KR870004022A - 플라본 유도체의 제조방법 - Google Patents
플라본 유도체의 제조방법 Download PDFInfo
- Publication number
- KR870004022A KR870004022A KR1019860008836A KR860008836A KR870004022A KR 870004022 A KR870004022 A KR 870004022A KR 1019860008836 A KR1019860008836 A KR 1019860008836A KR 860008836 A KR860008836 A KR 860008836A KR 870004022 A KR870004022 A KR 870004022A
- Authority
- KR
- South Korea
- Prior art keywords
- dimethyl
- dicarboxylate
- dihydropyridine
- methyl
- methylflavon
- Prior art date
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- 238000000034 method Methods 0.000 title claims 9
- 150000002212 flavone derivatives Chemical class 0.000 title 1
- -1 3,3-diphenylpropyl Chemical group 0.000 claims 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 8
- 125000004432 carbon atom Chemical group C* 0.000 claims 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 6
- 150000001875 compounds Chemical class 0.000 claims 6
- WAERSRVJRANDDH-UHFFFAOYSA-N 2,6-dimethyl-4-(3-methyl-4-oxo-2-phenylchromen-8-yl)-1,4-dihydropyridine-3,5-dicarboxylic acid Chemical compound OC(=O)C1=C(C)NC(C)=C(C(O)=O)C1C1=CC=CC2=C1OC(C=1C=CC=CC=1)=C(C)C2=O WAERSRVJRANDDH-UHFFFAOYSA-N 0.000 claims 5
- 125000004967 formylalkyl group Chemical group 0.000 claims 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 125000004966 cyanoalkyl group Chemical group 0.000 claims 4
- 150000002081 enamines Chemical class 0.000 claims 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims 3
- 150000007942 carboxylates Chemical class 0.000 claims 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 3
- 150000002500 ions Chemical class 0.000 claims 3
- QCGPDCMWVSEEGP-UHFFFAOYSA-N 5-o-ethyl 3-o-methyl 2,6-dimethyl-4-(3-methyl-4-oxo-2-phenylchromen-8-yl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC2=C1OC(C=1C=CC=CC=1)=C(C)C2=O QCGPDCMWVSEEGP-UHFFFAOYSA-N 0.000 claims 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 238000007259 addition reaction Methods 0.000 claims 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 2
- 150000001412 amines Chemical class 0.000 claims 2
- 125000003710 aryl alkyl group Chemical group 0.000 claims 2
- 125000003968 arylidene group Chemical class [H]C(c)=* 0.000 claims 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 125000004983 dialkoxyalkyl group Chemical group 0.000 claims 2
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 2
- 125000005843 halogen group Chemical group 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 229910052757 nitrogen Inorganic materials 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical group C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 claims 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- GOWBYUQOIPWVOY-UHFFFAOYSA-N 3-o-methyl 5-o-(2-oxopropyl) 2,6-dimethyl-4-(3-methyl-4-oxo-2-phenylchromen-8-yl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(C)=O)C1C1=CC=CC2=C1OC(C=1C=CC=CC=1)=C(C)C2=O GOWBYUQOIPWVOY-UHFFFAOYSA-N 0.000 claims 1
- MTRCFXCKWOXMMB-UHFFFAOYSA-N 3-o-methyl 5-o-phenyl 2,6-dimethyl-4-(3-methyl-4-oxo-2-phenylchromen-8-yl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC=2C=CC=CC=2)C1C1=CC=CC(C(C=2C)=O)=C1OC=2C1=CC=CC=C1 MTRCFXCKWOXMMB-UHFFFAOYSA-N 0.000 claims 1
- CPFCWZAHJKHFEM-UHFFFAOYSA-N 3-o-methyl 5-o-prop-2-ynyl 2,6-dimethyl-4-(3-methyl-4-oxo-2-phenylchromen-8-yl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC#C)C1C1=CC=CC2=C1OC(C=1C=CC=CC=1)=C(C)C2=O CPFCWZAHJKHFEM-UHFFFAOYSA-N 0.000 claims 1
- CVQAOVNKJQVSQB-UHFFFAOYSA-N 5-(3-methyl-4-oxo-2-phenylchromen-8-yl)oxycarbonyl-1,4-dihydropyridine-3-carboxylic acid Chemical compound CC1=C(OC2=C(C1=O)C=CC=C2OC(=O)C3=CNC=C(C3)C(=O)O)C4=CC=CC=C4 CVQAOVNKJQVSQB-UHFFFAOYSA-N 0.000 claims 1
- DOAIXSOENFTQKN-UHFFFAOYSA-N 5-o-(2,3-dihydroxypropyl) 3-o-methyl 2,6-dimethyl-4-(3-methyl-4-oxo-2-phenylchromen-8-yl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC(O)CO)C1C1=CC=CC2=C1OC(C=1C=CC=CC=1)=C(C)C2=O DOAIXSOENFTQKN-UHFFFAOYSA-N 0.000 claims 1
- WAFDFRUVZFDNRP-UHFFFAOYSA-N 5-o-(2-aminoethyl) 3-o-methyl 2,6-dimethyl-4-(3-methyl-4-oxo-2-phenylchromen-8-yl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN)C1C1=CC=CC2=C1OC(C=1C=CC=CC=1)=C(C)C2=O WAFDFRUVZFDNRP-UHFFFAOYSA-N 0.000 claims 1
- IMRGURKTMVGJRA-UHFFFAOYSA-N 5-o-(2-cyanoethyl) 3-o-methyl 2,6-dimethyl-4-(3-methyl-4-oxo-2-phenylchromen-8-yl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCC#N)C1C1=CC=CC2=C1OC(C=1C=CC=CC=1)=C(C)C2=O IMRGURKTMVGJRA-UHFFFAOYSA-N 0.000 claims 1
- AKSXPJQPAUFABA-UHFFFAOYSA-N 5-o-(2-ethylsulfanylethyl) 3-o-methyl 2,6-dimethyl-4-(3-methyl-4-oxo-2-phenylchromen-8-yl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCSCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC2=C1OC(C=1C=CC=CC=1)=C(C)C2=O AKSXPJQPAUFABA-UHFFFAOYSA-N 0.000 claims 1
- WDEUAVOAOYBPOY-UHFFFAOYSA-N 5-o-(2-ethylsulfonylethyl) 3-o-methyl 2,6-dimethyl-4-(3-methyl-4-oxo-2-phenylchromen-8-yl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCS(=O)(=O)CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC2=C1OC(C=1C=CC=CC=1)=C(C)C2=O WDEUAVOAOYBPOY-UHFFFAOYSA-N 0.000 claims 1
- VNKTZCAXDUPRIR-UHFFFAOYSA-N 5-o-benzyl 3-o-methyl 2,6-dimethyl-4-(3-methyl-4-oxo-2-phenylchromen-8-yl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCC=2C=CC=CC=2)C1C1=CC=CC(C(C=2C)=O)=C1OC=2C1=CC=CC=C1 VNKTZCAXDUPRIR-UHFFFAOYSA-N 0.000 claims 1
- YRHGGINOGDHMGX-UHFFFAOYSA-N 5-o-butyl 3-o-methyl 2,6-dimethyl-4-(3-methyl-4-oxo-2-phenylchromen-8-yl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC2=C1OC(C=1C=CC=CC=1)=C(C)C2=O YRHGGINOGDHMGX-UHFFFAOYSA-N 0.000 claims 1
- ZQFVQQGNIIBKJU-UHFFFAOYSA-N 5-o-cyclohexyl 3-o-methyl 2,6-dimethyl-4-(3-methyl-4-oxo-2-phenylchromen-8-yl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC2CCCCC2)C1C1=CC=CC(C(C=2C)=O)=C1OC=2C1=CC=CC=C1 ZQFVQQGNIIBKJU-UHFFFAOYSA-N 0.000 claims 1
- VTWSNKOFDHRYLY-UHFFFAOYSA-N CC1=C(OC2=C(C1=O)C=CC=C2C3C(=C(N(C(=C3C(=O)O)C)CCC4=NC=CN4)C)C(=O)O)C5=CC=CC=C5 Chemical compound CC1=C(OC2=C(C1=O)C=CC=C2C3C(=C(N(C(=C3C(=O)O)C)CCC4=NC=CN4)C)C(=O)O)C5=CC=CC=C5 VTWSNKOFDHRYLY-UHFFFAOYSA-N 0.000 claims 1
- JHMUQRLYDOJIDZ-UHFFFAOYSA-N CC1=C(OC2=C(C1=O)C=CC=C2C3C(=C(NC(=C3C(=O)OCCN4CCNCC4)C)C)C(=O)O)C5=CC=CC=C5 Chemical compound CC1=C(OC2=C(C1=O)C=CC=C2C3C(=C(NC(=C3C(=O)OCCN4CCNCC4)C)C)C(=O)O)C5=CC=CC=C5 JHMUQRLYDOJIDZ-UHFFFAOYSA-N 0.000 claims 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims 1
- 125000005354 acylalkyl group Chemical group 0.000 claims 1
- 150000001298 alcohols Chemical class 0.000 claims 1
- 125000003342 alkenyl group Chemical group 0.000 claims 1
- 125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 claims 1
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 claims 1
- 230000002213 calciumantagonistic effect Effects 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- MHPRFJAYKKVBLY-UHFFFAOYSA-N dimethyl 2,6-dimethyl-4-(3-methyl-4-oxo-2-phenylchromen-8-yl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC2=C1OC(C=1C=CC=CC=1)=C(C)C2=O MHPRFJAYKKVBLY-UHFFFAOYSA-N 0.000 claims 1
- CNXAUBUVSKWFPA-UHFFFAOYSA-N dimethyl 2-(hydroxymethyl)-6-methyl-4-(3-methyl-4-oxo-2-phenylchromen-8-yl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(CO)=C(C(=O)OC)C1C1=CC=CC2=C1OC(C=1C=CC=CC=1)=C(C)C2=O CNXAUBUVSKWFPA-UHFFFAOYSA-N 0.000 claims 1
- NKRUIUVMCAEUAH-UHFFFAOYSA-N dimethyl 2-cyano-6-methyl-4-(3-methyl-4-oxo-2-phenylchromen-8-yl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COC(=O)C1=C(C)NC(C#N)=C(C(=O)OC)C1C1=CC=CC2=C1OC(C=1C=CC=CC=1)=C(C)C2=O NKRUIUVMCAEUAH-UHFFFAOYSA-N 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- MPFLRYZEEAQMLQ-UHFFFAOYSA-N dinicotinic acid Chemical compound OC(=O)C1=CN=CC(C(O)=O)=C1 MPFLRYZEEAQMLQ-UHFFFAOYSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 125000001188 haloalkyl group Chemical group 0.000 claims 1
- 125000005842 heteroatom Chemical group 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 230000007062 hydrolysis Effects 0.000 claims 1
- 238000006460 hydrolysis reaction Methods 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 230000003287 optical effect Effects 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 238000010992 reflux Methods 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 210000002460 smooth muscle Anatomy 0.000 claims 1
- 229910000033 sodium borohydride Inorganic materials 0.000 claims 1
- 239000012279 sodium borohydride Substances 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/12—Drugs for disorders of the metabolism for electrolyte homeostasis
- A61P3/14—Drugs for disorders of the metabolism for electrolyte homeostasis for calcium homeostasis
-
- 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
- A61P9/08—Vasodilators for multiple indications
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Rheumatology (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
내용 없음
Description
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
Claims (11)
- 하기 일반식으로 표시되는 화합물 및 그의 광학 이성질체와 부분 입체 이성질체, 그리고 약학적으로 허용 가능한 염의 제조방법.상기 식에서, R 및 R1은 동일하거나 다를 수 있고, 1 내지 4 탄소원자를 갖는 알킬, 1~4 탄소원자를 갖는 히드록시알킬, 포르밀알킬 또는 시아노알킬이고, R2및 R3는 동일하거나 다를 수 있고, 1 내지 6 탄소원자를 갖는 직쇄 또는 측쇄알킬, 2 내지 6 탄소원자를 갖는 직쇄 또는 측쇄 알케닐, 2 내지 6 탄소원자를 갖는 알키닐, 5~7 탄소원자를 갖는 시클로알킬, 아랄킬, 페닐, 시아노알킬, 할로알킬, 모노- 또는 폴리-히드록시알킬, 알콕시알킬, 알킬티오알킬, 알킬술포닐알킬, 알킬옥시알킬, 아실알킬, 2~6 탄소원자를 갖는 직쇄 또는 측쇄 R4R5N-알킬이고, 상기에서 R4및 R5는 서로 동일하거나 다를 수 있고, 수소, 알킬, 시클로알킬, 아랄킬, 페닐, 3,3-디페닐프로필이고, 또는 질소원자와 함께 O,N 또는 NR6기(R6는 알킬이다)과 같은 다른 이종원자를 함유하는 포화 또는 비포화 4~7원환을 형성한다.
- 제 1 항에 있어서, 다음으로부터 선택됨을 특징으로 하는 식(Ⅰ)의 화합물의 제조방법 : 디메틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 비스2,N-피페리디노에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 이소프로필베타-클로로에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 이소프로필 2-N-피페리디노에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트-이소프로필2-(N-벤질-N-메틸아미노) 에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 이소프로필 2-(N-(3,3-디페닐프로필)-N-메틸아미노) 에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 2-시아노에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4디히드로피리딘-3,5-디카르복실레이트, 메틸 에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 2-시아노에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 [N-부틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 프로파르길 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 이소프로필 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 n-부틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트,메틸 프로파르길 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 알릴 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 알파-메틸알릴 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 벤질 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 2-옥소프로필 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 2,3-디히드록시프로필 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸2-에톡시에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 2-에틸티오에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸2-아세톡시에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 2-페닐에틸2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트,메틸2-(N,N-디메틸아미노)에틸 2,6-디메틸-4-(3-메틸플라본-9-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 2-아미노에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 2-(N-메틸-N-페닐아미노)에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 2-(N-메틸-N-시클로헥실아미노) 에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 2,N-모르폴리노에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 2,N-이미다졸릴에틸2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 2,N-피페리디노에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 2,N-피페리디노-1,1-디메틸에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 2,N-메틸아미노에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 2,N-(N′-메틸)피페라지노에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 t-부틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 시클로헥실 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 페닐 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 메틸 2-에틸술포닐에틸 2,6-디메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 디메틸 2-포르밀-6-메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 디메틸 2-히드록시메틸-6-메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트, 디메틸 2-시아노-6-메틸-4-(3-메틸플라본-8-일)-1,4-디히드로피리딘-3,5-디카르복실레이트,
- 제 1 항에 있어서, a) 식(Ⅱ)의 알데히드(앞으로 (Ⅱ)로 나타낸다)를 식(Ⅱ)의 케토에스테르 및 식(Ⅳ)의 엔아민과 반응시키거나, b)(Ⅱ)를 식(Ⅴ)의 화합물로 처리하고, 이렇게 얻은 아릴리덴 유도체를 식(Ⅵ)의 엔아민과 반응시키고, 마지막으로 식 R4R5NH의 아민과 반응시키고 또는 반응시키지 않고, 또는, c) 알데히드(Ⅱ)를 식(Ⅲ)의 케토에스테르와 반응시키고 그런 후에 얻은 아릴리덴 유도체에 식(Ⅶ)의 엔아민을 가하고, 이렇게 얻어진 시아노에틸에스테르를 가수 분해하여 식(Ⅷ)의 산을 얻고 공지방법을 따라 R3OH 또는 R3X의 유도체로 에스테르화함을 특징으로 하는 방법.상기 식에서, R,R1,R2, 및 R3는 상기 정의와 같고, R, R1은 공지 방법에 의해 포르밀 알킬 히드록시 알킬 또는 시아노알킬기로 전환될 수 있고,상기 식에서, R1은 상기 정의와 같고, X는 할로겐 원자이고,상기 식에서, R,R1,R4, 및 R5는 상기 정의와 같고;상기 식에서, R,R1,및 R2,는 상기 정의와 같고,상기 식에서, X는 할로겐 원자이고, R3는 상기 정의와 같다.
- 제 3 항에 있어서, 경로 a)가 저급알코올, 바람직하게는 에탄올 내에서 2~5시간 동안 적용된 알코올의 환류 온도로 수행됨을 특징으로 하는 방법.
- 제 3 항에 있어서, 경로 b)의 첫단계는 염소화 탄화수소, 바람직하게는 클로로포름에서 반응을 수행하고, 연이온(Ⅵ)의 부가반응은 저급알콜, 바람직하게는 이소프로판올에서 수행하고, 아민 R4R5NH와의 선택적 반응은 디메틸 포름아미드에서 고온으로, 바람직하게는 약100℃에서 수행함을 특징으로 하는 방법.
- 제 3 항에 있어서, 경로(C)의 첫단계는 염소화 탄화수소, 바람직하게는 클로로포름에서 수행하고, 이어서 엔아민의 부가반응은 알코올, 바람직하게는 이소프로판을 수행하고 산의 가수분해는 디메톡시에탄에서 그리고 에스테르화 디메틸포름아미드에서 수행함을 특징으로 하는 방법.
- 제 3 항부터 제 6 항까지에 있어서, R 또는 R1이중 디알콕시알킬인(Ⅶ) 또는 (Ⅲ)의 화합물을 고리화하고, 이어서 R 또는 R1에 상기 정의된 디알콕시 알킬기를 갖고 얻어진 1,4-디히드로피리딘환을 아세톤 내에서 염산으로 가수 분해 하여 R 또는 R1을 포르밀알킬기로 전환시킴을 특징으로 하는 방법.
- 제 3 항부터 제 7 항에 있어서, 포르밀 알킬기를 알코올, 바람직하게는 에탄올 내에서 소디움보로 히드리드를 사용하여 환원시켜, R 또는 R1을 해당하는 히드록시알킬기로 전환시킴을 특징으로 하는 방법.
- 제 3 항부터 제 7 항까지에 있어서, 포르밀 알킬기를 아세틱안히드리드에서 히드록실아민과 반응시켜 R 또는 R1을 해당하는 시아노알킬기로 전화시킴을 특징으로 하는 방법.
- 칼슘 길항 활성 및/또는 평활근(특히 방광) 이완 활성을 갖는, 제 1 항의 식(Ⅰ)의 화합물 및 적절한 담체와 희석제로 구성됨을 특징으로 하는 약학적 조성물.
- 제10항에 있어서, 유사한 종류의 약의 통상의 투여량으로 투여될 수 있는 경구 또는 비경구 투여 조성물.※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT22578/85A IT1190405B (it) | 1985-10-22 | 1985-10-22 | Derivati del flavone |
| IT22578 | 1985-10-22 | ||
| IT22578A/85 | 1985-10-22 |
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| Publication Number | Publication Date |
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| KR870004022A true KR870004022A (ko) | 1987-05-07 |
| KR910009269B1 KR910009269B1 (ko) | 1991-11-08 |
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| KR1019860008836A KR910009269B1 (ko) | 1985-10-22 | 1986-10-22 | 플라본 유도체의 제조방법 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100392468B1 (ko) * | 2000-09-18 | 2003-07-22 | 주식회사 엘지생명과학 | 사이클린 의존 키나아제의 저해제로서 유용한3-히드록시크로멘-4-온 유도체 |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4912223A (en) * | 1988-01-28 | 1990-03-27 | Nelson Research & Development Co. | 1,4-Dihydropyridines |
| US5580751A (en) * | 1990-09-14 | 1996-12-03 | Carlsberg A/S | Process for the preparation of C-terminally amidated peptides |
| US5244602A (en) * | 1990-12-03 | 1993-09-14 | Ppg Industries, Inc. | Photochromic naphthopyrans |
| DE4321030A1 (de) * | 1993-06-24 | 1995-01-05 | Bayer Ag | 4-bicyclisch substituierte Dihydropyridine, Verfahren zu ihrer Herstellung und ihre Verwendung in Arzneimittel |
| SE9703377D0 (sv) | 1997-09-18 | 1997-09-18 | Astra Ab | New compounds |
| AU2002217742B2 (en) | 2001-01-16 | 2008-02-21 | Astrazeneca Ab | Therapeutic heterocyclic compounds |
| DE102005034267A1 (de) | 2005-07-22 | 2007-01-25 | Bayer Healthcare Ag | 4-Chromenonyl-1,4-dihydropyridine und ihre Verwendung |
| DE102005034264A1 (de) | 2005-07-22 | 2007-02-01 | Bayer Healthcare Ag | 4-Chromenonyl-1,4-dihydropyridincarbonitrile und ihre Verwendung |
| CN103254122B (zh) * | 2013-06-19 | 2015-04-22 | 湖南师范大学 | 一种心血管药物尼伐地平的制备方法 |
| AR121719A1 (es) | 2020-04-03 | 2022-06-29 | Petra Pharma Corp | Inhibidores alostéricos de cromenona del fosfoinosítido 3-quinasa (pi3k) para el tratamiento de enfermedades |
| IL307950A (en) | 2021-05-03 | 2023-12-01 | Petra Pharma Corp | Allosteric chromanone inhibitors of PHOSPHOINOSITIDE 3-KINASE (PI3K) for the treatment of diseases |
| BR112023022890A2 (pt) | 2021-05-27 | 2024-01-23 | Petra Pharma Corp | Inibidores de cromenona alostéricos de fosfoinositídio 3-cinase (pi3k), composições farmacêuticas que os compreendem e usos dos mesmos |
| TW202329930A (zh) | 2021-09-30 | 2023-08-01 | 美商佩特拉製藥公司 | 用於治療疾病之磷酸肌醇3-激酶(pi3k)之異位色烯酮抑制劑 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2921070A (en) * | 1957-11-05 | 1960-01-12 | Recordati Lab Farmacologico S | Basic esters of 3-methylflavone-8-carboxylic acid |
| NZ201395A (en) * | 1981-07-30 | 1987-02-20 | Bayer Ag | Pharmaceutical compositions containing 1,4-dihydropyridines and certain of these dihydropyridines |
| DE3311005A1 (de) * | 1983-03-25 | 1984-09-27 | Bayer Ag, 5090 Leverkusen | Chromon- und thiochromonsubstituierte 1,4-dihydropyridinderivate, mehrere verfahren zu ihrer herstellung sowie ihre verwendung in arzneimitteln |
-
1985
- 1985-10-22 IT IT22578/85A patent/IT1190405B/it active
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1986
- 1986-10-03 IL IL80229A patent/IL80229A0/xx not_active IP Right Cessation
- 1986-10-14 GR GR862546A patent/GR862546B/el unknown
- 1986-10-15 AR AR86305576A patent/AR243883A1/es active
- 1986-10-15 NO NO864108A patent/NO167570C/no unknown
- 1986-10-16 NZ NZ217964A patent/NZ217964A/en unknown
- 1986-10-20 AT AT86830300T patent/ATE73453T1/de not_active IP Right Cessation
- 1986-10-20 EP EP86830300A patent/EP0223744B1/en not_active Expired - Lifetime
- 1986-10-20 ES ES8602677A patent/ES2002425A6/es not_active Expired
- 1986-10-20 DE DE8686830300T patent/DE3684244D1/de not_active Expired - Fee Related
- 1986-10-20 ZA ZA867941A patent/ZA867941B/xx unknown
- 1986-10-21 IE IE276886A patent/IE58330B1/en not_active IP Right Cessation
- 1986-10-21 JP JP61251553A patent/JPH0772186B2/ja not_active Expired - Lifetime
- 1986-10-21 HU HU864363A patent/HU202863B/hu not_active IP Right Cessation
- 1986-10-21 FI FI864260A patent/FI89167C/fi not_active IP Right Cessation
- 1986-10-21 CA CA000520953A patent/CA1330994C/en not_active Expired - Fee Related
- 1986-10-21 TN TNTNSN86144A patent/TNSN86144A1/fr unknown
- 1986-10-22 PH PH34400A patent/PH22766A/en unknown
- 1986-10-22 DK DK506386A patent/DK169408B1/da not_active IP Right Cessation
- 1986-10-22 EG EG662/86A patent/EG18109A/xx active
- 1986-10-22 KR KR1019860008836A patent/KR910009269B1/ko not_active IP Right Cessation
- 1986-10-22 PT PT83604A patent/PT83604B/pt not_active IP Right Cessation
- 1986-10-22 US US06/921,397 patent/US4806534A/en not_active Expired - Fee Related
- 1986-10-22 CN CN198686107544A patent/CN86107544A/zh active Pending
- 1986-10-22 AU AU64273/86A patent/AU596382B2/en not_active Ceased
-
1992
- 1992-05-23 SG SG551/92A patent/SG55192G/en unknown
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100392468B1 (ko) * | 2000-09-18 | 2003-07-22 | 주식회사 엘지생명과학 | 사이클린 의존 키나아제의 저해제로서 유용한3-히드록시크로멘-4-온 유도체 |
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