HU183046B - Process for producing hydanthoine derivatives - Google Patents
Process for producing hydanthoine derivatives Download PDFInfo
- Publication number
- HU183046B HU183046B HU77WE560A HUWE000560A HU183046B HU 183046 B HU183046 B HU 183046B HU 77WE560 A HU77WE560 A HU 77WE560A HU WE000560 A HUWE000560 A HU WE000560A HU 183046 B HU183046 B HU 183046B
- Authority
- HU
- Hungary
- Prior art keywords
- formula
- priority
- compound
- reaction
- june
- Prior art date
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- 238000000034 method Methods 0.000 title claims description 203
- 230000008569 process Effects 0.000 title claims description 156
- -1 5-tetrazolyl Chemical group 0.000 claims abstract description 182
- 150000001469 hydantoins Chemical class 0.000 claims abstract description 47
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 37
- 239000001257 hydrogen Substances 0.000 claims abstract description 37
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 29
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 27
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 15
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 13
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 11
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 10
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims abstract description 10
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 10
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 8
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 8
- 150000001602 bicycloalkyls Chemical group 0.000 claims abstract description 7
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims abstract description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 5
- 150000002431 hydrogen Chemical group 0.000 claims abstract 10
- 125000005843 halogen group Chemical group 0.000 claims abstract 6
- 150000001721 carbon Chemical group 0.000 claims abstract 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract 2
- 150000001875 compounds Chemical class 0.000 claims description 210
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 83
- 239000000203 mixture Substances 0.000 claims description 80
- 238000006243 chemical reaction Methods 0.000 claims description 79
- 239000007858 starting material Substances 0.000 claims description 51
- 238000002360 preparation method Methods 0.000 claims description 47
- 239000002585 base Substances 0.000 claims description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 24
- 239000011541 reaction mixture Substances 0.000 claims description 24
- 239000002904 solvent Substances 0.000 claims description 24
- 239000002253 acid Substances 0.000 claims description 22
- 150000002148 esters Chemical class 0.000 claims description 19
- 238000011065 in-situ storage Methods 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 239000003638 chemical reducing agent Substances 0.000 claims description 16
- XLJMAIOERFSOGZ-UHFFFAOYSA-N cyanic acid Chemical compound OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 claims description 16
- 229910052727 yttrium Inorganic materials 0.000 claims description 15
- 239000004202 carbamide Substances 0.000 claims description 14
- 230000002378 acidificating effect Effects 0.000 claims description 13
- 239000007787 solid Substances 0.000 claims description 13
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 12
- 239000007788 liquid Substances 0.000 claims description 12
- 238000007363 ring formation reaction Methods 0.000 claims description 12
- 238000010438 heat treatment Methods 0.000 claims description 11
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical group [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 229910000033 sodium borohydride Inorganic materials 0.000 claims description 10
- 239000012279 sodium borohydride Substances 0.000 claims description 10
- 229910052783 alkali metal Inorganic materials 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 9
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 9
- CWJSHJJYOPWUGX-UHFFFAOYSA-N chlorpropham Chemical compound CC(C)OC(=O)NC1=CC=CC(Cl)=C1 CWJSHJJYOPWUGX-UHFFFAOYSA-N 0.000 claims description 9
- 238000009472 formulation Methods 0.000 claims description 9
- 238000002955 isolation Methods 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 150000001408 amides Chemical class 0.000 claims description 8
- 125000003277 amino group Chemical group 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 239000012948 isocyanate Substances 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 230000009467 reduction Effects 0.000 claims description 7
- 238000006798 ring closing metathesis reaction Methods 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 5
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical group ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 5
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims description 5
- 150000008046 alkali metal hydrides Chemical class 0.000 claims description 5
- 150000004703 alkoxides Chemical class 0.000 claims description 5
- 239000000010 aprotic solvent Substances 0.000 claims description 5
- 150000003857 carboxamides Chemical class 0.000 claims description 5
- ROORDVPLFPIABK-UHFFFAOYSA-N diphenyl carbonate Chemical compound C=1C=CC=CC=1OC(=O)OC1=CC=CC=C1 ROORDVPLFPIABK-UHFFFAOYSA-N 0.000 claims description 5
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 238000007911 parenteral administration Methods 0.000 claims description 5
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 5
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 4
- 150000004820 halides Chemical class 0.000 claims description 4
- 230000003301 hydrolyzing effect Effects 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 150000008044 alkali metal hydroxides Chemical group 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 2
- 229910021626 Tin(II) chloride Inorganic materials 0.000 claims description 2
- 150000008065 acid anhydrides Chemical class 0.000 claims description 2
- 230000029936 alkylation Effects 0.000 claims description 2
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical group CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 238000005984 hydrogenation reaction Methods 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- 229910052705 radium Inorganic materials 0.000 claims description 2
- HCWPIIXVSYCSAN-UHFFFAOYSA-N radium atom Chemical compound [Ra] HCWPIIXVSYCSAN-UHFFFAOYSA-N 0.000 claims description 2
- 229910052707 ruthenium Inorganic materials 0.000 claims description 2
- 235000011150 stannous chloride Nutrition 0.000 claims description 2
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical group [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 claims description 2
- 125000002560 nitrile group Chemical group 0.000 claims 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 5
- 150000001649 bromium compounds Chemical class 0.000 claims 4
- 125000001246 bromo group Chemical group Br* 0.000 claims 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 3
- CMUOJBJRZUHRMU-UHFFFAOYSA-N nitrourea Chemical compound NC(=O)N[N+]([O-])=O CMUOJBJRZUHRMU-UHFFFAOYSA-N 0.000 claims 3
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims 2
- 125000005518 carboxamido group Chemical group 0.000 claims 2
- VXPLXMJHHKHSOA-UHFFFAOYSA-N propham Chemical compound CC(C)OC(=O)NC1=CC=CC=C1 VXPLXMJHHKHSOA-UHFFFAOYSA-N 0.000 claims 2
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 1
- 239000012736 aqueous medium Substances 0.000 claims 1
- 230000003197 catalytic effect Effects 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- 238000004898 kneading Methods 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 claims 1
- 229910001948 sodium oxide Inorganic materials 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 15
- 229940094443 oxytocics prostaglandins Drugs 0.000 abstract description 10
- 150000003180 prostaglandins Chemical class 0.000 abstract description 10
- 208000007536 Thrombosis Diseases 0.000 abstract description 5
- 230000004071 biological effect Effects 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 125000004442 acylamino group Chemical group 0.000 abstract 1
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 137
- 239000000243 solution Substances 0.000 description 82
- 229940091173 hydantoin Drugs 0.000 description 62
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical group O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 61
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 51
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 42
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
- 239000000047 product Substances 0.000 description 38
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 37
- 239000003921 oil Substances 0.000 description 35
- 235000019441 ethanol Nutrition 0.000 description 33
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
- 229940053195 antiepileptics hydantoin derivative Drugs 0.000 description 26
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- 239000012230 colorless oil Substances 0.000 description 19
- 239000004480 active ingredient Substances 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 239000012071 phase Substances 0.000 description 13
- 239000000741 silica gel Substances 0.000 description 13
- 229910002027 silica gel Inorganic materials 0.000 description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- 238000009835 boiling Methods 0.000 description 12
- 238000004220 aggregation Methods 0.000 description 11
- 230000002776 aggregation Effects 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- 239000013078 crystal Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 229910052681 coesite Inorganic materials 0.000 description 9
- 229910052906 cristobalite Inorganic materials 0.000 description 9
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical compound [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 description 9
- 229910052682 stishovite Inorganic materials 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- 229910052905 tridymite Inorganic materials 0.000 description 9
- CWNBYFYKHCQJOK-UHFFFAOYSA-N 7-[3-(3-cyclobutyl-3-hydroxypropyl)-2,5-dioxoimidazolidin-4-yl]heptanoic acid Chemical compound C1CCC1C(O)CCN1C(CCCCCCC(O)=O)C(=O)NC1=O CWNBYFYKHCQJOK-UHFFFAOYSA-N 0.000 description 8
- 241000282412 Homo Species 0.000 description 8
- 150000001298 alcohols Chemical class 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 210000000601 blood cell Anatomy 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 239000005457 ice water Substances 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- VGUWZCUCNQXGBU-UHFFFAOYSA-N 3-[(4-methylpiperazin-1-yl)methyl]-5-nitro-1h-indole Chemical compound C1CN(C)CCN1CC1=CNC2=CC=C([N+]([O-])=O)C=C12 VGUWZCUCNQXGBU-UHFFFAOYSA-N 0.000 description 7
- 241000124008 Mammalia Species 0.000 description 7
- YHIMFWJZBVHIPZ-UHFFFAOYSA-N diethyl 2-aminononanedioate Chemical compound CCOC(=O)CCCCCCC(N)C(=O)OCC YHIMFWJZBVHIPZ-UHFFFAOYSA-N 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 231100000252 nontoxic Toxicity 0.000 description 7
- 230000003000 nontoxic effect Effects 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 229940125797 compound 12 Drugs 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 238000001990 intravenous administration Methods 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 239000012043 crude product Substances 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 5
- 239000008215 water for injection Substances 0.000 description 5
- GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 description 4
- KLTVSWGXIAYTHO-UHFFFAOYSA-N 1-Octen-3-one Chemical compound CCCCCC(=O)C=C KLTVSWGXIAYTHO-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 229960000711 alprostadil Drugs 0.000 description 4
- 230000003042 antagnostic effect Effects 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- ISOLMABRZPQKOV-UHFFFAOYSA-N diethyl 2-acetamidopropanedioate Chemical compound CCOC(=O)C(NC(C)=O)C(=O)OCC ISOLMABRZPQKOV-UHFFFAOYSA-N 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 229930195733 hydrocarbon Natural products 0.000 description 4
- 150000002430 hydrocarbons Chemical class 0.000 description 4
- 239000012442 inert solvent Substances 0.000 description 4
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- GYWICHCAJSBIOV-UHFFFAOYSA-N diethyl 2-[(4-cyclopentyl-3-oxobutyl)amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(=O)CC1CCCC1 GYWICHCAJSBIOV-UHFFFAOYSA-N 0.000 description 1
- HZXVTURYOZCUJL-UHFFFAOYSA-N diethyl 2-[(4-ethyl-3-hydroxyhexyl)amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(O)C(CC)CC HZXVTURYOZCUJL-UHFFFAOYSA-N 0.000 description 1
- NWNDCIHHCCHEAY-UHFFFAOYSA-N diethyl 2-[(4-ethyl-3-oxohexyl)amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(=O)C(CC)CC NWNDCIHHCCHEAY-UHFFFAOYSA-N 0.000 description 1
- MJIVZLYXBUWJAP-UHFFFAOYSA-N diethyl 2-[(4-methyl-3-oxopentyl)amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(=O)C(C)C MJIVZLYXBUWJAP-UHFFFAOYSA-N 0.000 description 1
- JKTFYWWQNCDUKJ-UHFFFAOYSA-N diethyl 2-[(5-ethoxy-3-oxopentyl)amino]nonanedioate Chemical compound CCOCCC(=O)CCNC(C(=O)OCC)CCCCCCC(=O)OCC JKTFYWWQNCDUKJ-UHFFFAOYSA-N 0.000 description 1
- ABFCRBUZMITUEG-UHFFFAOYSA-N diethyl 2-[[3-(4-chlorophenyl)-3-oxopropyl]amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(=O)C1=CC=C(Cl)C=C1 ABFCRBUZMITUEG-UHFFFAOYSA-N 0.000 description 1
- CPINAZJFKYALHR-UHFFFAOYSA-N diethyl 2-[[3-(4-hydroxyphenyl)-3-oxopropyl]amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(=O)C1=CC=C(O)C=C1 CPINAZJFKYALHR-UHFFFAOYSA-N 0.000 description 1
- FPTOSMZDQOAYQF-UHFFFAOYSA-N diethyl 2-[[3-(4-nitrophenyl)-3-oxopropyl]amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(=O)C1=CC=C([N+]([O-])=O)C=C1 FPTOSMZDQOAYQF-UHFFFAOYSA-N 0.000 description 1
- DIPFELRTXLNTRF-UHFFFAOYSA-N diethyl 2-[[3-hydroxy-4,4-dimethyl-5-[3-(trifluoromethyl)phenyl]pentyl]amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(O)C(C)(C)CC1=CC=CC(C(F)(F)F)=C1 DIPFELRTXLNTRF-UHFFFAOYSA-N 0.000 description 1
- FQDFNBADEJXIQS-UHFFFAOYSA-N diethyl 2-[[3-oxo-4-[3-(trifluoromethyl)phenoxy]butyl]amino]nonanedioate Chemical compound CCOC(=O)CCCCCCC(C(=O)OCC)NCCC(=O)COC1=CC=CC(C(F)(F)F)=C1 FQDFNBADEJXIQS-UHFFFAOYSA-N 0.000 description 1
- AZJLJUNJOVEAQF-UHFFFAOYSA-N diethyl 2-acetamido-2-[3-(2-ethoxy-2-oxoethoxy)phenyl]propanedioate Chemical compound CCOC(=O)COC1=CC=CC(C(NC(C)=O)(C(=O)OCC)C(=O)OCC)=C1 AZJLJUNJOVEAQF-UHFFFAOYSA-N 0.000 description 1
- PEJPIKMZNYLSNX-UHFFFAOYSA-N diethyl 2-amino-2-(4-propoxybutyl)nonanedioate Chemical compound C(CC)OCCCCC(C(=O)OCC)(CCCCCCC(=O)OCC)N PEJPIKMZNYLSNX-UHFFFAOYSA-N 0.000 description 1
- WILUGQGTJYTAFC-UHFFFAOYSA-N diethyl 2-amino-2-[3-(3-methylphenoxy)propyl]nonanedioate Chemical compound C1(=CC(=CC=C1)OCCCC(C(=O)OCC)(CCCCCCC(=O)OCC)N)C WILUGQGTJYTAFC-UHFFFAOYSA-N 0.000 description 1
- HBIXEDBWHHWCSV-UHFFFAOYSA-N diethyl 2-aminodecanedioate Chemical compound CCOC(=O)CCCCCCCC(N)C(=O)OCC HBIXEDBWHHWCSV-UHFFFAOYSA-N 0.000 description 1
- NWVWLOFHLYLTOD-UHFFFAOYSA-N diethyl 2-aminonon-4-enedioate Chemical compound CCOC(=O)CCCC=CCC(N)C(=O)OCC NWVWLOFHLYLTOD-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- CQMYCPZZIPXILQ-UHFFFAOYSA-N diethyl nonanedioate Chemical compound CCOC(=O)CCCCCCCC(=O)OCC CQMYCPZZIPXILQ-UHFFFAOYSA-N 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 229960001342 dinoprost Drugs 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- DUQHIHDFBZRZKM-UHFFFAOYSA-N ethyl 2-[(3-cyclobutyl-3-hydroxypropyl)amino]-3-[3-(3-ethoxy-3-oxopropyl)phenyl]propanoate Chemical compound C1(CCC1)C(CCNC(C(=O)OCC)CC1=CC(=CC=C1)CCC(=O)OCC)O DUQHIHDFBZRZKM-UHFFFAOYSA-N 0.000 description 1
- BBGKXKOKHFAKNS-UHFFFAOYSA-N ethyl 2-[(3-cyclobutyl-3-oxopropyl)amino]-3-[3-(3-ethoxy-3-oxopropyl)phenyl]propanoate Chemical compound CCOC(=O)CCC1=CC=CC(CC(NCCC(=O)C2CCC2)C(=O)OCC)=C1 BBGKXKOKHFAKNS-UHFFFAOYSA-N 0.000 description 1
- OMLJXYCIWIGHEN-UHFFFAOYSA-N ethyl 2-[(3-cyclohexyl-3-oxopropyl)amino]-3-[3-(3-ethoxy-3-oxopropyl)phenyl]propanoate Chemical compound CCOC(=O)CCC1=CC=CC(CC(NCCC(=O)C2CCCCC2)C(=O)OCC)=C1 OMLJXYCIWIGHEN-UHFFFAOYSA-N 0.000 description 1
- GJUMJJPMVOILQT-UHFFFAOYSA-N ethyl 2-[(3-cyclopentyl-3-hydroxypropyl)amino]-3-[3-(3-ethoxy-3-oxopropyl)phenyl]propanoate Chemical compound C1(CCCC1)C(CCNC(C(=O)OCC)CC1=CC(=CC=C1)CCC(=O)OCC)O GJUMJJPMVOILQT-UHFFFAOYSA-N 0.000 description 1
- WMGRICUDSWBWHB-UHFFFAOYSA-N ethyl 2-[(3-cyclopentyl-3-hydroxypropyl)amino]-6-(2-ethoxy-2-oxoethoxy)hexanoate Chemical compound CCOC(=O)COCCCCC(C(=O)OCC)NCCC(O)C1CCCC1 WMGRICUDSWBWHB-UHFFFAOYSA-N 0.000 description 1
- YWMJQFOHSIWCCI-UHFFFAOYSA-N ethyl 2-[(3-cyclopentyl-3-oxopropyl)amino]-3-[3-(3-ethoxy-3-oxopropyl)phenyl]propanoate Chemical compound CCOC(=O)CCC1=CC=CC(CC(NCCC(=O)C2CCCC2)C(=O)OCC)=C1 YWMJQFOHSIWCCI-UHFFFAOYSA-N 0.000 description 1
- DJMXJCLTBXTETD-UHFFFAOYSA-N ethyl 2-[(3-cyclopentyl-3-oxopropyl)amino]-6-(2-ethoxy-2-oxoethoxy)hexanoate Chemical compound CCOC(=O)COCCCCC(C(=O)OCC)NCCC(=O)C1CCCC1 DJMXJCLTBXTETD-UHFFFAOYSA-N 0.000 description 1
- IWPQQEFLLHFOCF-UHFFFAOYSA-N ethyl 2-[(7-ethoxy-7-oxoheptyl)amino]decanoate Chemical compound CCCCCCCCC(C(=O)OCC)NCCCCCCC(=O)OCC IWPQQEFLLHFOCF-UHFFFAOYSA-N 0.000 description 1
- HFIGMKDWQUAIMO-UHFFFAOYSA-N ethyl 2-[3-(chloromethyl)phenoxy]acetate Chemical compound CCOC(=O)COC1=CC=CC(CCl)=C1 HFIGMKDWQUAIMO-UHFFFAOYSA-N 0.000 description 1
- KKBJRHWETQXPML-UHFFFAOYSA-N ethyl 2-amino-3-[3-(2-ethoxy-2-oxoethoxy)phenyl]propanoate Chemical compound CCOC(=O)COC1=CC=CC(CC(N)C(=O)OCC)=C1 KKBJRHWETQXPML-UHFFFAOYSA-N 0.000 description 1
- NPLFSFDTGSFRKJ-UHFFFAOYSA-N ethyl 2-amino-3-[3-(3-ethoxy-3-oxopropyl)phenyl]propanoate Chemical compound CCOC(=O)CCC1=CC=CC(CC(N)C(=O)OCC)=C1 NPLFSFDTGSFRKJ-UHFFFAOYSA-N 0.000 description 1
- XSTSHOZESJIYPK-UHFFFAOYSA-N ethyl 2-aminodecanoate Chemical compound CCCCCCCCC(N)C(=O)OCC XSTSHOZESJIYPK-UHFFFAOYSA-N 0.000 description 1
- GMBCCEOJUWMBPF-UHFFFAOYSA-N ethyl 2-formamidoacetate Chemical compound CCOC(=O)CNC=O GMBCCEOJUWMBPF-UHFFFAOYSA-N 0.000 description 1
- UGBXTARIWNGXAI-UHFFFAOYSA-N ethyl 3-[3-(2-ethoxy-2-oxoethoxy)phenyl]-2-(3-hydroxyoctylamino)propanoate Chemical compound CCCCCC(O)CCNC(C(=O)OCC)CC1=CC=CC(OCC(=O)OCC)=C1 UGBXTARIWNGXAI-UHFFFAOYSA-N 0.000 description 1
- KJEFVQQKGFWXAZ-UHFFFAOYSA-N ethyl 3-[3-(2-ethoxy-2-oxoethoxy)phenyl]-2-(3-oxooctylamino)propanoate Chemical compound CCCCCC(=O)CCNC(C(=O)OCC)CC1=CC=CC(OCC(=O)OCC)=C1 KJEFVQQKGFWXAZ-UHFFFAOYSA-N 0.000 description 1
- CQNHRAGQPQGULZ-UHFFFAOYSA-N ethyl 3-[3-(2-ethoxy-2-oxoethoxy)phenyl]-2-[(3-hydroxy-4,4-dimethylpentyl)amino]propanoate Chemical compound CCOC(=O)COC1=CC=CC(CC(NCCC(O)C(C)(C)C)C(=O)OCC)=C1 CQNHRAGQPQGULZ-UHFFFAOYSA-N 0.000 description 1
- ZIYLMJPIHPJHTN-UHFFFAOYSA-N ethyl 3-[3-(3-ethoxy-3-oxopropyl)phenyl]-2-(3-hydroxyoctylamino)propanoate Chemical compound OC(CCNC(C(=O)OCC)CC1=CC(=CC=C1)CCC(=O)OCC)CCCCC ZIYLMJPIHPJHTN-UHFFFAOYSA-N 0.000 description 1
- RDCOGZJEYGPUAX-UHFFFAOYSA-N ethyl 3-[3-(3-ethoxy-3-oxopropyl)phenyl]-2-(3-oxooctylamino)propanoate Chemical compound CCCCCC(=O)CCNC(C(=O)OCC)CC1=CC=CC(CCC(=O)OCC)=C1 RDCOGZJEYGPUAX-UHFFFAOYSA-N 0.000 description 1
- KSYUKHAFSKHNKU-UHFFFAOYSA-N ethyl 6-(2-ethoxy-2-oxoethoxy)-2-(3-hydroxyoctylamino)hexanoate Chemical compound CCCCCC(O)CCNC(C(=O)OCC)CCCCOCC(=O)OCC KSYUKHAFSKHNKU-UHFFFAOYSA-N 0.000 description 1
- UHMRYUZCEQOICZ-UHFFFAOYSA-N ethyl 6-(2-ethoxy-2-oxoethoxy)-2-(3-oxooctylamino)hexanoate Chemical compound CCCCCC(=O)CCNC(C(=O)OCC)CCCCOCC(=O)OCC UHMRYUZCEQOICZ-UHFFFAOYSA-N 0.000 description 1
- CINVJQRLJFYIQW-UHFFFAOYSA-N ethyl 7-(3-butyl-5-octyl-2,4-dioxoimidazolidin-1-yl)heptanoate Chemical compound CCCCCCCCC1N(CCCCCCC(=O)OCC)C(=O)N(CCCC)C1=O CINVJQRLJFYIQW-UHFFFAOYSA-N 0.000 description 1
- LVLVGCVVTGBMLQ-UHFFFAOYSA-N ethyl 7-(3-methyl-5-octyl-2,4-dioxoimidazolidin-1-yl)heptanoate Chemical compound CCCCCCCCC1N(CCCCCCC(=O)OCC)C(=O)N(C)C1=O LVLVGCVVTGBMLQ-UHFFFAOYSA-N 0.000 description 1
- GFSKDNLWYHCQGB-UHFFFAOYSA-N ethyl 7-[2,5-dioxo-3-(5-phenylpentyl)imidazolidin-4-yl]heptanoate Chemical compound O=C1NC(=O)C(CCCCCCC(=O)OCC)N1CCCCCC1=CC=CC=C1 GFSKDNLWYHCQGB-UHFFFAOYSA-N 0.000 description 1
- VKRLCNBNMMXEPM-UHFFFAOYSA-N ethyl 7-[5-(dibutoxymethyl)-2,4-dioxoimidazolidin-1-yl]heptanoate Chemical compound CCCCOC(OCCCC)C1N(CCCCCCC(=O)OCC)C(=O)NC1=O VKRLCNBNMMXEPM-UHFFFAOYSA-N 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
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- 239000008273 gelatin Substances 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000009499 grossing Methods 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
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- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- XWCQLLDGXBLGMD-UHFFFAOYSA-M magnesium;pentane;bromide Chemical compound [Mg+2].[Br-].CCCC[CH2-] XWCQLLDGXBLGMD-UHFFFAOYSA-M 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 201000005857 malignant hypertension Diseases 0.000 description 1
- 150000002690 malonic acid derivatives Chemical class 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- HZAXFHJVJLSVMW-UHFFFAOYSA-N monoethanolamine hydrochloride Natural products NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
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- 239000007800 oxidant agent Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- UCUUFSAXZMGPGH-UHFFFAOYSA-N penta-1,4-dien-3-one Chemical class C=CC(=O)C=C UCUUFSAXZMGPGH-UHFFFAOYSA-N 0.000 description 1
- ANRIQLNBZQLTFV-DZUOILHNSA-N pentagastrin Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1[C]2C=CC=CC2=NC=1)NC(=O)CCNC(=O)OC(C)(C)C)CCSC)C(N)=O)C1=CC=CC=C1 ANRIQLNBZQLTFV-DZUOILHNSA-N 0.000 description 1
- 229960000444 pentagastrin Drugs 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
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- 210000002381 plasma Anatomy 0.000 description 1
- 210000004623 platelet-rich plasma Anatomy 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
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- 238000009877 rendering Methods 0.000 description 1
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- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
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- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000011477 surgical intervention Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- CXDQUNGRRMTMPE-UHFFFAOYSA-N tert-butyl 3-[3-(bromomethyl)phenyl]propanoate Chemical compound CC(C)(C)OC(=O)CCC1=CC=CC(CBr)=C1 CXDQUNGRRMTMPE-UHFFFAOYSA-N 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
- 125000004187 tetrahydropyran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
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- 229940116362 tragacanth Drugs 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
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- 239000003071 vasodilator agent Substances 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/10—Oxygen atoms
- C07D309/12—Oxygen atoms only hydrogen atoms and one oxygen atom directly attached to ring carbon atoms, e.g. tetrahydropyranyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or 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 to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or 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 to ring carbon atoms
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
- C07D233/78—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or 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 to ring carbon atoms
- C07D233/86—Oxygen and sulfur atoms, e.g. thiohydantoin
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB2287776 | 1976-06-03 | ||
| GB5034076 | 1976-12-02 | ||
| GB1214577 | 1977-03-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HU183046B true HU183046B (en) | 1984-04-28 |
Family
ID=27256793
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU77WE560A HU183046B (en) | 1976-06-03 | 1977-06-02 | Process for producing hydanthoine derivatives |
Country Status (12)
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1602188A (en) * | 1977-12-01 | 1981-11-11 | Wellcome Found | Hydantoin derivatives |
| DK391678A (da) * | 1977-09-05 | 1979-03-06 | Wellcome Found | Nitrogen-heterocycliske forbindelser fremgangsmaade til deres fremstilling samt deres anvendelse |
| AU531493B2 (en) * | 1977-12-01 | 1983-08-25 | The Wellcome Foundation Limited | Thiohydantion derivatives |
| DE2963795D1 (en) * | 1978-01-23 | 1982-11-11 | Beecham Group Plc | Hydantoins and thiohydantoins, method for their preparation and pharmaceutical compositions containing them |
| EP0004723A1 (en) * | 1978-03-30 | 1979-10-17 | Beecham Group Plc | Deoxyhydantoins, processes for their preparation and pharmaceutical compositions containing them |
| GB1599740A (en) * | 1978-05-31 | 1981-10-07 | Wellcome Found | Hydantoin derivatives |
| AU4806979A (en) * | 1978-06-15 | 1979-12-20 | Beecham Group Limited | 1,2,4 triazole derivatives |
| EP0006352A1 (en) * | 1978-06-15 | 1980-01-09 | Beecham Group Plc | Hydantoins and thiohydantoins, process for their preparation and pharmaceutical compositions containing them |
| IL57504A0 (en) * | 1978-06-15 | 1979-10-31 | Beecham Group Ltd | Prostagandin analogues,their preparation and pharmaceutical compositions containing |
| AU4778279A (en) * | 1978-06-15 | 1979-12-20 | Beecham Group Limited | Prostaglandin analogues |
| IL59065A0 (en) * | 1979-01-18 | 1980-05-30 | Beecham Group Ltd | Hydantoin derivatives,their preparation pharmaceutical compositons containing them |
| EP0019223A1 (en) * | 1979-05-09 | 1980-11-26 | The Wellcome Foundation Limited | Optically active hydantoin derivatives, their synthesis, pharmaceutical formulations containing them, and intermediates |
| US4684735A (en) * | 1985-07-01 | 1987-08-04 | Stauffer Chemical Company | Promotion of raney nickel hydrogenation catalyst |
| JP3022878U (ja) * | 1995-08-18 | 1996-04-02 | 有限会社春江加工 | ミニディスク用ケース |
| PL370515A1 (en) | 2001-11-30 | 2005-05-30 | Eli Lilly And Company | Peroxisome proliferator activated receptor agonists |
| EP1631355B1 (en) * | 2003-06-06 | 2014-08-13 | Allergan, Inc. | Piperidinyl prostaglandin e analogs |
| US7179820B2 (en) * | 2003-06-06 | 2007-02-20 | Allergan, Inc. | Piperidinyl prostaglandin E analogs |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1524818A (en) * | 1974-11-29 | 1978-09-13 | Beecham Group Ltd | 12-azaprostaglandins |
-
1977
- 1977-06-02 CA CA000280455A patent/CA1176261A/en not_active Expired
- 1977-06-02 DE DE19772724948 patent/DE2724948A1/de not_active Ceased
- 1977-06-02 FR FR7716849A patent/FR2362839A1/fr active Granted
- 1977-06-02 ES ES459412A patent/ES459412A1/es not_active Expired
- 1977-06-02 NZ NZ184281A patent/NZ184281A/xx unknown
- 1977-06-02 SE SE7706428A patent/SE446336B/xx unknown
- 1977-06-02 DK DK244577A patent/DK244577A/da not_active Application Discontinuation
- 1977-06-02 HU HU77WE560A patent/HU183046B/hu unknown
- 1977-06-02 CH CH679677A patent/CH645631A5/de not_active IP Right Cessation
- 1977-06-02 NL NL7706064A patent/NL7706064A/xx not_active Application Discontinuation
- 1977-06-02 FI FI771763A patent/FI71930C/fi not_active IP Right Cessation
- 1977-06-02 JP JP6525277A patent/JPS52151168A/ja active Granted
-
1978
- 1978-06-01 ES ES470428A patent/ES470428A1/es not_active Expired
-
1979
- 1979-02-28 ES ES478156A patent/ES478156A1/es not_active Expired
- 1979-06-28 ES ES482010A patent/ES482010A1/es not_active Expired
-
1980
- 1980-03-25 ES ES489883A patent/ES8103057A1/es not_active Expired
-
1982
- 1982-05-19 SE SE8203161A patent/SE8203161L/sv not_active Application Discontinuation
-
1984
- 1984-02-07 CH CH576/84A patent/CH647511A5/de not_active IP Right Cessation
- 1984-02-07 CH CH57784A patent/CH646426A5/de not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| CH646426A5 (en) | 1984-11-30 |
| ES482010A1 (es) | 1980-08-16 |
| JPS6222986B2 (enrdf_load_stackoverflow) | 1987-05-20 |
| DK244577A (da) | 1977-12-04 |
| SE8203161L (sv) | 1982-05-19 |
| CA1176261A (en) | 1984-10-16 |
| ES459412A1 (es) | 1978-11-01 |
| FI71930B (fi) | 1986-11-28 |
| ES470428A1 (es) | 1979-09-01 |
| CH647511A5 (en) | 1985-01-31 |
| NL7706064A (nl) | 1977-12-06 |
| SE7706428L (sv) | 1977-12-04 |
| SE446336B (sv) | 1986-09-01 |
| FR2362839A1 (fr) | 1978-03-24 |
| CH645631A5 (en) | 1984-10-15 |
| ES489883A0 (es) | 1981-02-16 |
| ES8103057A1 (es) | 1981-02-16 |
| DE2724948A1 (de) | 1977-12-15 |
| ES478156A1 (es) | 1979-11-01 |
| JPS52151168A (en) | 1977-12-15 |
| FI771763A7 (fi) | 1977-12-04 |
| FI71930C (fi) | 1987-03-09 |
| NZ184281A (en) | 1980-04-28 |
| FR2362839B1 (enrdf_load_stackoverflow) | 1980-02-01 |
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