CS226731B2 - Method of preparing benzopyrane compounds - Google Patents

Method of preparing benzopyrane compounds Download PDF

Info

Publication number: CS226731B2
Authority: CS; Czechoslovakia
Prior art keywords: group; formula; compound; dihydro; benzopyran
Prior art date: 1980-06-17

Application number

CS814509A

Other languages

Czech (cs)

English (en)

Inventor

Masami Shiratsuchi

Noboru Shimizu

Hiromichi Shigyo

Yoshinori Kyotani

Hisashi Kunieda

Kiyoshi Kawamura

Seiichi Sato

Toshihiro Akashi

Original Assignee

Kowa Co

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.)

1980-06-17

Filing date

1981-06-16

Publication date

1984-04-16

1980-06-17 Priority claimed from JP8084180A external-priority patent/JPS6054317B2/ja

1980-12-25 Priority claimed from JP55182854A external-priority patent/JPS57106619A/ja

1981-06-16 Application filed by Kowa Co filed Critical Kowa Co

1984-04-16 Publication of CS226731B2 publication Critical patent/CS226731B2/cs

Links

238000000034 method Methods 0.000 title description 12
150000001562 benzopyrans Chemical class 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims description 125
238000006243 chemical reaction Methods 0.000 claims description 45
-1 hydrosulfonyl group Chemical group 0.000 claims description 25
125000000217 alkyl group Chemical group 0.000 claims description 16
239000002253 acid Substances 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 12
125000002947 alkylene group Chemical group 0.000 claims description 9
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
150000001412 amines Chemical class 0.000 claims description 6
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 4
239000007795 chemical reaction product Substances 0.000 claims description 4
229910052739 hydrogen Inorganic materials 0.000 claims description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
229910052736 halogen Inorganic materials 0.000 claims description 3
150000002367 halogens Chemical class 0.000 claims description 3
239000001257 hydrogen Substances 0.000 claims description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
230000015572 biosynthetic process Effects 0.000 claims description 2
125000001475 halogen functional group Chemical group 0.000 claims description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims 1
OOWCJRMYMAMSOH-UHFFFAOYSA-N [2,3,5,6-tetrafluoro-4-(methoxymethyl)phenyl]methyl 2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropane-1-carboxylate Chemical compound FC1=C(F)C(COC)=C(F)C(F)=C1COC(=O)C1C(C)(C)C1C=C(C)C OOWCJRMYMAMSOH-UHFFFAOYSA-N 0.000 claims 1
150000007513 acids Chemical class 0.000 claims 1
238000007259 addition reaction Methods 0.000 claims 1
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
239000011701 zinc Substances 0.000 claims 1
229910052725 zinc Inorganic materials 0.000 claims 1
125000003118 aryl group Chemical group 0.000 description 70
239000000243 solution Substances 0.000 description 53
238000002329 infrared spectrum Methods 0.000 description 36
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 36
239000000203 mixture Substances 0.000 description 35
239000002904 solvent Substances 0.000 description 35
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 33
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
239000007788 liquid Substances 0.000 description 33
239000003921 oil Substances 0.000 description 33
238000012360 testing method Methods 0.000 description 26
238000001228 spectrum Methods 0.000 description 25
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
239000013078 crystal Substances 0.000 description 22
239000003814 drug Substances 0.000 description 22
230000000694 effects Effects 0.000 description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
229940079593 drug Drugs 0.000 description 20
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
238000002844 melting Methods 0.000 description 16
230000008018 melting Effects 0.000 description 16
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
230000036772 blood pressure Effects 0.000 description 14
210000002216 heart Anatomy 0.000 description 14
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
238000010898 silica gel chromatography Methods 0.000 description 12
239000004593 Epoxy Substances 0.000 description 11
241000700159 Rattus Species 0.000 description 11
230000017531 blood circulation Effects 0.000 description 11
238000003756 stirring Methods 0.000 description 11
241000282472 Canis lupus familiaris Species 0.000 description 10
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
230000009467 reduction Effects 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
229940125890 compound Ia Drugs 0.000 description 9
230000008569 process Effects 0.000 description 9
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
230000000144 pharmacologic effect Effects 0.000 description 8
239000011780 sodium chloride Substances 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
238000005481 NMR spectroscopy Methods 0.000 description 7
230000008602 contraction Effects 0.000 description 7
238000001816 cooling Methods 0.000 description 7
239000008194 pharmaceutical composition Substances 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
239000000523 sample Substances 0.000 description 7
229920006395 saturated elastomer Polymers 0.000 description 7
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
206010020772 Hypertension Diseases 0.000 description 6
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 6
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 6
JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 6
229910052700 potassium Inorganic materials 0.000 description 6
239000011591 potassium Substances 0.000 description 6
239000000047 product Substances 0.000 description 6
238000010992 reflux Methods 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
208000024172 Cardiovascular disease Diseases 0.000 description 5
BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 5
229910002651 NO3 Inorganic materials 0.000 description 5
239000002876 beta blocker Substances 0.000 description 5
229940097320 beta blocking agent Drugs 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
239000001768 carboxy methyl cellulose Substances 0.000 description 5
229920002678 cellulose Polymers 0.000 description 5
239000001913 cellulose Substances 0.000 description 5
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
238000001914 filtration Methods 0.000 description 5
230000001052 transient effect Effects 0.000 description 5
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 4
229920002134 Carboxymethyl cellulose Polymers 0.000 description 4
229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
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 4
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 4
238000005576 amination reaction Methods 0.000 description 4
230000037396 body weight Effects 0.000 description 4
235000010948 carboxy methyl cellulose Nutrition 0.000 description 4
239000008112 carboxymethyl-cellulose Substances 0.000 description 4
238000004440 column chromatography Methods 0.000 description 4
230000000052 comparative effect Effects 0.000 description 4
235000014113 dietary fatty acids Nutrition 0.000 description 4
238000000921 elemental analysis Methods 0.000 description 4
239000000194 fatty acid Substances 0.000 description 4
229930195729 fatty acid Natural products 0.000 description 4
150000004665 fatty acids Chemical class 0.000 description 4
125000003055 glycidyl group Chemical group C(C1CO1)* 0.000 description 4
150000003944 halohydrins Chemical group 0.000 description 4
239000001863 hydroxypropyl cellulose Substances 0.000 description 4
235000010977 hydroxypropyl cellulose Nutrition 0.000 description 4
239000008101 lactose Substances 0.000 description 4
229910017604 nitric acid Inorganic materials 0.000 description 4
SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
239000003826 tablet Substances 0.000 description 4
230000002861 ventricular Effects 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
229930006000 Sucrose Natural products 0.000 description 3
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 3
230000001800 adrenalinergic effect Effects 0.000 description 3
230000003042 antagnostic effect Effects 0.000 description 3
239000002585 base Substances 0.000 description 3
230000000747 cardiac effect Effects 0.000 description 3
239000003638 chemical reducing agent Substances 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
230000003247 decreasing effect Effects 0.000 description 3
238000006735 epoxidation reaction Methods 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
125000005179 haloacetyl group Chemical group 0.000 description 3
230000001965 increasing effect Effects 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
230000005923 long-lasting effect Effects 0.000 description 3
239000012452 mother liquor Substances 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
230000002269 spontaneous effect Effects 0.000 description 3
239000007858 starting material Substances 0.000 description 3
238000007920 subcutaneous administration Methods 0.000 description 3
239000005720 sucrose Substances 0.000 description 3
230000002792 vascular Effects 0.000 description 3
JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 2
ZUTQBIIKJALUQO-UHFFFAOYSA-N 2-methyl-2h-chromene Chemical compound C1=CC=C2C=CC(C)OC2=C1 ZUTQBIIKJALUQO-UHFFFAOYSA-N 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
241000700199 Cavia porcellus Species 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
239000012359 Methanesulfonyl chloride Substances 0.000 description 2
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
230000009471 action Effects 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
239000002220 antihypertensive agent Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
230000004872 arterial blood pressure Effects 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
239000002775 capsule Substances 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
210000004351 coronary vessel Anatomy 0.000 description 2
230000007423 decrease Effects 0.000 description 2
230000035487 diastolic blood pressure Effects 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
239000003792 electrolyte Substances 0.000 description 2
CHNUOJQWGUIOLD-NFZZJPOKSA-N epalrestat Chemical compound C=1C=CC=CC=1\C=C(/C)\C=C1/SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-NFZZJPOKSA-N 0.000 description 2
125000003700 epoxy group Chemical group 0.000 description 2
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
210000001105 femoral artery Anatomy 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000008187 granular material Substances 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
230000026030 halogenation Effects 0.000 description 2
238000005658 halogenation reaction Methods 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
230000001077 hypotensive effect Effects 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
229940039009 isoproterenol Drugs 0.000 description 2
210000005240 left ventricle Anatomy 0.000 description 2
239000012280 lithium aluminium hydride Substances 0.000 description 2
230000007774 longterm Effects 0.000 description 2
231100000053 low toxicity Toxicity 0.000 description 2
210000003141 lower extremity Anatomy 0.000 description 2
210000003975 mesenteric artery Anatomy 0.000 description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
230000036513 peripheral conductance 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
230000002035 prolonged effect Effects 0.000 description 2
238000000746 purification Methods 0.000 description 2
150000003254 radicals Chemical class 0.000 description 2
239000000376 reactant Substances 0.000 description 2
210000002254 renal artery Anatomy 0.000 description 2
230000008327 renal blood flow Effects 0.000 description 2
206010038464 renal hypertension Diseases 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
229910001961 silver nitrate Inorganic materials 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
235000009518 sodium iodide Nutrition 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 2
210000003462 vein Anatomy 0.000 description 2
HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
AKXQYIALXOJBMK-UHFFFAOYSA-N 1-[6-bromo-3-(hydroxymethyl)-3,4-dihydro-2h-chromen-8-yl]ethanone Chemical compound C1C(CO)COC2=C1C=C(Br)C=C2C(=O)C AKXQYIALXOJBMK-UHFFFAOYSA-N 0.000 description 1
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 1
OWZJHUKNXSWZPY-UHFFFAOYSA-N 2-[(8-phenylmethoxy-3,4-dihydro-2h-chromen-6-yl)oxy]ethanol Chemical compound C=1C(OCCO)=CC=2CCCOC=2C=1OCC1=CC=CC=C1 OWZJHUKNXSWZPY-UHFFFAOYSA-N 0.000 description 1
UDBCGYRDBYCHAZ-UHFFFAOYSA-N 2-ethoxy-2h-chromene Chemical compound C1=CC=C2C=CC(OCC)OC2=C1 UDBCGYRDBYCHAZ-UHFFFAOYSA-N 0.000 description 1
125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
FEPBRPNAPUJUDS-UHFFFAOYSA-N 2-propoxy-2H-chromene Chemical compound O(CCC)C1OC2=CC=CC=C2C=C1 FEPBRPNAPUJUDS-UHFFFAOYSA-N 0.000 description 1
MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
YAESPGUTBOSZQY-UHFFFAOYSA-N 3-(hydroxymethyl)-6-methoxy-3,4-dihydro-2h-chromen-8-ol Chemical compound O1CC(CO)CC2=CC(OC)=CC(O)=C21 YAESPGUTBOSZQY-UHFFFAOYSA-N 0.000 description 1
JHAIKOVGZVTZJC-UHFFFAOYSA-N 3-propylpyrrolidin-2-ol Chemical compound C(CC)C1CCNC1O JHAIKOVGZVTZJC-UHFFFAOYSA-N 0.000 description 1
DXRHIVHYTQXOTJ-UHFFFAOYSA-N 6-(2-hydroxyethoxy)-3,4-dihydro-2h-chromen-8-ol Chemical compound O1CCCC2=CC(OCCO)=CC(O)=C21 DXRHIVHYTQXOTJ-UHFFFAOYSA-N 0.000 description 1
PMLGZAUXEAPFFU-UHFFFAOYSA-N 7-nitro-2h-chromene Chemical compound C1=CCOC2=CC([N+](=O)[O-])=CC=C21 PMLGZAUXEAPFFU-UHFFFAOYSA-N 0.000 description 1
LJXQMJUCAPBBQO-UHFFFAOYSA-N 8-phenylmethoxy-3,4-dihydro-2h-chromen-6-ol Chemical compound C=1C(O)=CC=2CCCOC=2C=1OCC1=CC=CC=C1 LJXQMJUCAPBBQO-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
206010002383 Angina Pectoris Diseases 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
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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
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239000000546 pharmaceutical excipient Substances 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
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239000011734 sodium Substances 0.000 description 1
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235000019698 starch Nutrition 0.000 description 1
239000006190 sub-lingual tablet Substances 0.000 description 1
239000000126 substance Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000005846 sugar alcohols Polymers 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
230000035488 systolic blood pressure Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
101150068774 thyX gene Proteins 0.000 description 1
239000010936 titanium Substances 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical class CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
LMJSLTNSBFUCMU-UHFFFAOYSA-N trichlormethiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC(C(Cl)Cl)NS2(=O)=O LMJSLTNSBFUCMU-UHFFFAOYSA-N 0.000 description 1
229960004813 trichlormethiazide Drugs 0.000 description 1
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210000002700 urine Anatomy 0.000 description 1
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235000019786 weight gain Nutrition 0.000 description 1
229940100445 wheat starch Drugs 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
- 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
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/64—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with oxygen atoms directly attached in position 8
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
- C07D311/66—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4 with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Cardiology (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Heart & Thoracic Surgery (AREA)
Veterinary Medicine (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Hospice & Palliative Care (AREA)
Pain & Pain Management (AREA)
Neurology (AREA)
Orthopedic Medicine & Surgery (AREA)
Physical Education & Sports Medicine (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

CS814509A 1980-06-17 1981-06-16 Method of preparing benzopyrane compounds CS226731B2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
JP8084180A JPS6054317B2 (ja)	1980-06-17	1980-06-17	新規ベンゾピラン誘導体
JP55182854A JPS57106619A (en)	1980-12-25	1980-12-25	Remedy for circulatory disease

Publications (1)

Publication Number	Publication Date
CS226731B2 true CS226731B2 (en)	1984-04-16

Family

ID=26421809

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS814509A CS226731B2 (en)	1980-06-17	1981-06-16	Method of preparing benzopyrane compounds

Country Status (16)

Country	Link
US (1)	US4394382A (pl)
EP (1)	EP0042299B1 (pl)
KR (1)	KR850000193B1 (pl)
AU (1)	AU543347B2 (pl)
CA (1)	CA1178598A (pl)
CS (1)	CS226731B2 (pl)
DD (1)	DD160453A5 (pl)
DE (1)	DE3166300D1 (pl)
DK (1)	DK154557C (pl)
ES (1)	ES8300104A1 (pl)
FI (1)	FI79307C (pl)
IE (1)	IE52067B1 (pl)
NO (1)	NO154495C (pl)
PL (1)	PL130537B1 (pl)
SU (1)	SU1212325A3 (pl)
ZA (1)	ZA814042B (pl)

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JPS5965076A (ja) *	1982-10-05	1984-04-13	Kowa Co	新規なキノリン誘導体
JPS60181083A (ja) *	1984-02-29	1985-09-14	Kowa Co	新規ラセミ体及びその変換方法
JPS60208973A (ja) *	1984-03-31	1985-10-21	Kowa Co	循環系疾患治療剤
GB8730051D0 (en) *	1987-12-23	1988-02-03	Beecham Group Plc	Novel compounds
CA2253802A1 (en) *	1996-05-14	1997-11-20	Peter Charles North	Benzofurans and benzopyrans as chronobiological agents
JP4000505B2 (ja)	1999-12-01	2007-10-31	第一三共株式会社	緑内障を治療するための併用剤
EP1545519B1 (en)	2002-08-19	2011-03-23	Pfizer Inc.	Combination therapy for hyperproliferative diseases
KR20050059274A (ko) *	2002-10-24	2005-06-17	코와 가부시키가이샤	신경섬유 재생 촉진제
US20050037063A1 (en) *	2003-07-21	2005-02-17	Bolton Anthony E.	Combined therapies
GT200600381A (es)	2005-08-25	2007-03-28		Compuestos organicos
US7741317B2 (en)	2005-10-21	2010-06-22	Bristol-Myers Squibb Company	LXR modulators
US7888376B2 (en)	2005-11-23	2011-02-15	Bristol-Myers Squibb Company	Heterocyclic CETP inhibitors
JP5498168B2 (ja)	2006-12-01	2014-05-21	ブリストル−マイヤーズスクイブカンパニー	アテローム性動脈硬化および循環器疾患の治療のためのｃｅｔｐ阻害剤としてのｎ−（（３−ベンジル）−２，２−（ビス−フェニル）−プロパン−１−アミン誘導体
TWI646091B (zh) *	2012-12-28	2019-01-01	日商衛斯克慧特股份有限公司	鹽類及晶形
SG11201507496UA (en)	2013-04-17	2015-11-27	Pfizer	N-piperidin-3-ylbenzamide derivatives for treating cardiovascular diseases
WO2016055901A1 (en)	2014-10-08	2016-04-14	Pfizer Inc.	Substituted amide compounds
US11248001B2 (en)	2019-01-18	2022-02-15	Astrazeneca Ab	PCSK9 inhibitors and methods of use thereof

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GB1493998A (en) *	1975-06-03	1977-12-07	Beecham Group Ltd	Propanolamine derivatives
JPS54106476A (en) *	1978-01-04	1979-08-21	Merck & Co Inc	Multiisubstituted 2233lower alkylaminoo22 r100propoxypyridine
DE2804625A1 (de) *	1978-02-03	1979-08-09	Thomae Gmbh Dr K	Neue 4-acylamino-phenyl-aethanolamine
DE2805404A1 (de) *	1978-02-09	1979-08-16	Merck Patent Gmbh	1-aryloxy-3-nitratoalkylamino-2-propanole und verfahren zu ihrer herstellung

1981
- 1981-06-09 US US06/271,927 patent/US4394382A/en not_active Expired - Lifetime
- 1981-06-11 AU AU71652/81A patent/AU543347B2/en not_active Expired
- 1981-06-12 CA CA000379656A patent/CA1178598A/en not_active Expired
- 1981-06-12 IE IE1312/81A patent/IE52067B1/en not_active IP Right Cessation
- 1981-06-15 FI FI811856A patent/FI79307C/fi not_active IP Right Cessation
- 1981-06-16 EP EP81302700A patent/EP0042299B1/en not_active Expired
- 1981-06-16 KR KR1019810002196A patent/KR850000193B1/ko not_active Expired
- 1981-06-16 DK DK264181A patent/DK154557C/da not_active IP Right Cessation
- 1981-06-16 CS CS814509A patent/CS226731B2/cs unknown
- 1981-06-16 ES ES503091A patent/ES8300104A1/es not_active Expired
- 1981-06-16 NO NO812042A patent/NO154495C/no not_active IP Right Cessation
- 1981-06-16 SU SU813300799A patent/SU1212325A3/ru active
- 1981-06-16 DE DE8181302700T patent/DE3166300D1/de not_active Expired
- 1981-06-16 ZA ZA814042A patent/ZA814042B/xx unknown
- 1981-06-17 DD DD81230894A patent/DD160453A5/de not_active IP Right Cessation
- 1981-06-17 PL PL1981231734A patent/PL130537B1/pl unknown

Also Published As

Publication number	Publication date
IE811312L (en)	1981-12-17
AU543347B2 (en)	1985-04-18
PL231734A1 (pl)	1982-08-16
NO154495B (no)	1986-06-23
SU1212325A3 (ru)	1986-02-15
AU7165281A (en)	1981-12-24
EP0042299A1 (en)	1981-12-23
KR830006268A (ko)	1983-09-20
FI79307B (fi)	1989-08-31
NO154495C (no)	1986-10-01
US4394382A (en)	1983-07-19
DD160453A5 (de)	1983-08-03
PL130537B1 (en)	1984-08-31
ZA814042B (en)	1982-06-30
DK154557C (da)	1989-04-17
DK264181A (da)	1981-12-18
ES503091A0 (es)	1982-10-01
NO812042L (no)	1981-12-18
IE52067B1 (en)	1987-06-10
KR850000193B1 (ko)	1985-03-05
EP0042299B1 (en)	1984-09-26
CA1178598A (en)	1984-11-27
FI811856L (fi)	1981-12-18
FI79307C (fi)	1989-12-11
DK154557B (da)	1988-11-28
ES8300104A1 (es)	1982-10-01
DE3166300D1 (en)	1984-10-31

Publication	Publication Date	Title
EP0126449B1 (en)	1987-12-23	Cardioselective aryloxy- and arylthio-hydroxypropyl piperazinyl acetanilides wich affect calcium entry
KR850000193B1 (ko)	1985-03-05	벤조피란 화합물의 제조방법
JPH0272171A (ja)	1990-03-12	新規なベンゾピラン誘導体およびその製法
JPH0123462B2 (pl)	1989-05-02
EP0632031B1 (en)	2000-05-03	Condensed benzoxa ring compound, production thereof, and pharmaceutical composition containing the same
DK148844B (da)	1985-10-21	Analogifremgangsmaade til fremstilling af dihydroxyalkylsubstituerede xanthinderivater
FR2562892A1 (fr)	1985-10-18	Nouveaux dihydropyridinyldicarboxylates amides et esters, utilisation de ces composes comme medicament, compositions pharmaceutiques comprenant de tels composes et procede pour la preparation de tels composes
US4062870A (en)	1977-12-13	Chroman derivatives
US4558129A (en)	1985-12-10	Benzodioxanyl-hydroxyethylene-piperazinyl acetanilides which effect calcium entry and β-blockade
EP0034461A1 (en)	1981-08-26	Aromatic aminoethanol compounds and salts thereof, pharmaceutical compositions comprising them and processes for their production
KR960009427B1 (ko)	1996-07-19	1,4-디히드로피리딘 유도체, 그의 약학적 조성물 및 그 제조방법
IE68313B1 (en)	1996-06-12	Chroman derivatives
EP0054304B1 (en)	1984-08-15	Alkylenedioxybenzene derivatives, acid addition salts thereof and a method for their preparation
SU860692A1 (ru)	1981-08-30	Способ получени производных аминопропанола или их солей
EP0157623B1 (en)	1989-03-22	Optically active isomers of benzopyran derivatives useful for treating cardiovascular disease
HU188061B (en)	1986-03-28	Process for the preparation of benzopyrane derivatives and pharmaceutical compositions containing said compounds as active ingredients
JPH0345042B2 (pl)	1991-07-09
US4672071A (en)	1987-06-09	Antihypertensive dihydropyridine compositions, optical isomers and intermediates
HUT58072A (en)	1992-01-28	Process for producing new benzopyranyl pyrrolinone derivatives
DK154021B (da)	1988-10-03	Analogifremgangsmaade til fremstilling af phenoxy-aminopropanolderivater og epoxider til anvendelse som udgangsmateriale ved denne fremgangsmaade
DK166779B1 (da)	1993-07-12	1,5-benzoxatiepinderivater eller farmaceutisk acceptable salte deraf, samt farmaceutisk praeparat indeholdende en saadan forbindelse
JPH08208630A (ja)	1996-08-13	新規な５−（アリールオキシメチル）オキサゾリン類、その製造方法及びそれを含有する薬学的組成物
JPH0379359B2 (pl)	1991-12-18
WO2012104659A1 (en)	2012-08-09	Novel ether linked compounds and improved treatments for cardiac and cardiovascular disease
CS273172B2 (en)	1991-03-12	Method of dihydropyridine derivatives production