DD151940A5 - Indolizine - Google Patents

Indolizine Download PDF

Info

Publication number: DD151940A5
Authority: DD; German Democratic Republic
Prior art keywords: indolizine; bromo; methoxy; benzoyl; hydroxy
Prior art date: 1979-07-06

Application number

DD80222415A

Other languages

German (de)

English (en)

Inventor

Gilbert Rosseels

Pierre Nokin

Original Assignee

Labaz Nv

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.)

1979-07-06

Filing date

1980-07-04

Publication date

1981-11-11

1980-07-04 Application filed by Labaz Nv filed Critical Labaz Nv

1981-11-11 Publication of DD151940A5 publication Critical patent/DD151940A5/de

Links

150000002478 indolizines Chemical class 0.000 title claims description 28
239000000460 chlorine Substances 0.000 claims abstract description 51
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 39
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 38
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 34
229910052794 bromium Inorganic materials 0.000 claims abstract description 34
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 28
239000001257 hydrogen Substances 0.000 claims abstract description 28
229910052801 chlorine Inorganic materials 0.000 claims abstract description 26
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 22
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 20
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 9
125000000217 alkyl group Chemical group 0.000 claims abstract description 9
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 6
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 5
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 4
229910052731 fluorine Inorganic materials 0.000 claims abstract description 4
239000011737 fluorine Substances 0.000 claims abstract description 4
125000003545 alkoxy group Chemical group 0.000 claims abstract description 3
125000005843 halogen group Chemical group 0.000 claims abstract description 3
125000001424 substituent group Chemical group 0.000 claims abstract description 3
150000001875 compounds Chemical class 0.000 claims description 89
-1 alkali metal acetate Chemical class 0.000 claims description 69
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 51
238000000034 method Methods 0.000 claims description 45
HOBCFUWDNJPFHB-UHFFFAOYSA-N indolizine Chemical compound C1=CC=CN2C=CC=C21 HOBCFUWDNJPFHB-UHFFFAOYSA-N 0.000 claims description 40
101000588924 Anthopleura elegantissima Delta-actitoxin-Ael1a Proteins 0.000 claims description 36
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 32
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 28
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
239000002904 solvent Substances 0.000 claims description 19
230000008569 process Effects 0.000 claims description 18
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 17
125000001246 bromo group Chemical group Br* 0.000 claims description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
238000002360 preparation method Methods 0.000 claims description 15
150000002431 hydrogen Chemical class 0.000 claims description 13
125000001309 chloro group Chemical group Cl* 0.000 claims description 11
125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
239000002253 acid Substances 0.000 claims description 6
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
229910052783 alkali metal Inorganic materials 0.000 claims description 5
150000008044 alkali metal hydroxides Chemical class 0.000 claims description 5
LGQXDKCKVGZOQN-UHFFFAOYSA-N indolizin-1-yl(phenyl)methanone Chemical class C1=CN2C=CC=CC2=C1C(=O)C1=CC=CC=C1 LGQXDKCKVGZOQN-UHFFFAOYSA-N 0.000 claims description 5
125000003118 aryl group Chemical group 0.000 claims description 3
150000003839 salts Chemical class 0.000 claims description 3
YIPHYCQSJTXLFM-UHFFFAOYSA-N 4-hydroxybenzoyl chloride Chemical class OC1=CC=C(C(Cl)=O)C=C1 YIPHYCQSJTXLFM-UHFFFAOYSA-N 0.000 claims description 2
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
229910052751 metal Inorganic materials 0.000 claims description 2
239000002184 metal Substances 0.000 claims description 2
238000010992 reflux Methods 0.000 claims description 2
125000003944 tolyl group Chemical group 0.000 claims description 2
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 1
239000012433 hydrogen halide Substances 0.000 claims 1
229910000039 hydrogen halide Inorganic materials 0.000 claims 1
PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 claims 1
238000006467 substitution reaction Methods 0.000 claims 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 1
101710169336 5'-deoxyadenosine deaminase Proteins 0.000 abstract description 26
102000055025 Adenosine deaminases Human genes 0.000 abstract description 26
102100033220 Xanthine oxidase Human genes 0.000 abstract description 22
108010093894 Xanthine oxidase Proteins 0.000 abstract description 22
230000009471 action Effects 0.000 abstract description 22
LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 abstract description 17
TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 abstract description 16
229940116269 uric acid Drugs 0.000 abstract description 16
125000003406 indolizinyl group Chemical class C=1(C=CN2C=CC=CC12)* 0.000 abstract description 9
230000003053 immunization Effects 0.000 abstract description 5
238000002649 immunization Methods 0.000 abstract description 5
101100072620 Streptomyces griseus ind2 gene Proteins 0.000 abstract 2
239000003096 antiparasitic agent Substances 0.000 abstract 1
229940125687 antiparasitic agent Drugs 0.000 abstract 1
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 96
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 35
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 32
239000000243 solution Substances 0.000 description 32
238000002844 melting Methods 0.000 description 26
230000008018 melting Effects 0.000 description 26
239000000203 mixture Substances 0.000 description 22
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 20
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 18
239000000047 product Substances 0.000 description 17
230000000694 effects Effects 0.000 description 16
239000002126 C01EB10 - Adenosine Substances 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
229960005305 adenosine Drugs 0.000 description 15
239000000126 substance Substances 0.000 description 15
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
208000035475 disorder Diseases 0.000 description 13
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
238000002474 experimental method Methods 0.000 description 12
FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 12
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 12
239000007858 starting material Substances 0.000 description 11
IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 10
230000000979 retarding effect Effects 0.000 description 10
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 9
OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 description 9
229960003459 allopurinol Drugs 0.000 description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
239000002244 precipitate Substances 0.000 description 8
238000003756 stirring Methods 0.000 description 8
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 7
230000015572 biosynthetic process Effects 0.000 description 7
150000001907 coumarones Chemical class 0.000 description 7
UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 6
150000003943 catecholamines Chemical class 0.000 description 6
239000003112 inhibitor Substances 0.000 description 6
230000000144 pharmacologic effect Effects 0.000 description 6
238000001953 recrystallisation Methods 0.000 description 6
LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 5
102000004190 Enzymes Human genes 0.000 description 5
108090000790 Enzymes Proteins 0.000 description 5
241000699670 Mus sp. Species 0.000 description 5
OIRDTQYFTABQOQ-UHTZMRCNSA-N Vidarabine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O OIRDTQYFTABQOQ-UHTZMRCNSA-N 0.000 description 5
238000010521 absorption reaction Methods 0.000 description 5
238000006243 chemical reaction Methods 0.000 description 5
239000012043 crude product Substances 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
238000000338 in vitro Methods 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
239000007787 solid Substances 0.000 description 5
IOSAAWHGJUZBOG-UHFFFAOYSA-N 3-(6-amino-9h-purin-9-yl)nonan-2-ol Chemical compound N1=CN=C2N(C(C(C)O)CCCCCC)C=NC2=C1N IOSAAWHGJUZBOG-UHFFFAOYSA-N 0.000 description 4
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 4
229930010555 Inosine Natural products 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
230000000052 comparative effect Effects 0.000 description 4
238000001816 cooling Methods 0.000 description 4
239000003814 drug Substances 0.000 description 4
230000002526 effect on cardiovascular system Effects 0.000 description 4
229960003786 inosine Drugs 0.000 description 4
125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 4
239000008055 phosphate buffer solution Substances 0.000 description 4
230000002829 reductive effect Effects 0.000 description 4
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
229960003636 vidarabine Drugs 0.000 description 4
ZPJKZBJVHUHXJN-UHFFFAOYSA-N (3-bromo-4-hydroxyphenyl)-(1-bromo-2-phenylindolizin-3-yl)methanone Chemical compound C1=C(Br)C(O)=CC=C1C(=O)C1=C(C=2C=CC=CC=2)C(Br)=C2N1C=CC=C2 ZPJKZBJVHUHXJN-UHFFFAOYSA-N 0.000 description 3
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
201000005569 Gout Diseases 0.000 description 3
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-Chlorosuccinimide Substances ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 3
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
230000002141 anti-parasite Effects 0.000 description 3
230000000259 anti-tumor effect Effects 0.000 description 3
230000000840 anti-viral effect Effects 0.000 description 3
239000002585 base Substances 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
230000008878 coupling Effects 0.000 description 3
238000010168 coupling process Methods 0.000 description 3
238000005859 coupling reaction Methods 0.000 description 3
230000001934 delay Effects 0.000 description 3
125000000950 dibromo group Chemical group Br* 0.000 description 3
125000003963 dichloro group Chemical group Cl* 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
238000006911 enzymatic reaction Methods 0.000 description 3
150000003949 imides Chemical class 0.000 description 3
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
238000007254 oxidation reaction Methods 0.000 description 3
HXNFUBHNUDHIGC-UHFFFAOYSA-N oxypurinol Chemical compound O=C1NC(=O)N=C2NNC=C21 HXNFUBHNUDHIGC-UHFFFAOYSA-N 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
239000001632 sodium acetate Substances 0.000 description 3
235000017281 sodium acetate Nutrition 0.000 description 3
230000001225 therapeutic effect Effects 0.000 description 3
230000002792 vascular Effects 0.000 description 3
125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 2
ZGNNFVXEWVYKRT-UHFFFAOYSA-N 2-ethylindolizine Chemical compound C1=CC=CN2C=C(CC)C=C21 ZGNNFVXEWVYKRT-UHFFFAOYSA-N 0.000 description 2
125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 2
FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
206010003445 Ascites Diseases 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
206010019280 Heart failures Diseases 0.000 description 2
241000700588 Human alphaherpesvirus 1 Species 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
OAOSWNJSSPIKDR-UHFFFAOYSA-N [1-bromo-2-(4-fluorophenyl)indolizin-3-yl]-(3-bromo-4-hydroxyphenyl)methanone Chemical compound C1=C(Br)C(O)=CC=C1C(=O)C1=C(C=2C=CC(F)=CC=2)C(Br)=C2N1C=CC=C2 OAOSWNJSSPIKDR-UHFFFAOYSA-N 0.000 description 2
230000003257 anti-anginal effect Effects 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
230000002490 cerebral effect Effects 0.000 description 2
239000007795 chemical reaction product Substances 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
231100000433 cytotoxic Toxicity 0.000 description 2
230000001472 cytotoxic effect Effects 0.000 description 2
230000009615 deamination Effects 0.000 description 2
238000006481 deamination reaction Methods 0.000 description 2
229940079593 drug Drugs 0.000 description 2
238000001035 drying Methods 0.000 description 2
230000002708 enhancing effect Effects 0.000 description 2
230000029142 excretion Effects 0.000 description 2
239000007903 gelatin capsule Substances 0.000 description 2
230000026030 halogenation Effects 0.000 description 2
238000005658 halogenation reaction Methods 0.000 description 2
239000012535 impurity Substances 0.000 description 2
230000001965 increasing effect Effects 0.000 description 2
210000004698 lymphocyte Anatomy 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
238000005259 measurement Methods 0.000 description 2
230000002503 metabolic effect Effects 0.000 description 2
239000002207 metabolite Substances 0.000 description 2
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
210000000056 organ Anatomy 0.000 description 2
230000003647 oxidation Effects 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
230000036470 plasma concentration Effects 0.000 description 2
230000002265 prevention Effects 0.000 description 2
230000004144 purine metabolism Effects 0.000 description 2
238000000926 separation method Methods 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
230000037380 skin damage Effects 0.000 description 2
230000036325 urinary excretion Effects 0.000 description 2
229940075420 xanthine Drugs 0.000 description 2
OTWCRANRZZNVAI-UHFFFAOYSA-N (1-bromo-2-ethylindolizin-3-yl)-(3,5-dibromo-4-hydroxyphenyl)methanone Chemical compound CCC=1C(Br)=C2C=CC=CN2C=1C(=O)C1=CC(Br)=C(O)C(Br)=C1 OTWCRANRZZNVAI-UHFFFAOYSA-N 0.000 description 1
PNNJKDZLVYFMDX-UHFFFAOYSA-N (1-bromo-2-ethylindolizin-3-yl)-(3-bromo-4-hydroxyphenyl)methanone Chemical compound CCC=1C(Br)=C2C=CC=CN2C=1C(=O)C1=CC=C(O)C(Br)=C1 PNNJKDZLVYFMDX-UHFFFAOYSA-N 0.000 description 1
VTCZTFSZRMOTKG-UHFFFAOYSA-N (1-bromo-2-ethylindolizin-3-yl)-(4-hydroxyphenyl)methanone Chemical compound CCC=1C(Br)=C2C=CC=CN2C=1C(=O)C1=CC=C(O)C=C1 VTCZTFSZRMOTKG-UHFFFAOYSA-N 0.000 description 1
SQIQWVNWXOJDCD-UHFFFAOYSA-N (1-chloro-2-ethylindolizin-3-yl)-(4-hydroxyphenyl)methanone Chemical compound CCC=1C(Cl)=C2C=CC=CN2C=1C(=O)C1=CC=C(O)C=C1 SQIQWVNWXOJDCD-UHFFFAOYSA-N 0.000 description 1
CUHMQFHFFWUDCG-UHFFFAOYSA-N (2-ethylindolizin-3-yl)-(4-hydroxyphenyl)methanone Chemical compound CCC=1C=C2C=CC=CN2C=1C(=O)C1=CC=C(O)C=C1 CUHMQFHFFWUDCG-UHFFFAOYSA-N 0.000 description 1
MTYOLTSXGCGEFL-UHFFFAOYSA-N (2-hydroxyindolizin-1-yl)-phenylmethanone Chemical compound OC=1C(=C2C=CC=CN2C1)C(C1=CC=CC=C1)=O MTYOLTSXGCGEFL-UHFFFAOYSA-N 0.000 description 1
RUKYQIMPYDSWNF-UHFFFAOYSA-N (3,5-dibromo-4-hydroxyphenyl)-(2-ethylindolizin-3-yl)methanone Chemical compound CCC=1C=C2C=CC=CN2C=1C(=O)C1=CC(Br)=C(O)C(Br)=C1 RUKYQIMPYDSWNF-UHFFFAOYSA-N 0.000 description 1
YNKYKLPZEYVHFE-UHFFFAOYSA-N (3,5-dichloro-4-hydroxyphenyl)-(2-ethylindolizin-3-yl)methanone Chemical compound CCC=1C=C2C=CC=CN2C=1C(=O)C1=CC(Cl)=C(O)C(Cl)=C1 YNKYKLPZEYVHFE-UHFFFAOYSA-N 0.000 description 1
HIXHJMWITGMFGT-UHFFFAOYSA-N (3-bromo-4-hydroxyphenyl)-(1-chloro-2-ethylindolizin-3-yl)methanone Chemical compound CCC=1C(Cl)=C2C=CC=CN2C=1C(=O)C1=CC=C(O)C(Br)=C1 HIXHJMWITGMFGT-UHFFFAOYSA-N 0.000 description 1
PCEPIRQOTCELRM-UHFFFAOYSA-N (3-bromo-4-hydroxyphenyl)-(1-methoxy-2-phenylindolizin-3-yl)methanone Chemical compound N12C=CC=CC2=C(OC)C(C=2C=CC=CC=2)=C1C(=O)C1=CC=C(O)C(Br)=C1 PCEPIRQOTCELRM-UHFFFAOYSA-N 0.000 description 1
UOLXLCMLZLHTRI-UHFFFAOYSA-N (3-bromo-4-hydroxyphenyl)-(2-ethylindolizin-3-yl)methanone Chemical compound CCC=1C=C2C=CC=CN2C=1C(=O)C1=CC=C(O)C(Br)=C1 UOLXLCMLZLHTRI-UHFFFAOYSA-N 0.000 description 1
ZWMJCUPLCGODOL-UHFFFAOYSA-N (3-bromo-4-hydroxyphenyl)-(2-methylindolizin-3-yl)methanone Chemical compound CC=1C=C2C=CC=CN2C=1C(=O)C1=CC=C(O)C(Br)=C1 ZWMJCUPLCGODOL-UHFFFAOYSA-N 0.000 description 1
HCJKTVFUGDWCLN-UHFFFAOYSA-N (3-bromo-4-hydroxyphenyl)-(2-phenylindolizin-3-yl)methanone Chemical compound C1(=CC=CC=C1)C=1C=C2C=CC=CN2C1C(C1=CC(=C(C=C1)O)Br)=O HCJKTVFUGDWCLN-UHFFFAOYSA-N 0.000 description 1
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GUJBTXFKAHACKE-UHFFFAOYSA-N BrC=1C(=C(N2C=CC=CC12)C(C1=CC(=C(C(=C1)Br)O)Br)=O)CCCCC Chemical compound BrC=1C(=C(N2C=CC=CC12)C(C1=CC(=C(C(=C1)Br)O)Br)=O)CCCCC GUJBTXFKAHACKE-UHFFFAOYSA-N 0.000 description 1
AFJFSDSKBKOFPE-UHFFFAOYSA-N BrC=1C(=C(N2C=CC=CC12)C(C1=CC=C(C=C1)O)=O)C1=CC(=C(C=C1)C)Cl Chemical compound BrC=1C(=C(N2C=CC=CC12)C(C1=CC=C(C=C1)O)=O)C1=CC(=C(C=C1)C)Cl AFJFSDSKBKOFPE-UHFFFAOYSA-N 0.000 description 1
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230000007812 deficiency Effects 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
230000004069 differentiation Effects 0.000 description 1
201000010099 disease Diseases 0.000 description 1
OPGYRRGJRBEUFK-UHFFFAOYSA-L disodium;diacetate Chemical compound [Na+].[Na+].CC([O-])=O.CC([O-])=O OPGYRRGJRBEUFK-UHFFFAOYSA-L 0.000 description 1
230000004064 dysfunction Effects 0.000 description 1
230000002500 effect on skin Effects 0.000 description 1
239000003480 eluent Substances 0.000 description 1
238000010828 elution Methods 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
229940071106 ethylenediaminetetraacetate Drugs 0.000 description 1
239000003337 fertilizer Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
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230000003259 immunoinhibitory effect Effects 0.000 description 1
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235000019359 magnesium stearate Nutrition 0.000 description 1
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150000005433 methoxybenzoic acid derivatives Chemical class 0.000 description 1
235000013336 milk Nutrition 0.000 description 1
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239000001267 polyvinylpyrrolidone Substances 0.000 description 1
VKJKEPKFPUWCAS-UHFFFAOYSA-M potassium chlorate Chemical compound [K+].[O-]Cl(=O)=O VKJKEPKFPUWCAS-UHFFFAOYSA-M 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
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125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
229940087562 sodium acetate trihydrate Drugs 0.000 description 1
235000017454 sodium diacetate Nutrition 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
- 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
- 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

Landscapes

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

DD80222415A 1979-07-06 1980-07-04 Indolizine DD151940A5 (de)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB7923599		1979-07-06

Publications (1)

Publication Number	Publication Date
DD151940A5 true DD151940A5 (de)	1981-11-11

Family

ID=10506339

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DD80222415A DD151940A5 (de)	1979-07-06	1980-07-04	Indolizine

Country Status (24)

Country	Link
US (1)	US4400387A (da)
EP (1)	EP0022762B1 (da)
JP (1)	JPS5618979A (da)
AR (1)	AR225314A1 (da)
AT (1)	AT375078B (da)
AU (1)	AU529725B2 (da)
CA (1)	CA1153379A (da)
DD (1)	DD151940A5 (da)
DE (1)	DE3060097D1 (da)
DK (1)	DK146962C (da)
ES (1)	ES493139A0 (da)
FI (1)	FI67217C (da)
GR (1)	GR69280B (da)
HU (1)	HU182151B (da)
IE (1)	IE49994B1 (da)
IN (1)	IN151594B (da)
NO (1)	NO153496C (da)
NZ (1)	NZ193926A (da)
OA (1)	OA06563A (da)
PL (1)	PL125597B1 (da)
PT (1)	PT71424A (da)
SU (1)	SU993817A3 (da)
YU (1)	YU171880A (da)
ZA (1)	ZA803434B (da)

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US6103702A (en) *	1999-05-24	2000-08-15	Board Of Trustees Of The University Of Illinois	Use of adenosine deaminase inhibitors to treat systemic inflammatory response syndrome
EP1200102A1 (en) *	1999-07-22	2002-05-02	Supergen, Inc.	Methods for treating autoimmune diseases
FR2805460A1 (fr)	2000-02-25	2001-08-31	Oreal	Compositions de teinture des fibres keratiniques contenant des derives d'indolizine cationiques et procede de teinture
FR2838123B1 (fr) *	2002-04-04	2005-06-10	Sanofi Synthelabo	Nouveaux derives d'indolozine-1,2,3 substituee, inhibiteurs selectifs du b-fgf
JP4048166B2 (ja) *	2002-11-18	2008-02-13	三井製糖株式会社	血糖値上昇抑制剤及び体脂肪蓄積抑制剤並びに食用材料
FR2859997B1 (fr) *	2003-09-18	2006-02-03	Sanofi Synthelabo	Nouveaux derives d'indolizine 1,2,3,6,7,8 substituee, inhibiteurs des fgfs, leur procede de preparation et les compositions pharmaceutiques les contenant.
AR051780A1 (es) *	2004-11-29	2007-02-07	Japan Tobacco Inc	Compuestos en anillo fusionados que contienen nitrogeno y utilizacion de los mismos
FR2896247B1 (fr)	2006-01-13	2008-02-29	Sanofi Aventis Sa	Composes dimeres agonistes des recepteurs des fgfs (fgfrs), leur procede de preparation et leur application en therapeutique
PT2415771E (pt)	2009-03-31	2013-10-03	Kissei Pharmaceutical	Derivado de indolizina e sua utilização para fins médicos
US20100261666A1 (en) *	2009-04-14	2010-10-14	The Board Of Trustees Of The University Of Illinois	Compositions and methods for the treatment of myocardial dysfunction associated with sirs or sepsis
EP2623505B1 (en) *	2010-09-29	2015-07-29	Kissei Pharmaceutical Co., Ltd.	(aza)indolizine derivatives as xanthine oxidase inhibitors
MX375068B (es) *	2015-09-10	2025-03-06	Jiangsu Atom Bioscience And Pharmaceutical Co Ltd	Un grupo de compuestos utilizados para el tratamiento o prevencion de hiperuricemia o gota.
CN108084186B (zh)	2016-11-16	2021-06-25	江苏新元素医药科技有限公司	Urat1抑制剂及其应用
WO2018090921A1 (zh)	2016-11-16	2018-05-24	江苏新元素医药科技有限公司	Urat1抑制剂及其应用
JP6915907B2 (ja) *	2017-05-26	2021-08-04	江▲蘇▼新元素医▲薬▼科技有限公司ＪｉａｎｇｓｕＡｔｏｍＢｉｏｓｃｉｅｎｃｅＡｎｄＰｈａｒｍａｃｅｕｔｉｃａｌＣｏ．，Ｌｔｄ．	尿酸排泄を促進するｕｒａｔ１阻害剤
CN114213331B (zh) *	2017-05-26	2024-06-21	江苏新元素医药科技有限公司	一类urat1抑制剂及其应用
US11453674B2 (en)	2018-01-19	2022-09-27	Evopoint Biosciences Co., Ltd.	Heterocyclic compound, preparation method and use thereof in medicine
CN110283167B (zh) *	2018-11-14	2026-04-10	贵州省中国科学院天然产物化学重点实验室	一种抗心率失常药物布托普洛嗪的制备方法
WO2022169974A1 (en)	2021-02-05	2022-08-11	Nexys Therapeutics, Inc.	Inhibitors of urat1 and pharmaceutical uses thereof
WO2023221078A1 (en) *	2022-05-20	2023-11-23	Jiangsu Atom Bioscience And Pharmaceutical Co., Ltd.	Solid forms of a compound for treating or preventing hyperuricemia or gout
WO2025237171A1 (zh) *	2024-05-11	2025-11-20	广州市联瑞制药有限公司	嘧啶并五元氮杂环酚类化合物及其应用

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* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SU430639A1 (ru)	1972-06-05	1978-02-28	Московский Ордена Ленина И Ордена Трудового Красного Знамени Государственный Университет Им.М.В.Ломоносова	Способ получени 1-пиридилиндолизинов
FI61030C (fi)	1976-02-19	1982-05-10	Sanofi Sa	Foerfarande foer framstaellning av terapeutiskt verkande 2-substituerade-1- eller 3-benzoyl-indolizinderivat
GB1518443A (en) *	1976-02-19	1978-07-19	Labaz	Indolizine derivatives and process for preparing the same

1980
- 1980-06-04 NZ NZ193926A patent/NZ193926A/en unknown
- 1980-06-09 ZA ZA00803434A patent/ZA803434B/xx unknown
- 1980-06-10 GR GR62170A patent/GR69280B/el unknown
- 1980-06-20 AU AU59487/80A patent/AU529725B2/en not_active Ceased
- 1980-06-20 PT PT71424A patent/PT71424A/pt unknown
- 1980-06-26 IN IN738/CAL/80A patent/IN151594B/en unknown
- 1980-06-30 DE DE8080870035T patent/DE3060097D1/de not_active Expired
- 1980-06-30 IE IE1349/80A patent/IE49994B1/en unknown
- 1980-06-30 EP EP80870035A patent/EP0022762B1/fr not_active Expired
- 1980-06-30 US US06/164,838 patent/US4400387A/en not_active Expired - Lifetime
- 1980-07-01 YU YU01718/80A patent/YU171880A/xx unknown
- 1980-07-02 AR AR281618A patent/AR225314A1/es active
- 1980-07-02 OA OA57151A patent/OA06563A/xx unknown
- 1980-07-03 SU SU802942500A patent/SU993817A3/ru active
- 1980-07-04 DD DD80222415A patent/DD151940A5/de unknown
- 1980-07-04 HU HU801674A patent/HU182151B/hu not_active IP Right Cessation
- 1980-07-04 CA CA000355421A patent/CA1153379A/en not_active Expired
- 1980-07-04 JP JP9216080A patent/JPS5618979A/ja active Pending
- 1980-07-04 ES ES493139A patent/ES493139A0/es active Granted
- 1980-07-04 DK DK291180A patent/DK146962C/da not_active IP Right Cessation
- 1980-07-04 NO NO802015A patent/NO153496C/no unknown
- 1980-07-04 PL PL1980225479A patent/PL125597B1/pl unknown
- 1980-07-07 AT AT0354380A patent/AT375078B/de not_active IP Right Cessation
- 1980-07-07 FI FI802165A patent/FI67217C/fi not_active IP Right Cessation

Also Published As

Publication number	Publication date
EP0022762B1 (fr)	1981-11-25
OA06563A (fr)	1981-07-31
GR69280B (da)	1982-05-13
NO153496C (no)	1986-05-14
PL225479A1 (da)	1981-10-30
ATA354380A (de)	1983-11-15
ZA803434B (en)	1981-05-27
US4400387A (en)	1983-08-23
IE49994B1 (en)	1986-01-22
FI67217C (fi)	1985-02-11
ES8105710A1 (es)	1981-06-16
AU529725B2 (en)	1983-06-16
PL125597B1 (en)	1983-05-31
CA1153379A (en)	1983-09-06
NZ193926A (en)	1984-05-31
PT71424A (en)	1980-07-01
DE3060097D1 (en)	1982-01-28
EP0022762A1 (fr)	1981-01-21
HU182151B (en)	1983-12-28
AT375078B (de)	1984-06-25
AR225314A1 (es)	1982-03-15
DK146962B (da)	1984-02-27
ES493139A0 (es)	1981-06-16
FI802165A7 (fi)	1981-01-07
SU993817A3 (ru)	1983-01-30
FI67217B (fi)	1984-10-31
JPS5618979A (en)	1981-02-23
DK291180A (da)	1981-01-07
DK146962C (da)	1984-08-06
IE801349L (en)	1981-01-06
AU5948780A (en)	1981-01-15
IN151594B (da)	1983-06-04
YU171880A (en)	1983-10-31
NO153496B (no)	1985-12-23
NO802015L (no)	1981-01-07

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DE60128329T2 (de)	2008-01-10	Pyrrolopyridazin-verbindungen
JPH01279864A (ja)	1989-11-10	新規の１，２―ジヒドロピリド〔３，４―ｂ〕―ピラジン類製造用の中間体
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