SK17042001A3 - Derivát indolylpiperidínu ako antihistaminické a antialergické činidlo - Google Patents

Derivát indolylpiperidínu ako antihistaminické a antialergické činidlo Download PDF

Info

Publication number: SK17042001A3
Authority: SK; Slovakia
Prior art keywords: piperidin; indol; ethoxy; acid; ethoxyethyl
Prior art date: 1999-06-04

Application number

SK1704-2001A

Other languages

English (en)

Slovak (sk)

Inventor

Santacana Lluis Pages

Pou Silvia Fonquerna

Duran Carles Puig

Forner Dolors Fernandez

Original Assignee

Almirall Prodesfarma, S. A.

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.)

1999-06-04

Filing date

2000-05-31

Publication date

2002-04-04

2000-05-31 Application filed by Almirall Prodesfarma, S. A. filed Critical Almirall Prodesfarma, S. A.

2002-04-04 Publication of SK17042001A3 publication Critical patent/SK17042001A3/sk

Links

HNQZRUDJRPSFAU-UHFFFAOYSA-N 2-piperidin-1-yl-1h-indole Chemical class C1CCCCN1C1=CC2=CC=CC=C2N1 HNQZRUDJRPSFAU-UHFFFAOYSA-N 0.000 title claims abstract description 24
239000000739 antihistaminic agent Substances 0.000 title claims abstract description 10
239000000043 antiallergic agent Substances 0.000 title description 4
230000001387 anti-histamine Effects 0.000 title description 3
-1 alkylenethio Chemical group 0.000 claims abstract description 127
125000000217 alkyl group Chemical group 0.000 claims abstract description 21
125000003545 alkoxy group Chemical group 0.000 claims abstract description 14
125000005843 halogen group Chemical group 0.000 claims abstract description 13
125000002947 alkylene group Chemical group 0.000 claims abstract description 11
125000005529 alkyleneoxy group Chemical group 0.000 claims abstract description 7
230000003266 anti-allergic effect Effects 0.000 claims abstract description 7
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 7
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims abstract description 7
GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims abstract description 6
239000001257 hydrogen Substances 0.000 claims abstract description 6
125000004450 alkenylene group Chemical group 0.000 claims abstract description 5
230000003326 anti-histaminergic effect Effects 0.000 claims abstract description 5
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 4
125000003831 tetrazolyl group Chemical group 0.000 claims abstract description 3
125000001589 carboacyl group Chemical group 0.000 claims abstract 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract 2
238000002360 preparation method Methods 0.000 claims description 113
150000001875 compounds Chemical class 0.000 claims description 90
239000000203 mixture Substances 0.000 claims description 76
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 73
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 67
238000000034 method Methods 0.000 claims description 48
239000005711 Benzoic acid Substances 0.000 claims description 41
235000010233 benzoic acid Nutrition 0.000 claims description 39
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
150000003839 salts Chemical class 0.000 claims description 21
125000004432 carbon atom Chemical group C* 0.000 claims description 14
239000002253 acid Substances 0.000 claims description 13
239000000460 chlorine Substances 0.000 claims description 12
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 12
230000000694 effects Effects 0.000 claims description 12
239000008194 pharmaceutical composition Substances 0.000 claims description 12
238000011282 treatment Methods 0.000 claims description 11
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
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 9
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
ONLRIYBCDNTLSC-UHFFFAOYSA-N 4-[2-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=C(C(O)=O)C=C1 ONLRIYBCDNTLSC-UHFFFAOYSA-N 0.000 claims description 8
229910052801 chlorine Inorganic materials 0.000 claims description 8
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 8
QCFSNBWEJWOEPW-UHFFFAOYSA-N 1-(2-ethoxyethyl)-3-piperidin-4-ylindole Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C1CCNCC1 QCFSNBWEJWOEPW-UHFFFAOYSA-N 0.000 claims description 7
NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 7
MIPYJZXZGANVJL-UHFFFAOYSA-N 2-[2-[4-[1-[(4-fluorophenyl)methyl]indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CC=C3N(CC=3C=CC(F)=CC=3)C=2)CC1 MIPYJZXZGANVJL-UHFFFAOYSA-N 0.000 claims description 7
125000003342 alkenyl group Chemical group 0.000 claims description 7
125000000304 alkynyl group Chemical group 0.000 claims description 7
SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 6
QIRDLEIUOYJRGZ-UHFFFAOYSA-N 2-methyl-2-[4-[4-[4-[1-(3-methylbutyl)indol-3-yl]piperidin-1-yl]butanoyl]phenyl]propanoic acid Chemical compound C12=CC=CC=C2N(CCC(C)C)C=C1C(CC1)CCN1CCCC(=O)C1=CC=C(C(C)(C)C(O)=O)C=C1 QIRDLEIUOYJRGZ-UHFFFAOYSA-N 0.000 claims description 6
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
208000006673 asthma Diseases 0.000 claims description 6
230000002526 effect on cardiovascular system Effects 0.000 claims description 6
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
230000008569 process Effects 0.000 claims description 6
235000019260 propionic acid Nutrition 0.000 claims description 6
WBMYDORIDCSVSO-UHFFFAOYSA-N 2-[2-[4-(1-pentylindol-3-yl)piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCCCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O WBMYDORIDCSVSO-UHFFFAOYSA-N 0.000 claims description 5
QSOACFIAXDGTQW-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O QSOACFIAXDGTQW-UHFFFAOYSA-N 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 5
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
QLHLGBNHXMZIQT-UHFFFAOYSA-N 2-[2-[4-(1h-indol-3-yl)piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CC=C3NC=2)CC1 QLHLGBNHXMZIQT-UHFFFAOYSA-N 0.000 claims description 4
QMFNTTFIGWXQNY-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-5-fluoroindol-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound C12=CC(F)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC(OC)=CC=C1C(O)=O QMFNTTFIGWXQNY-UHFFFAOYSA-N 0.000 claims description 4
NDRPQPJPFUMFQZ-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-5-fluoroindol-3-yl]piperidin-1-yl]ethoxy]-5-methylbenzoic acid Chemical compound C12=CC(F)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=C(C)C=C1C(O)=O NDRPQPJPFUMFQZ-UHFFFAOYSA-N 0.000 claims description 4
WIQGPOWORKUTND-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-7-methylindol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC(C)=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O WIQGPOWORKUTND-UHFFFAOYSA-N 0.000 claims description 4
JESNEQBROSADIH-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]acetic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C1CCN(CCOCC(O)=O)CC1 JESNEQBROSADIH-UHFFFAOYSA-N 0.000 claims description 4
VBXUDFDAMGGOQA-UHFFFAOYSA-N 2-[2-[4-[1-(cyclopropylmethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CC=C3N(CC3CC3)C=2)CC1 VBXUDFDAMGGOQA-UHFFFAOYSA-N 0.000 claims description 4
DMMMPWFSQYWCMG-UHFFFAOYSA-N 2-[2-[4-[1-[(4-fluorophenyl)methyl]indol-3-yl]piperidin-1-yl]ethoxy]acetic acid Chemical compound C1CN(CCOCC(=O)O)CCC1C(C1=CC=CC=C11)=CN1CC1=CC=C(F)C=C1 DMMMPWFSQYWCMG-UHFFFAOYSA-N 0.000 claims description 4
XLIGNZHKWRUBOD-UHFFFAOYSA-N 2-[2-[4-[7-bromo-1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]-5-methylbenzoic acid Chemical compound C12=CC=CC(Br)=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=C(C)C=C1C(O)=O XLIGNZHKWRUBOD-UHFFFAOYSA-N 0.000 claims description 4
SUYRJLMLWQRSTJ-UHFFFAOYSA-N 2-[4-[1-hydroxy-4-[4-(1-pentylindol-3-yl)piperidin-1-yl]butyl]phenyl]-2-methylpropanoic acid Chemical compound C12=CC=CC=C2N(CCCCC)C=C1C(CC1)CCN1CCCC(O)C1=CC=C(C(C)(C)C(O)=O)C=C1 SUYRJLMLWQRSTJ-UHFFFAOYSA-N 0.000 claims description 4
LONHPJBHRJQJHT-UHFFFAOYSA-N 3-[2-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC(C(O)=O)=C1 LONHPJBHRJQJHT-UHFFFAOYSA-N 0.000 claims description 4
OLYGEFPXSWBWOU-UHFFFAOYSA-N 3-[3-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]propoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCCOC1=CC=CC(C(O)=O)=C1 OLYGEFPXSWBWOU-UHFFFAOYSA-N 0.000 claims description 4
PKJMGCNGLZTAFR-UHFFFAOYSA-N 3-[3-[4-[1-[2-(2-methoxyethoxy)ethyl]indol-3-yl]piperidin-1-yl]propoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCOCCOC)C=C1C(CC1)CCN1CCCOC1=CC=CC(C(O)=O)=C1 PKJMGCNGLZTAFR-UHFFFAOYSA-N 0.000 claims description 4
XGQCLGOTLVBAIE-UHFFFAOYSA-N 3-[4-[1-[(4-fluorophenyl)methyl]indol-3-yl]piperidin-1-yl]propanoic acid Chemical compound C1CN(CCC(=O)O)CCC1C(C1=CC=CC=C11)=CN1CC1=CC=C(F)C=C1 XGQCLGOTLVBAIE-UHFFFAOYSA-N 0.000 claims description 4
GSUKJSDXOINYEV-UHFFFAOYSA-N 4-[4-(1-pentylindol-3-yl)piperidin-1-yl]butanoic acid Chemical compound C12=CC=CC=C2N(CCCCC)C=C1C1CCN(CCCC(O)=O)CC1 GSUKJSDXOINYEV-UHFFFAOYSA-N 0.000 claims description 4
IJIRUUMNBLISCP-UHFFFAOYSA-N 4-[4-[1-[(4-fluorophenyl)methyl]indol-3-yl]piperidin-1-yl]butanoic acid Chemical compound C1CN(CCCC(=O)O)CCC1C(C1=CC=CC=C11)=CN1CC1=CC=C(F)C=C1 IJIRUUMNBLISCP-UHFFFAOYSA-N 0.000 claims description 4
125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 4
YMTFBLJZFQOGDA-UHFFFAOYSA-N 5-[[4-(1-pentylindol-3-yl)piperidin-1-yl]methyl]furan-2-carboxylic acid Chemical compound C12=CC=CC=C2N(CCCCC)C=C1C(CC1)CCN1CC1=CC=C(C(O)=O)O1 YMTFBLJZFQOGDA-UHFFFAOYSA-N 0.000 claims description 4
ZXAUTBJTQGDDPZ-UHFFFAOYSA-N 5-[[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]methyl]furan-2-carboxylic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CC1=CC=C(C(O)=O)O1 ZXAUTBJTQGDDPZ-UHFFFAOYSA-N 0.000 claims description 4
JPHSHTODQABXIL-UHFFFAOYSA-N 5-[[4-[1-[(4-fluorophenyl)methyl]indol-3-yl]piperidin-1-yl]methyl]furan-2-carboxylic acid Chemical compound O1C(C(=O)O)=CC=C1CN1CCC(C=2C3=CC=CC=C3N(CC=3C=CC(F)=CC=3)C=2)CC1 JPHSHTODQABXIL-UHFFFAOYSA-N 0.000 claims description 4
KYQXAYYQCREFNM-UHFFFAOYSA-N 5-[[4-[1-[2-(2-methoxyethoxy)ethyl]indol-3-yl]piperidin-1-yl]methyl]furan-2-carboxylic acid Chemical compound C12=CC=CC=C2N(CCOCCOC)C=C1C(CC1)CCN1CC1=CC=C(C(O)=O)O1 KYQXAYYQCREFNM-UHFFFAOYSA-N 0.000 claims description 4
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 4
241001465754 Metazoa Species 0.000 claims description 4
208000024780 Urticaria Diseases 0.000 claims description 4
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims description 4
208000026935 allergic disease Diseases 0.000 claims description 4
210000003169 central nervous system Anatomy 0.000 claims description 4
AAEZWNBJUPWTNT-UHFFFAOYSA-N tert-butyl 4-(2-chloroethoxy)benzoate Chemical compound CC(C)(C)OC(=O)C1=CC=C(OCCCl)C=C1 AAEZWNBJUPWTNT-UHFFFAOYSA-N 0.000 claims description 4
NKNYSGLYIJGMTP-UHFFFAOYSA-N 2-[2-[4-(1-butylindol-3-yl)piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O NKNYSGLYIJGMTP-UHFFFAOYSA-N 0.000 claims description 3
OJZFCJFQRDSGQX-UHFFFAOYSA-N 2-[2-[4-(1-prop-2-ynylindol-3-yl)piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CC=C3N(CC#C)C=2)CC1 OJZFCJFQRDSGQX-UHFFFAOYSA-N 0.000 claims description 3
HHITYXUJELSBPS-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-4-fluoroindol-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound C12=C(F)C=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC(OC)=CC=C1C(O)=O HHITYXUJELSBPS-UHFFFAOYSA-N 0.000 claims description 3
SPOKTOSVUQLTOH-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-4-fluoroindol-3-yl]piperidin-1-yl]ethoxy]-5-methylbenzoic acid Chemical compound C12=C(F)C=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=C(C)C=C1C(O)=O SPOKTOSVUQLTOH-UHFFFAOYSA-N 0.000 claims description 3
QAZVGNJWLJEDFV-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-4-fluoroindol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=C(F)C=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O QAZVGNJWLJEDFV-UHFFFAOYSA-N 0.000 claims description 3
INVVRCPLVVQOGS-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-5-fluoroindol-3-yl]piperidin-1-yl]ethoxy]-6-fluorobenzoic acid Chemical compound C12=CC(F)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC(F)=C1C(O)=O INVVRCPLVVQOGS-UHFFFAOYSA-N 0.000 claims description 3
DGVYELQBTIBCMU-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-5-fluoroindol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC(F)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O DGVYELQBTIBCMU-UHFFFAOYSA-N 0.000 claims description 3
WYMUGVSTXZEYIJ-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-5-methoxyindol-3-yl]piperidin-1-yl]ethoxy]-6-fluorobenzoic acid Chemical compound C12=CC(OC)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC(F)=C1C(O)=O WYMUGVSTXZEYIJ-UHFFFAOYSA-N 0.000 claims description 3
ZEARTZKNFQZDKX-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-5-methoxyindol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC(OC)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O ZEARTZKNFQZDKX-UHFFFAOYSA-N 0.000 claims description 3
WYMKMMPHJBIHRY-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-6-fluoroindol-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound C12=CC=C(F)C=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC(OC)=CC=C1C(O)=O WYMKMMPHJBIHRY-UHFFFAOYSA-N 0.000 claims description 3
KGKISXJBNCHPAU-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-6-fluoroindol-3-yl]piperidin-1-yl]ethoxy]-5-methylbenzoic acid Chemical compound C12=CC=C(F)C=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=C(C)C=C1C(O)=O KGKISXJBNCHPAU-UHFFFAOYSA-N 0.000 claims description 3
XUQURAFGTLVXHN-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-6-fluoroindol-3-yl]piperidin-1-yl]ethoxy]-6-fluorobenzoic acid Chemical compound C12=CC=C(F)C=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC(F)=C1C(O)=O XUQURAFGTLVXHN-UHFFFAOYSA-N 0.000 claims description 3
BVRIYQUZSCWOSG-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-6-fluoroindol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=C(F)C=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O BVRIYQUZSCWOSG-UHFFFAOYSA-N 0.000 claims description 3
FGOSLGBBJZIYHE-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]-6-fluorobenzoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC(F)=C1C(O)=O FGOSLGBBJZIYHE-UHFFFAOYSA-N 0.000 claims description 3
LVAJRQDSXRFOTR-UHFFFAOYSA-N 2-[2-[4-[1-(2-methoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCOC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O LVAJRQDSXRFOTR-UHFFFAOYSA-N 0.000 claims description 3
OSFBNDLQBDNFRN-UHFFFAOYSA-N 2-[2-[4-[1-(2-methylpropyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CC(C)C)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O OSFBNDLQBDNFRN-UHFFFAOYSA-N 0.000 claims description 3
ILRDUQNXVKDHAM-UHFFFAOYSA-N 2-[2-[4-[1-(2-propoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCOCCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O ILRDUQNXVKDHAM-UHFFFAOYSA-N 0.000 claims description 3
VPOAVKKIGBXDMV-UHFFFAOYSA-N 2-[2-[4-[1-(3-methoxypropyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCCOC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O VPOAVKKIGBXDMV-UHFFFAOYSA-N 0.000 claims description 3
NYQGYEGBQNANJM-UHFFFAOYSA-N 2-[2-[4-[1-(3-methylbutyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCC(C)C)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O NYQGYEGBQNANJM-UHFFFAOYSA-N 0.000 claims description 3
YTJIIMFPVVISHG-UHFFFAOYSA-N 2-[2-[4-[1-(cyclohexylmethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CC=C3N(CC3CCCCC3)C=2)CC1 YTJIIMFPVVISHG-UHFFFAOYSA-N 0.000 claims description 3
PKDGHGYNWFKPAF-UHFFFAOYSA-N 2-[2-[4-[1-(cyclopropylmethyl)-6-fluoroindol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=C(F)C=C3N(CC3CC3)C=2)CC1 PKDGHGYNWFKPAF-UHFFFAOYSA-N 0.000 claims description 3
VJYYJODZGYTFFM-UHFFFAOYSA-N 2-[2-[4-[1-[(4-methoxyphenyl)methyl]indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C1=CC(OC)=CC=C1CN1C2=CC=CC=C2C(C2CCN(CCOC=3C(=CC=CC=3)C(O)=O)CC2)=C1 VJYYJODZGYTFFM-UHFFFAOYSA-N 0.000 claims description 3
NMUSDIXZEJLCTH-UHFFFAOYSA-N 2-[2-[4-[1-[(4-phenylmethoxyphenyl)methyl]indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CC=C3N(CC=3C=CC(OCC=4C=CC=CC=4)=CC=3)C=2)CC1 NMUSDIXZEJLCTH-UHFFFAOYSA-N 0.000 claims description 3
XRPDEOQYHIZYNY-UHFFFAOYSA-N 2-[2-[4-[1-[2-(2-methoxyethoxy)ethyl]indol-3-yl]piperidin-1-yl]ethoxy]acetic acid Chemical compound C12=CC=CC=C2N(CCOCCOC)C=C1C1CCN(CCOCC(O)=O)CC1 XRPDEOQYHIZYNY-UHFFFAOYSA-N 0.000 claims description 3
DTEVHRPFQBKFKZ-UHFFFAOYSA-N 2-[2-[4-[1-[2-(4-methoxyphenyl)ethyl]indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C1=CC(OC)=CC=C1CCN1C2=CC=CC=C2C(C2CCN(CCOC=3C(=CC=CC=3)C(O)=O)CC2)=C1 DTEVHRPFQBKFKZ-UHFFFAOYSA-N 0.000 claims description 3
KMVMABDALRFKCM-UHFFFAOYSA-N 2-[2-[4-[4-fluoro-1-(2-methoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound C12=C(F)C=CC=C2N(CCOC)C=C1C(CC1)CCN1CCOC1=CC(OC)=CC=C1C(O)=O KMVMABDALRFKCM-UHFFFAOYSA-N 0.000 claims description 3
PLUCWLKTQPYMOJ-UHFFFAOYSA-N 2-[2-[4-[4-fluoro-1-(2-methoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]-5-methylbenzoic acid Chemical compound C12=C(F)C=CC=C2N(CCOC)C=C1C(CC1)CCN1CCOC1=CC=C(C)C=C1C(O)=O PLUCWLKTQPYMOJ-UHFFFAOYSA-N 0.000 claims description 3
DGEZDVIEJXDCQA-UHFFFAOYSA-N 2-[2-[4-[4-fluoro-1-(2-methoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=C(F)C=CC=C2N(CCOC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O DGEZDVIEJXDCQA-UHFFFAOYSA-N 0.000 claims description 3
MWHMBIYNCCYPQI-UHFFFAOYSA-N 2-[2-[4-[5-bromo-1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound C12=CC(Br)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC(OC)=CC=C1C(O)=O MWHMBIYNCCYPQI-UHFFFAOYSA-N 0.000 claims description 3
GOWPJVSOMIHDDM-UHFFFAOYSA-N 2-[2-[4-[5-bromo-1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]-5-methylbenzoic acid Chemical compound C12=CC(Br)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=C(C)C=C1C(O)=O GOWPJVSOMIHDDM-UHFFFAOYSA-N 0.000 claims description 3
LYQYDLDTHBVSBI-UHFFFAOYSA-N 2-[2-[4-[5-bromo-1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]-6-fluorobenzoic acid Chemical compound C12=CC(Br)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC(F)=C1C(O)=O LYQYDLDTHBVSBI-UHFFFAOYSA-N 0.000 claims description 3
XADGZRXEEIMQPN-UHFFFAOYSA-N 2-[2-[4-[5-bromo-1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC(Br)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O XADGZRXEEIMQPN-UHFFFAOYSA-N 0.000 claims description 3
MYXRAYCZYBLISE-UHFFFAOYSA-N 2-[2-[4-[5-chloro-1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound C12=CC(Cl)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC(OC)=CC=C1C(O)=O MYXRAYCZYBLISE-UHFFFAOYSA-N 0.000 claims description 3
LLHPGPJNBDMHJH-UHFFFAOYSA-N 2-[2-[4-[5-chloro-1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]-5-methylbenzoic acid Chemical compound C12=CC(Cl)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=C(C)C=C1C(O)=O LLHPGPJNBDMHJH-UHFFFAOYSA-N 0.000 claims description 3
ZXVAQCXPJFHKGW-UHFFFAOYSA-N 2-[2-[4-[5-chloro-1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]-6-fluorobenzoic acid Chemical compound C12=CC(Cl)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC(F)=C1C(O)=O ZXVAQCXPJFHKGW-UHFFFAOYSA-N 0.000 claims description 3
BLKUTSXBXNFUNN-UHFFFAOYSA-N 2-[2-[4-[5-chloro-1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC(Cl)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O BLKUTSXBXNFUNN-UHFFFAOYSA-N 0.000 claims description 3
AKNGDPJHNUTJDE-UHFFFAOYSA-N 2-[2-[4-[6-bromo-1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]-5-methylbenzoic acid Chemical compound C12=CC=C(Br)C=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=C(C)C=C1C(O)=O AKNGDPJHNUTJDE-UHFFFAOYSA-N 0.000 claims description 3
LPNLDHOWPWSASA-UHFFFAOYSA-N 2-[2-[4-[6-bromo-1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=C(Br)C=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O LPNLDHOWPWSASA-UHFFFAOYSA-N 0.000 claims description 3
VUUZVHPYUMSGRB-UHFFFAOYSA-N 2-[2-[4-[7-bromo-1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound C12=CC=CC(Br)=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC(OC)=CC=C1C(O)=O VUUZVHPYUMSGRB-UHFFFAOYSA-N 0.000 claims description 3
OMSYYPWHMFLIDI-UHFFFAOYSA-N 2-[2-[4-[7-bromo-1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]-6-fluorobenzoic acid Chemical compound C12=CC=CC(Br)=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC(F)=C1C(O)=O OMSYYPWHMFLIDI-UHFFFAOYSA-N 0.000 claims description 3
QWQRGXJHFQEOOM-UHFFFAOYSA-N 2-[2-[4-[7-bromo-1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC(Br)=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O QWQRGXJHFQEOOM-UHFFFAOYSA-N 0.000 claims description 3
LGGDYILDGCNVJP-UHFFFAOYSA-N 2-[3-[3-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]propoxy]phenyl]acetic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCCOC1=CC=CC(CC(O)=O)=C1 LGGDYILDGCNVJP-UHFFFAOYSA-N 0.000 claims description 3
QXPDMAYRQMCNJJ-UHFFFAOYSA-N 2-[3-[4-(1-pentylindol-3-yl)piperidin-1-yl]propoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCCCC)C=C1C(CC1)CCN1CCCOC1=CC=CC=C1C(O)=O QXPDMAYRQMCNJJ-UHFFFAOYSA-N 0.000 claims description 3
HIKYNJRMLYWZMO-UHFFFAOYSA-N 2-[3-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]propoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCCOC1=CC=CC=C1C(O)=O HIKYNJRMLYWZMO-UHFFFAOYSA-N 0.000 claims description 3
LBZPNSVYWZQNDU-UHFFFAOYSA-N 2-[3-[4-[1-[(4-fluorophenyl)methyl]indol-3-yl]piperidin-1-yl]propoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCCN1CCC(C=2C3=CC=CC=C3N(CC=3C=CC(F)=CC=3)C=2)CC1 LBZPNSVYWZQNDU-UHFFFAOYSA-N 0.000 claims description 3
NUYSPCIQLGLALT-UHFFFAOYSA-N 2-[3-[4-[1-[2-(2-methoxyethoxy)ethyl]indol-3-yl]piperidin-1-yl]propoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCOCCOC)C=C1C(CC1)CCN1CCCOC1=CC=CC=C1C(O)=O NUYSPCIQLGLALT-UHFFFAOYSA-N 0.000 claims description 3
XOXXTZGQRMJCIA-UHFFFAOYSA-N 2-[4-[2-[4-(1h-indol-3-yl)piperidin-1-yl]ethyl]phenyl]-2-methylpropanoic acid Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1CCN1CCC(C=2C3=CC=CC=C3NC=2)CC1 XOXXTZGQRMJCIA-UHFFFAOYSA-N 0.000 claims description 3
LFHWAHCXXMHIDU-UHFFFAOYSA-N 2-[4-[2-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethyl]phenyl]-2-methylpropanoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCC1=CC=C(C(C)(C)C(O)=O)C=C1 LFHWAHCXXMHIDU-UHFFFAOYSA-N 0.000 claims description 3
XHKCJTILCZBBNJ-UHFFFAOYSA-N 2-[4-[3-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]propoxy]phenyl]acetic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCCOC1=CC=C(CC(O)=O)C=C1 XHKCJTILCZBBNJ-UHFFFAOYSA-N 0.000 claims description 3
LTDFGOPQQANPNG-UHFFFAOYSA-N 2-[4-[4-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]butanoyl]phenyl]-2-methylpropanoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCCC(=O)C1=CC=C(C(C)(C)C(O)=O)C=C1 LTDFGOPQQANPNG-UHFFFAOYSA-N 0.000 claims description 3
XFWCYOUPAMWZIT-UHFFFAOYSA-N 2-[4-[4-[4-[1-[(4-fluorophenyl)methyl]indol-3-yl]piperidin-1-yl]-1-hydroxybutyl]phenyl]-2-methylpropanoic acid Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C=2C3=CC=CC=C3N(CC=3C=CC(F)=CC=3)C=2)CC1 XFWCYOUPAMWZIT-UHFFFAOYSA-N 0.000 claims description 3
WDWGPVKQXKUYMD-UHFFFAOYSA-N 2-[[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CC1=CC=CC=C1C(O)=O WDWGPVKQXKUYMD-UHFFFAOYSA-N 0.000 claims description 3
ZIXKCKFYIITNOA-UHFFFAOYSA-N 2-methyl-2-[4-[2-[4-[1-(3-methylbutyl)indol-3-yl]piperidin-1-yl]ethyl]phenyl]propanoic acid Chemical compound C12=CC=CC=C2N(CCC(C)C)C=C1C(CC1)CCN1CCC1=CC=C(C(C)(C)C(O)=O)C=C1 ZIXKCKFYIITNOA-UHFFFAOYSA-N 0.000 claims description 3
VDNIYYAUQYHPBV-UHFFFAOYSA-N 3,5-dibromo-2-[2-[4-[1-(2-ethoxyethyl)-5-methoxyindol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC(OC)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=C(Br)C=C(Br)C=C1C(O)=O VDNIYYAUQYHPBV-UHFFFAOYSA-N 0.000 claims description 3
FAWAGJVGOIPRSX-UHFFFAOYSA-N 3,5-dibromo-2-[2-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=C(Br)C=C(Br)C=C1C(O)=O FAWAGJVGOIPRSX-UHFFFAOYSA-N 0.000 claims description 3
MPAATGOJVRZGQG-UHFFFAOYSA-N 3-[2-[4-(1-pentylindol-3-yl)piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCCCC)C=C1C(CC1)CCN1CCOC1=CC=CC(C(O)=O)=C1 MPAATGOJVRZGQG-UHFFFAOYSA-N 0.000 claims description 3
DSQQZXLADYAIGI-UHFFFAOYSA-N 3-[2-[4-[1-[(4-fluorophenyl)methyl]indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC(OCCN2CCC(CC2)C=2C3=CC=CC=C3N(CC=3C=CC(F)=CC=3)C=2)=C1 DSQQZXLADYAIGI-UHFFFAOYSA-N 0.000 claims description 3
HBVUBXMUMKERIB-UHFFFAOYSA-N 3-[2-[4-[1-[2-(2-methoxyethoxy)ethyl]indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCOCCOC)C=C1C(CC1)CCN1CCOC1=CC=CC(C(O)=O)=C1 HBVUBXMUMKERIB-UHFFFAOYSA-N 0.000 claims description 3
QWEBBOUXWRCKQN-UHFFFAOYSA-N 3-[3-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]propoxy]propanoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C1CCN(CCCOCCC(O)=O)CC1 QWEBBOUXWRCKQN-UHFFFAOYSA-N 0.000 claims description 3
OKTUVCQYFNNTKQ-UHFFFAOYSA-N 3-[3-[4-[1-(cyclopropylmethyl)indol-3-yl]piperidin-1-yl]propoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC(OCCCN2CCC(CC2)C=2C3=CC=CC=C3N(CC3CC3)C=2)=C1 OKTUVCQYFNNTKQ-UHFFFAOYSA-N 0.000 claims description 3
MYPCGGLFDRIXPT-UHFFFAOYSA-N 3-[3-[4-[1-[(4-fluorophenyl)methyl]indol-3-yl]piperidin-1-yl]propoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC(OCCCN2CCC(CC2)C=2C3=CC=CC=C3N(CC=3C=CC(F)=CC=3)C=2)=C1 MYPCGGLFDRIXPT-UHFFFAOYSA-N 0.000 claims description 3
SKMBWBBUAOZVEG-UHFFFAOYSA-N 3-[4-(1-pentylindol-3-yl)piperidin-1-yl]propanoic acid Chemical compound C12=CC=CC=C2N(CCCCC)C=C1C1CCN(CCC(O)=O)CC1 SKMBWBBUAOZVEG-UHFFFAOYSA-N 0.000 claims description 3
QHJBJQCVRDLUSB-UHFFFAOYSA-N 3-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]propanoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C1CCN(CCC(O)=O)CC1 QHJBJQCVRDLUSB-UHFFFAOYSA-N 0.000 claims description 3
DEQOKEQIUXJQRC-UHFFFAOYSA-N 3-[[4-(1-pentylindol-3-yl)piperidin-1-yl]methyl]benzoic acid Chemical compound C12=CC=CC=C2N(CCCCC)C=C1C(CC1)CCN1CC1=CC=CC(C(O)=O)=C1 DEQOKEQIUXJQRC-UHFFFAOYSA-N 0.000 claims description 3
ABPWVWWPAFWZTC-UHFFFAOYSA-N 3-[[4-(6-fluoro-1-pentylindol-3-yl)piperidin-1-yl]methyl]benzoic acid Chemical compound C12=CC=C(F)C=C2N(CCCCC)C=C1C(CC1)CCN1CC1=CC=CC(C(O)=O)=C1 ABPWVWWPAFWZTC-UHFFFAOYSA-N 0.000 claims description 3
FISUSZKGPGNBNT-UHFFFAOYSA-N 3-[[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CC1=CC=CC(C(O)=O)=C1 FISUSZKGPGNBNT-UHFFFAOYSA-N 0.000 claims description 3
OTCPYGJWSZHDTB-UHFFFAOYSA-N 3-[[4-[1-(cyclopropylmethyl)indol-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(CN2CCC(CC2)C=2C3=CC=CC=C3N(CC3CC3)C=2)=C1 OTCPYGJWSZHDTB-UHFFFAOYSA-N 0.000 claims description 3
XZGWPWNLPSAWGU-UHFFFAOYSA-N 4-[2-[4-(1-pentylindol-3-yl)piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCCCC)C=C1C(CC1)CCN1CCOC1=CC=C(C(O)=O)C=C1 XZGWPWNLPSAWGU-UHFFFAOYSA-N 0.000 claims description 3
WOTRCPQSLPHRIA-UHFFFAOYSA-N 4-[2-[4-[1-[2-(2-methoxyethoxy)ethyl]indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCOCCOC)C=C1C(CC1)CCN1CCOC1=CC=C(C(O)=O)C=C1 WOTRCPQSLPHRIA-UHFFFAOYSA-N 0.000 claims description 3
UMFXWTOKTPDSRO-UHFFFAOYSA-N 4-[3-[4-(1-pentylindol-3-yl)piperidin-1-yl]propoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCCCC)C=C1C(CC1)CCN1CCCOC1=CC=C(C(O)=O)C=C1 UMFXWTOKTPDSRO-UHFFFAOYSA-N 0.000 claims description 3
ZQNUSKSABULBKW-UHFFFAOYSA-N 4-[3-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]propoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCCOC1=CC=C(C(O)=O)C=C1 ZQNUSKSABULBKW-UHFFFAOYSA-N 0.000 claims description 3
GSJZLFRKBUYLMS-UHFFFAOYSA-N 4-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]butanoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C1CCN(CCCC(O)=O)CC1 GSJZLFRKBUYLMS-UHFFFAOYSA-N 0.000 claims description 3
OXHXNKZDMZXUTB-UHFFFAOYSA-N 4-[[4-[1-(3-methylbutyl)indol-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound C12=CC=CC=C2N(CCC(C)C)C=C1C(CC1)CCN1CC1=CC=C(C(O)=O)C=C1 OXHXNKZDMZXUTB-UHFFFAOYSA-N 0.000 claims description 3
LFRSPOBMQYNXFG-UHFFFAOYSA-N 5-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]pentanoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C1CCN(CCCCC(O)=O)CC1 LFRSPOBMQYNXFG-UHFFFAOYSA-N 0.000 claims description 3
KRYXUSSKEZBOCT-UHFFFAOYSA-N 5-[[4-(6-fluoro-1-pentylindol-3-yl)piperidin-1-yl]methyl]furan-2-carboxylic acid Chemical compound C12=CC=C(F)C=C2N(CCCCC)C=C1C(CC1)CCN1CC1=CC=C(C(O)=O)O1 KRYXUSSKEZBOCT-UHFFFAOYSA-N 0.000 claims description 3
RPRFEVOJAYPEJO-UHFFFAOYSA-N 6-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]hexanoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C1CCN(CCCCCC(O)=O)CC1 RPRFEVOJAYPEJO-UHFFFAOYSA-N 0.000 claims description 3
VCBNVCSDTOKKOV-UHFFFAOYSA-N 7-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]heptanoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C1CCN(CCCCCCC(O)=O)CC1 VCBNVCSDTOKKOV-UHFFFAOYSA-N 0.000 claims description 3
206010010741 Conjunctivitis Diseases 0.000 claims description 3
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
229910052731 fluorine Inorganic materials 0.000 claims description 3
229910052736 halogen Inorganic materials 0.000 claims description 3
150000002367 halogens Chemical class 0.000 claims description 3
125000002560 nitrile group Chemical group 0.000 claims description 3
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 3
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 3
ISRNSOPKRJFRMR-UHFFFAOYSA-N 1-(3-methylbutyl)-3-[1-[3-[2-(2h-tetrazol-5-yl)phenoxy]propyl]piperidin-4-yl]indole Chemical compound C12=CC=CC=C2N(CCC(C)C)C=C1C(CC1)CCN1CCCOC1=CC=CC=C1C=1N=NNN=1 ISRNSOPKRJFRMR-UHFFFAOYSA-N 0.000 claims description 2
ZDRUIODKMKJGOJ-UHFFFAOYSA-N 1-(3-methylbutyl)-3-[1-[3-[4-(2h-tetrazol-5-yl)phenoxy]propyl]piperidin-4-yl]indole Chemical compound C12=CC=CC=C2N(CCC(C)C)C=C1C(CC1)CCN1CCCOC(C=C1)=CC=C1C=1N=NNN=1 ZDRUIODKMKJGOJ-UHFFFAOYSA-N 0.000 claims description 2
ZSHYMGAUWNATNK-UHFFFAOYSA-N 2-[2-[4-(1-heptylindol-3-yl)piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCCCCCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O ZSHYMGAUWNATNK-UHFFFAOYSA-N 0.000 claims description 2
MRFSVLXYLQZTHT-UHFFFAOYSA-N 2-[2-[4-(1-pentylindol-3-yl)piperidin-1-yl]ethoxy]acetic acid Chemical compound C12=CC=CC=C2N(CCCCC)C=C1C1CCN(CCOCC(O)=O)CC1 MRFSVLXYLQZTHT-UHFFFAOYSA-N 0.000 claims description 2
HOLMXWXLIIOTTC-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-5-methoxyindol-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound C12=CC(OC)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC(OC)=CC=C1C(O)=O HOLMXWXLIIOTTC-UHFFFAOYSA-N 0.000 claims description 2
DTTZVMYXKPDNIC-UHFFFAOYSA-N 2-[2-[4-[1-[2-(2-methoxyethoxy)ethyl]indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCOCCOC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O DTTZVMYXKPDNIC-UHFFFAOYSA-N 0.000 claims description 2
BSFXTWGBUDAOAO-UHFFFAOYSA-N 2-[4-[3-[4-(1h-indol-3-yl)piperidin-1-yl]propoxy]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OCCCN1CCC(C=2C3=CC=CC=C3NC=2)CC1 BSFXTWGBUDAOAO-UHFFFAOYSA-N 0.000 claims description 2
CRZAKQGJEZICFO-UHFFFAOYSA-N 2-[4-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]butylsulfanyl]acetic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C1CCN(CCCCSCC(O)=O)CC1 CRZAKQGJEZICFO-UHFFFAOYSA-N 0.000 claims description 2
NPNSJRPLUBCWJW-UHFFFAOYSA-N 2-[4-[4-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]-1-hydroxybutyl]phenyl]-2-methylpropanoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCCC(O)C1=CC=C(C(C)(C)C(O)=O)C=C1 NPNSJRPLUBCWJW-UHFFFAOYSA-N 0.000 claims description 2
CGNGYPTWJXUOHE-UHFFFAOYSA-N 2-[[4-[1-(3-methylbutyl)indol-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound C12=CC=CC=C2N(CCC(C)C)C=C1C(CC1)CCN1CC1=CC=CC=C1C(O)=O CGNGYPTWJXUOHE-UHFFFAOYSA-N 0.000 claims description 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
XQWHUXXNURFZIU-UHFFFAOYSA-N 3,5-dibromo-2-[2-[4-[1-(2-ethoxyethyl)-6-fluoroindol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=C(F)C=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=C(Br)C=C(Br)C=C1C(O)=O XQWHUXXNURFZIU-UHFFFAOYSA-N 0.000 claims description 2
ATXRPHCEPHCREN-UHFFFAOYSA-N 3,5-dibromo-2-[2-[4-[5-bromo-1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC(Br)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=C(Br)C=C(Br)C=C1C(O)=O ATXRPHCEPHCREN-UHFFFAOYSA-N 0.000 claims description 2
VPOOFOBSBKIDGC-UHFFFAOYSA-N 3,5-dibromo-2-[2-[4-[7-bromo-1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC(Br)=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=C(Br)C=C(Br)C=C1C(O)=O VPOOFOBSBKIDGC-UHFFFAOYSA-N 0.000 claims description 2
GTBCYXXNEKLWEN-UHFFFAOYSA-N 3-[3-[4-(1-pentylindol-3-yl)piperidin-1-yl]propoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCCCC)C=C1C(CC1)CCN1CCCOC1=CC=CC(C(O)=O)=C1 GTBCYXXNEKLWEN-UHFFFAOYSA-N 0.000 claims description 2
WJOOEDOCJSIGIS-UHFFFAOYSA-N 3-[4-[2-[4-(1-pentylindol-3-yl)piperidin-1-yl]ethyl]phenyl]prop-2-enoic acid Chemical compound C12=CC=CC=C2N(CCCCC)C=C1C(CC1)CCN1CCC1=CC=C(C=CC(O)=O)C=C1 WJOOEDOCJSIGIS-UHFFFAOYSA-N 0.000 claims description 2
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
125000005452 alkenyloxyalkyl group Chemical group 0.000 claims description 2
150000001540 azides Chemical class 0.000 claims description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
125000001309 chloro group Chemical group Cl* 0.000 claims description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims description 2
239000011737 fluorine Substances 0.000 claims description 2
125000001153 fluoro group Chemical group F* 0.000 claims description 2
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
125000003884 phenylalkyl group Chemical group 0.000 claims description 2
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
125000004368 propenyl group Chemical group C(=CC)* 0.000 claims description 2
125000006225 propoxyethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 claims description 2
206010039083 rhinitis Diseases 0.000 claims description 2
208000017520 skin disease Diseases 0.000 claims description 2
125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 claims description 2
150000002431 hydrogen Chemical class 0.000 claims 2
YGMUXTWULKXKAO-UHFFFAOYSA-N 1-(2-ethoxyethyl)-3-[1-[3-[2-(2h-tetrazol-5-yl)phenoxy]propyl]piperidin-4-yl]indole Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCCOC1=CC=CC=C1C=1N=NNN=1 YGMUXTWULKXKAO-UHFFFAOYSA-N 0.000 claims 1
125000003352 4-tert-butyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
GCWMEINFHKQNRQ-UHFFFAOYSA-N C1(CC1)CN1C=C(C2=CC=CC=C12)C1CCN(CC1)CCOC1=CC=C(C=C1)CC(=O)O.C1(CC1)CN1C=C(C2=CC=CC=C12)C1CCN(CC1)CCCOC=1C=C(C=CC1)CC(=O)O Chemical compound C1(CC1)CN1C=C(C2=CC=CC=C12)C1CCN(CC1)CCOC1=CC=C(C=C1)CC(=O)O.C1(CC1)CN1C=C(C2=CC=CC=C12)C1CCN(CC1)CCCOC=1C=C(C=CC1)CC(=O)O GCWMEINFHKQNRQ-UHFFFAOYSA-N 0.000 claims 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 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 claims 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
125000004855 decalinyl group Chemical group C1(CCCC2CCCCC12)* 0.000 claims 1
125000006229 isopropoxyethyl group Chemical group [H]C([H])([H])C([H])(OC([H])([H])C([H])([H])*)C([H])([H])[H] 0.000 claims 1
CGCYGGUXGRIGKA-UHFFFAOYSA-N methyl 2-(2-ethoxyethyl)benzoate Chemical compound C(C)OCCC1=C(C(=O)OC)C=CC=C1 CGCYGGUXGRIGKA-UHFFFAOYSA-N 0.000 claims 1
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 59
239000012043 crude product Substances 0.000 description 49
KAIRZPVWWIMPFT-UHFFFAOYSA-N 3-piperidin-4-yl-1h-indole Chemical compound C1CNCCC1C1=CNC2=CC=CC=C12 KAIRZPVWWIMPFT-UHFFFAOYSA-N 0.000 description 47
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 42
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
239000000047 product Substances 0.000 description 37
239000002904 solvent Substances 0.000 description 37
239000000243 solution Substances 0.000 description 35
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 33
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 30
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 27
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 24
239000012312 sodium hydride Substances 0.000 description 24
229910000104 sodium hydride Inorganic materials 0.000 description 24
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 16
238000006243 chemical reaction Methods 0.000 description 16
MMYKTRPLXXWLBC-UHFFFAOYSA-N 1-bromo-2-ethoxyethane Chemical compound CCOCCBr MMYKTRPLXXWLBC-UHFFFAOYSA-N 0.000 description 15
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
235000019441 ethanol Nutrition 0.000 description 15
239000002480 mineral oil Substances 0.000 description 15
235000010446 mineral oil Nutrition 0.000 description 15
229910000027 potassium carbonate Inorganic materials 0.000 description 15
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
239000011541 reaction mixture Substances 0.000 description 14
238000010898 silica gel chromatography Methods 0.000 description 14
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
239000000725 suspension Substances 0.000 description 13
HUXJXNSHCKHFIL-UHFFFAOYSA-N 1-(2-bromoethoxy)-2-methoxyethane Chemical compound COCCOCCBr HUXJXNSHCKHFIL-UHFFFAOYSA-N 0.000 description 12
BLXSFCHWMBESKV-UHFFFAOYSA-N 1-iodopentane Chemical compound CCCCCI BLXSFCHWMBESKV-UHFFFAOYSA-N 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 11
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 11
241000700159 Rattus Species 0.000 description 11
IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 10
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
239000012044 organic layer Substances 0.000 description 10
238000003818 flash chromatography Methods 0.000 description 9
239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
239000007787 solid Substances 0.000 description 9
NVNPLEPBDPJYRZ-UHFFFAOYSA-N 1-(bromomethyl)-4-fluorobenzene Chemical compound FC1=CC=C(CBr)C=C1 NVNPLEPBDPJYRZ-UHFFFAOYSA-N 0.000 description 8
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 8
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 8
WLIZJZBJHVKCLV-UHFFFAOYSA-N methyl 2-[2-[4-(1h-indol-3-yl)piperidin-1-yl]ethoxy]benzoate Chemical compound COC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CC=C3NC=2)CC1 WLIZJZBJHVKCLV-UHFFFAOYSA-N 0.000 description 8
239000003826 tablet Substances 0.000 description 8
238000012360 testing method Methods 0.000 description 8
239000003960 organic solvent Substances 0.000 description 7
238000003756 stirring Methods 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
238000009739 binding Methods 0.000 description 6
210000004556 brain Anatomy 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
150000007529 inorganic bases Chemical class 0.000 description 6
GCCYBNZBCGRHRR-UHFFFAOYSA-N methyl 2-(2-chloroethoxy)benzoate Chemical compound COC(=O)C1=CC=CC=C1OCCCl GCCYBNZBCGRHRR-UHFFFAOYSA-N 0.000 description 6
150000004702 methyl esters Chemical class 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
238000010626 work up procedure Methods 0.000 description 6
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 5
230000029936 alkylation Effects 0.000 description 5
238000005804 alkylation reaction Methods 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical group OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 5
230000027455 binding Effects 0.000 description 5
230000036772 blood pressure Effects 0.000 description 5
SXWRTZOXMUOJER-UHFFFAOYSA-N hydron;piperidin-4-one;chloride;hydrate Chemical compound O.Cl.O=C1CCNCC1 SXWRTZOXMUOJER-UHFFFAOYSA-N 0.000 description 5
239000007788 liquid Substances 0.000 description 5
239000012048 reactive intermediate Substances 0.000 description 5
OFWCNOZEQASQHY-UHFFFAOYSA-N 1-(cyclopropylmethyl)-3-piperidin-4-ylindole Chemical compound C1=C(C2CCNCC2)C2=CC=CC=C2N1CC1CC1 OFWCNOZEQASQHY-UHFFFAOYSA-N 0.000 description 4
IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
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 4
241000699670 Mus sp. Species 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
238000009835 boiling Methods 0.000 description 4
239000002775 capsule Substances 0.000 description 4
238000001816 cooling Methods 0.000 description 4
239000006185 dispersion Substances 0.000 description 4
CVYKQPLWSDHSSV-UHFFFAOYSA-N ethyl 2-(2-chloroethoxy)acetate Chemical compound CCOC(=O)COCCCl CVYKQPLWSDHSSV-UHFFFAOYSA-N 0.000 description 4
VLSMHUVSLGUZOS-UHFFFAOYSA-N ethyl 4-(1h-indol-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1C1=CNC2=CC=CC=C12 VLSMHUVSLGUZOS-UHFFFAOYSA-N 0.000 description 4
OPXNFHAILOHHFO-UHFFFAOYSA-N ethyl 4-chlorobutanoate Chemical compound CCOC(=O)CCCCl OPXNFHAILOHHFO-UHFFFAOYSA-N 0.000 description 4
YDRFUQMSLPYQCI-UHFFFAOYSA-N ethyl 5-(bromomethyl)furan-2-carboxylate Chemical compound CCOC(=O)C1=CC=C(CBr)O1 YDRFUQMSLPYQCI-UHFFFAOYSA-N 0.000 description 4
238000001914 filtration Methods 0.000 description 4
229960001340 histamine Drugs 0.000 description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
ZOCKCIAIJHNKCW-UHFFFAOYSA-N methyl 2-(2-chloropropoxy)benzoate Chemical compound COC(=O)C1=CC=CC=C1OCC(C)Cl ZOCKCIAIJHNKCW-UHFFFAOYSA-N 0.000 description 4
TXMXVNPSFXZYJO-UHFFFAOYSA-N methyl 3-(2-chloroethoxy)benzoate Chemical compound COC(=O)C1=CC=CC(OCCCl)=C1 TXMXVNPSFXZYJO-UHFFFAOYSA-N 0.000 description 4
MSPVYVUNDLKMQN-UHFFFAOYSA-N methyl 3-(2-chloropropoxy)benzoate Chemical compound COC(=O)C1=CC=CC(OCC(C)Cl)=C1 MSPVYVUNDLKMQN-UHFFFAOYSA-N 0.000 description 4
150000007522 mineralic acids Chemical class 0.000 description 4
229910052757 nitrogen Inorganic materials 0.000 description 4
102000005962 receptors Human genes 0.000 description 4
108020003175 receptors Proteins 0.000 description 4
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
DUCZGLRXKNHEME-UHFFFAOYSA-N 1-(2-ethoxyethyl)-3-[1-[3-[4-(2h-tetrazol-5-yl)phenoxy]propyl]piperidin-4-yl]indole Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCCOC(C=C1)=CC=C1C=1N=NNN=1 DUCZGLRXKNHEME-UHFFFAOYSA-N 0.000 description 3
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
AARSYHRXVGSQHM-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-5-methoxyindol-3-yl]piperidin-1-yl]ethoxy]-5-methylbenzoic acid Chemical compound C12=CC(OC)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=C(C)C=C1C(O)=O AARSYHRXVGSQHM-UHFFFAOYSA-N 0.000 description 3
ZTNVVIAVLGPZSF-UHFFFAOYSA-N 3,5-dibromo-2-[2-[4-[1-(2-ethoxyethyl)-5-fluoroindol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC(F)=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=C(Br)C=C(Br)C=C1C(O)=O ZTNVVIAVLGPZSF-UHFFFAOYSA-N 0.000 description 3
FYBVBVZJKYOUFZ-UHFFFAOYSA-N 3-[4-[2-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethyl]phenyl]prop-2-enoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCC1=CC=C(C=CC(O)=O)C=C1 FYBVBVZJKYOUFZ-UHFFFAOYSA-N 0.000 description 3
ZJDCJZOQZJFGQK-UHFFFAOYSA-N 3-[4-[2-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethyl]phenyl]propanoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCC1=CC=C(CCC(O)=O)C=C1 ZJDCJZOQZJFGQK-UHFFFAOYSA-N 0.000 description 3
JWCRKHFKVHMTRJ-UHFFFAOYSA-N 3-[4-[2-[4-[1-[2-(2-methoxyethoxy)ethyl]indol-3-yl]piperidin-1-yl]ethyl]phenyl]prop-2-enoic acid Chemical compound C12=CC=CC=C2N(CCOCCOC)C=C1C(CC1)CCN1CCC1=CC=C(C=CC(O)=O)C=C1 JWCRKHFKVHMTRJ-UHFFFAOYSA-N 0.000 description 3
QEYMMOKECZBKAC-UHFFFAOYSA-N 3-chloropropanoic acid Chemical compound OC(=O)CCCl QEYMMOKECZBKAC-UHFFFAOYSA-N 0.000 description 3
ZEYHEAKUIGZSGI-UHFFFAOYSA-N 4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-N 0.000 description 3
AQSCHALQLXXKKC-UHFFFAOYSA-N 4-phenylmethoxybenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OCC1=CC=CC=C1 AQSCHALQLXXKKC-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
206010020772 Hypertension Diseases 0.000 description 3
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
239000004793 Polystyrene Substances 0.000 description 3
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
239000012267 brine Substances 0.000 description 3
239000007795 chemical reaction product Substances 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
239000012230 colorless oil Substances 0.000 description 3
125000001316 cycloalkyl alkyl group Chemical group 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
150000002148 esters Chemical class 0.000 description 3
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
239000000796 flavoring agent Substances 0.000 description 3
235000013355 food flavoring agent Nutrition 0.000 description 3
230000005764 inhibitory process Effects 0.000 description 3
239000008101 lactose Substances 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
239000012528 membrane Substances 0.000 description 3
YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 3
GHEGIGQXTBCPKN-UHFFFAOYSA-N methyl 4-(2-chloropropoxy)benzoate Chemical compound COC(=O)C1=CC=C(OCC(C)Cl)C=C1 GHEGIGQXTBCPKN-UHFFFAOYSA-N 0.000 description 3
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 3
238000012544 monitoring process Methods 0.000 description 3
125000002950 monocyclic group Chemical group 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
230000035515 penetration Effects 0.000 description 3
229920000642 polymer Polymers 0.000 description 3
229920002223 polystyrene Polymers 0.000 description 3
238000000746 purification Methods 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
239000006188 syrup Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
APWRZPQBPCAXFP-UHFFFAOYSA-N 1-(1-oxo-2H-isoquinolin-5-yl)-5-(trifluoromethyl)-N-[2-(trifluoromethyl)pyridin-4-yl]pyrazole-4-carboxamide Chemical compound O=C1NC=CC2=C(C=CC=C12)N1N=CC(=C1C(F)(F)F)C(=O)NC1=CC(=NC=C1)C(F)(F)F APWRZPQBPCAXFP-UHFFFAOYSA-N 0.000 description 2
FOZVXADQAHVUSV-UHFFFAOYSA-N 1-bromo-2-(2-bromoethoxy)ethane Chemical compound BrCCOCCBr FOZVXADQAHVUSV-UHFFFAOYSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
VMEWUJUJGKNDJZ-UHFFFAOYSA-N 2-[2-[4-(1-hexylindol-3-yl)piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCCCCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O VMEWUJUJGKNDJZ-UHFFFAOYSA-N 0.000 description 2
KTEZZEXASTZNJG-UHFFFAOYSA-N 2-[2-[4-(1-prop-2-enylindol-3-yl)piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CC=C3N(CC=C)C=2)CC1 KTEZZEXASTZNJG-UHFFFAOYSA-N 0.000 description 2
MLJHIRXKQLQHRL-UHFFFAOYSA-N 2-[2-[4-(1-propylindol-3-yl)piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O MLJHIRXKQLQHRL-UHFFFAOYSA-N 0.000 description 2
WUAPZVZDCHYLGI-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)-7-methylindol-3-yl]piperidin-1-yl]ethoxy]-5-methylbenzoic acid Chemical compound C12=CC=CC(C)=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=C(C)C=C1C(O)=O WUAPZVZDCHYLGI-UHFFFAOYSA-N 0.000 description 2
XUYOZHRTHKAKTL-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]-5-methylbenzoic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=C(C)C=C1C(O)=O XUYOZHRTHKAKTL-UHFFFAOYSA-N 0.000 description 2
GGZYFZOALZISQV-UHFFFAOYSA-N 2-[2-[4-[1-(2-propan-2-yloxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCOC(C)C)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O GGZYFZOALZISQV-UHFFFAOYSA-N 0.000 description 2
VGRHRQOHLGEVIC-UHFFFAOYSA-N 2-[2-[4-[1-[(4-tert-butylphenyl)methyl]indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1CN1C2=CC=CC=C2C(C2CCN(CCOC=3C(=CC=CC=3)C(O)=O)CC2)=C1 VGRHRQOHLGEVIC-UHFFFAOYSA-N 0.000 description 2
LEBSVPBBFMPHOV-UHFFFAOYSA-N 2-[3-[2-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]phenyl]acetic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC(CC(O)=O)=C1 LEBSVPBBFMPHOV-UHFFFAOYSA-N 0.000 description 2
FUDVVNJRXLXUKM-UHFFFAOYSA-N 2-[3-[2-[4-[1-(3-methylbutyl)indol-3-yl]piperidin-1-yl]ethoxy]phenyl]acetic acid Chemical compound C12=CC=CC=C2N(CCC(C)C)C=C1C(CC1)CCN1CCOC1=CC=CC(CC(O)=O)=C1 FUDVVNJRXLXUKM-UHFFFAOYSA-N 0.000 description 2
IJUCLZALAYNRPO-UHFFFAOYSA-N 2-[3-[2-[4-[1-(cyclopropylmethyl)indol-3-yl]piperidin-1-yl]ethoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OCCN2CCC(CC2)C=2C3=CC=CC=C3N(CC3CC3)C=2)=C1 IJUCLZALAYNRPO-UHFFFAOYSA-N 0.000 description 2
LCYYTYJEGJBMTO-UHFFFAOYSA-N 2-[3-[3-[4-[1-(3-methylbutyl)indol-3-yl]piperidin-1-yl]propoxy]phenyl]acetic acid Chemical compound C12=CC=CC=C2N(CCC(C)C)C=C1C(CC1)CCN1CCCOC1=CC=CC(CC(O)=O)=C1 LCYYTYJEGJBMTO-UHFFFAOYSA-N 0.000 description 2
CTKWLGZRRZMJMB-UHFFFAOYSA-N 2-[3-[3-[4-[1-(cyclopropylmethyl)indol-3-yl]piperidin-1-yl]propoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OCCCN2CCC(CC2)C=2C3=CC=CC=C3N(CC3CC3)C=2)=C1 CTKWLGZRRZMJMB-UHFFFAOYSA-N 0.000 description 2
PBVWEHJOAGLFKQ-UHFFFAOYSA-N 2-[4-[1-hydroxy-4-[4-[1-[2-(2-methoxyethoxy)ethyl]indol-3-yl]piperidin-1-yl]butyl]phenyl]-2-methylpropanoic acid Chemical compound C12=CC=CC=C2N(CCOCCOC)C=C1C(CC1)CCN1CCCC(O)C1=CC=C(C(C)(C)C(O)=O)C=C1 PBVWEHJOAGLFKQ-UHFFFAOYSA-N 0.000 description 2
HCBSJRILLFNCKC-UHFFFAOYSA-N 2-[4-[2-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]phenyl]acetic acid Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=C(CC(O)=O)C=C1 HCBSJRILLFNCKC-UHFFFAOYSA-N 0.000 description 2
SGBLMQWCBQDBDP-UHFFFAOYSA-N 2-[4-[2-[4-[1-(3-methylbutyl)indol-3-yl]piperidin-1-yl]ethoxy]phenyl]acetic acid Chemical compound C12=CC=CC=C2N(CCC(C)C)C=C1C(CC1)CCN1CCOC1=CC=C(CC(O)=O)C=C1 SGBLMQWCBQDBDP-UHFFFAOYSA-N 0.000 description 2
DXTGTULLPMCNRT-UHFFFAOYSA-N 2-[4-[3-[4-[1-(cyclopropylmethyl)indol-3-yl]piperidin-1-yl]propoxy]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OCCCN1CCC(C=2C3=CC=CC=C3N(CC3CC3)C=2)CC1 DXTGTULLPMCNRT-UHFFFAOYSA-N 0.000 description 2
YIDKOXXGEVBKAK-UHFFFAOYSA-N 2-[4-[4-[4-(1h-indol-3-yl)piperidin-1-yl]butanoyl]phenyl]-2-methylpropanoic acid Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(=O)CCCN1CCC(C=2C3=CC=CC=C3NC=2)CC1 YIDKOXXGEVBKAK-UHFFFAOYSA-N 0.000 description 2
HSZAPOCHXKEKDI-UHFFFAOYSA-N 2-[[4-(1h-indol-3-yl)piperidin-1-yl]methyl]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1CN1CCC(C=2C3=CC=CC=C3NC=2)CC1 HSZAPOCHXKEKDI-UHFFFAOYSA-N 0.000 description 2
XDZMPRGFOOFSBL-UHFFFAOYSA-N 2-ethoxybenzoic acid Chemical compound CCOC1=CC=CC=C1C(O)=O XDZMPRGFOOFSBL-UHFFFAOYSA-N 0.000 description 2
WLODJVVNLOYYEE-UHFFFAOYSA-N 2-propoxybenzonitrile Chemical compound CCCOC1=CC=CC=C1C#N WLODJVVNLOYYEE-UHFFFAOYSA-N 0.000 description 2
BYHQTRFJOGIQAO-GOSISDBHSA-N 3-(4-bromophenyl)-8-[(2R)-2-hydroxypropyl]-1-[(3-methoxyphenyl)methyl]-1,3,8-triazaspiro[4.5]decan-2-one Chemical compound C[C@H](CN1CCC2(CC1)CN(C(=O)N2CC3=CC(=CC=C3)OC)C4=CC=C(C=C4)Br)O BYHQTRFJOGIQAO-GOSISDBHSA-N 0.000 description 2
ZSGZESFWXBUNED-UHFFFAOYSA-N 3-[4-[1-[2-(2-methoxyethoxy)ethyl]indol-3-yl]piperidin-1-yl]propanoic acid Chemical compound C12=CC=CC=C2N(CCOCCOC)C=C1C1CCN(CCC(O)=O)CC1 ZSGZESFWXBUNED-UHFFFAOYSA-N 0.000 description 2
BSOAULUNXQUENG-UHFFFAOYSA-N 3-[[4-(1h-indol-3-yl)piperidin-1-yl]methyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(CN2CCC(CC2)C=2C3=CC=CC=C3NC=2)=C1 BSOAULUNXQUENG-UHFFFAOYSA-N 0.000 description 2
GZMZUFPMBUYDFX-UHFFFAOYSA-N 4-[3-[4-[1-[2-(2-methoxyethoxy)ethyl]indol-3-yl]piperidin-1-yl]propoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCOCCOC)C=C1C(CC1)CCN1CCCOC1=CC=C(C(O)=O)C=C1 GZMZUFPMBUYDFX-UHFFFAOYSA-N 0.000 description 2
HNCNMZFVAQIQSN-UHFFFAOYSA-N 4-[4-[1-[2-(2-methoxyethoxy)ethyl]indol-3-yl]piperidin-1-yl]butanoic acid Chemical compound C12=CC=CC=C2N(CCOCCOC)C=C1C1CCN(CCCC(O)=O)CC1 HNCNMZFVAQIQSN-UHFFFAOYSA-N 0.000 description 2
VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 2
KCBWAFJCKVKYHO-UHFFFAOYSA-N 6-(4-cyclopropyl-6-methoxypyrimidin-5-yl)-1-[[4-[1-propan-2-yl-4-(trifluoromethyl)imidazol-2-yl]phenyl]methyl]pyrazolo[3,4-d]pyrimidine Chemical compound C1(CC1)C1=NC=NC(=C1C1=NC=C2C(=N1)N(N=C2)CC1=CC=C(C=C1)C=1N(C=C(N=1)C(F)(F)F)C(C)C)OC KCBWAFJCKVKYHO-UHFFFAOYSA-N 0.000 description 2
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
229920002785 Croscarmellose sodium Polymers 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
IDRGFNPZDVBSSE-UHFFFAOYSA-N OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F Chemical compound OCCN1CCN(CC1)c1ccc(Nc2ncc3cccc(-c4cccc(NC(=O)C=C)c4)c3n2)c(F)c1F IDRGFNPZDVBSSE-UHFFFAOYSA-N 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
206010039085 Rhinitis allergic Diseases 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
230000009471 action Effects 0.000 description 2
125000002252 acyl group Chemical group 0.000 description 2
229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
150000008041 alkali metal carbonates Chemical class 0.000 description 2
125000005907 alkyl ester group Chemical group 0.000 description 2
230000002152 alkylating effect Effects 0.000 description 2
201000010105 allergic rhinitis Diseases 0.000 description 2
BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
238000003556 assay Methods 0.000 description 2
DCBDOYDVQJVXOH-UHFFFAOYSA-N azane;1h-indole Chemical compound N.C1=CC=C2NC=CC2=C1 DCBDOYDVQJVXOH-UHFFFAOYSA-N 0.000 description 2
239000002585 base Substances 0.000 description 2
AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 2
125000002843 carboxylic acid group Chemical group 0.000 description 2
210000000748 cardiovascular system Anatomy 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 2
235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
TZDFSADZWOUTMD-UHFFFAOYSA-N ethyl 4-(2-chloroethoxy)benzoate Chemical compound CCOC(=O)C1=CC=C(OCCCl)C=C1 TZDFSADZWOUTMD-UHFFFAOYSA-N 0.000 description 2
MGJQLAVGTCFPLT-UHFFFAOYSA-N ethyl 4-[1-(2-ethoxyethyl)indol-3-yl]piperidine-1-carboxylate Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C1CCN(C(=O)OCC)CC1 MGJQLAVGTCFPLT-UHFFFAOYSA-N 0.000 description 2
CKLXTORLESCEPD-UHFFFAOYSA-N ethyl 4-[1-(cyclopropylmethyl)indol-3-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1C(C1=CC=CC=C11)=CN1CC1CC1 CKLXTORLESCEPD-UHFFFAOYSA-N 0.000 description 2
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 2
FKRCODPIKNYEAC-UHFFFAOYSA-N ethyl propionate Chemical compound CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 2
238000000605 extraction Methods 0.000 description 2
229960003592 fexofenadine Drugs 0.000 description 2
235000011187 glycerol Nutrition 0.000 description 2
230000000004 hemodynamic effect Effects 0.000 description 2
230000007062 hydrolysis Effects 0.000 description 2
238000006460 hydrolysis reaction Methods 0.000 description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
230000001631 hypertensive effect Effects 0.000 description 2
150000002475 indoles Chemical class 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
239000007791 liquid phase Substances 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
238000002844 melting Methods 0.000 description 2
230000008018 melting Effects 0.000 description 2
229960000582 mepyramine Drugs 0.000 description 2
IOQQUBVUSXJNKN-UHFFFAOYSA-N methyl 2-[2-[4-[1-(2-ethoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoate Chemical compound C12=CC=CC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(=O)OC IOQQUBVUSXJNKN-UHFFFAOYSA-N 0.000 description 2
KRCMKUNIILUXPF-UHFFFAOYSA-N methyl 4-hydroxybenzoate;sodium Chemical compound [Na].COC(=O)C1=CC=C(O)C=C1 KRCMKUNIILUXPF-UHFFFAOYSA-N 0.000 description 2
ZLLQTDQOTFCCDF-UHFFFAOYSA-N methyl 4-phenylmethoxybenzoate Chemical compound C1=CC(C(=O)OC)=CC=C1OCC1=CC=CC=C1 ZLLQTDQOTFCCDF-UHFFFAOYSA-N 0.000 description 2
HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 2
OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
239000003921 oil Substances 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
150000003053 piperidines Chemical class 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
238000001525 receptor binding assay Methods 0.000 description 2
238000010992 reflux Methods 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
239000000932 sedative agent Substances 0.000 description 2
230000001624 sedative effect Effects 0.000 description 2
239000011734 sodium Substances 0.000 description 2
235000019333 sodium laurylsulphate Nutrition 0.000 description 2
239000004290 sodium methyl p-hydroxybenzoate Substances 0.000 description 2
235000010268 sodium methyl p-hydroxybenzoate Nutrition 0.000 description 2
230000009870 specific binding Effects 0.000 description 2
239000000126 substance Substances 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
WHWMOMRHHQLBQQ-UHFFFAOYSA-N tert-butyl 4-hydroxybenzoate Chemical compound CC(C)(C)OC(=O)C1=CC=C(O)C=C1 WHWMOMRHHQLBQQ-UHFFFAOYSA-N 0.000 description 2
150000003536 tetrazoles Chemical group 0.000 description 2
230000008728 vascular permeability Effects 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
MAYZWDRUFKUGGP-VIFPVBQESA-N (3s)-1-[5-tert-butyl-3-[(1-methyltetrazol-5-yl)methyl]triazolo[4,5-d]pyrimidin-7-yl]pyrrolidin-3-ol Chemical compound CN1N=NN=C1CN1C2=NC(C(C)(C)C)=NC(N3C[C@@H](O)CC3)=C2N=N1 MAYZWDRUFKUGGP-VIFPVBQESA-N 0.000 description 1
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
ZGYIXVSQHOKQRZ-COIATFDQSA-N (e)-n-[4-[3-chloro-4-(pyridin-2-ylmethoxy)anilino]-3-cyano-7-[(3s)-oxolan-3-yl]oxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N#CC1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC(C=C1Cl)=CC=C1OCC1=CC=CC=N1 ZGYIXVSQHOKQRZ-COIATFDQSA-N 0.000 description 1
DYEPMDSJNIXHHO-UHFFFAOYSA-N 1,2,2,4-tetramethyl-6-[phenyl-(1,2,2,4-tetramethylquinolin-6-yl)methyl]quinoline Chemical compound C1=C2C(C)=CC(C)(C)N(C)C2=CC=C1C(C=1C=C2C(C)=CC(C)(C)N(C)C2=CC=1)C1=CC=CC=C1 DYEPMDSJNIXHHO-UHFFFAOYSA-N 0.000 description 1
BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
ODTKBCUBSAPRBP-UHFFFAOYSA-N 1-bromo-1-(2-methoxyethoxy)ethane Chemical compound COCCOC(C)Br ODTKBCUBSAPRBP-UHFFFAOYSA-N 0.000 description 1
RMSGQZDGSZOJMU-UHFFFAOYSA-N 1-butyl-2-phenylbenzene Chemical group CCCCC1=CC=CC=C1C1=CC=CC=C1 RMSGQZDGSZOJMU-UHFFFAOYSA-N 0.000 description 1
GPTVQTPMFOLLOA-UHFFFAOYSA-N 1-chloro-2-ethoxyethane Chemical compound CCOCCCl GPTVQTPMFOLLOA-UHFFFAOYSA-N 0.000 description 1
BUZZUHJODKQYTF-UHFFFAOYSA-N 1-iodo-3-methylbutane Chemical compound CC(C)CCI BUZZUHJODKQYTF-UHFFFAOYSA-N 0.000 description 1
ANOOTOPTCJRUPK-UHFFFAOYSA-N 1-iodohexane Chemical compound CCCCCCI ANOOTOPTCJRUPK-UHFFFAOYSA-N 0.000 description 1
GCUOLJOTJRUDIZ-UHFFFAOYSA-N 2-(2-bromoethoxy)oxane Chemical compound BrCCOC1CCCCO1 GCUOLJOTJRUDIZ-UHFFFAOYSA-N 0.000 description 1
KJTANRPLBRWASS-UHFFFAOYSA-N 2-[2-[4-(1H-indol-3-yl)piperidin-1-yl]ethoxy]-3-methylbenzoic acid Chemical compound CC=1C(=C(C(=O)O)C=CC=1)OCCN1CCC(CC1)C1=CNC2=CC=CC=C12 KJTANRPLBRWASS-UHFFFAOYSA-N 0.000 description 1
LDOBTNXVDQXNQO-UHFFFAOYSA-N 2-[2-[4-[1-(2-hydroxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CC=C2N(CCO)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O LDOBTNXVDQXNQO-UHFFFAOYSA-N 0.000 description 1
XEQHNEYQMZPAAB-UHFFFAOYSA-N 2-[2-[4-[1-(2-prop-2-ynoxyethyl)indol-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CC=C3N(CCOCC#C)C=2)CC1 XEQHNEYQMZPAAB-UHFFFAOYSA-N 0.000 description 1
JIDPRKZOSRHXNH-UHFFFAOYSA-N 2-[3-[3-[4-(1h-indol-3-yl)piperidin-1-yl]propoxy]phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(OCCCN2CCC(CC2)C=2C3=CC=CC=C3NC=2)=C1 JIDPRKZOSRHXNH-UHFFFAOYSA-N 0.000 description 1
DSPLILVIUCKNHL-UHFFFAOYSA-N 2-[4-(3-chloropropoxy)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=C(OCCCCl)C=C1 DSPLILVIUCKNHL-UHFFFAOYSA-N 0.000 description 1
KBRRQKNQGRVNGK-UHFFFAOYSA-N 2-[4-[2-[4-[1-(cyclopropylmethyl)indol-3-yl]piperidin-1-yl]ethoxy]phenyl]acetic acid Chemical compound C1=CC(CC(=O)O)=CC=C1OCCN1CCC(C=2C3=CC=CC=C3N(CC3CC3)C=2)CC1 KBRRQKNQGRVNGK-UHFFFAOYSA-N 0.000 description 1
VTWFKEXRCDULPU-UHFFFAOYSA-N 2-[4-[3-[4-[1-(3-methylbutyl)indol-3-yl]piperidin-1-yl]propoxy]phenyl]acetic acid Chemical compound C12=CC=CC=C2N(CCC(C)C)C=C1C(CC1)CCN1CCCOC1=CC=C(CC(O)=O)C=C1 VTWFKEXRCDULPU-UHFFFAOYSA-N 0.000 description 1
IJWCZTXCOOBGNL-UHFFFAOYSA-N 2-ethoxy-3-piperidin-1-ylbenzoic acid Chemical compound C1=CC=C(C(O)=O)C(OCC)=C1N1CCCCC1 IJWCZTXCOOBGNL-UHFFFAOYSA-N 0.000 description 1
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
CIRSPTXGPFAXRE-UHFFFAOYSA-N 3-(1,2,3,6-tetrahydropyridin-4-yl)-1h-indole Chemical compound C1NCCC(C=2C3=CC=CC=C3NC=2)=C1 CIRSPTXGPFAXRE-UHFFFAOYSA-N 0.000 description 1
NOVOKHFRLBAZEC-UHFFFAOYSA-N 3-[4-[2-[4-[1-[2-(2-methoxyethoxy)ethyl]indol-3-yl]piperidin-1-yl]ethyl]phenyl]propanoic acid Chemical compound C12=CC=CC=C2N(CCOCCOC)C=C1C(CC1)CCN1CCC1=CC=C(CCC(O)=O)C=C1 NOVOKHFRLBAZEC-UHFFFAOYSA-N 0.000 description 1
BJGKVCKGUBYULR-UHFFFAOYSA-N 3-bromo-2-methylbenzoic acid Chemical compound CC1=C(Br)C=CC=C1C(O)=O BJGKVCKGUBYULR-UHFFFAOYSA-N 0.000 description 1
ZIUYNDUOFPXUOD-UHFFFAOYSA-N 4-(3-bromopropoxy)benzonitrile Chemical compound BrCCCOC1=CC=C(C#N)C=C1 ZIUYNDUOFPXUOD-UHFFFAOYSA-N 0.000 description 1
LDIIEYJOLCNWAM-UHFFFAOYSA-N 4-[2-[4-(1h-indol-3-yl)piperidin-1-yl]ethoxy]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1OCCN1CCC(C=2C3=CC=CC=C3NC=2)CC1 LDIIEYJOLCNWAM-UHFFFAOYSA-N 0.000 description 1
VQFAITGIMWXQQK-UHFFFAOYSA-N 5-fluoro-3-piperidin-4-yl-1h-indole Chemical compound C12=CC(F)=CC=C2NC=C1C1CCNCC1 VQFAITGIMWXQQK-UHFFFAOYSA-N 0.000 description 1
ODFFPRGJZRXNHZ-UHFFFAOYSA-N 5-fluoroindole Chemical compound FC1=CC=C2NC=CC2=C1 ODFFPRGJZRXNHZ-UHFFFAOYSA-N 0.000 description 1
KRDQQMGVPDMSNR-UHFFFAOYSA-N 5-methoxy-3-piperidin-4-yl-1h-indole Chemical compound C12=CC(OC)=CC=C2NC=C1C1CCNCC1 KRDQQMGVPDMSNR-UHFFFAOYSA-N 0.000 description 1
DWAQDRSOVMLGRQ-UHFFFAOYSA-N 5-methoxyindole Chemical compound COC1=CC=C2NC=CC2=C1 DWAQDRSOVMLGRQ-UHFFFAOYSA-N 0.000 description 1
YPKBCLZFIYBSHK-UHFFFAOYSA-N 5-methylindole Chemical compound CC1=CC=C2NC=CC2=C1 YPKBCLZFIYBSHK-UHFFFAOYSA-N 0.000 description 1
GUMREDIMNGJOEM-UHFFFAOYSA-N 6-[3-[(4-fluorophenoxy)methyl]-4-methoxyphenyl]-9,9-dimethyl-6,8,10,11-tetrahydro-5h-benzo[b][1,4]benzodiazepin-7-one Chemical compound COC1=CC=C(C2C3=C(CC(C)(C)CC3=O)NC3=CC=CC=C3N2)C=C1COC1=CC=C(F)C=C1 GUMREDIMNGJOEM-UHFFFAOYSA-N 0.000 description 1
YYFFEPUCAKVRJX-UHFFFAOYSA-N 6-fluoro-1h-indole Chemical compound FC1=CC=C2C=CNC2=C1 YYFFEPUCAKVRJX-UHFFFAOYSA-N 0.000 description 1
ONYNOPPOVKYGRS-UHFFFAOYSA-N 6-methylindole Natural products CC1=CC=C2C=CNC2=C1 ONYNOPPOVKYGRS-UHFFFAOYSA-N 0.000 description 1
RDSVSEFWZUWZHW-UHFFFAOYSA-N 7-bromo-1h-indole Chemical compound BrC1=CC=CC2=C1NC=C2 RDSVSEFWZUWZHW-UHFFFAOYSA-N 0.000 description 1
MBDGJGKQPDLTKP-UHFFFAOYSA-N 7-bromo-3-piperidin-4-yl-1h-indole Chemical compound C=1NC=2C(Br)=CC=CC=2C=1C1CCNCC1 MBDGJGKQPDLTKP-UHFFFAOYSA-N 0.000 description 1
LAOZOIXDYRKLIP-UHFFFAOYSA-N 7-methyl-3-piperidin-4-yl-1h-indole Chemical compound C=1NC=2C(C)=CC=CC=2C=1C1CCNCC1 LAOZOIXDYRKLIP-UHFFFAOYSA-N 0.000 description 1
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
206010067484 Adverse reaction Diseases 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
206010002091 Anaesthesia Diseases 0.000 description 1
COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
241000700199 Cavia porcellus Species 0.000 description 1
ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
206010010744 Conjunctivitis allergic Diseases 0.000 description 1
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
PXXNTAGJWPJAGM-VCOUNFBDSA-N Decaline Chemical compound C=1([C@@H]2C3)C=C(OC)C(OC)=CC=1OC(C=C1)=CC=C1CCC(=O)O[C@H]3C[C@H]1N2CCCC1 PXXNTAGJWPJAGM-VCOUNFBDSA-N 0.000 description 1
201000004624 Dermatitis Diseases 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
102000003834 Histamine H1 Receptors Human genes 0.000 description 1
108090000110 Histamine H1 Receptors Proteins 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
206010030113 Oedema Diseases 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
241000700157 Rattus norvegicus Species 0.000 description 1
235000004443 Ricinus communis Nutrition 0.000 description 1
WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
206010039897 Sedation Diseases 0.000 description 1
206010058679 Skin oedema Diseases 0.000 description 1
206010040914 Skin reaction Diseases 0.000 description 1
208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
229910000831 Steel Inorganic materials 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
DXGTUUQHTDOFFQ-UHFFFAOYSA-N [N].C1=CC=C2NC=CC2=C1 Chemical group [N].C1=CC=C2NC=CC2=C1 DXGTUUQHTDOFFQ-UHFFFAOYSA-N 0.000 description 1
239000013543 active substance Substances 0.000 description 1
230000006838 adverse reaction Effects 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
201000009961 allergic asthma Diseases 0.000 description 1
208000002205 allergic conjunctivitis Diseases 0.000 description 1
230000000172 allergic effect Effects 0.000 description 1
201000010435 allergic urticaria Diseases 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
235000019270 ammonium chloride Nutrition 0.000 description 1
LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 1
229960003022 amoxicillin Drugs 0.000 description 1
230000037005 anaesthesia Effects 0.000 description 1
238000000540 analysis of variance Methods 0.000 description 1
229940125715 antihistaminic agent Drugs 0.000 description 1
210000000709 aorta Anatomy 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
230000006793 arrhythmia Effects 0.000 description 1
206010003119 arrhythmia Diseases 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
208000024998 atopic conjunctivitis Diseases 0.000 description 1
208000010668 atopic eczema Diseases 0.000 description 1
230000004888 barrier function Effects 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
125000002619 bicyclic group Chemical group 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
238000009530 blood pressure measurement Methods 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
JAMFGQBENKSWOF-UHFFFAOYSA-N bromo(methoxy)methane Chemical compound COCBr JAMFGQBENKSWOF-UHFFFAOYSA-N 0.000 description 1
239000000872 buffer Substances 0.000 description 1
LGBHQFWRSMFRJF-UHFFFAOYSA-N butanedioic acid;oxalic acid Chemical compound OC(=O)C(O)=O.OC(=O)CCC(O)=O LGBHQFWRSMFRJF-UHFFFAOYSA-N 0.000 description 1
KMGBZBJJOKUPIA-UHFFFAOYSA-N butyl iodide Chemical compound CCCCI KMGBZBJJOKUPIA-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
239000004359 castor oil Substances 0.000 description 1
235000019438 castor oil Nutrition 0.000 description 1
229960001803 cetirizine Drugs 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
239000008119 colloidal silica Substances 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000004040 coloring Methods 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
SOYKEARSMXGVTM-HNNXBMFYSA-N dexchlorpheniramine Chemical compound C1([C@H](CCN(C)C)C=2N=CC=CC=2)=CC=C(Cl)C=C1 SOYKEARSMXGVTM-HNNXBMFYSA-N 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000001647 drug administration Methods 0.000 description 1
125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
JBFJILIHJYXGSO-UHFFFAOYSA-N ethyl 2-(2-chloroethoxy)-5-methylbenzoate Chemical compound CCOC(=O)C1=CC(C)=CC=C1OCCCl JBFJILIHJYXGSO-UHFFFAOYSA-N 0.000 description 1
ZGYXABNSOOACGL-UHFFFAOYSA-N ethyl 2-hydroxy-5-methylbenzoate Chemical compound CCOC(=O)C1=CC(C)=CC=C1O ZGYXABNSOOACGL-UHFFFAOYSA-N 0.000 description 1
MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
HHCXIJPUUQMOKU-UHFFFAOYSA-N ethyl 4-chloro-2-ethoxybenzoate Chemical compound CCOC(=O)C1=CC=C(Cl)C=C1OCC HHCXIJPUUQMOKU-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
229960003699 evans blue Drugs 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000012467 final product Substances 0.000 description 1
235000013305 food Nutrition 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
238000007429 general method Methods 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
239000008187 granular material Substances 0.000 description 1
159000000011 group IA salts 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
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
239000007943 implant Substances 0.000 description 1
238000011534 incubation Methods 0.000 description 1
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-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
208000015181 infectious disease Diseases 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
206010022437 insomnia Diseases 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
238000002955 isolation Methods 0.000 description 1
238000012417 linear regression Methods 0.000 description 1
239000012669 liquid formulation Substances 0.000 description 1
239000006210 lotion Substances 0.000 description 1
229940049920 malate Drugs 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
PYFUTMWBILAYFA-UHFFFAOYSA-N methyl 2-(2-chloroethoxy)-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C=C1OCCCl PYFUTMWBILAYFA-UHFFFAOYSA-N 0.000 description 1
VAXMCQWXYROFAP-UHFFFAOYSA-N methyl 2-(2-chloroethoxy)-5-methylbenzoate Chemical compound COC(=O)C1=CC(C)=CC=C1OCCCl VAXMCQWXYROFAP-UHFFFAOYSA-N 0.000 description 1
MPDZTQLWOJWFIM-UHFFFAOYSA-N methyl 2-[2-[4-(6-fluoro-1h-indol-3-yl)piperidin-1-yl]ethoxy]benzoate Chemical compound COC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=C(F)C=C3NC=2)CC1 MPDZTQLWOJWFIM-UHFFFAOYSA-N 0.000 description 1
ULWORPZJUIFPIC-UHFFFAOYSA-N methyl 2-[4-(4-chlorobutanoyl)phenyl]-2-methylpropanoate Chemical compound COC(=O)C(C)(C)C1=CC=C(C(=O)CCCCl)C=C1 ULWORPZJUIFPIC-UHFFFAOYSA-N 0.000 description 1
JQYUQKRFSSSGJM-UHFFFAOYSA-N methyl 2-hydroxy-5-methylbenzoate Chemical compound COC(=O)C1=CC(C)=CC=C1O JQYUQKRFSSSGJM-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
229960001047 methyl salicylate Drugs 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
239000011707 mineral Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
DBNQIOANXZVWIP-UHFFFAOYSA-N n,n-dimethyl-1,1-bis[(2-methylpropan-2-yl)oxy]methanamine Chemical compound CC(C)(C)OC(N(C)C)OC(C)(C)C DBNQIOANXZVWIP-UHFFFAOYSA-N 0.000 description 1
SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
229920005615 natural polymer Polymers 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
238000001543 one-way ANOVA Methods 0.000 description 1
229940126701 oral medication Drugs 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 1
PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
239000008363 phosphate buffer Substances 0.000 description 1
125000003367 polycyclic group Chemical group 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
ZRHANBBTXQZFSP-UHFFFAOYSA-M potassium;4-amino-3,5,6-trichloropyridine-2-carboxylate Chemical compound [K+].NC1=C(Cl)C(Cl)=NC(C([O-])=O)=C1Cl ZRHANBBTXQZFSP-UHFFFAOYSA-M 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
229960003910 promethazine Drugs 0.000 description 1
WCQDGRGDJWBPJX-UHFFFAOYSA-N propyl 4-hydroxybenzoate;sodium Chemical compound [Na].[Na].CCCOC(=O)C1=CC=C(O)C=C1 WCQDGRGDJWBPJX-UHFFFAOYSA-N 0.000 description 1
WXSLOYPZKHFWII-UHFFFAOYSA-N propyl 4-hydroxybenzoate;sodium Chemical compound [Na].CCCOC(=O)C1=CC=C(O)C=C1 WXSLOYPZKHFWII-UHFFFAOYSA-N 0.000 description 1
238000000159 protein binding assay Methods 0.000 description 1
210000001747 pupil Anatomy 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
229940081974 saccharin Drugs 0.000 description 1
235000019204 saccharin Nutrition 0.000 description 1
239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
230000036280 sedation Effects 0.000 description 1
239000000377 silicon dioxide Substances 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
230000035483 skin reaction Effects 0.000 description 1
231100000430 skin reaction Toxicity 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
239000004404 sodium propyl p-hydroxybenzoate Substances 0.000 description 1
235000010230 sodium propyl p-hydroxybenzoate Nutrition 0.000 description 1
229940045902 sodium stearyl fumarate Drugs 0.000 description 1
239000002594 sorbent Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000010959 steel Substances 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
238000000967 suction filtration Methods 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
229920001059 synthetic polymer Polymers 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
GYNPGVKSYUBDIO-UHFFFAOYSA-N tert-butyl 4-phenylmethoxybenzoate Chemical compound C1=CC(C(=O)OC(C)(C)C)=CC=C1OCC1=CC=CC=C1 GYNPGVKSYUBDIO-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
230000035922 thirst Effects 0.000 description 1
PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
230000002618 waking effect Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom 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
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/04—Drugs for disorders of the respiratory system for throat disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
General Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Chemical Kinetics & Catalysis (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pulmonology (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Otolaryngology (AREA)
Immunology (AREA)
Ophthalmology & Optometry (AREA)
Dermatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

SK1704-2001A 1999-06-04 2000-05-31 Derivát indolylpiperidínu ako antihistaminické a antialergické činidlo SK17042001A3 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
ES009901232A ES2165274B1 (es)	1999-06-04	1999-06-04	Nuevos derivados de indolilpiperidina como agentes antihistaminicos y antialergicos.
PCT/EP2000/005010 WO2000075130A1 (fr)	1999-06-04	2000-05-31	Derives d'indolylpiperidine utilises comme agents antihistaminiques et antiallergique

Publications (1)

Publication Number	Publication Date
SK17042001A3 true SK17042001A3 (sk)	2002-04-04

Family

ID=8308707

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK1704-2001A SK17042001A3 (sk)	1999-06-04	2000-05-31	Derivát indolylpiperidínu ako antihistaminické a antialergické činidlo

Country Status (35)

Country	Link
US (1)	US6683096B2 (fr)
EP (1)	EP1183251B1 (fr)
JP (1)	JP2003501424A (fr)
KR (1)	KR100683454B1 (fr)
CN (1)	CN1191246C (fr)
AR (1)	AR029640A1 (fr)
AT (1)	ATE259362T1 (fr)
AU (1)	AU773164B2 (fr)
BG (1)	BG106168A (fr)
BR (1)	BR0011340A (fr)
CA (1)	CA2375985A1 (fr)
CO (1)	CO5180556A1 (fr)
CZ (1)	CZ20014334A3 (fr)
DE (1)	DE60008239T2 (fr)
DK (1)	DK1183251T3 (fr)
EE (1)	EE04717B1 (fr)
ES (2)	ES2165274B1 (fr)
HK (1)	HK1040990A1 (fr)
HU (1)	HUP0203320A3 (fr)
IL (1)	IL146629A0 (fr)
MX (1)	MXPA01012425A (fr)
MY (1)	MY127033A (fr)
NO (1)	NO20015897D0 (fr)
NZ (1)	NZ515649A (fr)
PE (1)	PE20010208A1 (fr)
PL (1)	PL196774B1 (fr)
PT (1)	PT1183251E (fr)
RU (1)	RU2246493C2 (fr)
SI (1)	SI1183251T1 (fr)
SK (1)	SK17042001A3 (fr)
TR (1)	TR200103490T2 (fr)
TW (1)	TWI226889B (fr)
UA (1)	UA72517C2 (fr)
WO (1)	WO2000075130A1 (fr)
ZA (1)	ZA200109676B (fr)

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
EP1324996A2 (fr) *	2000-01-17	2003-07-09	Bayer CropScience AG	Arylcetones substituees
ES2172436B1 (es) *	2000-10-31	2004-01-16	Almirall Prodesfarma Sa	Derivados de indolilpiperidina como agentes antihistaminicos y antialergicos.
WO2002048105A2 (fr) *	2000-11-16	2002-06-20	Wyeth	Derives d'aryloxy-piperidinyle pour le traitement des depressions
ES2201899B1 (es) *	2002-04-01	2005-06-01	Almirall Prodesfarma, S.A.	Derivados de la azaindolilpiperidina como agentes antihistaminicos y antialergicos.
ES2201907B1 (es) *	2002-05-29	2005-06-01	Almirall Prodesfarma, S.A.	Nuevos derivados de indolilpiperidina como potentes agentes antihistaminicos y antialergicos.
WO2005049559A2 (fr)	2003-11-17	2005-06-02	Boehringer Ingelheim International Gmbh	Nouveaux indoles substitues par piperidines ou heteroderives associes
US20050245540A1 (en) *	2003-12-09	2005-11-03	Fujisawa Pharmaceutical Co., Ltd.	New methods
AU2005234596B8 (en)	2004-04-13	2011-06-16	Incyte Holdings Corporation	Piperazinylpiperidine derivatives as chemokine receptor antagonists
NZ551603A (en)	2004-06-24	2010-11-26	Incyte Corp	N-substituted piperidines and their use as pharmaceuticals
EP1773773A4 (fr) *	2004-06-24	2009-07-29	Incyte Corp	Composes amido et leur utilisation en tant que produits pharmaceutiques
US8129410B2 (en) *	2005-04-26	2012-03-06	Hypnion, Inc.	Benzisoxazole piperidine compounds and methods of use thereof
US7759365B2 (en)	2005-04-30	2010-07-20	Boehringer Ingelheim International Gmbh	Piperidine-substituted indoles
US20060275516A1 (en) *	2005-06-02	2006-12-07	Ram A N S	Compositions and methods for the treatment of allergic rhinitis
US20080108586A1 (en) *	2006-09-06	2008-05-08	Incyte Corporation	Combination therapy for human immunodeficiency virus infection
JP5581055B2 (ja) *	2006-10-27	2014-08-27	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	ピペリジル−プロパン−チオールｃｃｒ３モジュレーター
NZ579402A (en) *	2007-03-15	2012-03-30	Novartis Ag	Organic compounds for diagnosis and treatment of pathologies relating to the Hedgehog pathway
US20100041663A1 (en)	2008-07-18	2010-02-18	Novartis Ag	Organic Compounds as Smo Inhibitors
CN101560179B (zh) *	2009-05-25	2012-04-18	浙江大学	具有h3受体亲和能力的含氮吲哚衍生物和用途
CN101747321B (zh) *	2009-12-22	2013-01-02	浙江大学	吲哚-3-苄胺衍生物及制备方法和用途
EP3040334A1 (fr) *	2014-12-29	2016-07-06	Faes Farma, S.A.	Nouveaux dérivés de benzimidazole en tant qu'agents antihistaminiques
MX2024001155A (es) *	2021-07-30	2024-07-01	Confo Therapeutics N V	Compuestos para el tratamiento del dolor, en particular el dolor neuropatico, y/u otras enfermedades o trastornos que se asocian con at2r y/o se?alizacion mediada por at2r.

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4742057A (en) *	1985-12-05	1988-05-03	Fujisawa Pharmaceutical Co., Ltd.	Antiallergic thiazole compounds
JPS63301881A (ja) *	1987-06-01	1988-12-08	Fujisawa Pharmaceut Co Ltd	インドリルピペリジン誘導体
GB8800795D0 (en) *	1988-01-14	1988-02-17	Fujisawa Pharmaceutical Co	New indolylpiperidine compounds processes for preparations thereof & pharmaceutical composition comprising same
DK733788A (da) *	1988-01-14	1989-07-15	Fujisawa Pharmaceutical Co	Indolylpiperidinderivater og fremgangsmaade til fremstilling deraf
GB8900382D0 (en) *	1989-01-09	1989-03-08	Janssen Pharmaceutica Nv	2-aminopyrimidinone derivatives
PH30434A (en) *	1989-04-07	1997-05-09	Janssen Pharmaceutica Nv	Hydroxyalkylfuranyl derivatives
EP0626968B1 (fr) *	1992-02-13	2001-09-26	Merrell Pharmaceuticals Inc.	Derives piperidinyles thiacycliques
IT1271417B (it) *	1993-10-15	1997-05-28	Erregierre Ind Chim	Composti ad attivita' antiistaminica procedimento per la loro preperazione e composizioni farmaceutiche che li contengono.
DE19500689A1 (de)	1995-01-12	1996-07-18	Merck Patent Gmbh	Indolpiperidin-Derivate
DE19707628A1 (de)	1997-02-26	1998-08-27	Merck Patent Gmbh	Oxazolidinone
AR013669A1 (es) *	1997-10-07	2001-01-10	Smithkline Beecham Corp	Compuestos y metodos
AR028685A1 (es) *	2000-06-14	2003-05-21	Lundbeck & Co As H	Derivados de indol

1999
- 1999-06-04 ES ES009901232A patent/ES2165274B1/es not_active Expired - Fee Related
2000
- 2000-05-31 IL IL14662900A patent/IL146629A0/xx unknown
- 2000-05-31 EE EEP200100653A patent/EE04717B1/xx not_active IP Right Cessation
- 2000-05-31 SK SK1704-2001A patent/SK17042001A3/sk unknown
- 2000-05-31 CA CA002375985A patent/CA2375985A1/fr not_active Abandoned
- 2000-05-31 CZ CZ20014334A patent/CZ20014334A3/cs unknown
- 2000-05-31 BR BR0011340-9A patent/BR0011340A/pt not_active Application Discontinuation
- 2000-05-31 EP EP00940296A patent/EP1183251B1/fr not_active Expired - Lifetime
- 2000-05-31 PE PE2000000524A patent/PE20010208A1/es not_active Application Discontinuation
- 2000-05-31 NZ NZ515649A patent/NZ515649A/en unknown
- 2000-05-31 WO PCT/EP2000/005010 patent/WO2000075130A1/fr not_active Ceased
- 2000-05-31 MX MXPA01012425A patent/MXPA01012425A/es unknown
- 2000-05-31 MY MYPI20002439A patent/MY127033A/en unknown
- 2000-05-31 DK DK00940296T patent/DK1183251T3/da active
- 2000-05-31 RU RU2002100073/04A patent/RU2246493C2/ru not_active IP Right Cessation
- 2000-05-31 PT PT00940296T patent/PT1183251E/pt unknown
- 2000-05-31 TR TR2001/03490T patent/TR200103490T2/xx unknown
- 2000-05-31 JP JP2001502413A patent/JP2003501424A/ja not_active Ceased
- 2000-05-31 KR KR1020017015570A patent/KR100683454B1/ko not_active Expired - Fee Related
- 2000-05-31 CN CNB008112819A patent/CN1191246C/zh not_active Expired - Fee Related
- 2000-05-31 SI SI200030323T patent/SI1183251T1/xx unknown
- 2000-05-31 HU HU0203320A patent/HUP0203320A3/hu unknown
- 2000-05-31 DE DE2000608239 patent/DE60008239T2/de not_active Expired - Lifetime
- 2000-05-31 ES ES00940296T patent/ES2211559T3/es not_active Expired - Lifetime
- 2000-05-31 AU AU55276/00A patent/AU773164B2/en not_active Ceased
- 2000-05-31 UA UA2001118222A patent/UA72517C2/uk unknown
- 2000-05-31 HK HK02102119.0A patent/HK1040990A1/zh unknown
- 2000-05-31 AT AT00940296T patent/ATE259362T1/de not_active IP Right Cessation
- 2000-05-31 PL PL353164A patent/PL196774B1/pl not_active IP Right Cessation
- 2000-06-02 TW TW089110816A patent/TWI226889B/zh not_active IP Right Cessation
- 2000-06-02 AR ARP000102755A patent/AR029640A1/es not_active Application Discontinuation
- 2000-06-02 CO CO00041546A patent/CO5180556A1/es not_active Application Discontinuation
2001
- 2001-11-23 ZA ZA200109676A patent/ZA200109676B/en unknown
- 2001-12-03 BG BG106168A patent/BG106168A/bg unknown
- 2001-12-03 NO NO20015897A patent/NO20015897D0/no not_active Application Discontinuation
- 2001-12-04 US US10/006,416 patent/US6683096B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA2375985A1 (fr)	2000-12-14
ES2211559T3 (es)	2004-07-16
KR20020020721A (ko)	2002-03-15
AU773164B2 (en)	2004-05-20
RU2246493C2 (ru)	2005-02-20
US20020147344A1 (en)	2002-10-10
NO20015897L (no)	2001-12-03
CO5180556A1 (es)	2002-07-30
NO20015897D0 (no)	2001-12-03
PL353164A1 (en)	2003-10-20
EP1183251A1 (fr)	2002-03-06
ES2165274B1 (es)	2003-04-01
ZA200109676B (en)	2003-02-24
AR029640A1 (es)	2003-07-10
EE200100653A (et)	2003-02-17
KR100683454B1 (ko)	2007-02-20
WO2000075130A1 (fr)	2000-12-14
BR0011340A (pt)	2002-03-05
HUP0203320A2 (hu)	2003-02-28
DE60008239T2 (de)	2004-11-18
JP2003501424A (ja)	2003-01-14
DE60008239D1 (de)	2004-03-18
PE20010208A1 (es)	2001-03-19
DK1183251T3 (da)	2004-06-07
EE04717B1 (et)	2006-10-16
PL196774B1 (pl)	2008-01-31
ATE259362T1 (de)	2004-02-15
EP1183251B1 (fr)	2004-02-11
IL146629A0 (en)	2002-07-25
RU2002100073A (ru)	2004-01-10
ES2165274A1 (es)	2002-03-01
MY127033A (en)	2006-11-30
PT1183251E (pt)	2004-05-31
HUP0203320A3 (en)	2004-01-28
SI1183251T1 (en)	2004-06-30
AU5527600A (en)	2000-12-28
UA72517C2 (uk)	2005-03-15
TWI226889B (en)	2005-01-21
US6683096B2 (en)	2004-01-27
CN1368969A (zh)	2002-09-11
MXPA01012425A (es)	2002-06-04
CZ20014334A3 (cs)	2002-03-13
NZ515649A (en)	2003-08-29
BG106168A (bg)	2002-07-31
CN1191246C (zh)	2005-03-02
HK1040990A1 (zh)	2002-06-28
TR200103490T2 (tr)	2002-04-22

Publication	Publication Date	Title
SK17042001A3 (sk)	2002-04-04	Derivát indolylpiperidínu ako antihistaminické a antialergické činidlo
DK2800748T3 (en)	2017-07-17	CYCLIC AMIDE DERIVATIVES AS INHIBITORS OF 11-BETA-HYDROXYSTEROID DEHYDROGENASE AND APPLICATIONS THEREOF
JP2005527627A (ja)	2005-09-15	有効な抗ヒスタミン剤および抗アレルギー剤としての新規インドリルピペリジン誘導体
EP1689738A2 (fr)	2006-08-16	Antimigraineux heterocycliques
CA2728616C (fr)	2017-10-31	Antagonistes piperidyl-acrylamide de ccr2
BR112014015298B1 (pt)	2021-06-15	Composto derivado de aza-adamantano, composição farmacêutica e uso do composto
RU2695524C2 (ru)	2019-07-23	Производные 3,4-дигидро-2н-изохинолин-1-она и 2,3-дигидроизоиндол-1-oha, полезные в качестве ингибитора альдостеронсинтазы
US9695152B2 (en)	2017-07-04	3,4-dihydro-2H-isoquinoline-1-one and 2,3-dihydro-isoindol-1-one compounds
DE60118434T2 (de)	2006-12-14	Indolylpiperidinderivate als antihistaminische und antiallergische mittel
WO2002006272A1 (fr)	2002-01-24	Derives de polyfluoroalkyltriazole, leur preparation et leur utilisation en therapeutique
KR102322959B1 (ko)	2021-11-09	신규한 3,4-다이하이드로-2h-이소퀴놀린-1-온 및 2,3-다이하이드로-이소인돌-1-온 화합물
JPH08231504A (ja)	1996-09-10	２−（２−インドリルエチルアミノ）−１−（３−置換フェニル）エタノール誘導体
KR20160014610A (ko)	2016-02-11	신규한 3,4-다이하이드로-2h-이소퀴놀린-1-온 및 2,3-다이하이드로-이소인돌-1-온 화합물