGDOXQKP-UHFFFAOYSA-N 3-(2-chloro-6-fluorophenyl)-n-[3-[4-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl]propyl]-5-methyl-1,2-oxazole-4-carboxamide Chemical compound CC=1ON=C(C=2C(=CC=CC=2F)Cl)C=1C(=O)NCCCN(CC1)CCN1C1=CC=C(F)C=C1OCC(F)(F)F CIXALRUGDOXQKP-UHFFFAOYSA-N 0.000 claims 1
BIBMRCVZOOVSSW-UHFFFAOYSA-N 3-(2-chlorophenyl)-5-methyl-n-[3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl]propyl]-1,2-oxazole-4-carboxamide Chemical compound CC=1ON=C(C=2C(=CC=CC=2)Cl)C=1C(=O)NCCCN(CC1)CCN1C1=CC=CC=C1OCC(F)(F)F BIBMRCVZOOVSSW-UHFFFAOYSA-N 0.000 claims 1
DOVMWSFHORVQLK-UHFFFAOYSA-N 3-(2-fluorophenyl)-n-[3-[4-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl]propyl]-5-methyl-1,2-oxazole-4-carboxamide Chemical compound CC=1ON=C(C=2C(=CC=CC=2)F)C=1C(=O)NCCCN(CC1)CCN1C1=CC=C(F)C=C1OCC(F)(F)F DOVMWSFHORVQLK-UHFFFAOYSA-N 0.000 claims 1
MIBCESAHFHRICP-UHFFFAOYSA-N 3-(4-fluorophenyl)-n-[3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl]propyl]-1,2-oxazole-4-carboxamide Chemical compound C1=CC(F)=CC=C1C1=NOC=C1C(=O)NCCCN1CCN(C=2C(=CC=CC=2)OCC(F)(F)F)CC1 MIBCESAHFHRICP-UHFFFAOYSA-N 0.000 claims 1
DRZJSWSDRUEMMV-UHFFFAOYSA-N 3-phenyl-n-[3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl]propyl]-1,2-oxazole-4-carboxamide Chemical compound FC(F)(F)COC1=CC=CC=C1N1CCN(CCCNC(=O)C=2C(=NOC=2)C=2C=CC=CC=2)CC1 DRZJSWSDRUEMMV-UHFFFAOYSA-N 0.000 claims 1
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
HIYCBQVPMIVUBY-UHFFFAOYSA-N 5-ethyl-n-[3-[4-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl]propyl]-3-phenyl-1,2-oxazole-4-carboxamide Chemical compound CCC=1ON=C(C=2C=CC=CC=2)C=1C(=O)NCCCN(CC1)CCN1C1=CC=C(F)C=C1OCC(F)(F)F HIYCBQVPMIVUBY-UHFFFAOYSA-N 0.000 claims 1
XTOYTDCKZUBPSN-UHFFFAOYSA-N 5-methyl-3-phenyl-n-[3-[4-[2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl]propyl]-1,2-oxazole-4-carboxamide Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C(=O)NCCCN(CC1)CCN1C1=CC=CC=C1OCC(F)(F)F XTOYTDCKZUBPSN-UHFFFAOYSA-N 0.000 claims 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
125000005279 aryl sulfonyloxy group Chemical group 0.000 claims 1
229940126214 compound 3 Drugs 0.000 claims 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
239000011737 fluorine Substances 0.000 claims 1
GTGAZWYJQUSCGR-UHFFFAOYSA-N n-[3-[4-(4-chloro-2-methylphenyl)piperazin-1-yl]propyl]-5-methyl-3-phenyl-1,2-oxazole-4-carboxamide Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C(=O)NCCCN(CC1)CCN1C1=CC=C(Cl)C=C1C GTGAZWYJQUSCGR-UHFFFAOYSA-N 0.000 claims 1
RJVCLYVOUSAALR-UHFFFAOYSA-N n-[3-[4-(4-fluoro-2-methylphenyl)piperazin-1-yl]propyl]-5-methyl-3-phenyl-1,2-oxazole-4-carboxamide Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C(=O)NCCCN(CC1)CCN1C1=CC=C(F)C=C1C RJVCLYVOUSAALR-UHFFFAOYSA-N 0.000 claims 1
WGZBIHYWWBZODW-UHFFFAOYSA-N n-[3-[4-(4-fluoro-2-propan-2-yloxyphenyl)piperazin-1-yl]propyl]-5-methyl-3-phenyl-1,2-oxazole-4-carboxamide Chemical compound CC(C)OC1=CC(F)=CC=C1N1CCN(CCCNC(=O)C=2C(=NOC=2C)C=2C=CC=CC=2)CC1 WGZBIHYWWBZODW-UHFFFAOYSA-N 0.000 claims 1
VYMRMWQILRQHOS-UHFFFAOYSA-N n-[3-[4-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl]propyl]-3-phenyl-1,2-oxazole-4-carboxamide Chemical compound FC(F)(F)COC1=CC(F)=CC=C1N1CCN(CCCNC(=O)C=2C(=NOC=2)C=2C=CC=CC=2)CC1 VYMRMWQILRQHOS-UHFFFAOYSA-N 0.000 claims 1
MVIKXLCFXZBTDQ-UHFFFAOYSA-N n-[3-[4-[4-fluoro-2-(2,2,2-trifluoroethoxy)phenyl]piperazin-1-yl]propyl]-3-phenyl-5-(2-phenylethyl)-1,2-oxazole-4-carboxamide Chemical compound FC(F)(F)COC1=CC(F)=CC=C1N1CCN(CCCNC(=O)C=2C(=NOC=2CCC=2C=CC=CC=2)C=2C=CC=CC=2)CC1 MVIKXLCFXZBTDQ-UHFFFAOYSA-N 0.000 claims 1
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 68
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 29
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 26
206010004446 Benign prostatic hyperplasia Diseases 0.000 description 23
208000004403 Prostatic Hyperplasia Diseases 0.000 description 23
238000005160 1H NMR spectroscopy Methods 0.000 description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
239000000203 mixture Substances 0.000 description 21
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
108060003345 Adrenergic Receptor Proteins 0.000 description 18
102000017910 Adrenergic receptor Human genes 0.000 description 18
102000005962 receptors Human genes 0.000 description 18
108020003175 receptors Proteins 0.000 description 18
239000005557 antagonist Substances 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
230000000694 effects Effects 0.000 description 14
206010071289 Lower urinary tract symptoms Diseases 0.000 description 13
229910052938 sodium sulfate Inorganic materials 0.000 description 13
235000011152 sodium sulphate Nutrition 0.000 description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
238000003818 flash chromatography Methods 0.000 description 12
239000000243 solution Substances 0.000 description 11
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
238000001816 cooling Methods 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
210000001519 tissue Anatomy 0.000 description 9
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LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
229960001289 prazosin Drugs 0.000 description 8
210000003708 urethra Anatomy 0.000 description 8
210000001635 urinary tract Anatomy 0.000 description 8
IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 7
210000002307 prostate Anatomy 0.000 description 7
230000002829 reductive effect Effects 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
239000012267 brine Substances 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
208000024891 symptom Diseases 0.000 description 6
229910021529 ammonia Inorganic materials 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
230000004064 dysfunction Effects 0.000 description 5
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239000003921 oil Substances 0.000 description 5
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SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 4
CNIIGCLFLJGOGP-UHFFFAOYSA-N 2-(1-naphthalenylmethyl)-4,5-dihydro-1H-imidazole Chemical compound C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 CNIIGCLFLJGOGP-UHFFFAOYSA-N 0.000 description 4
229940126062 Compound A Drugs 0.000 description 4
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 4
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
230000036772 blood pressure Effects 0.000 description 4
125000001207 fluorophenyl group Chemical group 0.000 description 4
SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 4
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GDEFBLAPDVUMHR-UHFFFAOYSA-N tert-butyl 4-(5-hydroxy-2-methoxyphenyl)piperazine-1-carboxylate Chemical compound COC1=CC=C(O)C=C1N1CCN(C(=O)OC(C)(C)C)CC1 GDEFBLAPDVUMHR-UHFFFAOYSA-N 0.000 description 4
DIOHEXPTUTVCNX-UHFFFAOYSA-N 1,1,1-trifluoro-n-phenyl-n-(trifluoromethylsulfonyl)methanesulfonamide Chemical compound FC(F)(F)S(=O)(=O)N(S(=O)(=O)C(F)(F)F)C1=CC=CC=C1 DIOHEXPTUTVCNX-UHFFFAOYSA-N 0.000 description 3
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MCFBUIIRFZBRCU-UHFFFAOYSA-N 4-[1-[5-[6-(trifluoromethyl)-1h-benzimidazol-2-yl]pyridin-2-yl]piperidin-4-yl]oxycyclohexane-1-carboxylic acid Chemical compound C1CC(C(=O)O)CCC1OC1CCN(C=2N=CC(=CC=2)C=2NC3=CC(=CC=C3N=2)C(F)(F)F)CC1 MCFBUIIRFZBRCU-UHFFFAOYSA-N 0.000 description 3
UWPYDJFNRSFERK-UHFFFAOYSA-N 4-chloro-2-piperazin-1-ylphenol;dihydrobromide Chemical compound Br.Br.OC1=CC=C(Cl)C=C1N1CCNCC1 UWPYDJFNRSFERK-UHFFFAOYSA-N 0.000 description 3
GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 3
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DRHKJLXJIQTDTD-OAHLLOKOSA-N Tamsulosine Chemical compound CCOC1=CC=CC=C1OCCN[C@H](C)CC1=CC=C(OC)C(S(N)(=O)=O)=C1 DRHKJLXJIQTDTD-OAHLLOKOSA-N 0.000 description 3
239000000556 agonist Substances 0.000 description 3
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CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 3
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238000002844 melting Methods 0.000 description 3
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VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
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XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members 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
- C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
- 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
- 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
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
- 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
- A61P13/00—Drugs for disorders of the urinary system
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics

ZA200203942A 1999-10-18 2002-05-17 Isoxazolecarboxamide derivatives. ZA200203942B (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
IT1999MI002173A IT1314191B1 (it)	1999-10-18	1999-10-18	Derivati isossazolcarbossamidici

Publications (1)

Publication Number	Publication Date
ZA200203942B true ZA200203942B (en)	2003-01-02

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ZA200203942A ZA200203942B (en)	1999-10-18	2002-05-17	Isoxazolecarboxamide derivatives.

Country Status (25)

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EP (1)	EP1226131B1 (it)
JP (1)	JP2003512362A (it)
KR (1)	KR20020038944A (it)
CN (1)	CN1139579C (it)
AR (1)	AR029400A1 (it)
AT (1)	ATE256670T1 (it)
AU (1)	AU757614B2 (it)
BR (1)	BR0014851A (it)
CA (1)	CA2385472A1 (it)
DE (1)	DE60007347T2 (it)
DK (1)	DK1226131T3 (it)
ES (1)	ES2210033T3 (it)
HK (1)	HK1044940A1 (it)
HU (1)	HUP0203184A3 (it)
IL (1)	IL148837A0 (it)
IT (1)	IT1314191B1 (it)
MX (1)	MXPA02003432A (it)
MY (1)	MY120400A (it)
NO (1)	NO20021803L (it)
NZ (1)	NZ517884A (it)
PL (1)	PL356990A1 (it)
PT (1)	PT1226131E (it)
RU (1)	RU2002113096A (it)
WO (1)	WO2001029015A2 (it)
ZA (1)	ZA200203942B (it)

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AU2006331437B2 (en)	2005-12-27	2012-07-05	F. Hoffmann-La Roche Ag	Aryl-Isoxazol-4-yl-Imidazole derivatives
BRPI0706560A2 (pt)	2006-01-17	2011-03-29	Hoffmann La Roche	derivados de aril-isoxazol-4-il-imidazo [1,2-a] piridina úteis para o tratamento de doença de alzheimer por intermédio de receptores gaba
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US8389550B2 (en)	2009-02-25	2013-03-05	Hoffmann-La Roche Inc.	Isoxazoles / O-pyridines with ethyl and ethenyl linker
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KR101701533B1 (ko)	2009-05-05	2017-02-13	에프. 호프만-라 로슈 아게	아이속사졸-피리다진 유도체
KR101384829B1 (ko)	2009-05-05	2014-04-15	에프. 호프만-라 로슈 아게	이속사졸-피라졸 유도체
KR101354335B1 (ko)	2009-05-05	2014-02-19	에프. 호프만-라 로슈 아게	인지 장애의 치료에 사용되는 ｇａｂａａ 수용체 역 작용제로서의 아이속사졸-티아졸 유도체
CN102414206B (zh)	2009-05-05	2014-11-05	霍夫曼-拉罗奇有限公司	异*唑-吡啶衍生物
WO2010127978A1 (en)	2009-05-07	2010-11-11	F. Hoffmann-La Roche Ag	Isoxazole-pyridine derivatives as gaba modulators
US8785435B2 (en)	2011-10-20	2014-07-22	Hoffmann-La Roche Inc.	Solid forms
CN113121540B (zh) *	2020-01-15	2024-01-26	鲁南制药集团股份有限公司	一种西格列汀游离碱的合成方法

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DE4425146A1 (de) *	1994-07-15	1996-01-18	Basf Ag	Verwendung heterocyclischer Verbindungen

1999
- 1999-10-18 IT IT1999MI002173A patent/IT1314191B1/it active
2000
- 2000-10-10 MY MYPI20004718A patent/MY120400A/en unknown
- 2000-10-16 NZ NZ517884A patent/NZ517884A/en unknown
- 2000-10-16 JP JP2001531815A patent/JP2003512362A/ja active Pending
- 2000-10-16 DK DK00992436T patent/DK1226131T3/da active
- 2000-10-16 CA CA002385472A patent/CA2385472A1/en not_active Abandoned
- 2000-10-16 ES ES00992436T patent/ES2210033T3/es not_active Expired - Lifetime
- 2000-10-16 WO PCT/EP2000/010144 patent/WO2001029015A2/en active IP Right Grant
- 2000-10-16 MX MXPA02003432A patent/MXPA02003432A/es not_active Application Discontinuation
- 2000-10-16 AU AU28347/01A patent/AU757614B2/en not_active Ceased
- 2000-10-16 BR BR0014851-2A patent/BR0014851A/pt not_active IP Right Cessation
- 2000-10-16 EP EP00992436A patent/EP1226131B1/en not_active Expired - Lifetime
- 2000-10-16 KR KR1020027004663A patent/KR20020038944A/ko not_active Application Discontinuation
- 2000-10-16 PL PL00356990A patent/PL356990A1/xx not_active Application Discontinuation
- 2000-10-16 AT AT00992436T patent/ATE256670T1/de not_active IP Right Cessation
- 2000-10-16 CN CNB008143226A patent/CN1139579C/zh not_active Expired - Fee Related
- 2000-10-16 PT PT00992436T patent/PT1226131E/pt unknown
- 2000-10-16 RU RU2002113096/04A patent/RU2002113096A/ru not_active Application Discontinuation
- 2000-10-16 HU HU0203184A patent/HUP0203184A3/hu unknown
- 2000-10-16 DE DE60007347T patent/DE60007347T2/de not_active Expired - Fee Related
- 2000-10-16 IL IL14883700A patent/IL148837A0/xx unknown
- 2000-10-18 AR ARP000105475A patent/AR029400A1/es not_active Application Discontinuation
2002
- 2002-04-17 NO NO20021803A patent/NO20021803L/no not_active Application Discontinuation
- 2002-05-17 ZA ZA200203942A patent/ZA200203942B/en unknown
- 2002-08-13 HK HK02105918.6A patent/HK1044940A1/zh unknown

Also Published As

Publication number	Publication date
AU2834701A (en)	2001-04-30
HUP0203184A3 (en)	2004-12-28
IL148837A0 (en)	2002-09-12
NZ517884A (en)	2003-08-29
RU2002113096A (ru)	2003-11-10
WO2001029015A3 (en)	2001-11-01
CN1139579C (zh)	2004-02-25
CN1379767A (zh)	2002-11-13
DE60007347D1 (de)	2004-01-29
ITMI992173A1 (it)	2001-04-18
WO2001029015A2 (en)	2001-04-26
NO20021803D0 (no)	2002-04-17
NO20021803L (no)	2002-06-17
KR20020038944A (ko)	2002-05-24
DE60007347T2 (de)	2004-09-02
ATE256670T1 (de)	2004-01-15
HUP0203184A2 (hu)	2003-01-28
AU757614B2 (en)	2003-02-27
CA2385472A1 (en)	2001-04-26
HK1044940A1 (zh)	2002-11-08
MXPA02003432A (es)	2002-08-20
ITMI992173A0 (it)	1999-10-18
EP1226131A2 (en)	2002-07-31
DK1226131T3 (da)	2004-04-19
BR0014851A (pt)	2002-06-11
ES2210033T3 (es)	2004-07-01
PL356990A1 (en)	2004-07-12
EP1226131B1 (en)	2003-12-17
IT1314191B1 (it)	2002-12-06
MY120400A (en)	2005-10-31
JP2003512362A (ja)	2003-04-02
PT1226131E (pt)	2004-05-31
AR029400A1 (es)	2003-06-25

Publication	Publication Date	Title
ZA200203942B (en)	2003-01-02	Isoxazolecarboxamide derivatives.
KR100787131B1 (ko)	2007-12-21	Ｈｉｆ―１ 활성을 저해하는 화합물, 이의 제조방법 및이를 유효성분으로 함유하는 약학적 조성물
EA008476B1 (ru)	2007-06-29	Замещенные сульфонамиды, способ их получения и их применение в качестве лечебного средства для лечения расстройств цнс, ожирения и диабета типа ii
BRPI0619260A2 (pt)	2011-09-27	derivados de oxadiazol com atividade de receptor ctrh2, composição farmacêutica que os compreende e uso dos referidos derivados
US6680319B2 (en)	2004-01-20	Isoxazolecarboxamide derivatives
RU2335496C2 (ru)	2008-10-10	Арилкарбонилпиперазины и гетероарилкарбонилпиперазины для лечения опухолевых заболеваний (варианты), лекарственное средство (варианты), способ его получения и способ лечения опухолевых заболеваний
US6486163B1 (en)	2002-11-26	Thienopyranecarboxamide derivatives
KR20010070997A (ko)	2001-07-28	비페닐 유도체
MXPA04009142A (es)	2004-11-26	Tiopirimidina e isotiazolpirimidina inhibidoras de quinasas.
US6403594B1 (en)	2002-06-11	Benzopyran derivatives
EP1200445B1 (en)	2003-09-17	Thienopyranecarboxamide derivatives
JPH0920755A (ja)	1997-01-21	両性型三環系化合物
EP1222183B1 (en)	2003-04-23	Benzopyran derivatives
KR100786336B1 (ko)	2007-12-14	Ｈｉｆ―１ 활성을 저해하는 화합물, 이의 제조방법 및이를 유효성분으로 함유하는 약학적 조성물
WO2002060534A2 (en)	2002-08-08	Selective alpha 1 antagonists a + d
US20020183290A1 (en)	2002-12-05	Adrenergic receptor antagonists selective for both alpha1A-and alpha1D-subtypes and uses therefor
JPH06287182A (ja)	1994-10-11	アルキルグリシン誘導体