PH25966A - 2-methylthiomethyl-dihydro-pyridines and pharmaceutical compositions containing them - Google Patents

2-methylthiomethyl-dihydro-pyridines and pharmaceutical compositions containing them Download PDF

Info

Publication number: PH25966A
Authority: PH; Philippines
Prior art keywords: group; alkoxy; methyl; nitro; compound
Prior art date: 1986-12-11

Application number

PH36155A

Other languages

English (en)

Inventor

Marco Frigerio

Andrea Zaliani

Carmelo A Gandolfi

Odoardo Tofanetti

Sergio Tognella

Carblo Riva

Original Assignee

Boehringer Biochemia Srl

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.)

1986-12-11

Filing date

1987-12-02

Publication date

1992-01-13

1987-12-02 Application filed by Boehringer Biochemia Srl filed Critical Boehringer Biochemia Srl

1992-01-13 Publication of PH25966A publication Critical patent/PH25966A/en

Links

239000008194 pharmaceutical composition Substances 0.000 title claims description 6
CGSHQPUWUNBDDP-UHFFFAOYSA-N 2-(methylsulfanylmethyl)-1,2-dihydropyridine Chemical class CSCC1NC=CC=C1 CGSHQPUWUNBDDP-UHFFFAOYSA-N 0.000 title 1
150000001875 compounds Chemical class 0.000 claims description 46
-1 m-nitrophenvl Chemical class 0.000 claims description 19
238000000034 method Methods 0.000 claims description 14
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
229910052736 halogen Inorganic materials 0.000 claims description 9
150000002367 halogens Chemical class 0.000 claims description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
229910052739 hydrogen Inorganic materials 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
206010020772 Hypertension Diseases 0.000 claims description 5
125000001072 heteroaryl group Chemical group 0.000 claims description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
125000003118 aryl group Chemical group 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 3
150000002431 hydrogen Chemical class 0.000 claims description 3
125000002252 acyl group Chemical group 0.000 claims description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
125000000623 heterocyclic group Chemical group 0.000 claims description 2
229910052757 nitrogen Inorganic materials 0.000 claims description 2
229910052760 oxygen Inorganic materials 0.000 claims description 2
239000001301 oxygen Substances 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims 4
125000001424 substituent group Chemical group 0.000 claims 2
238000005281 X-ray Gandolfi Methods 0.000 claims 1
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
125000003368 amide group Chemical group 0.000 claims 1
150000001412 amines Chemical class 0.000 claims 1
229940125692 cardiovascular agent Drugs 0.000 claims 1
239000002327 cardiovascular agent Substances 0.000 claims 1
IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
239000000243 solution Substances 0.000 description 30
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
239000000203 mixture Substances 0.000 description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
239000002253 acid Substances 0.000 description 12
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
239000003921 oil Substances 0.000 description 11
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
239000012074 organic phase Substances 0.000 description 9
235000019441 ethanol Nutrition 0.000 description 8
239000012298 atmosphere Substances 0.000 description 7
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 7
239000002904 solvent Substances 0.000 description 7
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
239000007864 aqueous solution Substances 0.000 description 6
239000003480 eluent Substances 0.000 description 6
239000012299 nitrogen atmosphere Substances 0.000 description 6
239000012071 phase Substances 0.000 description 6
239000011734 sodium Substances 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
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 5
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
229910052708 sodium Inorganic materials 0.000 description 5
229910052938 sodium sulfate Inorganic materials 0.000 description 5
235000011152 sodium sulphate Nutrition 0.000 description 5
238000004440 column chromatography Methods 0.000 description 4
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
230000001413 cellular effect Effects 0.000 description 3
125000004093 cyano group Chemical group *C#N 0.000 description 3
238000001035 drying Methods 0.000 description 3
238000001704 evaporation Methods 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
238000001914 filtration Methods 0.000 description 3
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
229910052500 inorganic mineral Inorganic materials 0.000 description 3
239000012528 membrane Substances 0.000 description 3
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
239000011707 mineral Substances 0.000 description 3
235000010755 mineral Nutrition 0.000 description 3
230000003647 oxidation Effects 0.000 description 3
238000007254 oxidation reaction Methods 0.000 description 3
239000011591 potassium Substances 0.000 description 3
229910052700 potassium Inorganic materials 0.000 description 3
150000003839 salts Chemical class 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
239000007787 solid Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
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 2
241001465754 Metazoa Species 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
239000005864 Sulphur Chemical group 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 2
125000003342 alkenyl group Chemical group 0.000 description 2
YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
239000000460 chlorine Substances 0.000 description 2
125000005265 dialkylamine group Chemical group 0.000 description 2
238000011534 incubation Methods 0.000 description 2
239000008101 lactose Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
239000000047 product Substances 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
230000035484 reaction time Effects 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
229910021653 sulphate ion Inorganic materials 0.000 description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical compound NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 1
XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
102000008186 Collagen Human genes 0.000 description 1
108010035532 Collagen Proteins 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
241000283986 Lepus Species 0.000 description 1
101100059652 Mus musculus Cetn1 gene Proteins 0.000 description 1
101100059655 Mus musculus Cetn2 gene Proteins 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
241000283973 Oryctolagus cuniculus Species 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
ATTZFSUZZUNHBP-UHFFFAOYSA-N Piperonyl sulfoxide Chemical compound CCCCCCCCS(=O)C(C)CC1=CC=C2OCOC2=C1 ATTZFSUZZUNHBP-UHFFFAOYSA-N 0.000 description 1
125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
239000004133 Sodium thiosulphate Substances 0.000 description 1
235000021355 Stearic acid Nutrition 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
206010042434 Sudden death Diseases 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 1
PQLVXDKIJBQVDF-UHFFFAOYSA-N acetic acid;hydrate Chemical compound O.CC(O)=O PQLVXDKIJBQVDF-UHFFFAOYSA-N 0.000 description 1
MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
239000003377 acid catalyst Substances 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
125000005035 acylthio group Chemical group 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
210000000709 aorta Anatomy 0.000 description 1
229940114079 arachidonic acid Drugs 0.000 description 1
235000021342 arachidonic acid Nutrition 0.000 description 1
125000003435 aroyl group Chemical group 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000036772 blood pressure Effects 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
210000004027 cell Anatomy 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
238000006482 condensation reaction Methods 0.000 description 1
230000008602 contraction Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
235000013681 dietary sucrose Nutrition 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
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239000000839 emulsion Substances 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
230000002964 excitative effect Effects 0.000 description 1
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125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
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239000007903 gelatin capsule Substances 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
230000001631 hypertensive effect Effects 0.000 description 1
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238000007912 intraperitoneal administration Methods 0.000 description 1
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239000007788 liquid Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
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150000007524 organic acids Chemical class 0.000 description 1
150000004967 organic peroxy acids Chemical class 0.000 description 1
230000004792 oxidative damage Effects 0.000 description 1
230000001590 oxidative effect Effects 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
238000007911 parenteral administration Methods 0.000 description 1
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
150000004965 peroxy acids Chemical class 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
AXIPBRXJGSXLHF-UHFFFAOYSA-N piperidine;pyrrolidine Chemical compound C1CCNC1.C1CCNCC1 AXIPBRXJGSXLHF-UHFFFAOYSA-N 0.000 description 1
125000005936 piperidyl group Chemical group 0.000 description 1
FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000011533 pre-incubation Methods 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
235000019833 protease Nutrition 0.000 description 1
238000000746 purification Methods 0.000 description 1
230000009257 reactivity Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
229960004793 sucrose Drugs 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
125000001174 sulfone group Chemical group 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
239000001117 sulphuric acid Substances 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- 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
- A61P9/12—Antihypertensives
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two 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 directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Diabetes (AREA)
Hematology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Plural Heterocyclic Compounds (AREA)

PH36155A 1986-12-11 1987-12-02 2-methylthiomethyl-dihydro-pyridines and pharmaceutical compositions containing them PH25966A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
IT8622648A IT1213555B (it)	1986-12-11	1986-12-11	2 metiltiometildiidropiridine, un processo per laloro preparazione e composizioni farmaceutiche che le contengono.

Publications (1)

Publication Number	Publication Date
PH25966A true PH25966A (en)	1992-01-13

Family

ID=11198832

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
PH36155A PH25966A (en)	1986-12-11	1987-12-02	2-methylthiomethyl-dihydro-pyridines and pharmaceutical compositions containing them

Country Status (10)

Country	Link
US (1)	US4971984A (de)
EP (1)	EP0271059B1 (de)
JP (1)	JPS63170360A (de)
KR (1)	KR880007468A (de)
AT (1)	ATE96152T1 (de)
AU (1)	AU611872B2 (de)
DE (1)	DE3787878D1 (de)
IT (1)	IT1213555B (de)
PH (1)	PH25966A (de)
ZA (1)	ZA879301B (de)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
KR930011486B1 (ko) *	1985-08-06	1993-12-08	베링거 만하임 이탈리아 에스.피.에이.	제약상 유효한 2-티오메틸-치환-1,4-디히드로피리딘
EP2147679B1 (de)	2001-07-25	2014-06-25	Raptor Pharmaceutical, Inc.	Zusammensetzungen für den Blut-Hirn-Schrankentransport
US6699892B2 (en)	2002-06-04	2004-03-02	Yung Shin Pharmaceutical Industrial Co., Ltd.	Pharmaceutically acceptable salt of amlodipine and method of preparing the same
EP2392258B1 (de)	2005-04-28	2014-10-08	Proteus Digital Health, Inc.	Pharma-Informatiksystem
CN101594878A (zh)	2006-09-18	2009-12-02	雷普特药品公司	通过给予受体相关蛋白（rap）-缀合物对肝病症的治疗
PL3395372T3 (pl)	2009-02-20	2022-07-25	EnhanX Biopharm Inc.	Układ do dostarczania leków na bazie glutationu
CN102458374A (zh)	2009-05-06	2012-05-16	实验室护肤股份有限公司	包含活性剂-磷酸钙颗粒复合物的皮肤递送组合物及其使用方法
US20120077778A1 (en)	2010-09-29	2012-03-29	Andrea Bourdelais	Ladder-Frame Polyether Conjugates

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CS228917B2 (en) *	1981-03-14	1984-05-14	Pfizer	Method of preparing substituted derivatives of 1,4-dihydropyridine
NZ201395A (en) *	1981-07-30	1987-02-20	Bayer Ag	Pharmaceutical compositions containing 1,4-dihydropyridines and certain of these dihydropyridines
DE3207982A1 (de) *	1982-03-05	1983-09-08	Bayer Ag, 5090 Leverkusen	Neue 1,4-dihydropyridine, verfahren zu ihrer herstellung und ihrer verwendung in arzneimitteln
DK161312C (da) *	1982-03-11	1991-12-09	Pfizer	Analogifremgangsmaade til fremstilling af 2-aminoalkoxymethyl-4-phenyl-6-methyl-1,4-dihydropyridin-3,5-dicarboxylsyreestere eller syreadditionssalte deraf samt phthalimidoderivater til anvendelse som udgangsmateriale ved fremgangsmaaden
IL68604A0 (en) *	1982-05-21	1983-09-30	Haessle Ab	Processes for preparing therapeutically active dihydropyridines and intermediates for the processes
US4515799A (en) *	1983-02-02	1985-05-07	Pfizer Inc.	Dihydropyridine anti-ischaemic and antihypertensive agents
GB8306666D0 (en) *	1983-03-10	1983-04-13	Pfizer Ltd	Therapeutic agents
GB8412208D0 (en) *	1984-05-12	1984-06-20	Pfizer Ltd	Quinolone inotropic agents
GB8415386D0 (en) *	1984-06-15	1984-07-18	Pfizer Ltd	Therapeutic agents
DE3426732A1 (de) *	1984-07-20	1986-01-23	Bayer Ag, 5090 Leverkusen	Material fuer stuetzverbaende
EP0200524A3 (de) *	1985-05-03	1987-06-16	Pfizer Limited	Dihydropyridin-Calcium-Antagonisten
CA1267416A (en) *	1985-06-17	1990-04-03	Ila Sircar	1,4-dihydropyridine derivatives useful for the treatment of cardiovascular disorders
IT1204421B (it) *	1986-06-27	1989-03-01	Boehringer Biochemia Srl	2-(aminoalchiltio)metil-1,4-diidropiridine,un metodo per la loro preparazione e composizioni farmaceutiche che le contengono
KR930011486B1 (ko) *	1985-08-06	1993-12-08	베링거 만하임 이탈리아 에스.피.에이.	제약상 유효한 2-티오메틸-치환-1,4-디히드로피리딘
GB8526411D0 (en) *	1985-10-25	1985-11-27	Pfizer Ltd	Dihydropyridines
GB8527698D0 (en) *	1985-11-09	1985-12-11	Pfizer Ltd	Dihydropyridine antiischaemic & antihypertensive agents
EP0225175A3 (de) *	1985-11-28	1988-12-28	FISONS plc	Dihydropyridin-Derivate, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zusammensetzungen

1986
- 1986-12-11 IT IT8622648A patent/IT1213555B/it active
1987
- 1987-12-02 PH PH36155A patent/PH25966A/en unknown
- 1987-12-08 AT AT87118145T patent/ATE96152T1/de not_active IP Right Cessation
- 1987-12-08 DE DE87118145T patent/DE3787878D1/de not_active Expired - Lifetime
- 1987-12-08 EP EP87118145A patent/EP0271059B1/de not_active Expired - Lifetime
- 1987-12-10 AU AU82294/87A patent/AU611872B2/en not_active Ceased
- 1987-12-10 KR KR870014104A patent/KR880007468A/ko not_active Ceased
- 1987-12-10 ZA ZA879301A patent/ZA879301B/xx unknown
- 1987-12-10 JP JP62313104A patent/JPS63170360A/ja active Pending
- 1987-12-10 US US07/131,393 patent/US4971984A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
IT1213555B (it)	1989-12-20
AU8229487A (en)	1988-06-16
KR880007468A (ko)	1988-08-27
ZA879301B (en)	1988-08-31
IT8622648A0 (it)	1986-12-11
ATE96152T1 (de)	1993-11-15
DE3787878D1 (de)	1993-11-25
JPS63170360A (ja)	1988-07-14
EP0271059B1 (de)	1993-10-20
EP0271059A1 (de)	1988-06-15
US4971984A (en)	1990-11-20
AU611872B2 (en)	1991-06-27

Publication	Publication Date	Title
KR930011486B1 (ko)	1993-12-08	제약상 유효한 2-티오메틸-치환-1,4-디히드로피리딘
US5021433A (en)	1991-06-04	Novel pharmacological compounds
EP0535081A1 (de)	1993-04-07	Substituierte benzimidazole, verfahren zur herstellung und pharmazeutische verwendung
AU598793B2 (en)	1990-07-05	1,2,3,4-tetrahydro-6-substituted-4-aryl(or heterocyclo)-3- substituted-2-thioxo(or oxo)-5-pyrimidinecarboxylic acids and esters
FR2561647A1 (fr)	1985-09-27	Derives de 1-(hydroxymethyl)-1,6,7,11b-tetrahydro-2h,4h-(1,3)-oxazino- ou -thiazino(4,3,a)isoquinoleine, procede pour leur preparation et compositions pharmaceutiques les contenant
US4684655A (en)	1987-08-04	1,2,3,4-tetrahydro-6-substituted-4-aryl-3-substituted-2-thioxo(or oxo)-5-pyrimidinecarboxylic acids and esters and use thereof to lower blood pressure
PH25966A (en)	1992-01-13	2-methylthiomethyl-dihydro-pyridines and pharmaceutical compositions containing them
US4777172A (en)	1988-10-11	Pyrimidylalkylthio benzimidale compounds, pharmaceutical compositions and use
FR2607502A1 (fr)	1988-06-03	Derives de l'imidazole, leur preparation et compositions medicamenteuses les contenant
US5134151A (en)	1992-07-28	2-picolylamine derivatives
FR2613717A1 (fr)	1988-10-14	Derives d'acides pyrimidinecarboxyliques, a action therapeutique
US4859679A (en)	1989-08-22	Antiulcer (alkyldithio) quinoline derivatives
EP0246774A1 (de)	1987-11-25	Chemische Verbindungen
JP2004502773A (ja)	2004-01-29	抗癌剤としてのバリオリン誘導体
EP0282904B1 (de)	1992-08-26	2-Thiomethyl-substituierte Pyridine, Verfahren zu deren Herstellung und diese enthaltende Arzneimittel
US4179512A (en)	1979-12-18	4-Substituted-2-arylimidazoles
WO1995015962A1 (en)	1995-06-15	Substituted benzimidazole, processes for its preparation and its pharmaceutical use
KR100254106B1 (ko)	2000-05-01	4-퀴놀리논 유도체 또는 그의 염
EP0292981B1 (de)	1991-04-17	2-Selenomethyl-1,4-dihydropyridine, Verfahren zu deren Herstellung und diese enthaltende pharmazeutische Zusammensetzungen
EP0576349A1 (de)	1993-12-29	Indolizine Derivate, Herstellungsverfahren und Verwendung für die Herstellung von pharmazeutisch aktiven Aminoalkoxyphenylsulfonyl-Indolizine Verbindungen
EP0210571B1 (de)	1990-05-30	Phosphono pyridine und ihre 1,4-Dihydroderivate
EP0651747B1 (de)	1996-03-27	Carbostyrylderivate
EA008688B1 (ru)	2007-06-29	Новые соединения 4-оксо-4,6,7,8-тетрагидропирроло[1,2-а]пиразин-6-карбоксамида, способ их получения и фармацевтические композиции, которые их содержат
EP0282050B1 (de)	1993-10-06	Carbonyl- und Sulfonyl-Derivate von 2-(Aminoalkylthio)methyl-1,4-dihydropyridinen, Verfahren zu ihrer Herstellung und diese enthaltende pharmazeutische Zusammensetzungen
EP0379351A1 (de)	1990-07-25	1,4-Dihydropyridin-Derivate