PL92127B1 - - Google Patents
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- Publication number
- PL92127B1 PL92127B1 PL1973182184A PL18218473A PL92127B1 PL 92127 B1 PL92127 B1 PL 92127B1 PL 1973182184 A PL1973182184 A PL 1973182184A PL 18218473 A PL18218473 A PL 18218473A PL 92127 B1 PL92127 B1 PL 92127B1
- Authority
- PL
- Poland
- Prior art keywords
- piperidine
- formula
- hydroxy
- compounds
- phenylbenzyl
- Prior art date
Links
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 22
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 18
- 150000003053 piperidines Chemical class 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 238000000034 method Methods 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 description 20
- -1 α-hydroxy-α-phenylbenzyl Chemical group 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 150000003839 salts Chemical class 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 150000001412 amines Chemical class 0.000 description 5
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-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
- 239000002253 acid Substances 0.000 description 4
- 230000003266 anti-allergic effect Effects 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 235000019759 Maize starch Nutrition 0.000 description 3
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 229940124630 bronchodilator Drugs 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- UNPKOFGAQOEDMF-UHFFFAOYSA-N 4-benzhydrylidenepiperidine Chemical class C1CNCCC1=C(C=1C=CC=CC=1)C1=CC=CC=C1 UNPKOFGAQOEDMF-UHFFFAOYSA-N 0.000 description 2
- 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 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-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
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000005265 dialkylamine group Chemical group 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 229960001340 histamine Drugs 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 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
- 239000002480 mineral oil Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- WLTFPYVGECWXFO-UHFFFAOYSA-N 1-phenyl-4-piperidin-1-ylbutan-1-one Chemical compound C=1C=CC=CC=1C(=O)CCCN1CCCCC1 WLTFPYVGECWXFO-UHFFFAOYSA-N 0.000 description 1
- 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
- 125000005274 4-hydroxybenzoic acid group Chemical group 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 208000009079 Bronchial Spasm Diseases 0.000 description 1
- 208000014181 Bronchial disease Diseases 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- 241000700198 Cavia Species 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
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004147 Sorbitan trioleate Substances 0.000 description 1
- PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 230000003182 bronchodilatating effect Effects 0.000 description 1
- 239000000168 bronchodilator agent Substances 0.000 description 1
- UVZGOOXAARJPHD-UHFFFAOYSA-N butan-2-one;methanol Chemical compound OC.CCC(C)=O UVZGOOXAARJPHD-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 125000000490 cinnamyl group Chemical group C(C=CC1=CC=CC=C1)* 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 150000002085 enols Chemical class 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- JYGYEBCBALMPDC-UHFFFAOYSA-N heptane;propan-2-one Chemical compound CC(C)=O.CCCCCCC JYGYEBCBALMPDC-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000008263 liquid aerosol Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910000096 monohydride Inorganic materials 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000001997 phenyl group Chemical class [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- XMGMFRIEKMMMSU-UHFFFAOYSA-N phenylmethylbenzene Chemical group C=1C=CC=CC=1[C]C1=CC=CC=C1 XMGMFRIEKMMMSU-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008275 solid aerosol Substances 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- C07D211/06—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 no double bonds between ring members or between ring members and non-ring members
- C07D211/08—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/10—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
- C07D211/14—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- 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
- C07D211/06—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 no double bonds between ring members or between ring members and non-ring members
- C07D211/08—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
- C07D211/18—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D211/20—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
- C07D211/22—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 no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
-
- 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
- C07D211/68—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 one double bond between ring members or between a ring member and a non-ring member
- C07D211/70—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 one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Hydrogenated Pyridines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
Description
Przedmiotem wynalazku jest sposób wytwarza¬ nia nowych pochodnych piperydyny, w szczegól¬ nosci pochodnych 4-dwufenylometylo-4-/ a-hy- diroksy^a-tfenylobenzylo/ — oraz 4-dwufenyloime- tylenopiperydyny ewentualnie w postaci ich soli addycyjnych z kwiafcami, sluzacymi jiako srodki przeciwhistaiminowe, przeciwalergiczne oraz srodki rozszerzajace oskrzela.Nowe podstawione pochodne piperydyny po- sdadaja wzór ogólny 1, w którym R oznacza atom wodoru lub grupe hydroksylowa, R1 oznacza atom -wodoru lub R i R1 lacznie oznaczaja drugie wiazanie miedzy atomami wegla, do których sa przylaczone, n oznacza liczbe calkowita o wartosci 1—3, Z1 oznacza rodnik fenylowy podstawiony w pozycji orto, lub para nizsza grupe dwualkiioami- nowa, grupa pirolidynowa, piperydynowa, morfo- linowa, lub N-nizszoalkilopGperazynowa.W zakres wynalazku wchodza takze dopuszczal¬ ne w farmacji sole addycyjne z kwasami i poszcze¬ gólne izomery optyczne zwiazku o wzorze 1.Jak wynika ze wzoru 1 do zwiazków wytwarza¬ nych sposobem wedlug wynalazku naleza po¬ chodne 4 ogólnym 2, pochodne 4-/a-hydroksy-a-fenyloben- zylo/pijperydyny o wzorze ogólnym 3 oraz po¬ chodne 4-dwiufenyiometylenopiperydyny o wzorze ogólnym 4. We 'wzorach tych n i Z1 posiadaja zna¬ czenie podane powyzej.Okreslenie „nizszy rodnik alkilowy" oznacza ?o 2 prosjty lub irozgailejzioniy rodtnrik alkilowy o 1—4 ato¬ mach wegla. Przykladem takich nizszych grup alkilowych w zwiazkach o wzorach 1—4 wy¬ stepujacych jako bezposrednie podstawki lub w grupach dwualkiioaminowych albo w N-alkilopd- perazynie sa na przyklad rodniki: metylowy, ety¬ lowy, nnpropylowy, n-butylowy, izopropylowy, izobutylowy i IH-rzed-butyiowy.Do korzystnych zwiazków wytwarzanych spo¬ sobem wedlug wynalazku naleza zwiazki o wzo¬ rach 2 i 3, w kótrych n i Z1 posiadaja znaczenie podane powyzej. Charakteryzuja sie one najlepszy¬ mi wlasciwosciami przeciwhlistaminowymi, prze- ciwalergicznymi i zdolnoscia rozszerzenia oskrzeli.Ponadto zwiazki te wykazuja minimalne oddzialy¬ wanie na centralny uklad nerwowy i minimalne dzialanie depresyjne.Bardziej korzystnymi sa zwiazki o wzorze 3, w których n jest równe 3 a Z1 posiada znaczenie podane powyzej, odpowiadajace wzorowi 5.W zakres wynalazku wchodza takze dopuszczalne w farmacji sole addycyjne z kwasami oraz izomery optyczne i ich sole. Naleza do nich sole z kwasami nieorganicznymi i organicznymi, na przyklad chlorowodorem, bromowodorem, kwasem siarko- wym, fosforowym, z kwasami karboksylowymi, na przyklad octowym, propionowym, glikolowym, mlekowym, pirogronowym, malonowym, bursztyno¬ wym, fumarowym, jablkowym, winowym, cytryno¬ wym, askorbinowym, maleinowym, hydiroksyma- 92 12792127 leinowym, dwtf*lydroksyma4einoWyiri, berizoesó- wyim, fenylooctowym, 4-aminobenzoesowyim, 4-hy- diroksiybenzoesowyim, ainiranilowym, cynamonowym, salicylowym, 4-aminosalicylowyim, 2-fenoksyben- zoesowym, 2-acetoksybenzoesowym, migdalowym oraz sole z kwasami sulfonowymi, na przyklad me^nxtetflfonowyim, etanosulfonowym, jl-hy- droksyetanosulfbnowym i podobnymi.Przykladami zwiazków otrzymywanych spo¬ sobem wedlug wynalazku sa miedzy innymi: 4-/4-dwufenyflometylenopiperydyno/butyrofenon, 4-[4-/a-hydroksy-a-fenylobenzylo/piperydyno]-4'- -pdperydynobutyrdlenon, 2-/4-dwufenylometylo- £i{efrydyno7acetofenon, 4/-dwu-(n^propyloamdno-4- ^[4-/a-hydroksy-a-fenyiobenzylo/piperydyino]buity- fenon, i podobne.Przykladami bardziej korzystnych zwiazków sa miedzy innymi: 4-[4-/a-hydroksy-a-fenyloben- zylO/lpiperydyno]-4'-piperydynobutyrofenon, 4-f4-/a- -hydroksy-a-fenylobenzylo/piperydyno]-4'^dwume- tyloaiminobutyrofenon, 4-[4-/a-hydroksy-a-fenylo- benzylo/piperydynojbutyrofenon i podobne.Nowe zwiazki sluzace jako srodki przeciwhista- minowe, przeciwalergiczne i rozszerzajace oskrzela mozna stosowac same lub z odpowiednimi nosni¬ kami farmaceutycznymi, w postaci stalej lub cieklej, na przyklad w postaci tabletek, kapsulek, proszków, roztworów, zawiesin lub emulsji.Omawiane* zwiazki mozna podawac doustnie, pozajelitowe, na przyklad podskórnie, dozylnie, domiesniowo lub dootrzewnowe przez wkraplanie do nosa lub podawanie do blon skiiowyttfc tAfcish jak nos, gardlo, przewody oskrzelowe w postaci aerosolu plynnego lub stalego.Ilosc w jakiej stosuje sie nowe zwiazki moze sie zmieniac w szerokich granicach, w zaleznosci od pacjenta i sposobu podawania, i wynosi dla pojMyncze] dawki od 0,01 do 20 mg na kilogram wagi ciala. Przykladowo, dla uzyskania pozadanego eiekiii przeciwhdstaminowegó, praeciwalergicznego luft efektu rozszerzenia oskrzeli mozna stosowac tatsfetki zabierajace od 1 do 50 mg nowego zwiazku*, jfodajac je 1—4 razy dziennie.Stale formy farmaceutyczne sa formami typo¬ wymi, fifoga io byc zwykle zelatynowe kapsulki zawierajace nowe zwiazki i odpowiednie nosniki, na przyklad lufarykanty i obojetne wypelniacze, takie jak laktoza, sacharoza, skrobia kukurydziana i podobne. Mozna takze stosowac tabletki zawie¬ rajace nowe zwiazki ze zwyklymi podstawami farmaceutycznymi, na przyklad laktoza, sacharoza, skrobia kukurydziana i podobnymi, w polaczeniu z substancjami wiazacymi, takimi jak guma arabska, skrobia kukurydziana lub zelatyna, srodkami rozpraszajacymi, takimi jak skrobia kukurydziana lub ziemniaczana albo kwas algi¬ nowy oraz luibrykanitami, takimi jak kwas steary¬ nowy lub stearynian magnezu.Nowe zwiazki moga byc takze podawane w postaci iniekcyjnej, uzyskiwanej przez rozgosz¬ czenie lub zawieszenie w dopuszczalnych w far¬ macji rozcienczalnikach z dodatkiem nosników.Moga to byc jalowe roztwory w wodzie lub w olejach z dodatkiem lub bez dodatku substancji powierzchniowo czynnych i innych dopuszczalnych w farmacji atfjuwantów. Mozna stosowac oleje mineralne, zwierzece, roslMrJe *i*tr s-yntetyctfnt,- ii* przyklad olej arachidowy, sojowy, mineralny i po¬ dobne. Korzystnym jest na ogól stotfó-Watf w cha- raktorze roztworów iniekcyjnych roztwory w wodzie, soli fizjologicznej, roztworze wodnym dekstrozy i pokrewnych cukrów, roztworu w eta¬ nolu lub w glikolach, takich jak glikol propyle¬ nowy lub polietylenowy.Roztwory lub zawiesiny mozna stosowac w po- setaci aerosoli, pakujac je w cisnieniowe zbior¬ niczki lacznie z gazowym lub skroplonym srodkiem rozpylajacym, na przyklad dwuchlorodiwufluoro- metanem, samym lub w mieszaninie z dwuchlo- dwufluoroetanem, dwutlenkiem wejla, azotem, propanem, z dodatkiem zwyklych adjiuwanJtów, na przyklad innych rozpuszczalników lub srodków zwilzajacych, jakie moga byc niezbedne lub po¬ zadane. Mozna takze stosowac postaci bezcisnie- niowe, uzywajac rozpylaczy.Zawiesina do przyrzadzania aerosolu moze miecr przykladowo nastepujacy sklad: % wagowych x a) 4-[4-/a-hydroksy-a-fenyloben- zylc^iperydyno]lb(tttyrofenon/ro^m»iary czastek mniejsze od 10u] 20,0 b) irójoleinian sorbitolu 0,5 c) dWUchlóródwufluórometan 39,75 ^ d) dwuchlorodwufliuoroetan 39,75* 9t*#tancje a, b, c i d pakuje sie do wykonanych ze stali nierdzewnej pojemników o objejtosci 15 ml,, zaopatrzonych w zawór dozujacy porcje po 50 mg preparatu, co odpowiada 10 mg zwiazku a.Przydatnosc nowych zwiazków ilustruje na¬ stepujacy przyklad, wskazujacy ilosc zwiazku potfzetma do zahamowania w1 $0% b^bla pokrzyw¬ kowego Wywolywanego u swinek morskich sród- ^ skórna iniekcja 1 y histaminy. 4-(4-/a-ihydroksy-a- -f^ylldSemyio^pery^^ fenon wstrzykiwano po uplywie 1 godziny oct ws&zykndecia histaminy. Wartosc fifiw wynosi 3,4 mg/kg* ^ Najmniejsza ilosc zwiazku niezbedna dla zaha¬ mowania wywolanego rozpyleniem antygenu skurczu oskrzeli i s^rrfierci u swinek morskich wynosi przy podawaniu doustnym 4,0 mg na kilogram wagi ciala.^ Sposób wedlug wynalazku wytwarzania zwiaz¬ ków o wzorze 1, w którym ft, Rf, n i Zi maja wyzej podane znaczenie, polega na reakcji zwiaz¬ ku o wzorze ff, w kltórym R, R1 i n maja wyzej podane znaczenie, a & oznacza rodnik fenylowi 55 podstawiony atomem chlorowca, takim jak fluor, chlor, bfom lub jod, z amina taka jak nizsza dwu- alkiloamina, pirolidyna, piperydyna, morfolina lub N-nizszoalkilopiperazyna, Jesli stosuje sie lotna amine, przepuszcza sie ja przez roztwór w podstawionej atomem chlorowca pochodnej feny- lowej w dwumetylosulfotlenku, w ciagu 4—8 godzin; w temperaturze okolo 100°C. W przypadku wyzej wrzacej aminy, ,na przyklad piperydyny, któ¬ ra stosuje sie jednoczesnie w charakterze reagenta, gg rozpuszczalnika i zasady, stosuje sie jej nadmiar92127 6 i reakcje prowadzi w temperaturze wrzenia, w czasie 4—24 godzin.Przyklad I. 4-[4-/a-ihydroksy-a-ienyloben- zylo/piperydyno ]-4'-piperydynoibutyrafenon.Mieszanine zawierajaca 15 g (0,035 molal 4'-fluo- ro-4-[-4-/a^hydroksy-a-fenylobenzylo/piperydyno]- -4utyroi:enolu i rnala ilosc jodku potasowego w 100 ml piperydyny, utrzymuje sie w stanie wrze¬ nia pod chlodnica zwrotna w ciagu 22 godzin.Nadmiar nieprzereaigowanej piperydyny usuwa sie pod zmniejszonym cisnieniem a pozostalosc uciera z woda, wode dekantuje a pozostalosc rozpuszcza w metanolu i dodaje duza ilosc wody. Wytracony osad rozpuszcza sie w duzej objetosci eteru, suszy nad siarczanem magnezu, dodaje wegla aktyw¬ nego i saczy. Przesacz zateza sie do objetosci 50 ml i ochladza. Otrzymany produkt rekrystali- zuje sie z eteru otrzymujac tytulowy zwiazek o temperaturze topnienia 137,5—139°C.Przyklad II. 4'-dwuimetyIoaimlno-4-[4-/a-hy- droksy-a-fenylabenzylo/pdperydynoJbutyTofenon.Przez roztwór 18 g (0,041 mola) 4/-fluoro-4-[4-/a- -hydroksy-a-fenyloibenzylo/piperydyno}butyrofeno- nu w 150 ml dwuimetylosulfotienku przepuszcza sie szybki strumien dwumetyloaminy, w ciagu 6 godzin, w temperaturze 100°C. Wiekszosc roz¬ puszczalnika usuwa sie pod zmniejszonym cisnie¬ niem, w temperaturze 12Ó°C. Pozostala mieszanine wlewa sie do wodiy zawierajacej weglain sodowy i mala ilosc metanolu. Otrzymany osad odsacza sie i rozpuszcza w cieplym metanolu i alkoholu izopropylowym, odbarwia weglem aktywnym, saczy i ochladza. Wytracony osad odsacza sie i rekrystalizuje z mieszaniny aceton-heptan otrzy¬ mujac zwiazek tytulowy o temperaturze topnie¬ nia 148—150°C.Przyklad III. Stosujac postepowanie z przy¬ kladu I ale zastepujac piperydyne odpowiednia iloscia morfóliny, N-metyitópiperazyny lub piroli- dyny otrzymuje sie nastepujace zwiazki: 4-[4-/a- -hydroksy-a-fenyilobeiizylo/pipierydyno]-4'-(morfoli- nobutyrofenon o temperaturze topnienia 66—70°C, ^-^-/a^ydtctey-a-fenylobenzylo/piperydyno]^'- -/N^metylopiperazyno/iSutyrofenon o temperaturze topnienia 143^144,5°C, 4-[4-/a-|hydroksy-a-fenylo- benzylo/piperydyno]-4'-pirolidynobutyrofenon.Przyklad IV. Jednochlorowodorek 4'-dwu- metyloamino-2-/4-dwu!fenylomety toifenonu.Plrzez roztwór 20 g (0,0515 mola) 2-/4Hdwufenylo- metylopiperydyno/-4'-ifluo(roacetofenonu w 100 ml dwumetylosulfotlenku przepuszcza sie dwume- tyloamine, w ciagu 6 godzin, w tempera¬ turze 100°C. Wiekszosc rozpuszczalnika odparowuje sie pod zmniejszonym cisnieniem a pozostalosc dodaje sie do wody zawierajacej kwasny weglan sodowy. Wytracany osad przeksztalca sie w chlorowodorek, który skrystalizuje sie z octanu etylu lub butanolu lub mieszaniny etanol-octan etylu, otrzymujac zwiazek tytulowy o temperaturze topnienia 242—245°C (wolna zasada ma tem¬ perature topnienia 107—110°C).P r z y kl a d V. 4-[4-/dwufenylometyleno/pipery- dyno^-pfrolidynobiutyrofenon.Do 100 ml dwumetylosulfotlenku zawierajacego g (0,06 mola) 4'-ftooro-4-[4-/dwufenyIometyle- no/piperydyno]-butyrofenonu dodaje sie jeden rów- nowaznik pirolidyny i jeden równowaznik weglanu potasu. Mieszanine reakcyjna utrzymuje sie w temperaturze 100°C pod chlodnica zwrotna w ciagu 6 godzin, po czym odparowuje rozpuszczalnik.Pozostala substancje wylewa sie do wody i ekstrahuje eterem. Wyciag eterowy ogrzewa sie z eterowym roztworem HCL w celu otrzymania chlorowodorku, który oczyszcza sie z mieszaniny metanol-butanon i z powrotem przeksztalca w wolna zasade w znany sposób. Wolna zasade 2g rekrystalizuje sie z mieszaniny acetonu i heksanu, otrzymujac produkt o temperaturze topnie¬ nia 102—104°C. alkilopiperazynowa ewentualnie w postaci ich dopuszczalnych w farmacji soli, znamienny tym, ze zwiazek o wzorze Ogólnym 6, w którym R, R1 i n maja znaczenie podane powyzej a Z1 oznacza tt rodnik fenylowy podstawiony atomem chlorowca, takim jak fluor, chlor, brom lub jod poddaje sie reakcji z amina, taka jak nizsza dwualkiloamina, pirolidyna, piperydyna, morfolina lub N-nizszoal- kilopiperazyna, przy czym w przypadku lotnej £0 aminy reakcje prowadzi sie w temperaturze 100°C w ciagu 4—8 godzin, a w przypadku wyzej wrzacej aminy w temperaturze wrzenia mieszaniny reakcyjnej w ciagu 4—24 godzin.92 127 Wzór 1 l ii i {CH2)n-C-Z1 (CH2)n-C-Z1 Wzór 4 Wzór Wzór (CH2}n"C"Z Wzór Cena 10 zl PZGraf. Koszalin D-625. Naklad 110. Format A-4 PL PL
Claims (1)
1. Zastrzezenie patentowe Sposób wytwarzania nowych pochodnych pipery¬ dyny o wzorze Ogólnym 1, w którym R oznacza atom wodoru hub grupe hydroksylowa, R1 ozna¬ cza atom wódorii lub R i R1 lacznie oznacza- OT ja drugie wiazanie miedzy atomami wegla, do których sa przylaczone, n oznacza liczbe cal¬ kowita o wartosci 1—3, Z1 oznacza rodnik fenylowy podstawiony w pozycji orto lub para nizsza grupa dwualkiloarninowa, grupa pirolidy- ^ nowa, piperydynowa, morfolinowa lufo N-nizszo* PL PL
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US00221823A US3806526A (en) | 1972-01-28 | 1972-01-28 | 1-aroylalkyl-4-diphenylmethyl piperidines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| PL92127B1 true PL92127B1 (pl) | 1977-03-31 |
Family
ID=22829547
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL1973182184A PL92127B1 (pl) | 1972-01-28 | 1973-01-26 | |
| PL1973160415A PL89087B1 (pl) | 1972-01-28 | 1973-01-26 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
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| PL1973160415A PL89087B1 (pl) | 1972-01-28 | 1973-01-26 |
Country Status (27)
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| US (1) | US3806526A (pl) |
| JP (1) | JPS5115034B2 (pl) |
| AR (1) | AR195313A1 (pl) |
| AT (2) | AT321916B (pl) |
| AU (1) | AU464154B2 (pl) |
| BE (1) | BE794595A (pl) |
| CA (2) | CA994779A (pl) |
| CH (1) | CH584197A5 (pl) |
| CS (1) | CS177836B2 (pl) |
| DD (1) | DD104297A5 (pl) |
| DE (1) | DE2303305B2 (pl) |
| DK (1) | DK136714B (pl) |
| ES (1) | ES410730A1 (pl) |
| FR (1) | FR2181692B1 (pl) |
| GB (1) | GB1412605A (pl) |
| HU (1) | HU167948B (pl) |
| IE (1) | IE36984B1 (pl) |
| IL (1) | IL41058A (pl) |
| LU (1) | LU66915A1 (pl) |
| NL (1) | NL174348B (pl) |
| NO (1) | NO140059C (pl) |
| PH (1) | PH9202A (pl) |
| PL (2) | PL92127B1 (pl) |
| SE (1) | SE382059B (pl) |
| SU (1) | SU472502A3 (pl) |
| YU (1) | YU35581B (pl) |
| ZA (1) | ZA728542B (pl) |
Families Citing this family (47)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE794598A (fr) * | 1972-01-28 | 1973-05-16 | Richardson Merrell Inc | Nouveaux derives olefiniques de piperidines substituees en 4 et leur procede de preparation |
| US3992546A (en) * | 1973-10-18 | 1976-11-16 | Ciba-Geigy Corporation | 4-Piperidinobutyrophenones as neuroleptics |
| US4054570A (en) * | 1973-10-18 | 1977-10-18 | Ciba-Geigy Corporation | 4-Piperidinobutyrophenones |
| US3931197A (en) * | 1974-02-08 | 1976-01-06 | Richardson-Merrell Inc. | Substituted piperidine derivatives |
| US3941795A (en) * | 1974-02-08 | 1976-03-02 | Richardson-Merrell Inc. | α-ARYL-4-SUBSTITUTED PIPERIDINOALKANOL DERIVATIVES |
| US3946022A (en) * | 1974-03-04 | 1976-03-23 | Richardson-Merrell Inc. | Piperidine derivatives |
| US4105849A (en) * | 1974-09-30 | 1978-08-08 | G. D. Searle & Co. | [(Substituted )phenyl]phenylmethyl-1-(dialkylaminoalkyl)piperidines |
| US4032642A (en) * | 1974-12-11 | 1977-06-28 | A. H. Robins Company, Incorporated | 1-Substituted-4-benzylpiperidines |
| US3956296A (en) * | 1974-12-11 | 1976-05-11 | A. H. Robins Company, Incorporated | 1-Substituted-4-benzylpiperidines |
| US3922276A (en) * | 1974-12-11 | 1975-11-25 | Robins Co Inc A H | 1-Substituted-4-benzylidenepiperidines |
| US3984557A (en) * | 1974-12-26 | 1976-10-05 | A. H. Robins Company, Incorporated | Antiarrhythmia compositions and methods |
| US4163790A (en) * | 1977-05-11 | 1979-08-07 | A. H. Robins Company, Inc. | Method for increasing coronary blood flow in mammals |
| US4246268A (en) * | 1979-02-09 | 1981-01-20 | Richardson-Merrell Inc. | Neuroleptic-4-(naphthylmethyl)piperidine derivatives |
| US4254129A (en) * | 1979-04-10 | 1981-03-03 | Richardson-Merrell Inc. | Piperidine derivatives |
| US4285957A (en) * | 1979-04-10 | 1981-08-25 | Richardson-Merrell Inc. | 1-Piperidine-alkanol derivatives, pharmaceutical compositions thereof, and method of use thereof |
| US4285958A (en) * | 1979-04-10 | 1981-08-25 | Richardson-Merrell Inc. | 1-Piperidine-alkylene ketones, pharmaceutical compositions thereof and method of use thereof |
| US4254130A (en) * | 1979-04-10 | 1981-03-03 | Richardson-Merrell Inc. | Piperidine derivatives |
| IE49998B1 (en) * | 1979-08-06 | 1986-01-22 | Merrell Dow Pharma | 4-(naphthalenyloxy)piperidine derivatives |
| NO157931C (no) * | 1980-09-18 | 1988-06-15 | Ucb Sa | Analogifremgangsmaate for fremstilling av terapeutisk aktive 2-(4-(difenylmethylen)-1-piperidinyl)-eddiksyrer samt deres amider og salter. |
| US4810713A (en) * | 1985-12-20 | 1989-03-07 | A. H. Robins Company, Incorporated | Arylalkyl-heterocyclic amines, n-substituted by aryloxyalkyl groups used in a method for allergy treatment |
| EP0228893A3 (en) * | 1985-12-20 | 1990-01-03 | A.H. ROBINS COMPANY, INCORPORATED (a Delaware corporation) | Arylalkyl-heterocyclic amines, n-substituted by aryloxyalkyl group in allergy treatment |
| KR910006138B1 (ko) * | 1986-09-30 | 1991-08-16 | 에자이 가부시끼가이샤 | 환상아민 유도체 |
| KR960004827B1 (ko) * | 1987-01-20 | 1996-04-16 | 다이닛뽄 세이야꾸 가부시끼가이샤 | 헤테로아릴카르복시아미드 유도체, 그의 제조방법 및 그것을 함유하는 의약조성물 |
| IT1205685B (it) * | 1987-05-26 | 1989-03-31 | Erregierre Spa | Processo per la preparazione di alfa-(alchilfenil)-4-(idrossi difenilmetil)-1-piperidina butanolo |
| US5231105A (en) * | 1987-06-02 | 1993-07-27 | Ajinomoto Co., Inc. | Ethylamine derivatives and antihypertensives containing the same |
| US4912222A (en) * | 1988-06-17 | 1990-03-27 | Fisons Corporation | Antihistamines related to cyproheptadine |
| US5070087A (en) * | 1989-05-08 | 1991-12-03 | A. H. Robins Company, Incorporated | Aryl(alkyland alkylene)-N-((phenoxy and phenylthio)alkyl) aminoheterocyclics as cardiovascular, anthihistaminic, antisecretory and antiallergy agents |
| DE3917241A1 (de) * | 1989-05-26 | 1990-11-29 | Schaper & Bruemmer Gmbh | 4-(hydroxydiphenylmethyl)-1-piperidyl-phenylalkan-derivate |
| US5057524A (en) * | 1990-02-08 | 1991-10-15 | A. H. Robins Company Incorporated | 4-[diaryl)hydroxymethyl]-1-piperidinealkylcarboxylic acids, salts and esters useful in the treatment of allergic disorders |
| WO1993003025A1 (en) * | 1991-08-09 | 1993-02-18 | Yoshitomi Pharmaceutical Industries, Ltd. | Thiophene compound |
| FI943727A0 (fi) * | 1992-02-13 | 1994-08-12 | Merrell Dow Pharma | Piperidinyylitiasyklisiä johdannaisia |
| DK1026147T3 (da) * | 1993-06-24 | 2004-03-22 | Albany Molecular Res Inc | Forbindelser, der er anvendelige som mellemprodukter i fremstillingen af piperidinderivater |
| US20020007068A1 (en) * | 1999-07-16 | 2002-01-17 | D'ambra Thomas E. | Piperidine derivatives and process for their production |
| KR100333790B1 (ko) | 1993-06-25 | 2002-11-04 | 메렐 파마슈티칼스 인크. | 항히스타민성4-디페닐메틸/디페닐메톡시피페리딘유도체제조용신규중간체 |
| US6147216A (en) * | 1993-06-25 | 2000-11-14 | Merrell Pharmaceuticals Inc. | Intermediates useful for the preparation of antihistaminic piperidine derivatives |
| AU701042B2 (en) * | 1995-02-28 | 1999-01-21 | Aventisub Llc | Pharmaceutical composition for piperidinoalkanol compounds |
| HUP9801254A3 (en) * | 1995-05-08 | 1998-09-28 | Aventis Pharmaceuticals Inc Br | Alpha-(substituted alkylphenyl)-4-(hydroxydiphenylmethyl)-1-piperidine butanol derivatives, their preparation and their use as anti-histamines, anti-allergy agents and bronchodilators |
| US5574045A (en) * | 1995-06-06 | 1996-11-12 | Hoechst Marion Roussel, Inc. | Oral pharmaceutical composition of piperidinoalkanol compounds in solution form |
| US6153754A (en) * | 1995-12-21 | 2000-11-28 | Albany Molecular Research, Inc. | Process for production of piperidine derivatives |
| US6201124B1 (en) | 1995-12-21 | 2001-03-13 | Albany Molecular Research, Inc. | Process for production of piperidine derivatives |
| US5795985A (en) * | 1996-03-05 | 1998-08-18 | Ciba Specialty Chemicals Corporation | Phenyl alkyl ketone substituted by cyclic amine and a process for the preparation thereof |
| US5925761A (en) * | 1997-02-04 | 1999-07-20 | Sepracor Inc. | Synthesis of terfenadine and derivatives |
| SK283803B6 (sk) * | 1997-08-26 | 2004-02-03 | Aventis Pharmaceuticals Inc. | Farmaceutický prostriedok vo forme dvojvrstvovej tabletky na kombinovanie piperidinoalkanolu s dekongestantom |
| US6613907B2 (en) | 2000-11-08 | 2003-09-02 | Amr Technology, Inc. | Process for the production of piperidine derivatives with microorganisms |
| US7498345B2 (en) * | 2004-09-17 | 2009-03-03 | Albany Molecular Research, Inc. | Process for production of piperidine derivatives |
| CA2651732C (en) * | 2006-05-18 | 2014-10-14 | Mannkind Corporation | Intracellular kinase inhibitors |
| EP3150589A1 (en) * | 2007-06-08 | 2017-04-05 | MannKind Corporation | Ire-1a inhibitors |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3073835A (en) * | 1961-07-13 | 1963-01-15 | Searle & Co | 1-acyl-alpha, alpha-diphenyl-4-piperidinemethanols |
| US3081303A (en) * | 1961-10-13 | 1963-03-12 | Searle & Co | 1-aminoalkyl-alpha, alpha-diphenylpiperidine-methanols |
-
1972
- 1972-01-28 US US00221823A patent/US3806526A/en not_active Expired - Lifetime
- 1972-12-03 PH PH14153*UA patent/PH9202A/en unknown
- 1972-12-04 ZA ZA728542A patent/ZA728542B/xx unknown
- 1972-12-05 IE IE1691/72A patent/IE36984B1/xx unknown
- 1972-12-11 AU AU49894/72A patent/AU464154B2/en not_active Expired
- 1972-12-12 IL IL41058A patent/IL41058A/en unknown
- 1972-12-15 GB GB5799472A patent/GB1412605A/en not_active Expired
- 1972-12-20 CH CH1854472A patent/CH584197A5/xx not_active IP Right Cessation
- 1972-12-27 SU SU1865664A patent/SU472502A3/ru active
- 1972-12-27 JP JP47130134A patent/JPS5115034B2/ja not_active Expired
- 1972-12-29 AT AT1115572A patent/AT321916B/de not_active IP Right Cessation
- 1972-12-29 AT AT306574*1A patent/AT321912B/de not_active IP Right Cessation
-
1973
- 1973-01-08 YU YU32/73A patent/YU35581B/xx unknown
- 1973-01-16 CA CA161,366A patent/CA994779A/en not_active Expired
- 1973-01-16 CA CA161,367A patent/CA994784A/en not_active Expired
- 1973-01-17 HU HURI501A patent/HU167948B/hu unknown
- 1973-01-18 ES ES410730A patent/ES410730A1/es not_active Expired
- 1973-01-22 NL NLAANVRAGE7300869,A patent/NL174348B/xx not_active IP Right Cessation
- 1973-01-24 SE SE7300976A patent/SE382059B/xx unknown
- 1973-01-24 FR FR7302505A patent/FR2181692B1/fr not_active Expired
- 1973-01-24 DE DE2303305A patent/DE2303305B2/de active Granted
- 1973-01-25 DD DD168485A patent/DD104297A5/xx unknown
- 1973-01-26 PL PL1973182184A patent/PL92127B1/pl unknown
- 1973-01-26 BE BE794595D patent/BE794595A/xx not_active IP Right Cessation
- 1973-01-26 DK DK45173AA patent/DK136714B/da not_active IP Right Cessation
- 1973-01-26 AR AR246312A patent/AR195313A1/es active
- 1973-01-26 CS CS632A patent/CS177836B2/cs unknown
- 1973-01-26 PL PL1973160415A patent/PL89087B1/pl unknown
- 1973-01-26 LU LU66915A patent/LU66915A1/xx unknown
- 1973-01-26 NO NO328/73A patent/NO140059C/no unknown
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