CH637941A5 - Derives de l'acide picolinique substitues en position 5 et composition anti-hypertensive contenant ces derives. - Google Patents
Derives de l'acide picolinique substitues en position 5 et composition anti-hypertensive contenant ces derives. Download PDFInfo
- Publication number
- CH637941A5 CH637941A5 CH268779A CH268779A CH637941A5 CH 637941 A5 CH637941 A5 CH 637941A5 CH 268779 A CH268779 A CH 268779A CH 268779 A CH268779 A CH 268779A CH 637941 A5 CH637941 A5 CH 637941A5
- Authority
- CH
- Switzerland
- Prior art keywords
- group
- formula
- acid
- substituted
- picolinic acid
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims description 51
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical group OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 title claims description 44
- 230000003276 anti-hypertensive effect Effects 0.000 title claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 64
- -1 N-substituted amino amino group Chemical group 0.000 claims description 63
- 239000002253 acid Substances 0.000 claims description 43
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 22
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 229940081066 picolinic acid Drugs 0.000 claims description 19
- 125000005843 halogen group Chemical group 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 15
- 125000003277 amino group Chemical group 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 150000001408 amides Chemical class 0.000 claims description 11
- RXHAQWAUXWKINY-UHFFFAOYSA-N 5-(4-chlorophenoxy)pyridine-2-carboxylic acid Chemical compound C1=NC(C(=O)O)=CC=C1OC1=CC=C(Cl)C=C1 RXHAQWAUXWKINY-UHFFFAOYSA-N 0.000 claims description 10
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 9
- NPAUPKKDRMTHSQ-UHFFFAOYSA-N 5-(4-chlorobutoxy)pyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(OCCCCCl)C=N1 NPAUPKKDRMTHSQ-UHFFFAOYSA-N 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 8
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical group [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 6
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical group [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 6
- 125000004442 acylamino group Chemical group 0.000 claims description 6
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical group [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 6
- 125000002431 aminoalkoxy group Chemical group 0.000 claims description 6
- 229910052749 magnesium Inorganic materials 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- CHBNFEFUVKGTPY-UHFFFAOYSA-N 5-(2-chlorophenoxy)pyridine-2-carboxylic acid Chemical compound C1=NC(C(=O)O)=CC=C1OC1=CC=CC=C1Cl CHBNFEFUVKGTPY-UHFFFAOYSA-N 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000004436 sodium atom Chemical group 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- OMYLZYZQGXVCJW-UHFFFAOYSA-N 5-(5,5,5-trifluoropentoxy)pyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(OCCCCC(F)(F)F)C=N1 OMYLZYZQGXVCJW-UHFFFAOYSA-N 0.000 claims description 2
- JXPYTHDXGAGHBU-UHFFFAOYSA-N 5-[4-(trifluoromethyl)phenoxy]pyridine-2-carboxylic acid Chemical compound C1=NC(C(=O)O)=CC=C1OC1=CC=C(C(F)(F)F)C=C1 JXPYTHDXGAGHBU-UHFFFAOYSA-N 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- CKVQQDUSKCAIDZ-UHFFFAOYSA-N 5-(4,4,4-trifluorobutoxy)pyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(OCCCC(F)(F)F)C=N1 CKVQQDUSKCAIDZ-UHFFFAOYSA-N 0.000 claims 1
- 239000010931 gold Substances 0.000 claims 1
- 229910052737 gold Inorganic materials 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 82
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 54
- 238000006243 chemical reaction Methods 0.000 description 53
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- 239000000243 solution Substances 0.000 description 43
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 35
- 239000013078 crystal Substances 0.000 description 33
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
- 239000000460 chlorine Substances 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000012071 phase Substances 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 22
- 238000004458 analytical method Methods 0.000 description 22
- 238000002844 melting Methods 0.000 description 22
- 230000008018 melting Effects 0.000 description 22
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 22
- 239000000047 product Substances 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- DHLUJPLHLZJUBW-UHFFFAOYSA-N 6-methylpyridin-3-ol Chemical compound CC1=CC=C(O)C=N1 DHLUJPLHLZJUBW-UHFFFAOYSA-N 0.000 description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 18
- PEHSSTUGJUBZBI-UHFFFAOYSA-N indan-5-ol Chemical compound OC1=CC=C2CCCC2=C1 PEHSSTUGJUBZBI-UHFFFAOYSA-N 0.000 description 18
- 238000007254 oxidation reaction Methods 0.000 description 18
- 230000003647 oxidation Effects 0.000 description 17
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 17
- 239000000725 suspension Substances 0.000 description 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 16
- 239000007864 aqueous solution Substances 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
- 239000000706 filtrate Substances 0.000 description 13
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 13
- 238000001914 filtration Methods 0.000 description 12
- 230000036772 blood pressure Effects 0.000 description 11
- 239000012286 potassium permanganate Substances 0.000 description 11
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 10
- DGMPVYSXXIOGJY-UHFFFAOYSA-N Fusaric acid Chemical compound CCCCC1=CC=C(C(O)=O)N=C1 DGMPVYSXXIOGJY-UHFFFAOYSA-N 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 150000002367 halogens Chemical group 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- NESFDGDRYVANBC-UHFFFAOYSA-N 6-(hydroxymethyl)pyridin-3-ol Chemical compound OCC1=CC=C(O)C=N1 NESFDGDRYVANBC-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 150000007513 acids Chemical group 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 230000035484 reaction time Effects 0.000 description 7
- XXOUHKWIQVEQIH-UHFFFAOYSA-N 5-butoxypyridine-2-carboxylic acid Chemical compound CCCCOC1=CC=C(C(O)=O)N=C1 XXOUHKWIQVEQIH-UHFFFAOYSA-N 0.000 description 6
- 239000002220 antihypertensive agent Substances 0.000 description 6
- 229940030600 antihypertensive agent Drugs 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 159000000007 calcium salts Chemical class 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 150000004820 halides Chemical class 0.000 description 6
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- 239000012954 diazonium Substances 0.000 description 5
- 229910052751 metal Inorganic materials 0.000 description 5
- 239000002184 metal Substances 0.000 description 5
- 150000002989 phenols Chemical class 0.000 description 5
- YQGKMQPCIMTPCB-UHFFFAOYSA-N 5-(3-chloropropoxy)pyridine-2-carboxylic acid Chemical compound OC(=O)C1=CC=C(OCCCCl)C=N1 YQGKMQPCIMTPCB-UHFFFAOYSA-N 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 238000010531 catalytic reduction reaction Methods 0.000 description 4
- 150000001989 diazonium salts Chemical class 0.000 description 4
- 239000012065 filter cake Substances 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
- 239000007800 oxidant agent Substances 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- KMUONIBRACKNSN-UHFFFAOYSA-N potassium dichromate Chemical compound [K+].[K+].[O-][Cr](=O)(=O)O[Cr]([O-])(=O)=O KMUONIBRACKNSN-UHFFFAOYSA-N 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 235000010288 sodium nitrite Nutrition 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- IJTFVJJXAVCDFP-UHFFFAOYSA-N 5-(4-aminophenoxy)pyridine-2-carboxylic acid;dihydrochloride Chemical class Cl.Cl.C1=CC(N)=CC=C1OC1=CC=C(C(O)=O)N=C1 IJTFVJJXAVCDFP-UHFFFAOYSA-N 0.000 description 3
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 3
- QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 3
- 239000005751 Copper oxide Substances 0.000 description 3
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 3
- 229920000084 Gum arabic Polymers 0.000 description 3
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products 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 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 241000978776 Senegalia senegal Species 0.000 description 3
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- 239000000205 acacia gum Substances 0.000 description 3
- 230000007059 acute toxicity Effects 0.000 description 3
- 231100000403 acute toxicity Toxicity 0.000 description 3
- 125000005041 acyloxyalkyl group Chemical group 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229910000431 copper oxide Inorganic materials 0.000 description 3
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 3
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 3
- 229940045803 cuprous chloride Drugs 0.000 description 3
- 238000005469 granulation Methods 0.000 description 3
- 230000003179 granulation Effects 0.000 description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 3
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 3
- QBELEDRHMPMKHP-UHFFFAOYSA-N 1-bromo-2-chlorobenzene Chemical compound ClC1=CC=CC=C1Br QBELEDRHMPMKHP-UHFFFAOYSA-N 0.000 description 2
- SSFJWFZRATZQGA-UHFFFAOYSA-N 5-(4-bromophenoxy)-2-methylpyridine Chemical compound C1=NC(C)=CC=C1OC1=CC=C(Br)C=C1 SSFJWFZRATZQGA-UHFFFAOYSA-N 0.000 description 2
- LKLOIBKLYSDLFY-UHFFFAOYSA-N 5-(4-chlorophenoxy)-2-methylpyridine Chemical compound C1=NC(C)=CC=C1OC1=CC=C(Cl)C=C1 LKLOIBKLYSDLFY-UHFFFAOYSA-N 0.000 description 2
- MEZPFPIEWBDABE-UHFFFAOYSA-N 5-(4-methylphenoxy)pyridine-2-carboxylic acid Chemical compound C1=CC(C)=CC=C1OC1=CC=C(C(O)=O)N=C1 MEZPFPIEWBDABE-UHFFFAOYSA-N 0.000 description 2
- UJKWKNWJDWPCFW-UHFFFAOYSA-N 5-(4-nitrophenoxy)pyridine-2-carboxylic acid Chemical compound C1=NC(C(=O)O)=CC=C1OC1=CC=C([N+]([O-])=O)C=C1 UJKWKNWJDWPCFW-UHFFFAOYSA-N 0.000 description 2
- KTHFMMUXNXWKNS-UHFFFAOYSA-N 5-[2-(trifluoromethyl)phenoxy]pyridine-2-carboxylic acid Chemical compound C1=NC(C(=O)O)=CC=C1OC1=CC=CC=C1C(F)(F)F KTHFMMUXNXWKNS-UHFFFAOYSA-N 0.000 description 2
- LPJWNGXRBZGPSI-UHFFFAOYSA-N 5-[3-(trifluoromethyl)phenoxy]pyridine-2-carboxylic acid Chemical compound C1=NC(C(=O)O)=CC=C1OC1=CC=CC(C(F)(F)F)=C1 LPJWNGXRBZGPSI-UHFFFAOYSA-N 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 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 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- 150000008065 acid anhydrides Chemical class 0.000 description 2
- 239000003377 acid catalyst Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 2
- WRCVJCBJEBIBFI-UHFFFAOYSA-N ethyl 5-(4-chlorophenoxy)pyridine-2-carboxylate Chemical compound C1=NC(C(=O)OCC)=CC=C1OC1=CC=C(Cl)C=C1 WRCVJCBJEBIBFI-UHFFFAOYSA-N 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 150000005171 halobenzenes Chemical class 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 2
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 229910003446 platinum oxide Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000006662 (C2-C4) acyloxy group Chemical group 0.000 description 1
- YHRUOJUYPBUZOS-UHFFFAOYSA-N 1,3-dichloropropane Chemical compound ClCCCCl YHRUOJUYPBUZOS-UHFFFAOYSA-N 0.000 description 1
- SWJPEBQEEAHIGZ-UHFFFAOYSA-N 1,4-dibromobenzene Chemical compound BrC1=CC=C(Br)C=C1 SWJPEBQEEAHIGZ-UHFFFAOYSA-N 0.000 description 1
- KJDRSWPQXHESDQ-UHFFFAOYSA-N 1,4-dichlorobutane Chemical compound ClCCCCCl KJDRSWPQXHESDQ-UHFFFAOYSA-N 0.000 description 1
- NNMBNYHMJRJUBC-UHFFFAOYSA-N 1-bromo-3-(trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC(Br)=C1 NNMBNYHMJRJUBC-UHFFFAOYSA-N 0.000 description 1
- JRGGUPZKKTVKOV-UHFFFAOYSA-N 1-bromo-3-chlorobenzene Chemical compound ClC1=CC=CC(Br)=C1 JRGGUPZKKTVKOV-UHFFFAOYSA-N 0.000 description 1
- ZBTMRBYMKUEVEU-UHFFFAOYSA-N 1-bromo-4-methylbenzene Chemical compound CC1=CC=C(Br)C=C1 ZBTMRBYMKUEVEU-UHFFFAOYSA-N 0.000 description 1
- ZDFBKZUDCQQKAC-UHFFFAOYSA-N 1-bromo-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Br)C=C1 ZDFBKZUDCQQKAC-UHFFFAOYSA-N 0.000 description 1
- VQEZDLXEVJCRMO-UHFFFAOYSA-N 1-chloroethyl 2,2-dimethylpropanoate Chemical compound CC(Cl)OC(=O)C(C)(C)C VQEZDLXEVJCRMO-UHFFFAOYSA-N 0.000 description 1
- QUFPERUZCACWHQ-UHFFFAOYSA-N 2,3-dihydro-1H-inden-1-yl 5-(4-chlorobutoxy)pyridine-2-carboxylate Chemical compound N1=CC(OCCCCCl)=CC=C1C(=O)OC1C2=CC=CC=C2CC1 QUFPERUZCACWHQ-UHFFFAOYSA-N 0.000 description 1
- RILZRCJGXSFXNE-UHFFFAOYSA-N 2-[4-(trifluoromethoxy)phenyl]ethanol Chemical compound OCCC1=CC=C(OC(F)(F)F)C=C1 RILZRCJGXSFXNE-UHFFFAOYSA-N 0.000 description 1
- FDOLYWDBQOCBKI-UHFFFAOYSA-N 2-methyl-5-(4-methylphenoxy)pyridine Chemical compound C1=CC(C)=CC=C1OC1=CC=C(C)N=C1 FDOLYWDBQOCBKI-UHFFFAOYSA-N 0.000 description 1
- GPAVPOMMWYBWIL-UHFFFAOYSA-N 2-methyl-5-[3-(trifluoromethyl)phenoxy]pyridine Chemical compound C1=NC(C)=CC=C1OC1=CC=CC(C(F)(F)F)=C1 GPAVPOMMWYBWIL-UHFFFAOYSA-N 0.000 description 1
- ATVJXMYDOSMEPO-UHFFFAOYSA-N 3-prop-2-enoxyprop-1-ene Chemical compound C=CCOCC=C ATVJXMYDOSMEPO-UHFFFAOYSA-N 0.000 description 1
- QJPJQTDYNZXKQF-UHFFFAOYSA-N 4-bromoanisole Chemical compound COC1=CC=C(Br)C=C1 QJPJQTDYNZXKQF-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- UHPMCKVQTMMPCG-UHFFFAOYSA-N 5,8-dihydroxy-2-methoxy-6-methyl-7-(2-oxopropyl)naphthalene-1,4-dione Chemical compound CC1=C(CC(C)=O)C(O)=C2C(=O)C(OC)=CC(=O)C2=C1O UHPMCKVQTMMPCG-UHFFFAOYSA-N 0.000 description 1
- IZVRHXBPBVDYBF-UHFFFAOYSA-N 5-(2,4-dimethoxyphenoxy)pyridine-2-carboxylic acid Chemical compound COC1=C(OC=2C=CC(=NC=2)C(=O)O)C=CC(=C1)OC IZVRHXBPBVDYBF-UHFFFAOYSA-N 0.000 description 1
- WHVGGUIIUQHOAL-UHFFFAOYSA-N 5-(2-chlorophenoxy)-2-methylpyridine Chemical compound C1=NC(C)=CC=C1OC1=CC=CC=C1Cl WHVGGUIIUQHOAL-UHFFFAOYSA-N 0.000 description 1
- JALWKINJHJGLMI-UHFFFAOYSA-N 5-(2-chlorophenoxy)pyridine-2-carboxamide Chemical compound C1=NC(C(=O)N)=CC=C1OC1=CC=CC=C1Cl JALWKINJHJGLMI-UHFFFAOYSA-N 0.000 description 1
- XMWMXGOPVQDQTE-UHFFFAOYSA-N 5-(3-chlorophenoxy)-2-methylpyridine Chemical compound C1=NC(C)=CC=C1OC1=CC=CC(Cl)=C1 XMWMXGOPVQDQTE-UHFFFAOYSA-N 0.000 description 1
- RBYCZLPCBDKRPG-UHFFFAOYSA-N 5-(3-chlorophenoxy)pyridine-2-carboxylic acid Chemical compound C1=NC(C(=O)O)=CC=C1OC1=CC=CC(Cl)=C1 RBYCZLPCBDKRPG-UHFFFAOYSA-N 0.000 description 1
- PBJLDLUGOBLLMH-UHFFFAOYSA-N 5-(4-acetylphenoxy)pyridine-2-carboxylic acid Chemical compound C(C)(=O)C1=CC=C(OC=2C=CC(=NC=2)C(=O)O)C=C1 PBJLDLUGOBLLMH-UHFFFAOYSA-N 0.000 description 1
- XUYKNAKAUZALEJ-UHFFFAOYSA-N 5-(4-bromophenoxy)pyridine-2-carboxylic acid Chemical compound C1=NC(C(=O)O)=CC=C1OC1=CC=C(Br)C=C1 XUYKNAKAUZALEJ-UHFFFAOYSA-N 0.000 description 1
- QPXZVRUEENMWGK-UHFFFAOYSA-N 5-(4-chlorobutoxy)pyridine-2-carboxamide Chemical compound NC(=O)C1=CC=C(OCCCCCl)C=N1 QPXZVRUEENMWGK-UHFFFAOYSA-N 0.000 description 1
- GUJREVOWVMEPEX-UHFFFAOYSA-N 5-(4-chlorophenoxy)pyridine-2-carboxamide Chemical compound C1=NC(C(=O)N)=CC=C1OC1=CC=C(Cl)C=C1 GUJREVOWVMEPEX-UHFFFAOYSA-N 0.000 description 1
- DYUCWALCKOEDMS-UHFFFAOYSA-N 5-(4-methoxyphenoxy)-2-methylpyridine Chemical compound C1=CC(OC)=CC=C1OC1=CC=C(C)N=C1 DYUCWALCKOEDMS-UHFFFAOYSA-N 0.000 description 1
- DUABAGMUALWLPS-UHFFFAOYSA-N 5-(4-methoxyphenoxy)pyridine-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1OC1=CC=C(C(O)=O)N=C1 DUABAGMUALWLPS-UHFFFAOYSA-N 0.000 description 1
- OCYOPQMIQQOESK-UHFFFAOYSA-N 5-[2-(trifluoromethyl)phenoxy]pyridine-2-carboxamide Chemical compound C1=NC(C(=O)N)=CC=C1OC1=CC=CC=C1C(F)(F)F OCYOPQMIQQOESK-UHFFFAOYSA-N 0.000 description 1
- VWNSBPTWSFUTHE-UHFFFAOYSA-N 5-propoxypyridine-2-carboxylic acid Chemical compound CCCOC1=CC=C(C(O)=O)N=C1 VWNSBPTWSFUTHE-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 241000238876 Acari Species 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000020446 Cardiac disease Diseases 0.000 description 1
- 206010008190 Cerebrovascular accident Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 241000223218 Fusarium Species 0.000 description 1
- 125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- YWWIVAPTDUGCDE-UHFFFAOYSA-N [5-(3-chloropropoxy)pyridin-2-yl]methanol Chemical compound OCC1=CC=C(OCCCCl)C=N1 YWWIVAPTDUGCDE-UHFFFAOYSA-N 0.000 description 1
- OBCURBHILMISCR-UHFFFAOYSA-N [5-(4-nitrophenoxy)pyridin-2-yl]methanol Chemical compound C1=NC(CO)=CC=C1OC1=CC=C([N+]([O-])=O)C=C1 OBCURBHILMISCR-UHFFFAOYSA-N 0.000 description 1
- VZNBOUOHGXQJTK-UHFFFAOYSA-N [5-(5,5,5-trifluoropentoxy)pyridin-2-yl]methanol Chemical compound OCC1=CC=C(OCCCCC(F)(F)F)C=N1 VZNBOUOHGXQJTK-UHFFFAOYSA-N 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
- 230000004872 arterial blood pressure Effects 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- XQKKWWCELHKGKB-UHFFFAOYSA-L calcium acetate monohydrate Chemical compound O.[Ca+2].CC([O-])=O.CC([O-])=O XQKKWWCELHKGKB-UHFFFAOYSA-L 0.000 description 1
- 229940067460 calcium acetate monohydrate Drugs 0.000 description 1
- 235000013339 cereals Nutrition 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(I) oxide Inorganic materials [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 1
- JZCCFEFSEZPSOG-UHFFFAOYSA-L copper(II) sulfate pentahydrate Chemical compound O.O.O.O.O.[Cu+2].[O-]S([O-])(=O)=O JZCCFEFSEZPSOG-UHFFFAOYSA-L 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- KRFJLUBVMFXRPN-UHFFFAOYSA-N cuprous oxide Chemical compound [O-2].[Cu+].[Cu+] KRFJLUBVMFXRPN-UHFFFAOYSA-N 0.000 description 1
- 229940112669 cuprous oxide Drugs 0.000 description 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
- 230000020176 deacylation Effects 0.000 description 1
- 238000005947 deacylation reaction Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- IJGRMHOSHXDMSA-UHFFFAOYSA-O diazynium Chemical compound [NH+]#N IJGRMHOSHXDMSA-UHFFFAOYSA-O 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000001631 hypertensive effect Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- IWDCLRJOBJJRNH-UHFFFAOYSA-N p-cresol Chemical compound CC1=CC=C(O)C=C1 IWDCLRJOBJJRNH-UHFFFAOYSA-N 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 235000021178 picnic Nutrition 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 229940001584 sodium metabisulfite Drugs 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000001119 stannous chloride Substances 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 125000001680 trimethoxyphenyl group Chemical group 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP3296678A JPS54125680A (en) | 1978-03-24 | 1978-03-24 | 5-alkoxypicolinic acid ester, its preparation, and hypotensive agent containing the same |
JP3296778A JPS54125681A (en) | 1978-03-24 | 1978-03-24 | 5-substituted picolinic acid, its preparation, and hypotensive agent containing the same |
JP8048578A JPS559002A (en) | 1978-07-04 | 1978-07-04 | 5-substituted picolinic acid derivative, its preparation and hypotensive agent containing the same |
Publications (1)
Publication Number | Publication Date |
---|---|
CH637941A5 true CH637941A5 (fr) | 1983-08-31 |
Family
ID=27287919
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CH268779A CH637941A5 (fr) | 1978-03-24 | 1979-03-22 | Derives de l'acide picolinique substitues en position 5 et composition anti-hypertensive contenant ces derives. |
Country Status (9)
Country | Link |
---|---|
CA (1) | CA1115709A (it) |
CH (1) | CH637941A5 (it) |
DE (1) | DE2911492C2 (it) |
ES (1) | ES478918A1 (it) |
FR (1) | FR2422639A1 (it) |
GB (1) | GB2018753B (it) |
IT (1) | IT1115064B (it) |
NL (1) | NL178251C (it) |
SE (1) | SE446863B (it) |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5344572A (en) * | 1976-09-30 | 1978-04-21 | Meiji Seika Kaisha Ltd | 5-alkoxy-picolic acid, its preparation and hypotensives containing the same |
-
1979
- 1979-03-21 CA CA323,912A patent/CA1115709A/en not_active Expired
- 1979-03-22 IT IT48451/79A patent/IT1115064B/it active
- 1979-03-22 CH CH268779A patent/CH637941A5/fr not_active IP Right Cessation
- 1979-03-23 DE DE2911492A patent/DE2911492C2/de not_active Expired
- 1979-03-23 FR FR7907345A patent/FR2422639A1/fr active Granted
- 1979-03-23 NL NLAANVRAGE7902306,A patent/NL178251C/xx not_active IP Right Cessation
- 1979-03-23 GB GB7910324A patent/GB2018753B/en not_active Expired
- 1979-03-23 ES ES478918A patent/ES478918A1/es not_active Expired
- 1979-03-23 SE SE7902665A patent/SE446863B/sv not_active IP Right Cessation
Also Published As
Publication number | Publication date |
---|---|
FR2422639A1 (fr) | 1979-11-09 |
GB2018753A (en) | 1979-10-24 |
IT7948451A0 (it) | 1979-03-22 |
NL178251C (nl) | 1986-02-17 |
SE446863B (sv) | 1986-10-13 |
GB2018753B (en) | 1982-08-25 |
FR2422639B1 (it) | 1983-05-20 |
IT1115064B (it) | 1986-02-03 |
DE2911492C2 (de) | 1983-05-05 |
CA1115709A (en) | 1982-01-05 |
ES478918A1 (es) | 1979-12-16 |
DE2911492A1 (de) | 1979-09-27 |
SE7902665L (sv) | 1979-09-25 |
NL178251B (nl) | 1985-09-16 |
NL7902306A (nl) | 1979-09-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
FR2517303A1 (fr) | Derives d'imidazole | |
EP0706512A1 (fr) | Derives d'acetamide et leur utilisation comme modificateurs du comportement de prise alimentaire | |
EP0015038B1 (fr) | Composition pharmaceutique comprenant un dérivé de diphénylhydantoine, dérivés mis en oeuvre et leur préparation | |
CH655317A5 (fr) | Derives de l'acide 3-amino 2-oxo azetidine 1-sulfonique, leur preparation, medicaments et compositions les renfermant. | |
EP0040573B1 (fr) | Dérivés de l'acide 4-hydroxy 3-quinoléine carboxylique substitués en 2, leur préparation, leur application comme médicament, les compositions les renfermant et les intermédiaires nouveaux obtenus | |
FR2493315A1 (fr) | Derive de piperazine, procede pour sa preparation et composition analgesique en contenant | |
FR2560196A1 (fr) | Nouvelles 8a-acylaminoergolines, leur preparation et leur utilisation comme medicaments | |
EP0021940A1 (fr) | Nouveaux dérivés aminés du benzothiazole, leur procédé de préparation et leur application en thérapeutique | |
CA1145752A (fr) | Procede de preparation de nouveaux derives du n'tetrahydropyridinyl-indoles et de leurs sels | |
CH648285A5 (fr) | Acides benzoyl-3-nitro-2-phenylacetiques et sels metalliques, amides et esters correspondants utiles notamment comme medicaments anti-inflammatoires, procede et composes pour leur preparation. | |
CA2074365A1 (fr) | Derives de l'uree, leur preparation et les medicaments les contenant | |
EP0133176B1 (fr) | Composition pharmaceutique ou vétérinaire destinée à combattre des troubles ischémiques cardiaques | |
LU83307A1 (fr) | Derives d'adenosine a activite anti-inflammatoire et analgesique,ainsi que des compositions therapeutiques contenant ces derives comme principe actif | |
CH630606A5 (en) | Phenylamidine derivatives useful especially in therapeutics | |
CH637941A5 (fr) | Derives de l'acide picolinique substitues en position 5 et composition anti-hypertensive contenant ces derives. | |
LU81554A1 (de) | Alkylthiophenoxyalkylamines | |
EP0001947B1 (fr) | Dérivés de l'amino-2 thiazoline, procédé de préparation et compositions pharmaceutiques les contenant | |
FR2507180A1 (fr) | Nouvelles phenylalkylamines, leur preparation et leur application comme medicaments | |
CA1105022A (fr) | Procede de preparation de nouveaux derives de la benzophenone | |
FR2462420A1 (fr) | Esters o-alcoxycarbonyl-phenyliques d'un acide anthranilique, leur preparation et compositions pharmaceutiques en contenant | |
BE875070A (fr) | Derives d'acides picoliniques substitues en position 5, procede de preparation de ces derives et composition anti-hypertensive en contenant | |
FR2600059A1 (fr) | Derives de l'acide benzoique et leur procede de preparation | |
FR2491471A1 (fr) | Benzoxazolinones substituees, leur preparation et leur application en therapeutique | |
FR2751646A1 (fr) | Phenoxypropanolamine a action antagoniste beta3-adrenergique | |
EP0226475A1 (fr) | Nouveaux dérivés de la diphénoxyethylamine, leur procédé d'obtention et les compositions pharmaceutiques en renfermant |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PL | Patent ceased |