BG60471B2 - Хетероциклични амидни производни - Google Patents
Хетероциклични амидни производни Download PDFInfo
- Publication number
- BG60471B2 BG60471B2 BG098072A BG9807293A BG60471B2 BG 60471 B2 BG60471 B2 BG 60471B2 BG 098072 A BG098072 A BG 098072A BG 9807293 A BG9807293 A BG 9807293A BG 60471 B2 BG60471 B2 BG 60471B2
- Authority
- BG
- Bulgaria
- Prior art keywords
- formula
- ylmethyl
- methyl
- compound
- group
- Prior art date
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- -1 Heterocyclic amide Chemical class 0.000 title claims abstract description 220
- 150000001875 compounds Chemical class 0.000 claims abstract description 239
- 238000000034 method Methods 0.000 claims abstract description 90
- 239000002253 acid Substances 0.000 claims abstract description 40
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 80
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 63
- 125000000217 alkyl group Chemical group 0.000 claims description 51
- 229910052739 hydrogen Inorganic materials 0.000 claims description 47
- 239000001257 hydrogen Substances 0.000 claims description 42
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 41
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 28
- 229910052799 carbon Inorganic materials 0.000 claims description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 150000002148 esters Chemical class 0.000 claims description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
- 239000003085 diluting agent Substances 0.000 claims description 16
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 229910052740 iodine Inorganic materials 0.000 claims description 15
- 239000002168 alkylating agent Substances 0.000 claims description 14
- 229940100198 alkylating agent Drugs 0.000 claims description 14
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 14
- 229910052736 halogen Inorganic materials 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 14
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 150000003254 radicals Chemical group 0.000 claims description 13
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
- 239000002585 base Substances 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 12
- 239000000460 chlorine Substances 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 11
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 11
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 10
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- 150000002473 indoazoles Chemical class 0.000 claims description 10
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 10
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 10
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 10
- 125000004149 thio group Chemical group *S* 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 238000000354 decomposition reaction Methods 0.000 claims description 9
- 229910052731 fluorine Inorganic materials 0.000 claims description 9
- 239000011737 fluorine Substances 0.000 claims description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 8
- 230000029936 alkylation Effects 0.000 claims description 8
- 238000005804 alkylation reaction Methods 0.000 claims description 8
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 8
- NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 claims description 8
- 239000011593 sulfur Substances 0.000 claims description 8
- 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 7
- 125000005605 benzo group Chemical group 0.000 claims description 7
- 239000012948 isocyanate Substances 0.000 claims description 7
- 150000002513 isocyanates Chemical class 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 125000006219 1-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
- 239000002841 Lewis acid Substances 0.000 claims description 6
- 230000010933 acylation Effects 0.000 claims description 6
- 238000005917 acylation reaction Methods 0.000 claims description 6
- 229910052783 alkali metal Inorganic materials 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- 150000007517 lewis acids Chemical class 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 claims description 5
- YEEZWCHGZNKEEK-UHFFFAOYSA-N Zafirlukast Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)=CC=C1CC(C1=C2)=CN(C)C1=CC=C2NC(=O)OC1CCCC1 YEEZWCHGZNKEEK-UHFFFAOYSA-N 0.000 claims description 5
- 230000002378 acidificating effect Effects 0.000 claims description 5
- 150000001565 benzotriazoles Chemical class 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000006302 indol-3-yl methyl group Chemical group [H]N1C([H])=C(C2=C([H])C([H])=C([H])C([H])=C12)C([H])([H])* 0.000 claims description 5
- 150000002475 indoles Chemical class 0.000 claims description 5
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000001989 1,3-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([H])C([*:2])=C1[H] 0.000 claims description 4
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 4
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 4
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- 150000001556 benzimidazoles Chemical class 0.000 claims description 4
- 150000001721 carbon Chemical group 0.000 claims description 4
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 4
- 150000001768 cations Chemical class 0.000 claims description 4
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 4
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- 150000002540 isothiocyanates Chemical class 0.000 claims description 4
- 125000003564 m-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(C#N)=C1[H])C([H])([H])* 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 229910001923 silver oxide Inorganic materials 0.000 claims description 4
- 229930192474 thiophene Natural products 0.000 claims description 4
- 150000003577 thiophenes Chemical class 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- PVTXJGJDOHYFOX-UHFFFAOYSA-N 2h-1,4-benzoxazine Chemical class C1=CC=C2N=CCOC2=C1 PVTXJGJDOHYFOX-UHFFFAOYSA-N 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 229910052782 aluminium Inorganic materials 0.000 claims description 3
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- SKOXHEZNXXKBOY-UHFFFAOYSA-N cyclopentyl n-[3-[[4-(benzenesulfonylcarbamoyl)-2-methoxyphenyl]methyl]-1-methylindazol-5-yl]carbamate Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C=CC=CC=2)=CC=C1CC(C1=C2)=NN(C)C1=CC=C2NC(=O)OC1CCCC1 SKOXHEZNXXKBOY-UHFFFAOYSA-N 0.000 claims description 3
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 239000012024 dehydrating agents Substances 0.000 claims description 3
- 230000018044 dehydration Effects 0.000 claims description 3
- 238000006297 dehydration reaction Methods 0.000 claims description 3
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 150000002476 indolines Chemical class 0.000 claims description 3
- 229910052751 metal Inorganic materials 0.000 claims description 3
- 239000002184 metal Substances 0.000 claims description 3
- NGJQHMGDZSEEFT-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[[6-[(2-cyclopentylacetyl)amino]benzimidazol-1-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C=CC=CC=2)=CC=C1CN(C1=C2)C=NC1=CC=C2NC(=O)CC1CCCC1 NGJQHMGDZSEEFT-UHFFFAOYSA-N 0.000 claims description 3
- XLKFMZOFGNVMEV-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[[6-[(2-cyclopentylacetyl)amino]benzotriazol-1-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C=CC=CC=2)=CC=C1CN(C1=C2)N=NC1=CC=C2NC(=O)CC1CCCC1 XLKFMZOFGNVMEV-UHFFFAOYSA-N 0.000 claims description 3
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 3
- CSNIZNHTOVFARY-UHFFFAOYSA-N 1,2-benzothiazole Chemical class C1=CC=C2C=NSC2=C1 CSNIZNHTOVFARY-UHFFFAOYSA-N 0.000 claims description 2
- ZXSQEZNORDWBGZ-UHFFFAOYSA-N 1,3-dihydropyrrolo[2,3-b]pyridin-2-one Chemical compound C1=CN=C2NC(=O)CC2=C1 ZXSQEZNORDWBGZ-UHFFFAOYSA-N 0.000 claims description 2
- HFFXLYHRNRKAPM-UHFFFAOYSA-N 2,4,5-trichloro-n-(5-methyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C(=CC(Cl)=C(Cl)C=2)Cl)=N1 HFFXLYHRNRKAPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- YRLORWPBJZEGBX-UHFFFAOYSA-N 3,4-dihydro-2h-1,4-benzoxazine Chemical class C1=CC=C2NCCOC2=C1 YRLORWPBJZEGBX-UHFFFAOYSA-N 0.000 claims description 2
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 2
- 239000005977 Ethylene Substances 0.000 claims description 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 2
- 150000001342 alkaline earth metals Chemical class 0.000 claims description 2
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 2
- 150000003863 ammonium salts Chemical class 0.000 claims description 2
- 150000001450 anions Chemical class 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 150000008316 benzisoxazoles Chemical class 0.000 claims description 2
- 125000001589 carboacyl group Chemical group 0.000 claims description 2
- 125000002843 carboxylic acid group Chemical group 0.000 claims description 2
- 238000006880 cross-coupling reaction Methods 0.000 claims description 2
- 150000002440 hydroxy compounds Chemical class 0.000 claims description 2
- LOCAIGRSOJUCTB-UHFFFAOYSA-N indazol-3-one Chemical class C1=CC=C2C(=O)N=NC2=C1 LOCAIGRSOJUCTB-UHFFFAOYSA-N 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 229910001958 silver carbonate Inorganic materials 0.000 claims description 2
- LKZMBDSASOBTPN-UHFFFAOYSA-L silver carbonate Substances [Ag].[O-]C([O-])=O LKZMBDSASOBTPN-UHFFFAOYSA-L 0.000 claims description 2
- 150000003573 thiols Chemical class 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims 3
- MGMIPHDTLAASLA-UHFFFAOYSA-N cyclopentyl n-[3-[[4-(benzenesulfonylcarbamoyl)-2-methoxyphenyl]methyl]-1-benzothiophen-5-yl]carbamate Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C=CC=CC=2)=CC=C1CC(C1=C2)=CSC1=CC=C2NC(=O)OC1CCCC1 MGMIPHDTLAASLA-UHFFFAOYSA-N 0.000 claims 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 2
- 230000003993 interaction Effects 0.000 claims 2
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 2
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 claims 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims 1
- 125000004414 alkyl thio group Chemical group 0.000 claims 1
- FBOSKQVOIHEWAX-UHFFFAOYSA-N benzothiazine Chemical class C1=CC=C2N=CCSC2=C1 FBOSKQVOIHEWAX-UHFFFAOYSA-N 0.000 claims 1
- ZYFXZSJLWGWRDB-UHFFFAOYSA-N cyclopentyl n-[3-[[4-(benzenesulfonylcarbamoyl)-2-methoxyphenyl]methyl]-1-(2-methoxyethyl)indol-5-yl]carbamate Chemical compound C12=CC(NC(=O)OC3CCCC3)=CC=C2N(CCOC)C=C1CC(C(=C1)OC)=CC=C1C(=O)NS(=O)(=O)C1=CC=CC=C1 ZYFXZSJLWGWRDB-UHFFFAOYSA-N 0.000 claims 1
- ZZGWEFLUSUHZRZ-UHFFFAOYSA-N cyclopentyl n-[3-[[4-(benzenesulfonylcarbamoyl)-2-methoxyphenyl]methyl]-1-methylindol-5-yl]carbamate Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C=CC=CC=2)=CC=C1CC(C1=C2)=CN(C)C1=CC=C2NC(=O)OC1CCCC1 ZZGWEFLUSUHZRZ-UHFFFAOYSA-N 0.000 claims 1
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 150000002460 imidazoles Chemical class 0.000 claims 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- 239000010802 sludge Substances 0.000 claims 1
- 150000001408 amides Chemical class 0.000 abstract description 4
- KJUGUADJHNHALS-UHFFFAOYSA-N 1H-tetrazole Substances C=1N=NNN=1 KJUGUADJHNHALS-UHFFFAOYSA-N 0.000 abstract description 2
- 150000003536 tetrazoles Chemical class 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 219
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 195
- 239000000243 solution Substances 0.000 description 111
- 239000000203 mixture Substances 0.000 description 107
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 105
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 82
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- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- YUHSMQQNPRLEEJ-UHFFFAOYSA-N methyl 3-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=CC(CBr)=C1 YUHSMQQNPRLEEJ-UHFFFAOYSA-N 0.000 description 1
- DMPXTRBUJIRVOO-UHFFFAOYSA-N methyl 3-methoxy-4-[(1-methyl-5-nitroindol-3-yl)methyl]benzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CC1=CN(C)C2=CC=C([N+]([O-])=O)C=C12 DMPXTRBUJIRVOO-UHFFFAOYSA-N 0.000 description 1
- OIZWUIAESOTUNM-UHFFFAOYSA-N methyl 3-methoxy-4-[(3-methoxy-6-nitroindazol-1-yl)methyl]benzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC([N+]([O-])=O)=CC=C2C(OC)=N1 OIZWUIAESOTUNM-UHFFFAOYSA-N 0.000 description 1
- UZKUCUPQOOZWJC-UHFFFAOYSA-N methyl 3-methoxy-4-[(5-nitro-1h-indol-3-yl)methyl]benzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CC1=CNC2=CC=C([N+]([O-])=O)C=C12 UZKUCUPQOOZWJC-UHFFFAOYSA-N 0.000 description 1
- IKJXWRDOCSSGNY-UHFFFAOYSA-N methyl 3-methoxy-4-[(6-nitrobenzimidazol-1-yl)methyl]benzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC([N+]([O-])=O)=CC=C2N=C1 IKJXWRDOCSSGNY-UHFFFAOYSA-N 0.000 description 1
- KASDYVFLPLXSEU-UHFFFAOYSA-N methyl 3-methoxy-4-[(6-nitrobenzotriazol-1-yl)methyl]benzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC([N+]([O-])=O)=CC=C2N=N1 KASDYVFLPLXSEU-UHFFFAOYSA-N 0.000 description 1
- UEPDIZBSKPSDAF-UHFFFAOYSA-N methyl 3-methoxy-4-[[6-(2-phenylbutanoylamino)benzimidazol-1-yl]methyl]benzoate Chemical compound C=1C=CC=CC=1C(CC)C(=O)NC(C=C12)=CC=C1N=CN2CC1=CC=C(C(=O)OC)C=C1OC UEPDIZBSKPSDAF-UHFFFAOYSA-N 0.000 description 1
- LLEXCSBUSVRBCA-UHFFFAOYSA-N methyl 3-methoxy-4-methylbenzoate Chemical compound COC(=O)C1=CC=C(C)C(OC)=C1 LLEXCSBUSVRBCA-UHFFFAOYSA-N 0.000 description 1
- IBOYYFNVXYCDLD-UHFFFAOYSA-N methyl 4-[(5-amino-1-benzothiophen-3-yl)methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CC1=CSC2=CC=C(N)C=C12 IBOYYFNVXYCDLD-UHFFFAOYSA-N 0.000 description 1
- YUQYQCYIZFMTFM-UHFFFAOYSA-N methyl 4-[(5-amino-1-cyclopentylindol-3-yl)methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CC(C1=CC(N)=CC=C11)=CN1C1CCCC1 YUQYQCYIZFMTFM-UHFFFAOYSA-N 0.000 description 1
- FFDQUHXGCGMVDT-UHFFFAOYSA-N methyl 4-[(5-amino-1-ethylindol-3-yl)methyl]-3-methoxybenzoate Chemical compound C12=CC(N)=CC=C2N(CC)C=C1CC1=CC=C(C(=O)OC)C=C1OC FFDQUHXGCGMVDT-UHFFFAOYSA-N 0.000 description 1
- YVFFMKLKTCAENK-UHFFFAOYSA-N methyl 4-[(5-amino-1-propylindol-3-yl)methyl]-3-methoxybenzoate Chemical compound C12=CC(N)=CC=C2N(CCC)C=C1CC1=CC=C(C(=O)OC)C=C1OC YVFFMKLKTCAENK-UHFFFAOYSA-N 0.000 description 1
- CHTXQHJSTRIBOX-UHFFFAOYSA-N methyl 4-[(5-amino-1h-indol-3-yl)methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CC1=CNC2=CC=C(N)C=C12 CHTXQHJSTRIBOX-UHFFFAOYSA-N 0.000 description 1
- CVURLPMDBOAEHV-UHFFFAOYSA-N methyl 4-[(6-amino-3-methoxyindazol-1-yl)methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC(N)=CC=C2C(OC)=N1 CVURLPMDBOAEHV-UHFFFAOYSA-N 0.000 description 1
- BOEJZITWPVNSCU-UHFFFAOYSA-N methyl 4-[2-acetyloxyimino-2-[3-amino-5-(cyclopentyloxycarbonylamino)-2-methylphenyl]ethyl]-3-methoxybenzoate Chemical compound C(C)(=O)ON=C(CC1=C(C=C(C(=O)OC)C=C1)OC)C1=C(C(=CC(=C1)NC(=O)OC1CCCC1)N)C BOEJZITWPVNSCU-UHFFFAOYSA-N 0.000 description 1
- LKWBXIIEIYGPNX-UHFFFAOYSA-N methyl 4-[[1-benzyl-5-(hexanoylamino)indol-3-yl]methyl]-3-methoxybenzoate Chemical compound C1=C(CC=2C(=CC(=CC=2)C(=O)OC)OC)C2=CC(NC(=O)CCCCC)=CC=C2N1CC1=CC=CC=C1 LKWBXIIEIYGPNX-UHFFFAOYSA-N 0.000 description 1
- JXNMRDUQHALOCR-UHFFFAOYSA-N methyl 4-[[5-(2-ethylhexanoylamino)-1-methylindol-3-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)C(CC)CCCC)=CC=C2N(C)C=C1CC1=CC=C(C(=O)OC)C=C1OC JXNMRDUQHALOCR-UHFFFAOYSA-N 0.000 description 1
- YMEQWNQVXTZRAW-UHFFFAOYSA-N methyl 4-[[5-(2-ethylhexanoylamino)-1h-indol-3-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)C(CC)CCCC)=CC=C2NC=C1CC1=CC=C(C(=O)OC)C=C1OC YMEQWNQVXTZRAW-UHFFFAOYSA-N 0.000 description 1
- YMJGINHVOLKJCQ-UHFFFAOYSA-N methyl 4-[[5-(cyclopentyloxycarbonylamino)-1-(2-methoxyethyl)indol-3-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)OC3CCCC3)=CC=C2N(CCOC)C=C1CC1=CC=C(C(=O)OC)C=C1OC YMJGINHVOLKJCQ-UHFFFAOYSA-N 0.000 description 1
- YZQVHUSWTAQOFI-UHFFFAOYSA-N methyl 4-[[5-(cyclopentyloxycarbonylamino)-1-(3-methylbut-2-enyl)indol-3-yl]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CC(C1=C2)=CN(CC=C(C)C)C1=CC=C2NC(=O)OC1CCCC1 YZQVHUSWTAQOFI-UHFFFAOYSA-N 0.000 description 1
- ZQJQSFUOZWSHQW-UHFFFAOYSA-N methyl 4-[[5-(cyclopentyloxycarbonylamino)-1-(cyclopropylmethyl)indol-3-yl]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CC(C1=CC(NC(=O)OC2CCCC2)=CC=C11)=CN1CC1CC1 ZQJQSFUOZWSHQW-UHFFFAOYSA-N 0.000 description 1
- CFQKOXAHEPUJBE-UHFFFAOYSA-N methyl 4-[[5-(cyclopentyloxycarbonylamino)-1-hexylindol-3-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)OC3CCCC3)=CC=C2N(CCCCCC)C=C1CC1=CC=C(C(=O)OC)C=C1OC CFQKOXAHEPUJBE-UHFFFAOYSA-N 0.000 description 1
- ATNCAFJKGARVAJ-UHFFFAOYSA-N methyl 4-[[5-(cyclopentyloxycarbonylamino)-1-propylindol-3-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)OC3CCCC3)=CC=C2N(CCC)C=C1CC1=CC=C(C(=O)OC)C=C1OC ATNCAFJKGARVAJ-UHFFFAOYSA-N 0.000 description 1
- ONZDXHKKSHJFGV-UHFFFAOYSA-N methyl 4-[[5-(hexanoylamino)-1-benzothiophen-3-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)CCCCC)=CC=C2SC=C1CC1=CC=C(C(=O)OC)C=C1OC ONZDXHKKSHJFGV-UHFFFAOYSA-N 0.000 description 1
- PPBZAJPIBZRTGU-UHFFFAOYSA-N methyl 4-[[5-(hexanoylamino)-1-methylindol-3-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)CCCCC)=CC=C2N(C)C=C1CC1=CC=C(C(=O)OC)C=C1OC PPBZAJPIBZRTGU-UHFFFAOYSA-N 0.000 description 1
- FVLXQUNPZKKYFF-UHFFFAOYSA-N methyl 4-[[5-(hexanoylamino)-1h-indol-3-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)CCCCC)=CC=C2NC=C1CC1=CC=C(C(=O)OC)C=C1OC FVLXQUNPZKKYFF-UHFFFAOYSA-N 0.000 description 1
- KSZJXIKZBJLPOS-UHFFFAOYSA-N methyl 4-[[5-[(2-cyclopentylacetyl)amino]-1-[2-(dimethylamino)-2-oxoethyl]indol-3-yl]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CC(C1=C2)=CN(CC(=O)N(C)C)C1=CC=C2NC(=O)CC1CCCC1 KSZJXIKZBJLPOS-UHFFFAOYSA-N 0.000 description 1
- GSMLRFUJEYTMFY-UHFFFAOYSA-N methyl 4-[[5-[(2-cyclopentylacetyl)amino]-1-ethyl-2,3-dihydroindol-3-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)CC3CCCC3)=CC=C2N(CC)CC1CC1=CC=C(C(=O)OC)C=C1OC GSMLRFUJEYTMFY-UHFFFAOYSA-N 0.000 description 1
- LLUBTFRUUBZFHX-UHFFFAOYSA-N methyl 4-[[5-[(2-cyclopentylacetyl)amino]-1-ethylindol-3-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)CC3CCCC3)=CC=C2N(CC)C=C1CC1=CC=C(C(=O)OC)C=C1OC LLUBTFRUUBZFHX-UHFFFAOYSA-N 0.000 description 1
- FBHBYMSSVYOKCE-UHFFFAOYSA-N methyl 4-[[5-[(2-cyclopentylacetyl)amino]-1-prop-2-ynylindol-3-yl]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CC(C1=C2)=CN(CC#C)C1=CC=C2NC(=O)CC1CCCC1 FBHBYMSSVYOKCE-UHFFFAOYSA-N 0.000 description 1
- RPWXOZTWSDWUJP-UHFFFAOYSA-N methyl 4-[[5-[(2-cyclopentylacetyl)amino]-1-propylindol-3-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)CC3CCCC3)=CC=C2N(CCC)C=C1CC1=CC=C(C(=O)OC)C=C1OC RPWXOZTWSDWUJP-UHFFFAOYSA-N 0.000 description 1
- AAMUISONQQOGAQ-UHFFFAOYSA-N methyl 4-[[5-[(2-cyclopentylacetyl)amino]-1h-indol-3-yl]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CC(C1=C2)=CNC1=CC=C2NC(=O)CC1CCCC1 AAMUISONQQOGAQ-UHFFFAOYSA-N 0.000 description 1
- RXZZQXKVPJLDBI-UHFFFAOYSA-N methyl 4-[[5-amino-1-(2-methoxyethyl)indol-3-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(N)=CC=C2N(CCOC)C=C1CC1=CC=C(C(=O)OC)C=C1OC RXZZQXKVPJLDBI-UHFFFAOYSA-N 0.000 description 1
- CBMBUNJUFIVCOM-UHFFFAOYSA-N methyl 4-[[5-amino-1-(3-methylbut-2-enyl)indol-3-yl]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CC1=CN(CC=C(C)C)C2=CC=C(N)C=C12 CBMBUNJUFIVCOM-UHFFFAOYSA-N 0.000 description 1
- XDOZKDRMTOZREV-UHFFFAOYSA-N methyl 4-[[5-amino-1-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]indol-3-yl]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CC1=CN(CC(=O)OC(C)(C)C)C2=CC=C(N)C=C12 XDOZKDRMTOZREV-UHFFFAOYSA-N 0.000 description 1
- HOGGATCYTRRMMM-UHFFFAOYSA-N methyl 4-[[6-(butoxycarbonylamino)benzimidazol-1-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)OCCCC)=CC=C2N=CN1CC1=CC=C(C(=O)OC)C=C1OC HOGGATCYTRRMMM-UHFFFAOYSA-N 0.000 description 1
- XWUCPDVSJJUSFY-UHFFFAOYSA-N methyl 4-[[6-(hexanoylamino)-2,3-dihydro-1,4-benzoxazin-4-yl]methyl]-3-methoxybenzoate Chemical compound C12=CC(NC(=O)CCCCC)=CC=C2OCCN1CC1=CC=C(C(=O)OC)C=C1OC XWUCPDVSJJUSFY-UHFFFAOYSA-N 0.000 description 1
- YRCJEXBWEJFYDU-UHFFFAOYSA-N methyl 4-[[6-[(2-cyclopentylacetyl)amino]benzimidazol-1-yl]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC(NC(=O)CC3CCCC3)=CC=C2N=C1 YRCJEXBWEJFYDU-UHFFFAOYSA-N 0.000 description 1
- ZYJAZOYZHXWVCX-UHFFFAOYSA-N methyl 4-[[6-[(2-cyclopentylacetyl)amino]benzotriazol-1-yl]methyl]-3-methoxybenzoate Chemical compound COC1=CC(C(=O)OC)=CC=C1CN1C2=CC(NC(=O)CC3CCCC3)=CC=C2N=N1 ZYJAZOYZHXWVCX-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 125000004092 methylthiomethyl group Chemical group [H]C([H])([H])SC([H])([H])* 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- VGGNVBNNVSIGKG-UHFFFAOYSA-N n,n,2-trimethylaziridine-1-carboxamide Chemical compound CC1CN1C(=O)N(C)C VGGNVBNNVSIGKG-UHFFFAOYSA-N 0.000 description 1
- KWERPWGWCMUCQE-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[[5-(2-ethylhexanoylamino)-1-methylindol-3-yl]methyl]-3-methoxybenzamide Chemical compound C12=CC(NC(=O)C(CC)CCCC)=CC=C2N(C)C=C1CC(C(=C1)OC)=CC=C1C(=O)NS(=O)(=O)C1=CC=CC=C1 KWERPWGWCMUCQE-UHFFFAOYSA-N 0.000 description 1
- CVTDNWBPWCXPFN-UHFFFAOYSA-N n-(benzenesulfonyl)-4-[[5-[(2-cyclopentylacetyl)amino]-1-methylindol-3-yl]methyl]-3-methoxybenzamide Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C=CC=CC=2)=CC=C1CC(C1=C2)=CN(C)C1=CC=C2NC(=O)CC1CCCC1 CVTDNWBPWCXPFN-UHFFFAOYSA-N 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- ZBRJXVVKPBZPAN-UHFFFAOYSA-L nickel(2+);triphenylphosphane;dichloride Chemical compound [Cl-].[Cl-].[Ni+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 ZBRJXVVKPBZPAN-UHFFFAOYSA-L 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002923 oximes Chemical class 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 235000011197 perejil Nutrition 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000015843 photosynthesis, light reaction Effects 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- TZLVRPLSVNESQC-UHFFFAOYSA-N potassium azide Chemical compound [K+].[N-]=[N+]=[N-] TZLVRPLSVNESQC-UHFFFAOYSA-N 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 1
- CUQOHAYJWVTKDE-UHFFFAOYSA-N potassium;butan-1-olate Chemical compound [K+].CCCC[O-] CUQOHAYJWVTKDE-UHFFFAOYSA-N 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 229910052705 radium Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- HKZLPVFGJNLROG-UHFFFAOYSA-M silver monochloride Chemical compound [Cl-].[Ag+] HKZLPVFGJNLROG-UHFFFAOYSA-M 0.000 description 1
- KZJPVUDYAMEDRM-UHFFFAOYSA-M silver;2,2,2-trifluoroacetate Chemical compound [Ag+].[O-]C(=O)C(F)(F)F KZJPVUDYAMEDRM-UHFFFAOYSA-M 0.000 description 1
- VFWRGKJLLYDFBY-UHFFFAOYSA-N silver;hydrate Chemical compound O.[Ag].[Ag] VFWRGKJLLYDFBY-UHFFFAOYSA-N 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 235000019337 sorbitan trioleate Nutrition 0.000 description 1
- 229960000391 sorbitan trioleate Drugs 0.000 description 1
- 230000003033 spasmogenic effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 238000007655 standard test method Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- YJBKVPRVZAQTPY-UHFFFAOYSA-J tetrachlorostannane;dihydrate Chemical compound O.O.Cl[Sn](Cl)(Cl)Cl YJBKVPRVZAQTPY-UHFFFAOYSA-J 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 description 1
- ZWZVWGITAAIFPS-UHFFFAOYSA-N thiophosgene Chemical compound ClC(Cl)=S ZWZVWGITAAIFPS-UHFFFAOYSA-N 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 210000005092 tracheal tissue Anatomy 0.000 description 1
- 238000009901 transfer hydrogenation reaction Methods 0.000 description 1
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
- 229940029284 trichlorofluoromethane Drugs 0.000 description 1
- YZYUDDMXMLCTOX-UHFFFAOYSA-N trichloromethylcyclopentane Chemical compound ClC(Cl)(Cl)C1CCCC1 YZYUDDMXMLCTOX-UHFFFAOYSA-N 0.000 description 1
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 1
- 230000002455 vasospastic effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
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- C07D249/16—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms condensed with carbocyclic rings or ring systems
- C07D249/18—Benzotriazoles
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- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
- C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
- C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
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- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/52—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes
- C07D333/54—Benzo[b]thiophenes; Hydrogenated benzo[b]thiophenes with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
- C07D333/60—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing aromatic rings
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- Chemical & Material Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
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- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Indole Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB858509882A GB8509882D0 (en) | 1985-04-17 | 1985-04-17 | Heterocyclic amide derivatives |
GB858525658A GB8525658D0 (en) | 1985-10-17 | 1985-10-17 | Heterocyclic amide derivatives |
Publications (1)
Publication Number | Publication Date |
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BG60471B2 true BG60471B2 (bg) | 1995-04-28 |
Family
ID=26289139
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
BG098072A BG60471B2 (bg) | 1985-04-17 | 1993-08-26 | Хетероциклични амидни производни |
Country Status (26)
Country | Link |
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US (6) | US4859692A (sv) |
EP (1) | EP0199543B1 (sv) |
JP (2) | JPH0667904B2 (sv) |
KR (1) | KR900004384B1 (sv) |
CN (1) | CN1017425B (sv) |
AR (1) | AR242569A1 (sv) |
AU (1) | AU596582B2 (sv) |
BG (1) | BG60471B2 (sv) |
CA (1) | CA1340567C (sv) |
CS (1) | CS399791A3 (sv) |
CY (1) | CY1705A (sv) |
DE (1) | DE3682698D1 (sv) |
DK (1) | DK167354B1 (sv) |
ES (6) | ES8802220A1 (sv) |
FI (1) | FI83865C (sv) |
GB (1) | GB8607294D0 (sv) |
HK (1) | HK120994A (sv) |
HU (1) | HU196968B (sv) |
IE (1) | IE59140B1 (sv) |
IL (1) | IL78569A (sv) |
NO (1) | NO171452C (sv) |
NZ (1) | NZ215850A (sv) |
PH (1) | PH26763A (sv) |
PT (1) | PT82389B (sv) |
SA (1) | SA93140396A (sv) |
ZW (1) | ZW8786A1 (sv) |
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1986
- 1986-03-24 GB GB868607294A patent/GB8607294D0/en active Pending
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- 1986-04-16 AU AU56164/86A patent/AU596582B2/en not_active Expired
- 1986-04-16 US US06/852,798 patent/US4859692A/en not_active Expired - Lifetime
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- 1986-04-16 IE IE100086A patent/IE59140B1/en not_active IP Right Cessation
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- 1986-04-16 ZW ZW87/86A patent/ZW8786A1/xx unknown
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- 1986-04-17 KR KR1019860002977A patent/KR900004384B1/ko not_active IP Right Cessation
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1987
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- 1987-07-31 ES ES557643A patent/ES8802494A1/es not_active Expired
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1989
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1991
- 1991-12-20 CS CS913997A patent/CS399791A3/cs unknown
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1992
- 1992-11-25 US US07/981,718 patent/US5338734A/en not_active Expired - Lifetime
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1993
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1994
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