NO910187L - Fremgangsmaate for fremstilling av indolsubstituerte, heteroaromatiske femringforbindelser. - Google Patents

Fremgangsmaate for fremstilling av indolsubstituerte, heteroaromatiske femringforbindelser.

Info

Publication number: NO910187L
Authority: NO; Norway
Prior art keywords: indol; ethylamine; oxadiazol; dimethyl; ylmethyl
Prior art date: 1990-01-17

Application number

NO91910187A

Other languages

English (en)

Norwegian (no)

Other versions

NO910187D0 (no

Inventor

Raymond Baker

Austin J Reeve

Leslie J Street

Original Assignee

Merck Sharp & Dohme

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1990-01-17

Filing date

1991-01-16

Publication date

1991-07-18

1990-01-17 Priority claimed from GB909001018A external-priority patent/GB9001018D0/en

1990-04-17 Priority claimed from GB909008587A external-priority patent/GB9008587D0/en

1991-01-16 Application filed by Merck Sharp & Dohme filed Critical Merck Sharp & Dohme

1991-01-16 Publication of NO910187D0 publication Critical patent/NO910187D0/no

1991-07-18 Publication of NO910187L publication Critical patent/NO910187L/no

Links

238000000034 method Methods 0.000 title claims description 61
238000002360 preparation method Methods 0.000 title claims description 23
VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical class OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 title 1
239000000556 agonist Substances 0.000 claims abstract description 10
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 290
150000001875 compounds Chemical class 0.000 claims description 104
150000003839 salts Chemical class 0.000 claims description 53
229910052739 hydrogen Inorganic materials 0.000 claims description 48
239000001257 hydrogen Substances 0.000 claims description 46
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 25
150000002430 hydrocarbons Chemical class 0.000 claims description 20
239000004215 Carbon black (E152) Substances 0.000 claims description 18
229930195733 hydrocarbon Natural products 0.000 claims description 18
229910052757 nitrogen Inorganic materials 0.000 claims description 18
150000002431 hydrogen Chemical class 0.000 claims description 17
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 16
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 16
239000001301 oxygen Substances 0.000 claims description 16
229910052760 oxygen Inorganic materials 0.000 claims description 16
125000000217 alkyl group Chemical group 0.000 claims description 15
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
239000005864 Sulphur Substances 0.000 claims description 13
238000006243 chemical reaction Methods 0.000 claims description 13
239000000651 prodrug Substances 0.000 claims description 13
229940002612 prodrug Drugs 0.000 claims description 13
125000002947 alkylene group Chemical group 0.000 claims description 12
229910052736 halogen Inorganic materials 0.000 claims description 12
150000002367 halogens Chemical class 0.000 claims description 12
239000003153 chemical reaction reagent Substances 0.000 claims description 10
125000001072 heteroaryl group Chemical group 0.000 claims description 10
125000004432 carbon atom Chemical group C* 0.000 claims description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
150000001450 anions Chemical class 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
229910052799 carbon Inorganic materials 0.000 claims description 7
239000003814 drug Substances 0.000 claims description 7
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
238000010561 standard procedure Methods 0.000 claims description 7
239000002243 precursor Substances 0.000 claims description 6
125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 5
BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical compound C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 claims description 4
LUPGHCUZARGGAG-UHFFFAOYSA-N 5-[3-(1-methylpiperidin-4-yl)-1h-indol-5-yl]-1,2,4-oxadiazol-3-amine Chemical compound C1CN(C)CCC1C1=CNC2=CC=C(C=3ON=C(N)N=3)C=C12 LUPGHCUZARGGAG-UHFFFAOYSA-N 0.000 claims description 4
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
238000007126 N-alkylation reaction Methods 0.000 claims description 4
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
239000003937 drug carrier Substances 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
CQXMPRCDEFWGEN-UHFFFAOYSA-N n-[4-[[5-[[3-(1-methylpiperidin-4-yl)-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]methyl]phenyl]methanesulfonamide Chemical compound C1CN(C)CCC1C(C1=C2)=CNC1=CC=C2CC1=NC(CC=2C=CC(NS(C)(=O)=O)=CC=2)=NO1 CQXMPRCDEFWGEN-UHFFFAOYSA-N 0.000 claims description 4
230000008569 process Effects 0.000 claims description 4
229910052717 sulfur Inorganic materials 0.000 claims description 4
SFVYCZXNJHFLNP-UHFFFAOYSA-N 5-[[3-(1-methylpiperidin-4-yl)-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-amine Chemical compound C1CN(C)CCC1C(C1=C2)=CNC1=CC=C2CC1=NC(N)=NO1 SFVYCZXNJHFLNP-UHFFFAOYSA-N 0.000 claims description 3
150000001408 amides Chemical class 0.000 claims description 3
125000006575 electron-withdrawing group Chemical group 0.000 claims description 3
125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 3
238000004519 manufacturing process Methods 0.000 claims description 3
150000002825 nitriles Chemical class 0.000 claims description 3
125000004430 oxygen atom Chemical group O* 0.000 claims description 3
239000011593 sulfur Chemical group 0.000 claims description 3
MPSSFKDXUNOCMC-UHFFFAOYSA-N 1-[4-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]phenyl]-n-methylmethanesulfonamide Chemical compound C1=CC(CS(=O)(=O)NC)=CC=C1C1=NOC(CC=2C=C3C(CCN(C)C)=CNC3=CC=2)=N1 MPSSFKDXUNOCMC-UHFFFAOYSA-N 0.000 claims description 2
VOQRRSFSAOOBOA-UHFFFAOYSA-N 1-[4-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]piperazin-1-yl]ethanone Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(ON=1)=NC=1N1CCN(C(C)=O)CC1 VOQRRSFSAOOBOA-UHFFFAOYSA-N 0.000 claims description 2
IMBUWDPVLHNYMC-UHFFFAOYSA-N 1-tert-butyl-3-[2-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]ethyl]urea Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC1=NC(CCNC(=O)NC(C)(C)C)=NO1 IMBUWDPVLHNYMC-UHFFFAOYSA-N 0.000 claims description 2
PGGBQIXTFVYDAU-UHFFFAOYSA-N 2-[5-(3-benzyl-1,2,4-oxadiazol-5-yl)-1h-indol-3-yl]-n,n-dimethylethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1C(ON=1)=NC=1CC1=CC=CC=C1 PGGBQIXTFVYDAU-UHFFFAOYSA-N 0.000 claims description 2
LSUAPUGYEULDQN-UHFFFAOYSA-N 2-[5-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1C(ON=1)=NC=1C1CC1 LSUAPUGYEULDQN-UHFFFAOYSA-N 0.000 claims description 2
RGZGVSMFNKBYQY-UHFFFAOYSA-N 2-[5-(3-ethyl-1,2,4-oxadiazol-5-yl)-1h-indol-3-yl]ethanamine Chemical compound CCC1=NOC(C=2C=C3C(CCN)=CNC3=CC=2)=N1 RGZGVSMFNKBYQY-UHFFFAOYSA-N 0.000 claims description 2
FDPKHZFSVDEEFR-UHFFFAOYSA-N 2-[5-(3-phenyl-1,2,4-oxadiazol-5-yl)-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1C(ON=1)=NC=1C1=CC=CC=C1 FDPKHZFSVDEEFR-UHFFFAOYSA-N 0.000 claims description 2
PKBMHXUBNRYPMY-UHFFFAOYSA-N 2-[5-(5-benzyl-1,2,4-oxadiazol-3-yl)-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1C(N=1)=NOC=1CC1=CC=CC=C1 PKBMHXUBNRYPMY-UHFFFAOYSA-N 0.000 claims description 2
CXOIDKMODXFHCK-UHFFFAOYSA-N 2-[5-(5-methyl-1,2,4-oxadiazol-3-yl)-1h-indol-3-yl]ethanamine Chemical compound O1C(C)=NC(C=2C=C3C(CCN)=CNC3=CC=2)=N1 CXOIDKMODXFHCK-UHFFFAOYSA-N 0.000 claims description 2
NAWLGGCQEZUAJT-UHFFFAOYSA-N 2-[5-[(3-benzyl-1,2,4-oxadiazol-5-yl)methyl]-1h-indol-3-yl]-n,n-dimethylethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(ON=1)=NC=1CC1=CC=CC=C1 NAWLGGCQEZUAJT-UHFFFAOYSA-N 0.000 claims description 2
NHIRYTRRCNWYFT-UHFFFAOYSA-N 2-[5-[(3-benzyl-1,2,4-oxadiazol-5-yl)methyl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1CC(ON=1)=NC=1CC1=CC=CC=C1 NHIRYTRRCNWYFT-UHFFFAOYSA-N 0.000 claims description 2
PHNPQGKBBZNFFK-UHFFFAOYSA-N 2-[5-[(3-naphthalen-1-yl-1,2,4-oxadiazol-5-yl)methyl]-1h-indol-3-yl]ethanamine Chemical compound C1=CC=C2C(C=3N=C(ON=3)CC3=CC=C4NC=C(C4=C3)CCN)=CC=CC2=C1 PHNPQGKBBZNFFK-UHFFFAOYSA-N 0.000 claims description 2
DUCJXOYLGYOOQB-UHFFFAOYSA-N 2-[5-[(3-phenyl-1,2,4-oxadiazol-5-yl)methyl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1CC(ON=1)=NC=1C1=CC=CC=C1 DUCJXOYLGYOOQB-UHFFFAOYSA-N 0.000 claims description 2
LCMKXAZDWQVTEJ-UHFFFAOYSA-N 2-[5-[(5-benzyl-1,2,4-oxadiazol-3-yl)methyl]-1h-indol-3-yl]-n,n-dimethylethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(N=1)=NOC=1CC1=CC=CC=C1 LCMKXAZDWQVTEJ-UHFFFAOYSA-N 0.000 claims description 2
IEJZWIUEFHBSOU-UHFFFAOYSA-N 2-[5-[(5-benzyl-1,2,4-oxadiazol-3-yl)methyl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1CC(N=1)=NOC=1CC1=CC=CC=C1 IEJZWIUEFHBSOU-UHFFFAOYSA-N 0.000 claims description 2
FEBZQFFWELBCOG-UHFFFAOYSA-N 2-[5-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]-1h-indol-3-yl]ethanamine Chemical compound O1C(C)=NC(CC=2C=C3C(CCN)=CNC3=CC=2)=N1 FEBZQFFWELBCOG-UHFFFAOYSA-N 0.000 claims description 2
KYUWHJMADOFUBT-UHFFFAOYSA-N 2-[5-[2-(3-benzyl-1,2,4-oxadiazol-5-yl)ethyl]-1h-indol-3-yl]-n,n-dimethylethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CCC(ON=1)=NC=1CC1=CC=CC=C1 KYUWHJMADOFUBT-UHFFFAOYSA-N 0.000 claims description 2
SCFZGOGBRPRNPV-UHFFFAOYSA-N 2-[5-[2-(3-benzyl-1,2,4-oxadiazol-5-yl)ethyl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1CCC(ON=1)=NC=1CC1=CC=CC=C1 SCFZGOGBRPRNPV-UHFFFAOYSA-N 0.000 claims description 2
WBZVRZYJUXWCRS-UHFFFAOYSA-N 2-[5-[2-[3-[(4-methoxyphenyl)methyl]-1,2,4-oxadiazol-5-yl]ethyl]-1h-indol-3-yl]ethanamine Chemical compound C1=CC(OC)=CC=C1CC1=NOC(CCC=2C=C3C(CCN)=CNC3=CC=2)=N1 WBZVRZYJUXWCRS-UHFFFAOYSA-N 0.000 claims description 2
OVCUAXXAZOYIFP-UHFFFAOYSA-N 2-[5-[3-(2-phenylethyl)-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1C(ON=1)=NC=1CCC1=CC=CC=C1 OVCUAXXAZOYIFP-UHFFFAOYSA-N 0.000 claims description 2
JTBDYCCVUAQYMO-UHFFFAOYSA-N 2-[5-[3-(3-benzyl-1,2,4-oxadiazol-5-yl)propyl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1CCCC(ON=1)=NC=1CC1=CC=CC=C1 JTBDYCCVUAQYMO-UHFFFAOYSA-N 0.000 claims description 2
HSJQSSUOMJZTMK-UHFFFAOYSA-N 2-[5-[3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)propyl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1CCCC(ON=1)=NC=1C1CC1 HSJQSSUOMJZTMK-UHFFFAOYSA-N 0.000 claims description 2
FZVHHUSZLLUIQC-UHFFFAOYSA-N 2-[5-[3-(3-methyl-1,2,4-oxadiazol-5-yl)propyl]-1h-indol-3-yl]ethanamine Chemical compound CC1=NOC(CCCC=2C=C3C(CCN)=CNC3=CC=2)=N1 FZVHHUSZLLUIQC-UHFFFAOYSA-N 0.000 claims description 2
NJDHGOXGGNXAKI-UHFFFAOYSA-N 2-[5-[3-(3-phenylpropyl)-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1C(ON=1)=NC=1CCCC1=CC=CC=C1 NJDHGOXGGNXAKI-UHFFFAOYSA-N 0.000 claims description 2
NPFRJMBPAZUERU-UHFFFAOYSA-N 2-[5-[3-(aminomethyl)-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1C1=NC(CN)=NO1 NPFRJMBPAZUERU-UHFFFAOYSA-N 0.000 claims description 2
ZBVQOYFWQDPVBU-UHFFFAOYSA-N 2-[5-[3-(methoxymethyl)-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]ethanamine Chemical compound COCC1=NOC(C=2C=C3C(CCN)=CNC3=CC=2)=N1 ZBVQOYFWQDPVBU-UHFFFAOYSA-N 0.000 claims description 2
YSBPVPHNOKZUKE-UHFFFAOYSA-N 2-[5-[3-[(2-methoxyphenyl)methyl]-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]-n,n-dimethylethanamine Chemical compound COC1=CC=CC=C1CC1=NOC(C=2C=C3C(CCN(C)C)=CNC3=CC=2)=N1 YSBPVPHNOKZUKE-UHFFFAOYSA-N 0.000 claims description 2
TWZLBEKNARALNH-UHFFFAOYSA-N 2-[5-[3-[(2-methoxyphenyl)methyl]-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]ethanamine Chemical compound COC1=CC=CC=C1CC1=NOC(C=2C=C3C(CCN)=CNC3=CC=2)=N1 TWZLBEKNARALNH-UHFFFAOYSA-N 0.000 claims description 2
XYSVDZDGDYOEQP-UHFFFAOYSA-N 2-[5-[3-[(3-methoxyphenyl)methyl]-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]ethanamine Chemical compound COC1=CC=CC(CC=2N=C(ON=2)C=2C=C3C(CCN)=CNC3=CC=2)=C1 XYSVDZDGDYOEQP-UHFFFAOYSA-N 0.000 claims description 2
LJFAPKDDNIXRTD-UHFFFAOYSA-N 2-[5-[3-[(4-methylsulfonylphenyl)methyl]-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]ethanamine Chemical compound C1=CC(S(=O)(=O)C)=CC=C1CC1=NOC(C=2C=C3C(CCN)=CNC3=CC=2)=N1 LJFAPKDDNIXRTD-UHFFFAOYSA-N 0.000 claims description 2
NISBLVDKMALBFA-UHFFFAOYSA-N 2-[5-[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]-1,2,4-oxadiazol-3-yl]ethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1C1=NC(CCN)=NO1 NISBLVDKMALBFA-UHFFFAOYSA-N 0.000 claims description 2
MVCDNIJSCRIQST-UHFFFAOYSA-N 2-[5-[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]-1,2,4-oxadiazol-3-yl]ethylurea Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1C1=NC(CCNC(N)=O)=NO1 MVCDNIJSCRIQST-UHFFFAOYSA-N 0.000 claims description 2
RJQWPRYMOKNGFR-UHFFFAOYSA-N 2-[5-[3-[[4-(trifluoromethyl)phenyl]methyl]-1,2,4-oxadiazol-5-yl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN)=CNC2=CC=C1C(ON=1)=NC=1CC1=CC=C(C(F)(F)F)C=C1 RJQWPRYMOKNGFR-UHFFFAOYSA-N 0.000 claims description 2
AWKHPNLMHRTDEQ-UHFFFAOYSA-N 2-[5-[[3-(aminomethyl)-1,2,4-oxadiazol-5-yl]methyl]-1h-indol-3-yl]-n,n-dimethylethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC1=NC(CN)=NO1 AWKHPNLMHRTDEQ-UHFFFAOYSA-N 0.000 claims description 2
NROOPDGYHXQHJT-UHFFFAOYSA-N 2-[5-[[3-[(2-methoxyphenyl)methyl]-1,2,4-oxadiazol-5-yl]methyl]-1h-indol-3-yl]ethanamine Chemical compound COC1=CC=CC=C1CC1=NOC(CC=2C=C3C(CCN)=CNC3=CC=2)=N1 NROOPDGYHXQHJT-UHFFFAOYSA-N 0.000 claims description 2
JCZWGZKYZYBIIG-UHFFFAOYSA-N 2-[5-[[3-[(6-methoxypyridin-3-yl)methyl]-1,2,4-oxadiazol-5-yl]methyl]-1h-indol-3-yl]-n,n-dimethylethanamine Chemical compound C1=NC(OC)=CC=C1CC1=NOC(CC=2C=C3C(CCN(C)C)=CNC3=CC=2)=N1 JCZWGZKYZYBIIG-UHFFFAOYSA-N 0.000 claims description 2
KFICIUZZUVCGKV-UHFFFAOYSA-N 2-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]acetamide Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC1=NC(CC(N)=O)=NO1 KFICIUZZUVCGKV-UHFFFAOYSA-N 0.000 claims description 2
QPFQAMAECLOAMI-UHFFFAOYSA-N 2-[5-[[3-[4-(benzenesulfonyl)piperazin-1-yl]-1,2,4-oxadiazol-5-yl]methyl]-1h-indol-3-yl]-n,n-dimethylethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(ON=1)=NC=1N(CC1)CCN1S(=O)(=O)C1=CC=CC=C1 QPFQAMAECLOAMI-UHFFFAOYSA-N 0.000 claims description 2
PRTCSIDNPRTJHA-UHFFFAOYSA-N 4-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]-n-methylbenzamide Chemical compound C1=CC(C(=O)NC)=CC=C1C1=NOC(CC=2C=C3C(CCN(C)C)=CNC3=CC=2)=N1 PRTCSIDNPRTJHA-UHFFFAOYSA-N 0.000 claims description 2
SEQRRDDBAQJBTP-UHFFFAOYSA-N 4-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]-n-methylpiperazine-1-carboxamide Chemical compound C1CN(C(=O)NC)CCN1C1=NOC(CC=2C=C3C(CCN(C)C)=CNC3=CC=2)=N1 SEQRRDDBAQJBTP-UHFFFAOYSA-N 0.000 claims description 2
PXRPVIKQMBGGBX-UHFFFAOYSA-N 4-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]benzamide Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(ON=1)=NC=1C1=CC=C(C(N)=O)C=C1 PXRPVIKQMBGGBX-UHFFFAOYSA-N 0.000 claims description 2
KPULPRRFVSBRHP-UHFFFAOYSA-N 4-[[5-[3-(2-aminoethyl)-1h-indol-5-yl]-1,2,4-oxadiazol-3-yl]methyl]-n-methylbenzamide Chemical compound C1=CC(C(=O)NC)=CC=C1CC1=NOC(C=2C=C3C(CCN)=CNC3=CC=2)=N1 KPULPRRFVSBRHP-UHFFFAOYSA-N 0.000 claims description 2
HUZDZSZTHSEWGI-UHFFFAOYSA-N 4-[[5-[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]-1,2,4-oxadiazol-3-yl]methyl]-n-methylbenzamide Chemical compound C1=CC(C(=O)NC)=CC=C1CC1=NOC(C=2C=C3C(CCN(C)C)=CNC3=CC=2)=N1 HUZDZSZTHSEWGI-UHFFFAOYSA-N 0.000 claims description 2
JUIAOPBIMMONAG-UHFFFAOYSA-N 4-[[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]methyl]-n-methylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)NC)=CC=C1CC1=NOC(CC=2C=C3C(CCN(C)C)=CNC3=CC=2)=N1 JUIAOPBIMMONAG-UHFFFAOYSA-N 0.000 claims description 2
RZROEUJADIXUOQ-UHFFFAOYSA-N 4-[[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]methyl]benzamide Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(ON=1)=NC=1CC1=CC=C(C(N)=O)C=C1 RZROEUJADIXUOQ-UHFFFAOYSA-N 0.000 claims description 2
QMDXYKSJNYUFML-UHFFFAOYSA-N 5-[2-[3-(2-aminoethyl)-1h-indol-5-yl]ethyl]-n,n-dimethyl-1,2,4-oxadiazol-3-amine Chemical compound CN(C)C1=NOC(CCC=2C=C3C(CCN)=CNC3=CC=2)=N1 QMDXYKSJNYUFML-UHFFFAOYSA-N 0.000 claims description 2
CVSXIEGQYNXATH-UHFFFAOYSA-N 5-[2-[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]ethyl]-1,2,4-oxadiazol-3-amine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CCC1=NC(N)=NO1 CVSXIEGQYNXATH-UHFFFAOYSA-N 0.000 claims description 2
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ODWWYPWUUNAYNE-UHFFFAOYSA-N 5-[[3-[2-(methylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-amine Chemical compound C1=C2C(CCNC)=CNC2=CC=C1CC1=NC(N)=NO1 ODWWYPWUUNAYNE-UHFFFAOYSA-N 0.000 claims description 2
HLASJCWOXFJYMI-UHFFFAOYSA-N [4-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]phenyl]methanesulfonamide Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(ON=1)=NC=1C1=CC=C(CS(N)(=O)=O)C=C1 HLASJCWOXFJYMI-UHFFFAOYSA-N 0.000 claims description 2
TYZGYMTXECGHII-UHFFFAOYSA-N [4-[[5-[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]-1,2,4-oxadiazol-3-yl]methyl]phenyl]urea Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1C(ON=1)=NC=1CC1=CC=C(NC(N)=O)C=C1 TYZGYMTXECGHII-UHFFFAOYSA-N 0.000 claims description 2
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JDJSHFZUPXMVFS-UHFFFAOYSA-N [5-[[3-(2-aminoethyl)-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]-(azetidin-1-yl)methanone Chemical compound C1=C2C(CCN)=CNC2=CC=C1CC(ON=1)=NC=1C(=O)N1CCC1 JDJSHFZUPXMVFS-UHFFFAOYSA-N 0.000 claims description 2
IFUOITWMTIXSAZ-UHFFFAOYSA-N [5-[[3-(2-aminoethyl)-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]-pyrrolidin-1-ylmethanone Chemical compound C1=C2C(CCN)=CNC2=CC=C1CC(ON=1)=NC=1C(=O)N1CCCC1 IFUOITWMTIXSAZ-UHFFFAOYSA-N 0.000 claims description 2
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125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
150000001728 carbonyl compounds Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
229920002301 cellulose acetate Polymers 0.000 description 1
229960000541 cetyl alcohol Drugs 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
238000000576 coating method Methods 0.000 description 1
239000003240 coconut oil Substances 0.000 description 1
235000019864 coconut oil Nutrition 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
230000008602 contraction Effects 0.000 description 1
235000012343 cottonseed oil Nutrition 0.000 description 1
239000002385 cottonseed oil Substances 0.000 description 1
238000006352 cycloaddition reaction Methods 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
239000012024 dehydrating agents‎ Substances 0.000 description 1
230000003111 delayed effect Effects 0.000 description 1
238000013461 design Methods 0.000 description 1
FHIVAFMUCKRCQO-UHFFFAOYSA-N diazinon Chemical compound CCOP(=S)(OCC)OC1=CC(C)=NC(C(C)C)=N1 FHIVAFMUCKRCQO-UHFFFAOYSA-N 0.000 description 1
125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
125000004987 dibenzofuryl group Chemical group C1(=CC=CC=2OC3=C(C21)C=CC=C3)* 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
NSNHWTBQMQIDCF-UHFFFAOYSA-N dihydrate;hydrochloride Chemical compound O.O.Cl NSNHWTBQMQIDCF-UHFFFAOYSA-N 0.000 description 1
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
210000001198 duodenum Anatomy 0.000 description 1
230000004064 dysfunction Effects 0.000 description 1
239000008157 edible vegetable oil Substances 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
239000002702 enteric coating Substances 0.000 description 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 description 1
CFNDVXUTYPXOPG-UHFFFAOYSA-N ethyl 2-(4-aminophenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(N)C=C1 CFNDVXUTYPXOPG-UHFFFAOYSA-N 0.000 description 1
QNUMWVBHRJVVGE-UHFFFAOYSA-N ethyl 2-(4-hydrazinylphenyl)acetate Chemical compound CCOC(=O)CC1=CC=C(NN)C=C1 QNUMWVBHRJVVGE-UHFFFAOYSA-N 0.000 description 1
DENTXBGEUCFNQB-UHFFFAOYSA-N ethyl 2-(4-hydrazinylphenyl)acetate;hydrochloride Chemical compound Cl.CCOC(=O)CC1=CC=C(NN)C=C1 DENTXBGEUCFNQB-UHFFFAOYSA-N 0.000 description 1
ZIWMVOSMGSZSOD-UHFFFAOYSA-N ethyl 2-[3-[2-(benzylamino)ethyl]-1h-indol-5-yl]acetate Chemical compound C12=CC(CC(=O)OCC)=CC=C2NC=C1CCNCC1=CC=CC=C1 ZIWMVOSMGSZSOD-UHFFFAOYSA-N 0.000 description 1
SFCWQWGJQSMIQU-UHFFFAOYSA-N ethyl 2-[3-[2-[benzyl(methyl)amino]ethyl]-1h-indol-5-yl]acetate Chemical compound C12=CC(CC(=O)OCC)=CC=C2NC=C1CCN(C)CC1=CC=CC=C1 SFCWQWGJQSMIQU-UHFFFAOYSA-N 0.000 description 1
FGJRUEMYWFUGMC-UHFFFAOYSA-N ethyl 3-[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]propanoate Chemical compound CCOC(=O)CCC1=CC=C2NC=C(CCN(C)C)C2=C1 FGJRUEMYWFUGMC-UHFFFAOYSA-N 0.000 description 1
JYYDHGMTXHCSKZ-UHFFFAOYSA-N ethyl 4-hydrazinylbenzoate Chemical compound CCOC(=O)C1=CC=C(NN)C=C1 JYYDHGMTXHCSKZ-UHFFFAOYSA-N 0.000 description 1
BTZOWQCBGLZWSD-UHFFFAOYSA-N ethyl 4-hydrazinylbenzoate;hydrochloride Chemical compound Cl.CCOC(=O)C1=CC=C(NN)C=C1 BTZOWQCBGLZWSD-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
RWWBQEQQATYWJI-UHFFFAOYSA-N ethyl n-[(hydroxyamino)methylidene]carbamate Chemical compound CCOC(=O)NC=NO RWWBQEQQATYWJI-UHFFFAOYSA-N 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000001747 exhibiting effect Effects 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000012054 flavored emulsion Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
239000006260 foam Substances 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
150000002240 furans Chemical class 0.000 description 1
125000002541 furyl group Chemical group 0.000 description 1
239000007789 gas Substances 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
208000001288 gastroparesis Diseases 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
229920000159 gelatin Polymers 0.000 description 1
235000019322 gelatine Nutrition 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
238000007429 general method Methods 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000004795 grignard reagents Chemical class 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
125000000592 heterocycloalkyl group Chemical group 0.000 description 1
125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
QMEZUZOCLYUADC-UHFFFAOYSA-N hydrate;dihydrochloride Chemical compound O.Cl.Cl QMEZUZOCLYUADC-UHFFFAOYSA-N 0.000 description 1
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
IENZCGNHSIMFJE-UHFFFAOYSA-N indole-5-carboxylic acid Chemical compound OC(=O)C1=CC=C2NC=CC2=C1 IENZCGNHSIMFJE-UHFFFAOYSA-N 0.000 description 1
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
125000001041 indolyl group Chemical group 0.000 description 1
239000004615 ingredient Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
125000005956 isoquinolyl group Chemical group 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000010410 layer Substances 0.000 description 1
239000007788 liquid Substances 0.000 description 1
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical class [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
230000005923 long-lasting effect Effects 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
239000011976 maleic acid Substances 0.000 description 1
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230000007246 mechanism Effects 0.000 description 1
239000012528 membrane Substances 0.000 description 1
BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 description 1
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QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 description 1
BORSYCGQRHMTEQ-UHFFFAOYSA-N methyl 2-[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]acetate Chemical compound COC(=O)CC1=CC=C2NC=C(CCN(C)C)C2=C1 BORSYCGQRHMTEQ-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 1
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
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238000012986 modification Methods 0.000 description 1
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AEXITZJSLGALNH-UHFFFAOYSA-N n'-hydroxyethanimidamide Chemical compound CC(N)=NO AEXITZJSLGALNH-UHFFFAOYSA-N 0.000 description 1
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QXERQJKIWJMSFG-UHFFFAOYSA-N n,n-dimethyl-2-[5-[[3-(pyridin-3-ylmethyl)-1,2,4-oxadiazol-5-yl]methyl]-1h-indol-3-yl]ethanamine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(ON=1)=NC=1CC1=CC=CN=C1 QXERQJKIWJMSFG-UHFFFAOYSA-N 0.000 description 1
ASMZENICLGHQCH-UHFFFAOYSA-N n-[2-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]ethyl]benzamide Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(ON=1)=NC=1CCNC(=O)C1=CC=CC=C1 ASMZENICLGHQCH-UHFFFAOYSA-N 0.000 description 1
PEUXFENVJFMMFH-UHFFFAOYSA-N n-[2-[5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]ethyl]pyrrolidine-1-carboxamide Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(ON=1)=NC=1CCNC(=O)N1CCCC1 PEUXFENVJFMMFH-UHFFFAOYSA-N 0.000 description 1
MPSISMSDHLPFGV-UHFFFAOYSA-N n-[4-[[5-[3-(2-aminoethyl)-1h-indol-5-yl]-1,2,4-oxadiazol-3-yl]methyl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1CC1=NOC(C=2C=C3C(CCN)=CNC3=CC=2)=N1 MPSISMSDHLPFGV-UHFFFAOYSA-N 0.000 description 1
SORYYVCYBRVPBK-UHFFFAOYSA-N n-[4-[[5-[[3-(2-aminoethyl)-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-yl]methyl]phenyl]methanesulfonamide Chemical compound C1=CC(NS(=O)(=O)C)=CC=C1CC1=NOC(CC=2C=C3C(CCN)=CNC3=CC=2)=N1 SORYYVCYBRVPBK-UHFFFAOYSA-N 0.000 description 1
MMBCMRWFDJLAHP-UHFFFAOYSA-N n-benzyl-5-[[3-[2-(dimethylamino)ethyl]-1h-indol-5-yl]methyl]-1,2,4-oxadiazol-3-amine Chemical compound C1=C2C(CCN(C)C)=CNC2=CC=C1CC(ON=1)=NC=1NCC1=CC=CC=C1 MMBCMRWFDJLAHP-UHFFFAOYSA-N 0.000 description 1
229920001206 natural gum Polymers 0.000 description 1
238000011587 new zealand white rabbit Methods 0.000 description 1
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OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
239000012053 oil suspension Substances 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
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RUUUEDQTOQAKTD-UHFFFAOYSA-N oxalic acid;tetrahydrate Chemical compound O.O.O.O.OC(=O)C(O)=O RUUUEDQTOQAKTD-UHFFFAOYSA-N 0.000 description 1
150000002916 oxazoles Chemical class 0.000 description 1
239000007800 oxidant agent Substances 0.000 description 1
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
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208000007777 paroxysmal Hemicrania Diseases 0.000 description 1
239000000312 peanut oil Substances 0.000 description 1
RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 1
125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
239000008024 pharmaceutical diluent Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
DGTNSSLYPYDJGL-UHFFFAOYSA-N phenyl isocyanate Chemical compound O=C=NC1=CC=CC=C1 DGTNSSLYPYDJGL-UHFFFAOYSA-N 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000005936 piperidyl group Chemical group 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
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235000015320 potassium carbonate Nutrition 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
230000036515 potency Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
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JKANAVGODYYCQF-UHFFFAOYSA-N prop-2-yn-1-amine Chemical compound NCC#C JKANAVGODYYCQF-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
150000003242 quaternary ammonium salts Chemical class 0.000 description 1
125000005493 quinolyl group Chemical group 0.000 description 1
239000002287 radioligand Substances 0.000 description 1
230000008929 regeneration Effects 0.000 description 1
238000011069 regeneration method Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
238000006798 ring closing metathesis reaction Methods 0.000 description 1
210000003752 saphenous vein Anatomy 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
201000000980 schizophrenia Diseases 0.000 description 1
150000003334 secondary amides Chemical class 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000004208 shellac Substances 0.000 description 1
ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
229940113147 shellac Drugs 0.000 description 1
235000013874 shellac Nutrition 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
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
230000009870 specific binding Effects 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
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238000006467 substitution reaction Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
FWMUJAIKEJWSSY-UHFFFAOYSA-N sulfur dichloride Chemical compound ClSCl FWMUJAIKEJWSSY-UHFFFAOYSA-N 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
210000000538 tail Anatomy 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
229960001367 tartaric acid Drugs 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
DDYPJNWKAJAWRL-UHFFFAOYSA-N tert-butyl 3-[2-(dimethylamino)ethyl]-5-[2-[(4-methoxyphenyl)methoxy]-2-oxoethyl]indole-1-carboxylate Chemical compound C1=CC(OC)=CC=C1COC(=O)CC1=CC=C(N(C=C2CCN(C)C)C(=O)OC(C)(C)C)C2=C1 DDYPJNWKAJAWRL-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
150000003511 tertiary amides Chemical class 0.000 description 1
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
150000004867 thiadiazoles Chemical group 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
150000003557 thiazoles Chemical class 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000007970 thio esters Chemical class 0.000 description 1
229930192474 thiophene Natural products 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
239000005526 vasoconstrictor agent Substances 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
238000010626 work up procedure Methods 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical Kinetics & Catalysis (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)
Public Health (AREA)
Pain & Pain Management (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Neurosurgery (AREA)
Heart & Thoracic Surgery (AREA)
Cardiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Indole Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

NO91910187A 1990-01-17 1991-01-16 Fremgangsmaate for fremstilling av indolsubstituerte, heteroaromatiske femringforbindelser. NO910187L (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB909001018A GB9001018D0 (en)	1990-01-17	1990-01-17	Therapeutic agents
GB909008587A GB9008587D0 (en)	1990-04-17	1990-04-17	Therapeutic agents

Publications (2)

Publication Number	Publication Date
NO910187D0 NO910187D0 (no)	1991-01-16
NO910187L true NO910187L (no)	1991-07-18

Family

ID=26296509

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO91910187A NO910187L (no)	1990-01-17	1991-01-16	Fremgangsmaate for fremstilling av indolsubstituerte, heteroaromatiske femringforbindelser.

Country Status (15)

Country	Link
EP (1)	EP0438230B1 (de)
JP (1)	JPH06100558A (de)
KR (1)	KR910014373A (de)
CN (1)	CN1053429A (de)
AT (1)	ATE152110T1 (de)
AU (1)	AU6944091A (de)
CA (1)	CA2034189A1 (de)
CS (1)	CS8691A2 (de)
DE (1)	DE69125731T2 (de)
FI (1)	FI910228L (de)
HU (1)	HU910128D0 (de)
IE (1)	IE910139A1 (de)
IL (1)	IL96891A0 (de)
NO (1)	NO910187L (de)
PT (1)	PT96477A (de)

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1991
- 1991-01-07 IL IL96891A patent/IL96891A0/xx unknown
- 1991-01-10 AT AT91300180T patent/ATE152110T1/de not_active IP Right Cessation
- 1991-01-10 EP EP91300180A patent/EP0438230B1/de not_active Expired - Lifetime
- 1991-01-10 DE DE69125731T patent/DE69125731T2/de not_active Expired - Fee Related
- 1991-01-15 PT PT96477A patent/PT96477A/pt not_active Application Discontinuation
- 1991-01-15 CA CA002034189A patent/CA2034189A1/en not_active Abandoned
- 1991-01-16 HU HU91128A patent/HU910128D0/hu unknown
- 1991-01-16 NO NO91910187A patent/NO910187L/no unknown
- 1991-01-16 AU AU69440/91A patent/AU6944091A/en not_active Abandoned
- 1991-01-16 KR KR1019910000593A patent/KR910014373A/ko not_active Withdrawn
- 1991-01-16 IE IE013991A patent/IE910139A1/en unknown
- 1991-01-16 CS CS9186A patent/CS8691A2/cs unknown
- 1991-01-16 FI FI910228A patent/FI910228L/fi unknown
- 1991-01-17 JP JP3216736A patent/JPH06100558A/ja active Pending
- 1991-01-17 CN CN91100380A patent/CN1053429A/zh active Pending

Also Published As

Publication number	Publication date
JPH06100558A (ja)	1994-04-12
FI910228A7 (fi)	1991-07-18
CS8691A2 (en)	1991-09-15
HU910128D0 (en)	1991-08-28
NO910187D0 (no)	1991-01-16
IE910139A1 (en)	1991-07-17
DE69125731T2 (de)	1997-11-27
AU6944091A (en)	1991-07-25
EP0438230A2 (de)	1991-07-24
FI910228L (fi)	1991-07-18
EP0438230A3 (en)	1992-02-12
CA2034189A1 (en)	1991-07-18
ATE152110T1 (de)	1997-05-15
CN1053429A (zh)	1991-07-31
IL96891A0 (en)	1992-03-29
FI910228A0 (fi)	1991-01-16
KR910014373A (ko)	1991-08-31
PT96477A (pt)	1991-10-15
DE69125731D1 (de)	1997-05-28
EP0438230B1 (de)	1997-04-23

Publication	Publication Date	Title
NO910187L (no)	1991-07-18	Fremgangsmaate for fremstilling av indolsubstituerte, heteroaromatiske femringforbindelser.
US5317103A (en)	1994-05-31	Indole-substituted five-membered heteroaromatic compounds as 5-HT1 agonists
US5208248A (en)	1993-05-04	Indazole-substituted five-membered heteroaromatic compounds
TWI265807B (en)	2006-11-11	Tachykinin receptor antagonists
US5041456A (en)	1991-08-20	Pharmaceutically useful 3-(indol-3-yl)-1,2,4-oxa- and thiadiazoles substituted in the 5-position by an amino containing group
EP0494774A1 (de)	1992-07-15	Indazol-substituierte 5-Kettenglieder heteroaromatische Verbindungen
MXPA05001590A (es)	2005-05-23	Compuestos que tienen actividad en los receptores metabotropicos de glutamato.
CA2751534A1 (en)	2010-09-10	Novel phenyl imidazoles and phenyl triazoles as gamma-secretase modulators
CZ283001B6 (cs)	1997-12-17	5-Arylindolové deriváty, meziprodukty pro jejich výrobu a famaceutické prostředky na jejich bázi
CN104024250B (zh)	2016-01-27	作为痕量胺相关受体(taar)的杂环衍生物
CA2869232A1 (en)	2013-12-27	New bicyclic thiophenylamide compounds
US5670522A (en)	1997-09-23	Dopamine receptor subtype ligands
AU714701B2 (en)	2000-01-06	Novel thiophene derivative and pharmaceutical composition thereof
JP6529998B2 (ja)	2019-06-12	うつ病、糖尿病及びパーキンソン病のような幾つかの障害の処置において使用するためのｔａａｒ調節薬としてのピラゾールカルボキサミド誘導体
US6080745A (en)	2000-06-27	Fused tricyclic heteroaromatic derivatives as dopamine receptor subtype ligands
CA2208652A1 (en)	1997-12-26	Pharmaceutical compounds
CA2623154A1 (en)	2007-04-12	Novel fused pyrrole derivative
US5194440A (en)	1993-03-16	Substituted cyclic sulphamide derivatives
CA2211189A1 (en)	1996-08-08	Substituted 1,4-piperazine-heteroaryl derivatives as 5-ht1d receptor agonists
CA2168738A1 (en)	1995-03-16	Fused tricyclic heteroaromatic derivatives as dopamine receptor subtype ligands
US5510359A (en)	1996-04-23	Heteroaromatic 5-hydroxytryptamine receptor agonists
US20120028931A1 (en)	2012-02-02	Heterocyclic m-glu5 antagonists
WO1995014672A1 (en)	1995-06-01	Isoxazole and pyrazole derivatives as dopamine receptor subtype ligands
GB2289465A (en)	1995-11-22	Five-membered heteroaromatic 5-HT receptor agonists
TWI296622B (en)	2008-05-11	Dihydro-benzo[b][1,4]diazepin-2-one derivatives as mglur2 antagonists ii