BG106168A - Индолилпиперидинови производни като антихистаминови и антиалергични средства - Google Patents

Индолилпиперидинови производни като антихистаминови и антиалергични средства Download PDF

Info

Publication number: BG106168A
Authority: BG; Bulgaria
Prior art keywords: ethoxy; piperidin; indol; ethyl; benzoic acid
Prior art date: 1999-06-04

Application number

BG106168A

Other languages

Bulgarian (bg)

English (en)

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

2001-12-03

Publication date

2002-07-31

2001-12-03 Application filed by Almirall Prodesfarma, S.A. filed Critical Almirall Prodesfarma, S.A.

2002-07-31 Publication of BG106168A publication Critical patent/BG106168A/bg

Links

239000000739 antihistaminic agent Substances 0.000 title claims abstract description 9
HNQZRUDJRPSFAU-UHFFFAOYSA-N 2-piperidin-1-yl-1h-indole Chemical class C1CCCCN1C1=CC2=CC=CC=C2N1 HNQZRUDJRPSFAU-UHFFFAOYSA-N 0.000 title abstract description 12
239000000043 antiallergic agent Substances 0.000 title description 4
230000001387 anti-histamine Effects 0.000 title description 2
-1 alkylenthio Chemical group 0.000 claims abstract description 267
125000000217 alkyl group Chemical group 0.000 claims abstract description 23
125000003545 alkoxy group Chemical group 0.000 claims abstract description 15
125000005843 halogen group Chemical group 0.000 claims abstract description 15
125000002947 alkylene group Chemical group 0.000 claims abstract description 13
125000004450 alkenylene group Chemical group 0.000 claims abstract description 7
125000005529 alkyleneoxy group Chemical group 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
230000003266 anti-allergic effect Effects 0.000 claims abstract description 6
239000001257 hydrogen Substances 0.000 claims abstract description 6
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 6
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 5
125000001589 carboacyl group Chemical group 0.000 claims abstract description 5
230000003326 anti-histaminergic effect Effects 0.000 claims abstract description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 4
125000003831 tetrazolyl group Chemical group 0.000 claims abstract description 4
239000005711 Benzoic acid Substances 0.000 claims description 182
238000002360 preparation method Methods 0.000 claims description 114
150000001875 compounds Chemical class 0.000 claims description 102
238000000034 method Methods 0.000 claims description 91
239000000203 mixture Substances 0.000 claims description 88
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 80
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 72
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 33
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 31
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 30
125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 24
WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 21
150000003839 salts Chemical class 0.000 claims description 20
235000010233 benzoic acid Nutrition 0.000 claims description 18
239000000460 chlorine Substances 0.000 claims description 10
229910052801 chlorine Inorganic materials 0.000 claims description 10
230000000694 effects Effects 0.000 claims description 10
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 9
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 8
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
125000003342 alkenyl group Chemical group 0.000 claims description 7
125000000304 alkynyl group Chemical group 0.000 claims description 7
208000006673 asthma Diseases 0.000 claims description 7
235000019260 propionic acid Nutrition 0.000 claims description 7
125000000753 cycloalkyl group Chemical group 0.000 claims description 6
208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
241001465754 Metazoa Species 0.000 claims description 5
208000024780 Urticaria Diseases 0.000 claims description 5
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 5
208000026935 allergic disease Diseases 0.000 claims description 5
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
230000002526 effect on cardiovascular system Effects 0.000 claims description 5
239000011737 fluorine Substances 0.000 claims description 5
229910052731 fluorine Inorganic materials 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
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 4
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 4
206010010741 Conjunctivitis Diseases 0.000 claims description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 4
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
GCCYBNZBCGRHRR-UHFFFAOYSA-N methyl 2-(2-chloroethoxy)benzoate Chemical compound COC(=O)C1=CC=CC=C1OCCCl GCCYBNZBCGRHRR-UHFFFAOYSA-N 0.000 claims description 4
125000002560 nitrile group Chemical group 0.000 claims description 4
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
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 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
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 3
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 3
125000005081 alkoxyalkoxyalkyl group Chemical group 0.000 claims description 3
125000004432 carbon atom Chemical group C* 0.000 claims description 3
210000000748 cardiovascular system Anatomy 0.000 claims description 3
125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
206010039083 rhinitis Diseases 0.000 claims description 3
208000017520 skin disease Diseases 0.000 claims description 3
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 3
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 claims 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 claims description 2
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 2
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 2
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 2
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 2
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 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 claims description 2
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 2
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 2
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 2
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 2
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 2
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 2
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 2
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 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
125000005452 alkenyloxyalkyl group Chemical group 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
125000001246 bromo group Chemical group Br* 0.000 claims description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 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
MNWFXJYAOYHMED-UHFFFAOYSA-N hexane carboxylic acid Natural products CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 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
230000007062 hydrolysis Effects 0.000 claims description 2
238000006460 hydrolysis reaction Methods 0.000 claims description 2
125000006229 isopropoxyethyl group Chemical group [H]C([H])([H])C([H])(OC([H])([H])C([H])([H])*)C([H])([H])[H] 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
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 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
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
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
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 1
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 1
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 1
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 1
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 1
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 1
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 claims 1
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 1
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 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 claims 1
FQPJQRKRTHUSCR-UHFFFAOYSA-N 3-[1-[3-[3-(2h-tetrazol-5-yl)phenoxy]propyl]piperidin-4-yl]-1h-indole Chemical compound C1CC(C=2C3=CC=CC=C3NC=2)CCN1CCCOC(C=1)=CC=CC=1C1=NN=NN1 FQPJQRKRTHUSCR-UHFFFAOYSA-N 0.000 claims 1
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 1
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XPNZHYBMQLVHDS-UHFFFAOYSA-N ethyl 4-(1h-indol-3-yl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OCC)CCC(C=2C3=CC=CC=C3NC=2)=C1 XPNZHYBMQLVHDS-UHFFFAOYSA-N 0.000 description 1
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 1
TZDFSADZWOUTMD-UHFFFAOYSA-N ethyl 4-(2-chloroethoxy)benzoate Chemical compound CCOC(=O)C1=CC=C(OCCCl)C=C1 TZDFSADZWOUTMD-UHFFFAOYSA-N 0.000 description 1
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 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
238000002474 experimental method Methods 0.000 description 1
238000013265 extended release Methods 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000012530 fluid Substances 0.000 description 1
235000013305 food Nutrition 0.000 description 1
229940050411 fumarate Drugs 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
239000003365 glass fiber Substances 0.000 description 1
239000008187 granular material Substances 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
YPGCWEMNNLXISK-UHFFFAOYSA-N hydratropic acid Chemical compound OC(=O)C(C)C1=CC=CC=C1 YPGCWEMNNLXISK-UHFFFAOYSA-N 0.000 description 1
239000007943 implant Substances 0.000 description 1
238000002513 implantation Methods 0.000 description 1
238000011534 incubation Methods 0.000 description 1
125000000593 indol-1-yl group Chemical group [H]C1=C([H])C([H])=C2N([*])C([H])=C([H])C2=C1[H] 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
238000010253 intravenous injection Methods 0.000 description 1
SNHMUERNLJLMHN-UHFFFAOYSA-N iodobenzene Chemical compound IC1=CC=CC=C1 SNHMUERNLJLMHN-UHFFFAOYSA-N 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
238000002955 isolation Methods 0.000 description 1
238000012417 linear regression Methods 0.000 description 1
229940049920 malate Drugs 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
239000000463 material Substances 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
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 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
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 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
235000010755 mineral Nutrition 0.000 description 1
239000011707 mineral Substances 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
238000012544 monitoring process Methods 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
FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
229920005615 natural polymer Polymers 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
238000002414 normal-phase solid-phase extraction 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
238000007911 parenteral administration Methods 0.000 description 1
239000008188 pellet Substances 0.000 description 1
230000000149 penetrating effect Effects 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
239000000825 pharmaceutical preparation Substances 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 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
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
239000012254 powdered material Substances 0.000 description 1
238000011085 pressure filtration Methods 0.000 description 1
229960003910 promethazine Drugs 0.000 description 1
238000001525 receptor binding assay Methods 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
238000010898 silica gel chromatography Methods 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
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000004290 sodium methyl p-hydroxybenzoate Substances 0.000 description 1
235000010268 sodium methyl p-hydroxybenzoate 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
PESXGULMKCKJCC-UHFFFAOYSA-M sodium;4-methoxycarbonylphenolate Chemical compound [Na+].COC(=O)C1=CC=C([O-])C=C1 PESXGULMKCKJCC-UHFFFAOYSA-M 0.000 description 1
IXMINYBUNCWGER-UHFFFAOYSA-M sodium;4-propoxycarbonylphenolate Chemical compound [Na+].CCCOC(=O)C1=CC=C([O-])C=C1 IXMINYBUNCWGER-UHFFFAOYSA-M 0.000 description 1
HSFQBFMEWSTNOW-UHFFFAOYSA-N sodium;carbanide Chemical group [CH3-].[Na+] HSFQBFMEWSTNOW-UHFFFAOYSA-N 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
239000007929 subcutaneous injection Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
229940086735 succinate Drugs 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
229920001059 synthetic polymer Polymers 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
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 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
150000003536 tetrazoles Chemical class 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)

BG106168A 1999-06-04 2001-12-03 Индолилпиперидинови производни като антихистаминови и антиалергични средства BG106168A (bg)

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 (en)	1999-06-04	2000-05-31	Indolylpiperidine derivatives as antihistaminic and antiallergic agents

Publications (1)

Publication Number	Publication Date
BG106168A true BG106168A (bg)	2002-07-31

Family

ID=8308707

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG106168A BG106168A (bg)	1999-06-04	2001-12-03	Индолилпиперидинови производни като антихистаминови и антиалергични средства

Country Status (35)

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

Families Citing this family (21)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BR0107624A (pt)	2000-01-17	2002-11-12	Bayer Ag	Arilcetonas substituìdas
ES2172436B1 (es)	2000-10-31	2004-01-16	Almirall Prodesfarma Sa	Derivados de indolilpiperidina como agentes antihistaminicos y antialergicos.
AU2002243394A1 (en) *	2000-11-16	2002-06-24	Wyeth	Aryloxy piperidinyl derivatives for the treatment of depression
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.
EP1687294B1 (en)	2003-11-17	2014-05-21	Boehringer Ingelheim International GmbH	Novel piperidine-substituted indoles-or hetero-derivatives thereof and their use as modulators of chemokine receptor (ccr-3)
US20050245540A1 (en) *	2003-12-09	2005-11-03	Fujisawa Pharmaceutical Co., Ltd.	New methods
KR101235090B1 (ko)	2004-04-13	2013-02-20	인사이트 코포레이션	케모킨 수용체 길항제로서의 피페라지닐피페리딘 유도체
US20060009491A1 (en) *	2004-06-24	2006-01-12	Incyte Corporation	Amido compounds and their use as pharmaceuticals
EP1758580A4 (en)	2004-06-24	2008-01-16	Incyte Corp	N-SUBSTITUTED PIPERIDINE AND ITS USE AS A MEDICAMENT
EP1877390B1 (en) *	2005-04-26	2010-03-24	Hypnion, Inc.	Benzisoxazole piperazine compounds and methods of use thereof
WO2006117314A2 (en)	2005-04-30	2006-11-09	Boehringer Ingelheim International Gmbh	Novel piperidin- substituted indoles and their use as ccr-3 modulators
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
WO2008049874A1 (en)	2006-10-27	2008-05-02	Boehringer Ingelheim International Gmbh	Piperidyl-propane-thiol ccr3 modulators
JP5550352B2 (ja)	2007-03-15	2014-07-16	ノバルティスアーゲー	有機化合物およびその使用
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 (en) *	2014-12-29	2016-07-06	Faes Farma, S.A.	New benzimidazole derivatives as antihistamine agents
PE20241304A1 (es) *	2021-07-30	2024-06-24	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 senalizacion 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
DK733788A (da) *	1988-01-14	1989-07-15	Fujisawa Pharmaceutical Co	Indolylpiperidinderivater og fremgangsmaade til fremstilling deraf
GB8800795D0 (en) *	1988-01-14	1988-02-17	Fujisawa Pharmaceutical Co	New indolylpiperidine compounds processes for preparations thereof & pharmaceutical composition comprising same
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 (en) *	1992-02-13	2001-09-26	Merrell Pharmaceuticals Inc.	Piperidinyl thiacyclic derivatives
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 RU RU2002100073/04A patent/RU2246493C2/ru not_active IP Right Cessation
- 2000-05-31 SK SK1704-2001A patent/SK17042001A3/sk unknown
- 2000-05-31 CZ CZ20014334A patent/CZ20014334A3/cs unknown
- 2000-05-31 DE DE2000608239 patent/DE60008239T2/de not_active Expired - Lifetime
- 2000-05-31 AT AT00940296T patent/ATE259362T1/de not_active IP Right Cessation
- 2000-05-31 PE PE2000000524A patent/PE20010208A1/es not_active Application Discontinuation
- 2000-05-31 HK HK02102119.0A patent/HK1040990A1/zh unknown
- 2000-05-31 TR TR2001/03490T patent/TR200103490T2/xx unknown
- 2000-05-31 CN CNB008112819A patent/CN1191246C/zh not_active Expired - Fee Related
- 2000-05-31 JP JP2001502413A patent/JP2003501424A/ja not_active Ceased
- 2000-05-31 DK DK00940296T patent/DK1183251T3/da active
- 2000-05-31 KR KR1020017015570A patent/KR100683454B1/ko not_active Expired - Fee Related
- 2000-05-31 PL PL353164A patent/PL196774B1/pl not_active IP Right Cessation
- 2000-05-31 EP EP00940296A patent/EP1183251B1/en not_active Expired - Lifetime
- 2000-05-31 UA UA2001118222A patent/UA72517C2/uk unknown
- 2000-05-31 ES ES00940296T patent/ES2211559T3/es not_active Expired - Lifetime
- 2000-05-31 PT PT00940296T patent/PT1183251E/pt unknown
- 2000-05-31 BR BR0011340-9A patent/BR0011340A/pt not_active Application Discontinuation
- 2000-05-31 MY MYPI20002439A patent/MY127033A/en unknown
- 2000-05-31 NZ NZ515649A patent/NZ515649A/en unknown
- 2000-05-31 HU HU0203320A patent/HUP0203320A3/hu unknown
- 2000-05-31 AU AU55276/00A patent/AU773164B2/en not_active Ceased
- 2000-05-31 WO PCT/EP2000/005010 patent/WO2000075130A1/en not_active Ceased
- 2000-05-31 SI SI200030323T patent/SI1183251T1/xx unknown
- 2000-05-31 CA CA002375985A patent/CA2375985A1/en not_active Abandoned
- 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 MX MXPA01012425A patent/MXPA01012425A/es unknown
- 2000-06-02 CO CO00041546A patent/CO5180556A1/es not_active Application Discontinuation
- 2000-06-02 AR ARP000102755A patent/AR029640A1/es not_active Application Discontinuation
- 2000-06-02 TW TW089110816A patent/TWI226889B/zh not_active IP Right Cessation
2001
- 2001-11-23 ZA ZA200109676A patent/ZA200109676B/en unknown
- 2001-12-03 NO NO20015897A patent/NO20015897D0/no not_active Application Discontinuation
- 2001-12-03 BG BG106168A patent/BG106168A/bg unknown
- 2001-12-04 US US10/006,416 patent/US6683096B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
JP2003501424A (ja)	2003-01-14
CZ20014334A3 (cs)	2002-03-13
NO20015897L (no)	2001-12-03
RU2246493C2 (ru)	2005-02-20
DE60008239T2 (de)	2004-11-18
AU5527600A (en)	2000-12-28
PL196774B1 (pl)	2008-01-31
HK1040990A1 (zh)	2002-06-28
US6683096B2 (en)	2004-01-27
CA2375985A1 (en)	2000-12-14
SI1183251T1 (en)	2004-06-30
US20020147344A1 (en)	2002-10-10
ES2211559T3 (es)	2004-07-16
MXPA01012425A (es)	2002-06-04
DK1183251T3 (da)	2004-06-07
ES2165274A1 (es)	2002-03-01
NZ515649A (en)	2003-08-29
CO5180556A1 (es)	2002-07-30
TR200103490T2 (tr)	2002-04-22
PT1183251E (pt)	2004-05-31
PE20010208A1 (es)	2001-03-19
ATE259362T1 (de)	2004-02-15
RU2002100073A (ru)	2004-01-10
AR029640A1 (es)	2003-07-10
EE200100653A (et)	2003-02-17
HUP0203320A3 (en)	2004-01-28
KR20020020721A (ko)	2002-03-15
SK17042001A3 (sk)	2002-04-04
NO20015897D0 (no)	2001-12-03
EP1183251A1 (en)	2002-03-06
ES2165274B1 (es)	2003-04-01
HUP0203320A2 (hu)	2003-02-28
ZA200109676B (en)	2003-02-24
EE04717B1 (et)	2006-10-16
DE60008239D1 (de)	2004-03-18
KR100683454B1 (ko)	2007-02-20
UA72517C2 (uk)	2005-03-15
MY127033A (en)	2006-11-30
CN1191246C (zh)	2005-03-02
BR0011340A (pt)	2002-03-05
AU773164B2 (en)	2004-05-20
IL146629A0 (en)	2002-07-25
WO2000075130A1 (en)	2000-12-14
PL353164A1 (en)	2003-10-20
CN1368969A (zh)	2002-09-11
TWI226889B (en)	2005-01-21
EP1183251B1 (en)	2004-02-11

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US6683096B2 (en)	2004-01-27	Indolylpiperidine derivatives as antihistaminic and antiallergic agents
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DE60118434T2 (de)	2006-12-14	Indolylpiperidinderivate als antihistaminische und antiallergische mittel
JP2004277319A (ja)	2004-10-07	１−（４−ピペリジニルメチル）ピペリジニルアミド誘導体およびそれを含有する医薬組成物
RU2199535C2 (ru)	2003-02-27	Новые карбоксизамещенные циклические производные карбоксамида
BRPI0619266A2 (pt)	2011-09-27	compostos, processo para a sua manufatura, composições farmacêuticas, métodos para o tratamento e/ou prevenção de enfermidades que estão associadas com a modulação de receptores de h3, obesidade, diabetes do tipo ii e seu uso
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WO2002006272A1 (fr)	2002-01-24	Derives de polyfluoroalkyltriazole, leur preparation et leur utilisation en therapeutique
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KR20040085215A (ko)	2004-10-07	5-헤테로아릴 치환 인돌