FI107155B - Menetelmä farmakologisesti käyttökelpoisten 1-(imidatso[1,2-a]pyridin-6-yyli)-sykloheksaanikarbotioamidijohdannaisten valmistamiseksi - Google Patents

Menetelmä farmakologisesti käyttökelpoisten 1-(imidatso[1,2-a]pyridin-6-yyli)-sykloheksaanikarbotioamidijohdannaisten valmistamiseksi Download PDF

Info

Publication number: FI107155B
Authority: FI; Finland
Prior art keywords: jossa; compound; som; formula; imidazo
Prior art date: 1993-09-21

Application number

FI944207A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI944207A7 (fi

FI944207A0 (fi

Inventor

Hitoshi Oinuma

Yasuhiro Kabasawa

Fumihiro Ozaki

Keiji Ishibashi

Takashi Hasegawa

Toshiaki Ogawa

Satoshi Katayama

Shigeru Souda

Manabu Shirato

Katsuhiro Moriya

Original Assignee

Eisai Co Ltd

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.)

1993-09-21

Filing date

1994-09-12

Publication date

2001-06-15

1994-09-12 Application filed by Eisai Co Ltd filed Critical Eisai Co Ltd

1994-09-12 Publication of FI944207A0 publication Critical patent/FI944207A0/fi

1995-03-22 Publication of FI944207A7 publication Critical patent/FI944207A7/fi

2001-06-15 Application granted granted Critical

2001-06-15 Publication of FI107155B publication Critical patent/FI107155B/fi

Links

-1 1- (imidazo [1,2-a] pyridin-6-yl) -cyclohexanecarbothioamide derivatives Chemical class 0.000 title claims description 208
238000000034 method Methods 0.000 title claims description 35
238000002360 preparation method Methods 0.000 title claims description 19
230000008569 process Effects 0.000 title claims description 10
150000001875 compounds Chemical class 0.000 claims abstract description 148
125000000217 alkyl group Chemical group 0.000 claims abstract description 16
150000003839 salts Chemical class 0.000 claims abstract description 15
239000003814 drug Substances 0.000 claims abstract description 12
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
239000001257 hydrogen Substances 0.000 claims abstract description 10
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 15
238000009833 condensation Methods 0.000 claims description 9
230000005494 condensation Effects 0.000 claims description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
125000001424 substituent group Chemical group 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 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 4
239000003086 colorant Substances 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 4
150000002367 halogens Chemical class 0.000 claims description 4
125000001624 naphthyl group Chemical group 0.000 claims description 4
239000000546 pharmaceutical excipient Substances 0.000 claims description 4
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 3
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 3
125000004093 cyano group Chemical group *C#N 0.000 claims description 3
125000002541 furyl group Chemical group 0.000 claims description 3
150000002431 hydrogen Chemical class 0.000 claims description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
125000003226 pyrazolyl group Chemical group 0.000 claims description 3
125000005493 quinolyl group Chemical group 0.000 claims description 3
125000001544 thienyl group Chemical group 0.000 claims description 3
125000003118 aryl group Chemical group 0.000 claims description 2
125000005956 isoquinolyl group Chemical group 0.000 claims description 2
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
125000000168 pyrrolyl group Chemical group 0.000 claims description 2
KAKZBPTYRLMSJV-UHFFFAOYSA-N Butadiene Chemical group C=CC=C KAKZBPTYRLMSJV-UHFFFAOYSA-N 0.000 claims 2
DDWAYLMBOCIQBX-UHFFFAOYSA-N N-imidazo[1,2-a]pyridin-6-ylcyclohexanecarbothioamide Chemical class C1(CCCCC1)C(NC=1C=CC=2N(C=1)C=CN=2)=S DDWAYLMBOCIQBX-UHFFFAOYSA-N 0.000 claims 1
LJSQFQKUNVCTIA-UHFFFAOYSA-N diethyl sulfide Chemical group CCSCC LJSQFQKUNVCTIA-UHFFFAOYSA-N 0.000 claims 1
238000009432 framing Methods 0.000 claims 1
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims 1
102000004257 Potassium Channel Human genes 0.000 abstract description 9
108020001213 potassium channel Proteins 0.000 abstract description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
201000010099 disease Diseases 0.000 abstract description 5
229940124597 therapeutic agent Drugs 0.000 abstract description 3
230000009471 action Effects 0.000 abstract description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract description 2
239000001301 oxygen Substances 0.000 abstract description 2
229910052760 oxygen Inorganic materials 0.000 abstract description 2
230000003449 preventive effect Effects 0.000 abstract description 2
125000000113 cyclohexyl group Chemical class [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 abstract 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 1
125000001072 heteroaryl group Chemical group 0.000 abstract 1
125000003107 substituted aryl group Chemical group 0.000 abstract 1
229910052717 sulfur Chemical group 0.000 abstract 1
239000011593 sulfur Chemical group 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 186
239000000203 mixture Substances 0.000 description 117
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 100
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 84
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 75
239000002904 solvent Substances 0.000 description 75
239000000843 powder Substances 0.000 description 40
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 36
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 30
239000000243 solution Substances 0.000 description 28
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
239000012071 phase Substances 0.000 description 24
238000010898 silica gel chromatography Methods 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 23
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 18
229920006395 saturated elastomer Polymers 0.000 description 18
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 16
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 16
238000004821 distillation Methods 0.000 description 16
235000002639 sodium chloride Nutrition 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
230000000694 effects Effects 0.000 description 14
208000006673 asthma Diseases 0.000 description 13
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
235000017557 sodium bicarbonate Nutrition 0.000 description 12
229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 11
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 11
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
235000011114 ammonium hydroxide Nutrition 0.000 description 11
239000007787 solid Substances 0.000 description 11
238000001816 cooling Methods 0.000 description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 9
239000002253 acid Substances 0.000 description 9
239000002585 base Substances 0.000 description 9
CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 8
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
239000003921 oil Substances 0.000 description 8
235000019198 oils Nutrition 0.000 description 8
238000010992 reflux Methods 0.000 description 8
125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 7
239000003795 chemical substances by application Substances 0.000 description 7
238000004519 manufacturing process Methods 0.000 description 7
230000003287 optical effect Effects 0.000 description 7
UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 7
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
239000013078 crystal Substances 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
229910052987 metal hydride Inorganic materials 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
229910000029 sodium carbonate Inorganic materials 0.000 description 6
239000000126 substance Substances 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
YTRZCFTTXUXYMZ-UHFFFAOYSA-N [2-imidazo[1,2-a]pyridin-6-yl-2-(methylcarbamothioyl)cyclohexyl] 2-aminoacetate Chemical compound C1=CC2=NC=CN2C=C1C1(C(=S)NC)CCCCC1OC(=O)CN YTRZCFTTXUXYMZ-UHFFFAOYSA-N 0.000 description 5
238000010511 deprotection reaction Methods 0.000 description 5
229940079593 drug Drugs 0.000 description 5
150000002170 ethers Chemical class 0.000 description 5
229930195733 hydrocarbon Natural products 0.000 description 5
150000002430 hydrocarbons Chemical class 0.000 description 5
239000002198 insoluble material Substances 0.000 description 5
125000006239 protecting group Chemical group 0.000 description 5
238000000746 purification Methods 0.000 description 5
229910000033 sodium borohydride Inorganic materials 0.000 description 5
239000012279 sodium borohydride Substances 0.000 description 5
239000007858 starting material Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
FSYKKLYZXJSNPZ-UHFFFAOYSA-N N-methylaminoacetic acid Natural products C[NH2+]CC([O-])=O FSYKKLYZXJSNPZ-UHFFFAOYSA-N 0.000 description 4
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
108010077895 Sarcosine Proteins 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
230000008602 contraction Effects 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
239000011777 magnesium Substances 0.000 description 4
229910052749 magnesium Inorganic materials 0.000 description 4
150000004681 metal hydrides Chemical class 0.000 description 4
229940043230 sarcosine Drugs 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
208000024891 symptom Diseases 0.000 description 4
238000012360 testing method Methods 0.000 description 4
YDUHRASLHANMSB-UHFFFAOYSA-N 1-methylcyclohexane-1-carbothioamide Chemical compound NC(=S)C1(C)CCCCC1 YDUHRASLHANMSB-UHFFFAOYSA-N 0.000 description 3
KZHVNYHHYRWKBH-UHFFFAOYSA-N 2-hydroxy-1-imidazo[1,2-a]pyridin-6-yl-n-methylcyclohexane-1-carbothioamide Chemical compound C1=CC2=NC=CN2C=C1C1(C(=S)NC)CCCCC1O KZHVNYHHYRWKBH-UHFFFAOYSA-N 0.000 description 3
BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
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 3
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
239000002841 Lewis acid Substances 0.000 description 3
239000012359 Methanesulfonyl chloride Substances 0.000 description 3
150000008065 acid anhydrides Chemical class 0.000 description 3
150000001298 alcohols Chemical class 0.000 description 3
HAXFWIACAGNFHA-UHFFFAOYSA-N aldrithiol Chemical compound C=1C=CC=NC=1SSC1=CC=CC=N1 HAXFWIACAGNFHA-UHFFFAOYSA-N 0.000 description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 3
HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 3
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 3
238000000605 extraction Methods 0.000 description 3
238000001914 filtration Methods 0.000 description 3
150000004820 halides Chemical class 0.000 description 3
239000005457 ice water Substances 0.000 description 3
150000007529 inorganic bases Chemical class 0.000 description 3
150000007517 lewis acids Chemical class 0.000 description 3
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
150000007530 organic bases Chemical class 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
239000003880 polar aprotic solvent Substances 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
239000000047 product Substances 0.000 description 3
230000000069 prophylactic effect Effects 0.000 description 3
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238000011160 research Methods 0.000 description 3
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229910052708 sodium Inorganic materials 0.000 description 3
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239000003826 tablet Substances 0.000 description 3
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 2
NDQIKWFYLYRWTH-UHFFFAOYSA-N 1-imidazo[1,2-a]pyridin-6-yl-n-methyl-2-[2-(naphthalen-1-ylsulfonylamino)ethylamino]cyclohexane-1-carbothioamide Chemical compound C1=CC2=NC=CN2C=C1C1(C(=S)NC)C(NCCNS(=O)(=O)C=2C3=CC=CC=C3C=CC=2)CCCC1 NDQIKWFYLYRWTH-UHFFFAOYSA-N 0.000 description 2
VSCMRJBXIXMLEJ-UHFFFAOYSA-N 1-imidazo[1,2-a]pyridin-6-yl-n-methyl-2-oxocyclohexane-1-carbothioamide Chemical compound C1=CC2=NC=CN2C=C1C1(C(=S)NC)CCCCC1=O VSCMRJBXIXMLEJ-UHFFFAOYSA-N 0.000 description 2
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239000005711 Benzoic acid Substances 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
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206010020751 Hypersensitivity Diseases 0.000 description 2
206010020772 Hypertension Diseases 0.000 description 2
ILUJQPXNXACGAN-UHFFFAOYSA-N O-methylsalicylic acid Chemical compound COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
230000002378 acidificating effect Effects 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
235000019270 ammonium chloride Nutrition 0.000 description 2
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
239000008346 aqueous phase Substances 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
230000008859 change Effects 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
239000008187 granular material Substances 0.000 description 2
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BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
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VNNLHYZDXIBHKZ-UHFFFAOYSA-N thiophene-2-sulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CS1 VNNLHYZDXIBHKZ-UHFFFAOYSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Neurology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Engineering & Computer Science (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Bioinformatics & Cheminformatics (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pyridine Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Thiazole And Isothizaole Compounds (AREA)

FI944207A 1993-09-21 1994-09-12 Menetelmä farmakologisesti käyttökelpoisten 1-(imidatso[1,2-a]pyridin-6-yyli)-sykloheksaanikarbotioamidijohdannaisten valmistamiseksi FI107155B (fi)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP23453893		1993-09-21
JP23453893		1993-09-21

Publications (3)

Publication Number	Publication Date
FI944207A0 FI944207A0 (fi)	1994-09-12
FI944207A7 FI944207A7 (fi)	1995-03-22
FI107155B true FI107155B (fi)	2001-06-15

Family

ID=16972600

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI944207A FI107155B (fi)	1993-09-21	1994-09-12	Menetelmä farmakologisesti käyttökelpoisten 1-(imidatso[1,2-a]pyridin-6-yyli)-sykloheksaanikarbotioamidijohdannaisten valmistamiseksi

Country Status (14)

Country	Link
US (2)	US5478839A (de)
EP (1)	EP0644182B1 (de)
KR (1)	KR0149066B1 (de)
CN (1)	CN1100031C (de)
AT (1)	ATE166046T1 (de)
AU (1)	AU686642B2 (de)
CA (1)	CA2131749A1 (de)
DE (1)	DE69410198T2 (de)
FI (1)	FI107155B (de)
HU (1)	HU221198B1 (de)
NO (1)	NO302234B1 (de)
NZ (1)	NZ264480A (de)
RU (1)	RU2129113C1 (de)
ZA (1)	ZA947146B (de)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1054877A1 (de)	1998-02-11	2000-11-29	Du Pont Pharmaceuticals Company	Cyclische sulfonamid-derivate als metallprotease-inhibitoren
RU2220178C1 (ru) *	2002-08-09	2003-12-27	Общество с ограниченной ответственностью "Фирма "Вивана"	Ударогасящее покрытие
JP4838537B2 (ja) *	2005-05-25	2011-12-14	株式会社資生堂	不全角化抑制剤、毛穴縮小剤又は肌荒れ防止・改善剤及び皮膚外用組成物
WO2008057855A2 (en)	2006-11-01	2008-05-15	Bristol-Myers Squibb Company	Heterocyclic compounds as modulators of glucocorticoid receptor, ap-i, and/or np-kappa-b activity

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SU414254A1 (de) *	1972-09-28	1974-02-05
US4200640A (en) *	1976-04-02	1980-04-29	Chugai Seiyaku Kabushiki Kaisha	Nitric ester of N-(2-hydroxyethyl)nicotinamide and pharmaceutical use
JPS60189291A (ja) *	1984-03-09	1985-09-26	株式会社日立製作所	電子部品の自動插入装置
GB9000342D0 (en) *	1990-01-08	1990-03-07	May & Baker Ltd	New compositions of matter
GB9002879D0 (en) *	1990-02-08	1990-04-04	May & Baker Ltd	New compositions of matter
HUT66229A (en) *	1991-10-14	1994-10-28	Eisai Co Ltd	Thioformamide derivatives and process for producing them and pharmaceutical compositions containing them

1994
- 1994-09-02 US US08/300,201 patent/US5478839A/en not_active Expired - Lifetime
- 1994-09-07 AU AU71696/94A patent/AU686642B2/en not_active Ceased
- 1994-09-09 CA CA002131749A patent/CA2131749A1/en not_active Abandoned
- 1994-09-12 FI FI944207A patent/FI107155B/fi not_active IP Right Cessation
- 1994-09-14 DE DE69410198T patent/DE69410198T2/de not_active Expired - Lifetime
- 1994-09-14 AT AT94114467T patent/ATE166046T1/de not_active IP Right Cessation
- 1994-09-14 EP EP94114467A patent/EP0644182B1/de not_active Expired - Lifetime
- 1994-09-15 ZA ZA947146A patent/ZA947146B/xx unknown
- 1994-09-17 KR KR1019940023821A patent/KR0149066B1/ko not_active Expired - Fee Related
- 1994-09-19 NZ NZ264480A patent/NZ264480A/en unknown
- 1994-09-19 NO NO943472A patent/NO302234B1/no unknown
- 1994-09-20 CN CN94117892A patent/CN1100031C/zh not_active Expired - Fee Related
- 1994-09-20 RU RU94033470A patent/RU2129113C1/ru not_active IP Right Cessation
- 1994-09-20 HU HU9402702A patent/HU221198B1/hu not_active IP Right Cessation
1995
- 1995-09-19 US US08/531,201 patent/US5605907A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
DE69410198T2 (de)	1999-03-11
CN1100031C (zh)	2003-01-29
AU686642B2 (en)	1998-02-12
CN1106380A (zh)	1995-08-09
CA2131749A1 (en)	1995-03-22
HU9402702D0 (en)	1994-12-28
KR0149066B1 (ko)	1998-10-15
NZ264480A (en)	1995-07-26
FI944207A7 (fi)	1995-03-22
HU221198B1 (en)	2002-08-28
AU7169694A (en)	1995-04-06
RU94033470A (ru)	1996-08-10
NO943472L (no)	1995-03-22
RU2129113C1 (ru)	1999-04-20
KR950008446A (ko)	1995-04-17
NO302234B1 (no)	1998-02-09
FI944207A0 (fi)	1994-09-12
ATE166046T1 (de)	1998-05-15
US5478839A (en)	1995-12-26
EP0644182A1 (de)	1995-03-22
ZA947146B (en)	1996-03-15
HUT68036A (en)	1995-05-29
DE69410198D1 (de)	1998-06-18
EP0644182B1 (de)	1998-05-13
NO943472D0 (no)	1994-09-19
US5605907A (en)	1997-02-25

Legal Events

Date	Code	Title	Description
2006-03-31	MA	Patent expired

Publication	Publication Date	Title
JP4842829B2 (ja)	2011-12-21	含窒素縮合複素環化合物
US9458110B2 (en)	2016-10-04	Phenylpyrazole derivatives as potent ROCK1 and ROCK2 inhibitors
AU686115B2 (en)	1998-02-05	Imidazo (I,2-a) pyridine derivatives as bradykinin antagonists, pharmaceuticals and processes for their preparation
FI96688C (fi)	1996-08-12	Menetelmä valmistaa terapeuttisesti aktiivista 3-(2-substituoitu-3-okso-2,3-dihydropyridatsin-6-yyli)-2-fenyylipyratsolo/1,5-a/pyridiinejä
US20100179137A1 (en)	2010-07-15	Pyridone compound
JPH0649027A (ja)	1994-02-22	インドール誘導体
JP2002513013A (ja)	2002-05-08	グアニジン誘導体
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JP2002521334A (ja)	2002-07-16	置換ベンズイミダゾール抗ウィルス剤
BRPI0808378A2 (pt)	2014-07-01	Composto de 6-benzil-2,3,4,7-treta-hidro-indolo[2,3-c] quinolina úteis como inibidores de pde5
EP1051415B1 (de)	2003-09-24	Benzamidderivate als vasopressin-antagonisten
EP0228006A1 (de)	1987-07-08	Imidazopyridinverbindungen und Verfahren zu ihrer Herstellung
JPH10504820A (ja)	1998-05-12	Ｎ−置換されたフェノチアジン類の使用
WO2019091277A1 (zh)	2019-05-16	2-(1h-吡唑-3-基)苯酚类化合物及其应用
EP0644182B1 (de)	1998-05-13	Cyclohexanderivate als Kaliumkanalaktivatoren
EP1095039B1 (de)	2003-08-27	Neuartige, pharmazeutisch aktive verbindung
EP0556813A1 (de)	1993-08-25	Amphotere tricyclische Verbindungen als antihistaminische und antiallergische Mittel
EP0812841A1 (de)	1997-12-17	Kristall von N-((Chinolin-2-yl)-Phenyl)Sulfonamiden und Verfahren zu deren Herstellung
EP2373628B1 (de)	2013-01-16	Bicyclische Imidazolderivate
HK1214244A1 (zh)	2016-07-22	咪唑并吡啶衍生物
JP3725188B2 (ja)	2005-12-07	シクロヘキサン誘導体
TW388760B (en)	2000-05-01	Cyclohexane derivatives
HUT50825A (en)	1990-03-28	Process for producing 3-methylenespiro/benzofuran piperidine/ derivatives and pharmaceutical compositions comprising same
JPH09118660A (ja)	1997-05-06	芳香族ヒドロキサム酸誘導体、製造法および剤