DE60306138T2 - Azaindolylpiperidinderivate als antihistaminika und antiallergika - Google Patents

Info

Publication number

DE60306138T2

DE60306138T2 DE60306138T DE60306138T DE60306138T2 DE 60306138 T2 DE60306138 T2 DE 60306138T2 DE 60306138 T DE60306138 T DE 60306138T DE 60306138 T DE60306138 T DE 60306138T DE 60306138 T2 DE60306138 T2 DE 60306138T2

Authority

DE

Germany

Prior art keywords

pyrrolo

pyridin

ylmethyl

piperidin

ethoxy

Prior art date

2002-04-01

Legal status (The legal status 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 status listed.)

Expired - Lifetime

Links

• Espacenet
• Global Dossier
• DPMA
• Discuss

• 238000000034 method Methods 0.000 claims abstract description 120
• 238000002360 preparation method Methods 0.000 claims abstract description 106
• 230000008569 process Effects 0.000 claims abstract description 18
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 8
• 102000000543 Histamine Receptors Human genes 0.000 claims abstract description 6
• 108010002059 Histamine Receptors Proteins 0.000 claims abstract description 6
• 150000001875 compounds Chemical class 0.000 claims description 200
• -1 monoalkylamino Chemical group 0.000 claims description 104
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 50
• 125000000217 alkyl group Chemical group 0.000 claims description 44
• 125000001424 substituent group Chemical group 0.000 claims description 43
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 34
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 29
• 125000003545 alkoxy group Chemical group 0.000 claims description 28
• 239000001257 hydrogen Substances 0.000 claims description 26
• 229910052739 hydrogen Inorganic materials 0.000 claims description 26
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
• WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 20
• 125000004432 carbon atom Chemical group C* 0.000 claims description 19
• 125000004414 alkyl thio group Chemical group 0.000 claims description 18
• 239000005711 Benzoic acid Substances 0.000 claims description 17
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
• 125000003118 aryl group Chemical group 0.000 claims description 17
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
• 238000011282 treatment Methods 0.000 claims description 17
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 16
• 229910052736 halogen Inorganic materials 0.000 claims description 16
• 150000002367 halogens Chemical class 0.000 claims description 16
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 16
• 125000004442 acylamino group Chemical group 0.000 claims description 14
• 229910052757 nitrogen Inorganic materials 0.000 claims description 14
• 125000004043 oxo group Chemical group O=* 0.000 claims description 14
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
• 125000003342 alkenyl group Chemical group 0.000 claims description 13
• 125000000304 alkynyl group Chemical group 0.000 claims description 13
• 125000005843 halogen group Chemical group 0.000 claims description 13
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
• 235000010233 benzoic acid Nutrition 0.000 claims description 12
• 125000001183 hydrocarbyl group Chemical group 0.000 claims description 11
• 125000004122 cyclic group Chemical group 0.000 claims description 10
• 125000000623 heterocyclic group Chemical group 0.000 claims description 10
• 239000000460 chlorine Substances 0.000 claims description 9
• 229910052801 chlorine Inorganic materials 0.000 claims description 9
• 150000002431 hydrogen Chemical class 0.000 claims description 9
• 150000003839 salts Chemical class 0.000 claims description 9
• LUFMOZOQECBNQC-UHFFFAOYSA-N tert-butyl 4-(1h-pyrrolo[2,3-b]pyridin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=CNC2=NC=CC=C12 LUFMOZOQECBNQC-UHFFFAOYSA-N 0.000 claims description 9
• HDQYSDCHSNUTGL-UHFFFAOYSA-N 2-[2-[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C(OCCN2CCC(CC2)C=2C3=CC=NC=C3N(CC3=COC=C3)C=2)=C1 HDQYSDCHSNUTGL-UHFFFAOYSA-N 0.000 claims description 8
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
• 239000002253 acid Substances 0.000 claims description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
• BMUYJOWZKQXKOE-UHFFFAOYSA-N 5-[[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]methyl]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC=C1CN1CCC(C=2C3=CC=NC=C3N(CC=3SC(Cl)=CC=3)C=2)CC1 BMUYJOWZKQXKOE-UHFFFAOYSA-N 0.000 claims description 7
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
• 125000002541 furyl group Chemical group 0.000 claims description 7
• 125000005429 oxyalkyl group Chemical group 0.000 claims description 7
• 229910052760 oxygen Inorganic materials 0.000 claims description 7
• 125000001544 thienyl group Chemical group 0.000 claims description 7
• GPLZHAHAZANCSC-UHFFFAOYSA-N 2-methoxy-5-[[4-(1-propan-2-ylpyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl]methyl]benzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC=C1CN1CCC(C=2C3=CC=CN=C3N(C(C)C)C=2)CC1 GPLZHAHAZANCSC-UHFFFAOYSA-N 0.000 claims description 6
• 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 6
• 208000010668 atopic eczema Diseases 0.000 claims description 6
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 6
• 239000012048 reactive intermediate Substances 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• SNGUQRZEUFQWHT-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O SNGUQRZEUFQWHT-UHFFFAOYSA-N 0.000 claims description 5
• WFAAFNCXCYKWBJ-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=NC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O WFAAFNCXCYKWBJ-UHFFFAOYSA-N 0.000 claims description 5
• ZBKYOTKMQSYKRY-UHFFFAOYSA-N 2-[2-[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=NC=C3N(CC3=COC=C3)C=2)CC1 ZBKYOTKMQSYKRY-UHFFFAOYSA-N 0.000 claims description 5
• ZPSWGWBXSHLFNU-UHFFFAOYSA-N 2-[2-[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CN=C3N(CC=3SC(Cl)=CC=3)C=2)CC1 ZPSWGWBXSHLFNU-UHFFFAOYSA-N 0.000 claims description 5
• XGEOPONOZQNMEY-UHFFFAOYSA-N 3-[[4-[1-(2-methoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound C12=CC=CN=C2N(CCOC)C=C1C(CC1)CCN1CC1=CC=CC(C(O)=O)=C1 XGEOPONOZQNMEY-UHFFFAOYSA-N 0.000 claims description 5
• CTZBDSDZHHYARK-UHFFFAOYSA-N 4-chloro-2-[2-[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1OCCN1CCC(C=2C3=CC=CN=C3N(CC3=COC=C3)C=2)CC1 CTZBDSDZHHYARK-UHFFFAOYSA-N 0.000 claims description 5
• JLKYHWIEHOTYKV-UHFFFAOYSA-N 5-[[4-(1-butylpyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl]methyl]-2-methoxybenzoic acid Chemical compound C12=CC=CN=C2N(CCCC)C=C1C(CC1)CCN1CC1=CC=C(OC)C(C(O)=O)=C1 JLKYHWIEHOTYKV-UHFFFAOYSA-N 0.000 claims description 5
• 125000005530 alkylenedioxy group Chemical group 0.000 claims description 5
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 5
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
• 239000003085 diluting agent Substances 0.000 claims description 5
• 201000010099 disease Diseases 0.000 claims description 5
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
• 229910052731 fluorine Inorganic materials 0.000 claims description 5
• 239000011737 fluorine Substances 0.000 claims description 5
• 125000001072 heteroaryl group Chemical group 0.000 claims description 5
• KSLWREGLMLNVMN-UHFFFAOYSA-N methyl 2-[2-[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoate Chemical compound COC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CN=C3N(CC=3SC(Cl)=CC=3)C=2)CC1 KSLWREGLMLNVMN-UHFFFAOYSA-N 0.000 claims description 5
• 125000004076 pyridyl group Chemical group 0.000 claims description 5
• 125000004001 thioalkyl group Chemical group 0.000 claims description 5
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 5
• JLBWRGCWXKZRJW-UHFFFAOYSA-N 2-[2-[4-[1-(furan-2-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C(OCCN2CCC(CC2)C=2C3=CC=CN=C3N(CC=3OC=CC=3)C=2)=C1 JLBWRGCWXKZRJW-UHFFFAOYSA-N 0.000 claims description 4
• ZQIWWDOOQWHJPG-UHFFFAOYSA-N 5-[[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC=C1CN1CCC(C=2C3=CC=CN=C3N(CC=3SC(Cl)=CC=3)C=2)CC1 ZQIWWDOOQWHJPG-UHFFFAOYSA-N 0.000 claims description 4
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 4
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 4
• 230000000172 allergic effect Effects 0.000 claims description 4
• 230000008485 antagonism Effects 0.000 claims description 4
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical group OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
• 229910052794 bromium Inorganic materials 0.000 claims description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
• 125000001153 fluoro group Chemical group F* 0.000 claims description 4
• 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 4
• KAIVTQDGZJDFBC-UHFFFAOYSA-N methyl 2-[2-[4-(1-butylpyrrolo[2,3-c]pyridin-3-yl)piperidin-1-yl]ethoxy]benzoate Chemical compound C12=CC=NC=C2N(CCCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(=O)OC KAIVTQDGZJDFBC-UHFFFAOYSA-N 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
• 229920006395 saturated elastomer Polymers 0.000 claims description 4
• YAMHSQLSSFOFQM-UHFFFAOYSA-N 2-[2-[4-(1-butylpyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl]ethoxy]-6-methoxybenzoic acid Chemical compound C12=CC=CN=C2N(CCCC)C=C1C(CC1)CCN1CCOC1=CC=CC(OC)=C1C(O)=O YAMHSQLSSFOFQM-UHFFFAOYSA-N 0.000 claims description 3
• QTCXRHSDHFQNAN-UHFFFAOYSA-N 2-[2-[4-(1-butylpyrrolo[2,3-c]pyridin-3-yl)piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound C12=CC=NC=C2N(CCCC)C=C1C(CC1)CCN1CCOC1=CC(OC)=CC=C1C(O)=O QTCXRHSDHFQNAN-UHFFFAOYSA-N 0.000 claims description 3
• FHIVBUZOMPSZLJ-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]-3-methoxybenzoic acid Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=C(OC)C=CC=C1C(O)=O FHIVBUZOMPSZLJ-UHFFFAOYSA-N 0.000 claims description 3
• YQUYNCAMUDVXTO-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]-6-methoxybenzoic acid Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC(OC)=C1C(O)=O YQUYNCAMUDVXTO-UHFFFAOYSA-N 0.000 claims description 3
• CUERHJXIOLWGMQ-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]-3-methoxybenzoic acid Chemical compound C12=CC=NC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=C(OC)C=CC=C1C(O)=O CUERHJXIOLWGMQ-UHFFFAOYSA-N 0.000 claims description 3
• WFLVYJBACWIQNA-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound C12=CC=NC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC(OC)=CC=C1C(O)=O WFLVYJBACWIQNA-UHFFFAOYSA-N 0.000 claims description 3
• BUUXHSMNLYXNAC-UHFFFAOYSA-N 2-[2-[4-[1-(2-methoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CN=C2N(CCOC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O BUUXHSMNLYXNAC-UHFFFAOYSA-N 0.000 claims description 3
• USXYPDDJWRXISA-UHFFFAOYSA-N 2-[2-[4-[1-(furan-2-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]-3-methoxybenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1OCCN1CCC(C=2C3=CC=CN=C3N(CC=3OC=CC=3)C=2)CC1 USXYPDDJWRXISA-UHFFFAOYSA-N 0.000 claims description 3
• FUJWSWJBDIAYII-UHFFFAOYSA-N 2-[2-[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]-3-methoxybenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1OCCN1CCC(C=2C3=CC=CN=C3N(CC3=COC=C3)C=2)CC1 FUJWSWJBDIAYII-UHFFFAOYSA-N 0.000 claims description 3
• JOJUCYRLKAWJSW-UHFFFAOYSA-N 2-[2-[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]-6-methoxybenzoic acid Chemical compound COC1=CC=CC(OCCN2CCC(CC2)C=2C3=CC=CN=C3N(CC3=COC=C3)C=2)=C1C(O)=O JOJUCYRLKAWJSW-UHFFFAOYSA-N 0.000 claims description 3
• NHESMZIWTNJWKB-UHFFFAOYSA-N 2-[2-[4-[1-(thiophen-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CN=C3N(CC3=CSC=C3)C=2)CC1 NHESMZIWTNJWKB-UHFFFAOYSA-N 0.000 claims description 3
• PCXYZWXZCFILSG-UHFFFAOYSA-N 2-[2-[4-[1-[(4-fluorophenyl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]acetic acid Chemical compound C1CN(CCOCC(=O)O)CCC1C(C1=CC=CN=C11)=CN1CC1=CC=C(F)C=C1 PCXYZWXZCFILSG-UHFFFAOYSA-N 0.000 claims description 3
• YXPIORGNLYCAPD-UHFFFAOYSA-N 2-[2-[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]-3-methoxybenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1OCCN1CCC(C=2C3=CC=CN=C3N(CC=3SC(Cl)=CC=3)C=2)CC1 YXPIORGNLYCAPD-UHFFFAOYSA-N 0.000 claims description 3
• HHZDWZCBWRJQSJ-UHFFFAOYSA-N 2-fluoro-5-[[4-[1-(furan-2-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound C1=C(F)C(C(=O)O)=CC(CN2CCC(CC2)C=2C3=CC=CN=C3N(CC=3OC=CC=3)C=2)=C1 HHZDWZCBWRJQSJ-UHFFFAOYSA-N 0.000 claims description 3
• GWOKTOOZHCKSKM-UHFFFAOYSA-N 2-fluoro-5-[[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound C1=C(F)C(C(=O)O)=CC(CN2CCC(CC2)C=2C3=CC=CN=C3N(CC3=COC=C3)C=2)=C1 GWOKTOOZHCKSKM-UHFFFAOYSA-N 0.000 claims description 3
• GZQAXGLVHONJDL-UHFFFAOYSA-N 2-methoxy-5-[[4-[1-(thiophen-2-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC=C1CN1CCC(C=2C3=CC=CN=C3N(CC=3SC=CC=3)C=2)CC1 GZQAXGLVHONJDL-UHFFFAOYSA-N 0.000 claims description 3
• HIIGYTCUWVFMBZ-UHFFFAOYSA-N 2-methoxy-5-[[4-[1-(thiophen-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC=C1CN1CCC(C=2C3=CC=CN=C3N(CC3=CSC=C3)C=2)CC1 HIIGYTCUWVFMBZ-UHFFFAOYSA-N 0.000 claims description 3
• GLWBWAMLHRPJLG-UHFFFAOYSA-N 2-methoxy-5-[[4-[1-(thiophen-3-ylmethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC=C1CN1CCC(C=2C3=CC=NC=C3N(CC3=CSC=C3)C=2)CC1 GLWBWAMLHRPJLG-UHFFFAOYSA-N 0.000 claims description 3
• FSFNKRJHLLDAOA-UHFFFAOYSA-N 2-methoxy-6-[2-[4-[1-(2-methoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CN=C2N(CCOC)C=C1C(CC1)CCN1CCOC1=CC=CC(OC)=C1C(O)=O FSFNKRJHLLDAOA-UHFFFAOYSA-N 0.000 claims description 3
• RGWFKURIQPFFAC-UHFFFAOYSA-N 3-[[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]-2,4-dimethoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C(OC)=C1CN1CCC(C=2C3=CC=CN=C3N(CC3=COC=C3)C=2)CC1 RGWFKURIQPFFAC-UHFFFAOYSA-N 0.000 claims description 3
• VYGHEFOTIWYYIH-UHFFFAOYSA-N 3-[[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]methyl]-2-methoxybenzoic acid Chemical compound C1=CC=C(C(O)=O)C(OC)=C1CN1CCC(C=2C3=CC=NC=C3N(CC3=COC=C3)C=2)CC1 VYGHEFOTIWYYIH-UHFFFAOYSA-N 0.000 claims description 3
• VCFJCCZCEXVVQN-UHFFFAOYSA-N 3-[[4-[1-(thiophen-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(CN2CCC(CC2)C=2C3=CC=CN=C3N(CC3=CSC=C3)C=2)=C1 VCFJCCZCEXVVQN-UHFFFAOYSA-N 0.000 claims description 3
• JWZWFBIOICQNLJ-UHFFFAOYSA-N 4-(5-amino-1h-pyrrolo[3,2-b]pyridin-3-yl)piperidine-1-carboxylic acid Chemical compound C12=NC(N)=CC=C2NC=C1C1CCN(C(O)=O)CC1 JWZWFBIOICQNLJ-UHFFFAOYSA-N 0.000 claims description 3
• QSFKMUVYQMHSIP-UHFFFAOYSA-N 4-bromo-3-[[4-[1-(2-ethoxyethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound C12=CC=NC=C2N(CCOCC)C=C1C(CC1)CCN1CC1=CC(C(O)=O)=CC=C1Br QSFKMUVYQMHSIP-UHFFFAOYSA-N 0.000 claims description 3
• BVVAEJZEFBEQBX-UHFFFAOYSA-N 4-chloro-2-[2-[4-[1-(2-ethoxyethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=NC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC(Cl)=CC=C1C(O)=O BVVAEJZEFBEQBX-UHFFFAOYSA-N 0.000 claims description 3
• HMMCNVWRELMEIY-UHFFFAOYSA-N 4-chloro-2-[2-[4-[1-(furan-2-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1OCCN1CCC(C=2C3=CC=CN=C3N(CC=3OC=CC=3)C=2)CC1 HMMCNVWRELMEIY-UHFFFAOYSA-N 0.000 claims description 3
• PAEUDCIFYSZWON-UHFFFAOYSA-N 4-chloro-2-[2-[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1OCCN1CCC(C=2C3=CC=NC=C3N(CC3=COC=C3)C=2)CC1 PAEUDCIFYSZWON-UHFFFAOYSA-N 0.000 claims description 3
• RGIHZBDPLGPUTA-UHFFFAOYSA-N 4-methoxy-2-[2-[4-[1-(thiophen-3-ylmethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound COC1=CC=C(C(O)=O)C(OCCN2CCC(CC2)C=2C3=CC=NC=C3N(CC3=CSC=C3)C=2)=C1 RGIHZBDPLGPUTA-UHFFFAOYSA-N 0.000 claims description 3
• PJZCLLWRUOXVPI-UHFFFAOYSA-N 5-[[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]methyl]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC=C1CN1CCC(C=2C3=CC=NC=C3N(CC3=COC=C3)C=2)CC1 PJZCLLWRUOXVPI-UHFFFAOYSA-N 0.000 claims description 3
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
• 150000001204 N-oxides Chemical class 0.000 claims description 3
• 208000024780 Urticaria Diseases 0.000 claims description 3
• 230000029936 alkylation Effects 0.000 claims description 3
• 238000005804 alkylation reaction Methods 0.000 claims description 3
• 208000006673 asthma 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
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• 239000003814 drug Substances 0.000 claims description 3
• 230000006872 improvement Effects 0.000 claims description 3
• 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 3
• WPYKNYCMQYQCMK-UHFFFAOYSA-N methyl 3-[[4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoate Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C(CC1)CCN1CC1=CC=CC(C(=O)OC)=C1 WPYKNYCMQYQCMK-UHFFFAOYSA-N 0.000 claims description 3
• QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 3
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
• XGKCMESITOKAMR-UHFFFAOYSA-N 2-[2-[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]-3-methoxybenzoic acid Chemical compound COC1=CC=CC(C(O)=O)=C1OCCN1CCC(C=2C3=CC=NC=C3N(CC=3SC(Cl)=CC=3)C=2)CC1 XGKCMESITOKAMR-UHFFFAOYSA-N 0.000 claims description 2
• OQTJVYQNOSWYDE-UHFFFAOYSA-N 2-[2-[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C(OCCN2CCC(CC2)C=2C3=CC=NC=C3N(CC=3SC(Cl)=CC=3)C=2)=C1 OQTJVYQNOSWYDE-UHFFFAOYSA-N 0.000 claims description 2
• FQCCVQWWEWDMQK-UHFFFAOYSA-N 2-[2-[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=NC=C3N(CC=3SC(Cl)=CC=3)C=2)CC1 FQCCVQWWEWDMQK-UHFFFAOYSA-N 0.000 claims description 2
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 2
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
• QTTHISCALRTDBN-UHFFFAOYSA-N 3-[[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]-2-methoxybenzoic acid Chemical compound C1=CC=C(C(O)=O)C(OC)=C1CN1CCC(C=2C3=CC=CN=C3N(CC3=COC=C3)C=2)CC1 QTTHISCALRTDBN-UHFFFAOYSA-N 0.000 claims description 2
• GWUZINHBOBFKRW-UHFFFAOYSA-N 4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-c]pyridin-3-yl]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1C(C1=CC=NC=C11)=CN1CC1=CC=C(Cl)S1 GWUZINHBOBFKRW-UHFFFAOYSA-N 0.000 claims description 2
• NBEDHXLALVXNAC-UHFFFAOYSA-N 5-[[4-[1-(2-ethoxyethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]methyl]-2-methoxybenzoic acid Chemical compound C12=CC=NC=C2N(CCOCC)C=C1C(CC1)CCN1CC1=CC=C(OC)C(C(O)=O)=C1 NBEDHXLALVXNAC-UHFFFAOYSA-N 0.000 claims description 2
• 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 2
• 206010012434 Dermatitis allergic Diseases 0.000 claims description 2
• 206010039085 Rhinitis allergic Diseases 0.000 claims description 2
• 125000002015 acyclic group Chemical group 0.000 claims description 2
• 125000002252 acyl group Chemical group 0.000 claims description 2
• 208000002205 allergic conjunctivitis Diseases 0.000 claims description 2
• 201000010105 allergic rhinitis Diseases 0.000 claims description 2
• 201000010435 allergic urticaria Diseases 0.000 claims description 2
• 208000024998 atopic conjunctivitis Diseases 0.000 claims description 2
• 201000008937 atopic dermatitis Diseases 0.000 claims description 2
• 125000000532 dioxanyl group Chemical group 0.000 claims description 2
• 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
• XOMLSCJDPYLFGG-UHFFFAOYSA-N ethyl 5-[[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]-2-methoxybenzoate Chemical compound C1=C(OC)C(C(=O)OCC)=CC(CN2CCC(CC2)C=2C3=CC=CN=C3N(CC3=COC=C3)C=2)=C1 XOMLSCJDPYLFGG-UHFFFAOYSA-N 0.000 claims description 2
• ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• 125000002950 monocyclic group Chemical group 0.000 claims description 2
• 125000003566 oxetanyl group Chemical group 0.000 claims description 2
• 229930195734 saturated hydrocarbon Natural products 0.000 claims description 2
• DDODQZRVMICRRX-UHFFFAOYSA-N tert-butyl 4-(1h-pyrrolo[3,2-c]pyridin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C1=CNC2=CC=NC=C12 DDODQZRVMICRRX-UHFFFAOYSA-N 0.000 claims description 2
• VIJVZDFDGKKUBV-UHFFFAOYSA-N tert-butyl 4-[6-(dimethylamino)-1h-pyrrolo[3,2-c]pyridin-3-yl]piperidine-1-carboxylate Chemical compound C1=2C=NC(N(C)C)=CC=2NC=C1C1CCN(C(=O)OC(C)(C)C)CC1 VIJVZDFDGKKUBV-UHFFFAOYSA-N 0.000 claims description 2
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 2
• 125000004014 thioethyl group Chemical group [H]SC([H])([H])C([H])([H])* 0.000 claims description 2
• 229930195735 unsaturated hydrocarbon Natural products 0.000 claims description 2
• 230000001575 pathological effect Effects 0.000 claims 3
• KZKRRZFCAYOXQE-UHFFFAOYSA-N 1$l^{2}-azinane Chemical group C1CC[N]CC1 KZKRRZFCAYOXQE-UHFFFAOYSA-N 0.000 claims 2
• 125000004438 haloalkoxy group Chemical group 0.000 claims 2
• BTBFUBUCCJKJOZ-UHFFFAOYSA-N 1-(2-Furanylmethyl)-1H-pyrrole Chemical compound C1=CC=CN1CC1=CC=CO1 BTBFUBUCCJKJOZ-UHFFFAOYSA-N 0.000 claims 1
• XGXRBEJYAVAVRH-UHFFFAOYSA-N 2-[2-[4-[1-(2-methoxyethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=NC=C2N(CCOC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O XGXRBEJYAVAVRH-UHFFFAOYSA-N 0.000 claims 1
• RYDBBGOQGJZUAF-UHFFFAOYSA-N 2-[2-[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C(OCCN2CCC(CC2)C=2C3=CC=CN=C3N(CC=3SC(Cl)=CC=3)C=2)=C1 RYDBBGOQGJZUAF-UHFFFAOYSA-N 0.000 claims 1
• GSFNQBFZFXUTBN-UHFFFAOYSA-N 2-chlorothiophene Chemical compound ClC1=CC=CS1 GSFNQBFZFXUTBN-UHFFFAOYSA-N 0.000 claims 1
• BVLSLATVPDOVPS-UHFFFAOYSA-N 3-[[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(CN2CCC(CC2)C=2C3=CC=CN=C3N(CC=3SC(Cl)=CC=3)C=2)=C1 BVLSLATVPDOVPS-UHFFFAOYSA-N 0.000 claims 1
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 1
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 1
• UUEQPXRMPYCNBY-UHFFFAOYSA-N C(C)OC(=O)N1CCC(CC1)C1=CN(C2=CN=CC=C21)CCCC.C(C)OC(=O)N2CCC(CC2)C2=CN(C1=CN=CC=C12)CC1=COC=C1 Chemical compound C(C)OC(=O)N1CCC(CC1)C1=CN(C2=CN=CC=C21)CCCC.C(C)OC(=O)N2CCC(CC2)C2=CN(C1=CN=CC=C12)CC1=COC=C1 UUEQPXRMPYCNBY-UHFFFAOYSA-N 0.000 claims 1
• JPFMLZYLHWQPQB-UHFFFAOYSA-N C(C)OC(=O)N1CCC(CC1)C1=CN(C2=NC=CC=C21)CC2=COC=C2.O2C=C(C=C2)CN2C=C(C=1C2=NC=CC1)C1CCN(CC1)C(=O)OC(C)(C)C Chemical compound C(C)OC(=O)N1CCC(CC1)C1=CN(C2=NC=CC=C21)CC2=COC=C2.O2C=C(C=C2)CN2C=C(C=1C2=NC=CC1)C1CCN(CC1)C(=O)OC(C)(C)C JPFMLZYLHWQPQB-UHFFFAOYSA-N 0.000 claims 1
• RQAHBJQHHZGFAX-UHFFFAOYSA-N C(CCC)N1C=C(C=2C1=CN=CC2)C2CCN(CC2)CC=2C=C(C(=O)O)C=CC2.BrC2=C(C=C(C(=O)O)C=C2)CN2CCC(CC2)C2=CN(C1=CN=CC=C12)CCCC Chemical compound C(CCC)N1C=C(C=2C1=CN=CC2)C2CCN(CC2)CC=2C=C(C(=O)O)C=CC2.BrC2=C(C=C(C(=O)O)C=C2)CN2CCC(CC2)C2=CN(C1=CN=CC=C12)CCCC RQAHBJQHHZGFAX-UHFFFAOYSA-N 0.000 claims 1
• DXGBUVMOVVHBJR-UHFFFAOYSA-N ClC1=CC=C(S1)CN1C=C(C=2C1=NC=CC2)C2CCN(CC2)C(=O)O.C(C)OC(=O)N2CCC(CC2)C2=CN(C1=NC=CC=C12)CC1=COC=C1 Chemical compound ClC1=CC=C(S1)CN1C=C(C=2C1=NC=CC2)C2CCN(CC2)C(=O)O.C(C)OC(=O)N2CCC(CC2)C2=CN(C1=NC=CC=C12)CC1=COC=C1 DXGBUVMOVVHBJR-UHFFFAOYSA-N 0.000 claims 1
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 1
• INCMYIZXGSTCCN-UHFFFAOYSA-N ethyl 3-[[4-[1-(2-methoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoate Chemical compound CCOC(=O)C1=CC=CC(CN2CCC(CC2)C=2C3=CC=CN=C3N(CCOC)C=2)=C1 INCMYIZXGSTCCN-UHFFFAOYSA-N 0.000 claims 1
• XTNZRXHTTPRDRY-UHFFFAOYSA-N ethyl 4-(1-butylpyrrolo[2,3-b]pyridin-3-yl)piperidine-1-carboxylate;ethyl 4-[1-(2-ethoxyethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidine-1-carboxylate Chemical compound C12=CC=CN=C2N(CCCC)C=C1C1CCN(C(=O)OCC)CC1.C12=CC=NC=C2N(CCOCC)C=C1C1CCN(C(=O)OCC)CC1 XTNZRXHTTPRDRY-UHFFFAOYSA-N 0.000 claims 1
• 230000007062 hydrolysis Effects 0.000 claims 1
• 238000006460 hydrolysis reaction Methods 0.000 claims 1
• FTINIVPXVUZWGL-UHFFFAOYSA-N methyl 3-[[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoate Chemical compound COC(=O)C1=CC=CC(CN2CCC(CC2)C=2C3=CC=CN=C3N(CC3=COC=C3)C=2)=C1 FTINIVPXVUZWGL-UHFFFAOYSA-N 0.000 claims 1
• 239000001301 oxygen Substances 0.000 claims 1
• 239000005557 antagonist Substances 0.000 abstract description 2
• 238000002560 therapeutic procedure Methods 0.000 abstract description 2
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
• 239000000203 mixture Substances 0.000 description 66
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 55
• 239000000243 solution Substances 0.000 description 55
• 238000010626 work up procedure Methods 0.000 description 50
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 48
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 44
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
• 239000002904 solvent Substances 0.000 description 39
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 35
• 239000000047 product Substances 0.000 description 32
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 31
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
• 238000000746 purification Methods 0.000 description 30
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
• 238000002844 melting Methods 0.000 description 22
• 230000008018 melting Effects 0.000 description 22
• 238000002953 preparative HPLC Methods 0.000 description 20
• 235000019441 ethanol Nutrition 0.000 description 19
• NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 18
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 18
• 239000012074 organic phase Substances 0.000 description 18
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 17
• 230000001960 triggered effect Effects 0.000 description 17
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 15
• 235000019341 magnesium sulphate Nutrition 0.000 description 15
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
• OPVBOUWKBVKFDB-UHFFFAOYSA-N ethyl 4-(1h-pyrrolo[2,3-b]pyridin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1C1=CNC2=NC=CC=C12 OPVBOUWKBVKFDB-UHFFFAOYSA-N 0.000 description 13
• 241000700159 Rattus Species 0.000 description 12
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
• 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 description 12
• 125000004494 ethyl ester group Chemical group 0.000 description 11
• 239000011780 sodium chloride Substances 0.000 description 11
• FYUXXVXJDUHKBA-UHFFFAOYSA-N 1-(2-ethoxyethyl)-3-piperidin-4-ylpyrrolo[2,3-b]pyridine Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C1CCNCC1 FYUXXVXJDUHKBA-UHFFFAOYSA-N 0.000 description 9
• WZAOTRHGJBEFOH-UHFFFAOYSA-N 1-(furan-3-ylmethyl)-3-piperidin-4-ylpyrrolo[2,3-b]pyridine Chemical compound C1=C(C2CCNCC2)C2=CC=CN=C2N1CC=1C=COC=1 WZAOTRHGJBEFOH-UHFFFAOYSA-N 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• CVYSHYLNDIHEIM-UHFFFAOYSA-N ethyl 4-(1h-pyrrolo[2,3-b]pyridin-3-yl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OCC)CCC(C=2C3=CC=CN=C3NC=2)=C1 CVYSHYLNDIHEIM-UHFFFAOYSA-N 0.000 description 9
• 229960001340 histamine Drugs 0.000 description 9
• 239000000741 silica gel Substances 0.000 description 9
• 229910002027 silica gel Inorganic materials 0.000 description 9
• MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 8
• 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 8
• 239000012267 brine Substances 0.000 description 8
• 238000001914 filtration Methods 0.000 description 8
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 7
• 230000000694 effects Effects 0.000 description 7
• RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 7
• 238000003818 flash chromatography Methods 0.000 description 7
• 239000000725 suspension Substances 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
• 238000009739 binding Methods 0.000 description 6
• 239000003054 catalyst Substances 0.000 description 6
• 238000006243 chemical reaction Methods 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
• 239000012312 sodium hydride Substances 0.000 description 6
• 229910000104 sodium hydride Inorganic materials 0.000 description 6
• FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
• 239000007787 solid Substances 0.000 description 6
• KTFXOKQUEIYPRG-UHFFFAOYSA-N 1-butyl-3-piperidin-4-ylpyrrolo[2,3-b]pyridine Chemical compound C12=CC=CN=C2N(CCCC)C=C1C1CCNCC1 KTFXOKQUEIYPRG-UHFFFAOYSA-N 0.000 description 5
• KVZBYJJEIWTOJR-UHFFFAOYSA-N 2-[2-[4-(1-butylpyrrolo[2,3-c]pyridin-3-yl)piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=NC=C2N(CCCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O KVZBYJJEIWTOJR-UHFFFAOYSA-N 0.000 description 5
• AKCDNCFPJFMVIU-UHFFFAOYSA-N 2-methoxy-5-[[4-[1-(2-methoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound C12=CC=CN=C2N(CCOC)C=C1C(CC1)CCN1CC1=CC=C(OC)C(C(O)=O)=C1 AKCDNCFPJFMVIU-UHFFFAOYSA-N 0.000 description 5
• HOEQXFUBJFGJKA-UHFFFAOYSA-N 3-(bromomethyl)furan Chemical compound BrCC=1C=COC=1 HOEQXFUBJFGJKA-UHFFFAOYSA-N 0.000 description 5
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
• 239000000739 antihistaminic agent Substances 0.000 description 5
• 230000027455 binding Effects 0.000 description 5
• 239000007788 liquid Substances 0.000 description 5
• 239000012044 organic layer Substances 0.000 description 5
• 238000010992 reflux Methods 0.000 description 5
• 229910052938 sodium sulfate Inorganic materials 0.000 description 5
• 235000011152 sodium sulphate Nutrition 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
• PMWBHTABZSVWGE-UHFFFAOYSA-N 1-(2-methoxyethyl)-3-piperidin-4-ylpyrrolo[2,3-b]pyridine Chemical compound C12=CC=CN=C2N(CCOC)C=C1C1CCNCC1 PMWBHTABZSVWGE-UHFFFAOYSA-N 0.000 description 4
• NYAFLSKGRUOXAZ-UHFFFAOYSA-N 1-(furan-2-ylmethyl)-3-piperidin-4-ylpyrrolo[2,3-b]pyridine Chemical compound C1=C(C2CCNCC2)C2=CC=CN=C2N1CC1=CC=CO1 NYAFLSKGRUOXAZ-UHFFFAOYSA-N 0.000 description 4
• YEYNSHGGLTXUGT-UHFFFAOYSA-N 1-[(5-chlorothiophen-2-yl)methyl]-3-piperidin-4-ylpyrrolo[2,3-b]pyridine Chemical compound S1C(Cl)=CC=C1CN1C2=NC=CC=C2C(C2CCNCC2)=C1 YEYNSHGGLTXUGT-UHFFFAOYSA-N 0.000 description 4
• GIBHKXNVHBMLQI-UHFFFAOYSA-N 2-[2-[4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC(OC)=CC=C1C(O)=O GIBHKXNVHBMLQI-UHFFFAOYSA-N 0.000 description 4
• ACFYLYPXDPMTEE-UHFFFAOYSA-N 2-[2-[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C(OCCN2CCC(CC2)C=2C3=CC=CN=C3N(CC3=COC=C3)C=2)=C1 ACFYLYPXDPMTEE-UHFFFAOYSA-N 0.000 description 4
• MZHXMVHYSUBCMH-UHFFFAOYSA-N 3-[[4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C(CC1)CCN1CC1=CC=CC(C(O)=O)=C1 MZHXMVHYSUBCMH-UHFFFAOYSA-N 0.000 description 4
• PFUKDWUSZXMLBY-UHFFFAOYSA-N 3-[[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(CN2CCC(CC2)C=2C3=CC=CN=C3N(CC3=COC=C3)C=2)=C1 PFUKDWUSZXMLBY-UHFFFAOYSA-N 0.000 description 4
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• 241000699670 Mus sp. Species 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• 230000002378 acidificating effect Effects 0.000 description 4
• 230000001476 alcoholic effect Effects 0.000 description 4
• 125000004429 atom Chemical group 0.000 description 4
• 230000036772 blood pressure Effects 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 238000001816 cooling Methods 0.000 description 4
• OROXHPJZXQVNDH-UHFFFAOYSA-N ethyl 4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1C(C1=CC=CN=C11)=CN1CC1=COC=C1 OROXHPJZXQVNDH-UHFFFAOYSA-N 0.000 description 4
• JYBCUJJBMSMEJV-UHFFFAOYSA-N ethyl 4-[1-(furan-3-ylmethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1C(C1=CC=NC=C11)=CN1CC1=COC=C1 JYBCUJJBMSMEJV-UHFFFAOYSA-N 0.000 description 4
• BUPHWDPLYUEXFS-UHFFFAOYSA-N ethyl 5-(bromomethyl)-2-methoxybenzoate Chemical compound CCOC(=O)C1=CC(CBr)=CC=C1OC BUPHWDPLYUEXFS-UHFFFAOYSA-N 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
• YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 4
• 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 4
• 230000007935 neutral effect Effects 0.000 description 4
• MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 4
• 229910003445 palladium oxide Inorganic materials 0.000 description 4
• 229910003446 platinum oxide Inorganic materials 0.000 description 4
• 229910000027 potassium carbonate Inorganic materials 0.000 description 4
• 239000011541 reaction mixture Substances 0.000 description 4
• 102000005962 receptors Human genes 0.000 description 4
• 108020003175 receptors Proteins 0.000 description 4
• PNEIBIZNGDLQFF-UHFFFAOYSA-N tert-butyl 4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(C1=CC=CN=C11)=CN1CC1=CC=C(Cl)S1 PNEIBIZNGDLQFF-UHFFFAOYSA-N 0.000 description 4
• GGIUSBKFFGCDNE-UHFFFAOYSA-N 1-(2-ethoxyethyl)-3-piperidin-4-ylpyrrolo[2,3-c]pyridine Chemical compound C12=CC=NC=C2N(CCOCC)C=C1C1CCNCC1 GGIUSBKFFGCDNE-UHFFFAOYSA-N 0.000 description 3
• ZPTLKXYOGYUDCX-UHFFFAOYSA-N 1-(furan-3-ylmethyl)-3-piperidin-4-ylpyrrolo[2,3-c]pyridine Chemical compound C1=C(C2CCNCC2)C2=CC=NC=C2N1CC=1C=COC=1 ZPTLKXYOGYUDCX-UHFFFAOYSA-N 0.000 description 3
• RSRCENWRTZQQQO-UHFFFAOYSA-N 1-[(5-chlorothiophen-2-yl)methyl]-3-piperidin-4-ylpyrrolo[2,3-c]pyridine Chemical compound S1C(Cl)=CC=C1CN1C2=CN=CC=C2C(C2CCNCC2)=C1 RSRCENWRTZQQQO-UHFFFAOYSA-N 0.000 description 3
• MMYKTRPLXXWLBC-UHFFFAOYSA-N 1-bromo-2-ethoxyethane Chemical compound CCOCCBr MMYKTRPLXXWLBC-UHFFFAOYSA-N 0.000 description 3
• HRKQGYREQRIVLK-UHFFFAOYSA-N 1-butyl-3-piperidin-4-ylpyrrolo[2,3-c]pyridine Chemical compound C12=CC=NC=C2N(CCCC)C=C1C1CCNCC1 HRKQGYREQRIVLK-UHFFFAOYSA-N 0.000 description 3
• VGUDDLHJEJFLJO-UHFFFAOYSA-N 2-[2-[4-(1-butylpyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl]ethoxy]-4-methoxybenzoic acid Chemical compound C12=CC=CN=C2N(CCCC)C=C1C(CC1)CCN1CCOC1=CC(OC)=CC=C1C(O)=O VGUDDLHJEJFLJO-UHFFFAOYSA-N 0.000 description 3
• OQDGBIQQFFTLKL-UHFFFAOYSA-N 3-(1,2,3,6-tetrahydropyridin-4-yl)-1h-pyrrolo[2,3-b]pyridine Chemical compound C1NCCC(C=2C3=CC=CN=C3NC=2)=C1 OQDGBIQQFFTLKL-UHFFFAOYSA-N 0.000 description 3
• UMEKKMQTWYNMKE-UHFFFAOYSA-N 5-[[4-[1-(furan-2-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC=C1CN1CCC(C=2C3=CC=CN=C3N(CC=3OC=CC=3)C=2)CC1 UMEKKMQTWYNMKE-UHFFFAOYSA-N 0.000 description 3
• NZXNSHJALAITOR-UHFFFAOYSA-N 5-[[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC=C1CN1CCC(C=2C3=CC=CN=C3N(CC3=COC=C3)C=2)CC1 NZXNSHJALAITOR-UHFFFAOYSA-N 0.000 description 3
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 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
• 239000004480 active ingredient Substances 0.000 description 3
• 208000026935 allergic disease Diseases 0.000 description 3
• 230000003266 anti-allergic effect Effects 0.000 description 3
• 229940125715 antihistaminic agent Drugs 0.000 description 3
• 230000015572 biosynthetic process Effects 0.000 description 3
• 230000008499 blood brain barrier function Effects 0.000 description 3
• 210000001218 blood-brain barrier Anatomy 0.000 description 3
• 238000009835 boiling Methods 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 208000035475 disorder Diseases 0.000 description 3
• RASHZTATTXHBRR-UHFFFAOYSA-N ethyl 3-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]pyrrolo[2,3-b]pyridine-1-carboxylate Chemical compound C12=CC=CN=C2N(C(=O)OCC)C=C1C1CCN(C(=O)OC(C)(C)C)CC1 RASHZTATTXHBRR-UHFFFAOYSA-N 0.000 description 3
• REAVZTXTGVGRRZ-UHFFFAOYSA-N ethyl 4-(1-butylpyrrolo[2,3-b]pyridin-3-yl)piperidine-1-carboxylate Chemical compound C12=CC=CN=C2N(CCCC)C=C1C1CCN(C(=O)OCC)CC1 REAVZTXTGVGRRZ-UHFFFAOYSA-N 0.000 description 3
• DCHSCSDZQAECIM-UHFFFAOYSA-N ethyl 4-(1-butylpyrrolo[2,3-c]pyridin-3-yl)piperidine-1-carboxylate Chemical compound C12=CC=NC=C2N(CCCC)C=C1C1CCN(C(=O)OCC)CC1 DCHSCSDZQAECIM-UHFFFAOYSA-N 0.000 description 3
• YWQFDZOXRMBADC-UHFFFAOYSA-N ethyl 4-(1h-pyrrolo[2,3-c]pyridin-3-yl)piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1C1=CNC2=CN=CC=C12 YWQFDZOXRMBADC-UHFFFAOYSA-N 0.000 description 3
• OPZGXVAJOVHYGS-UHFFFAOYSA-N ethyl 4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidine-1-carboxylate Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C1CCN(C(=O)OCC)CC1 OPZGXVAJOVHYGS-UHFFFAOYSA-N 0.000 description 3
• FLZYNRMDLUOBDQ-UHFFFAOYSA-N ethyl 4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-c]pyridin-3-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1C(C1=CC=NC=C11)=CN1CC1=CC=C(Cl)S1 FLZYNRMDLUOBDQ-UHFFFAOYSA-N 0.000 description 3
• LUBGFMZTGFXIIN-UHFFFAOYSA-N ethyl 4-oxopiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(=O)CC1 LUBGFMZTGFXIIN-UHFFFAOYSA-N 0.000 description 3
• 239000000796 flavoring agent Substances 0.000 description 3
• 235000019634 flavors Nutrition 0.000 description 3
• 239000012442 inert solvent Substances 0.000 description 3
• 230000005764 inhibitory process Effects 0.000 description 3
• 150000007529 inorganic bases Chemical class 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 239000012528 membrane Substances 0.000 description 3
• YHWXJFHOUGAOFG-UHFFFAOYSA-N methyl 2-[2-[4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoate Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC(OC)=CC=C1C(=O)OC YHWXJFHOUGAOFG-UHFFFAOYSA-N 0.000 description 3
• ZGGHCYOBUSXZEM-UHFFFAOYSA-N methyl 2-[2-[4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoate Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(=O)OC ZGGHCYOBUSXZEM-UHFFFAOYSA-N 0.000 description 3
• WZUPJQUJRYKALY-UHFFFAOYSA-N methyl 2-[2-[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoate Chemical compound COC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CN=C3N(CC3=COC=C3)C=2)CC1 WZUPJQUJRYKALY-UHFFFAOYSA-N 0.000 description 3
• 150000007522 mineralic acids Chemical class 0.000 description 3
• 229910052763 palladium Inorganic materials 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• 238000001525 receptor binding assay Methods 0.000 description 3
• 239000011734 sodium Substances 0.000 description 3
• ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 239000006188 syrup Substances 0.000 description 3
• 235000020357 syrup Nutrition 0.000 description 3
• 230000008728 vascular permeability Effects 0.000 description 3
• 239000003981 vehicle Substances 0.000 description 3
• ZPCOESNBUMJARU-QFOIDUMCSA-N (e)-2-[4-[7-[(4-fluorophenyl)methyl]pyrrolo[2,3-d]pyrimidin-5-yl]piperidin-1-yl]but-2-enoic acid Chemical compound C1CN(/C(=C/C)C(O)=O)CCC1C(C1=CN=CN=C11)=CN1CC1=CC=C(F)C=C1 ZPCOESNBUMJARU-QFOIDUMCSA-N 0.000 description 2
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
• OPZGCBYPPMYWPS-UHFFFAOYSA-N 1-(cyclopropylmethyl)-3-piperidin-4-ylpyrrolo[2,3-b]pyridine Chemical compound C1=C(C2CCNCC2)C2=CC=CN=C2N1CC1CC1 OPZGCBYPPMYWPS-UHFFFAOYSA-N 0.000 description 2
• INUIJZNHVAUKSL-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]-3-piperidin-4-ylpyrrolo[2,3-b]pyridine Chemical compound C1=CC(F)=CC=C1CN1C2=NC=CC=C2C(C2CCNCC2)=C1 INUIJZNHVAUKSL-UHFFFAOYSA-N 0.000 description 2
• YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 2
• UOUCHRBTWUJIFR-UHFFFAOYSA-N 2,4-dimethoxy-3-[[4-[1-(2-methoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound C12=CC=CN=C2N(CCOC)C=C1C(CC1)CCN1CC1=C(OC)C=CC(C(O)=O)=C1OC UOUCHRBTWUJIFR-UHFFFAOYSA-N 0.000 description 2
• OFPWMRMIFDHXFE-UHFFFAOYSA-N 2-(bromomethyl)pyridine Chemical compound BrCC1=CC=CC=N1 OFPWMRMIFDHXFE-UHFFFAOYSA-N 0.000 description 2
• PLBZUUUHIHCRBU-UHFFFAOYSA-N 2-[2-[4-(1-butylpyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl]ethoxy]-3-methoxybenzoic acid Chemical compound C12=CC=CN=C2N(CCCC)C=C1C(CC1)CCN1CCOC1=C(OC)C=CC=C1C(O)=O PLBZUUUHIHCRBU-UHFFFAOYSA-N 0.000 description 2
• JGARMSCVJNQBNU-UHFFFAOYSA-N 2-[2-[4-(1-butylpyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl]ethoxy]-4-chlorobenzoic acid Chemical compound C12=CC=CN=C2N(CCCC)C=C1C(CC1)CCN1CCOC1=CC(Cl)=CC=C1C(O)=O JGARMSCVJNQBNU-UHFFFAOYSA-N 0.000 description 2
• YBIXNUQZWKBEHO-UHFFFAOYSA-N 2-[2-[4-(1-butylpyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CN=C2N(CCCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O YBIXNUQZWKBEHO-UHFFFAOYSA-N 0.000 description 2
• FUQUVZMTNPRBJA-UHFFFAOYSA-N 2-[2-[4-(1-butylpyrrolo[2,3-c]pyridin-3-yl)piperidin-1-yl]ethoxy]-3-methoxybenzoic acid Chemical compound C12=CC=NC=C2N(CCCC)C=C1C(CC1)CCN1CCOC1=C(OC)C=CC=C1C(O)=O FUQUVZMTNPRBJA-UHFFFAOYSA-N 0.000 description 2
• GIRKPSLBNJYIFD-UHFFFAOYSA-N 2-[2-[4-(1-butylpyrrolo[2,3-c]pyridin-3-yl)piperidin-1-yl]ethoxy]-4-chlorobenzoic acid Chemical compound C12=CC=NC=C2N(CCCC)C=C1C(CC1)CCN1CCOC1=CC(Cl)=CC=C1C(O)=O GIRKPSLBNJYIFD-UHFFFAOYSA-N 0.000 description 2
• APCAIJPRKLEXHA-UHFFFAOYSA-N 2-[2-[4-(1-propan-2-ylpyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CN=C2N(C(C)C)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(O)=O APCAIJPRKLEXHA-UHFFFAOYSA-N 0.000 description 2
• PYOLLCHDGHDHPE-UHFFFAOYSA-N 2-[2-[4-[1-(cyclopropylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CN=C3N(CC3CC3)C=2)CC1 PYOLLCHDGHDHPE-UHFFFAOYSA-N 0.000 description 2
• TWYLFUNGJMMWTL-UHFFFAOYSA-N 2-[2-[4-[1-(furan-2-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CN=C3N(CC=3OC=CC=3)C=2)CC1 TWYLFUNGJMMWTL-UHFFFAOYSA-N 0.000 description 2
• RJJPSTWRBLUFKC-UHFFFAOYSA-N 2-[2-[4-[1-(furan-2-ylmethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=NC=C3N(CC=3OC=CC=3)C=2)CC1 RJJPSTWRBLUFKC-UHFFFAOYSA-N 0.000 description 2
• QXSSAEPAJDFISP-UHFFFAOYSA-N 2-[2-[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CN=C3N(CC3=COC=C3)C=2)CC1 QXSSAEPAJDFISP-UHFFFAOYSA-N 0.000 description 2
• AMELPBNZUXWNBN-UHFFFAOYSA-N 2-[2-[4-[1-(thiophen-2-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CN=C3N(CC=3SC=CC=3)C=2)CC1 AMELPBNZUXWNBN-UHFFFAOYSA-N 0.000 description 2
• GSZFBUGFXKOHJW-UHFFFAOYSA-N 2-[2-[4-[1-(thiophen-2-ylmethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=NC=C3N(CC=3SC=CC=3)C=2)CC1 GSZFBUGFXKOHJW-UHFFFAOYSA-N 0.000 description 2
• OYUFIRBHPQLTMV-UHFFFAOYSA-N 2-[2-[4-[1-[(4-fluorophenyl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=CC=C1OCCN1CCC(C=2C3=CC=CN=C3N(CC=3C=CC(F)=CC=3)C=2)CC1 OYUFIRBHPQLTMV-UHFFFAOYSA-N 0.000 description 2
• OHNUPNKFGDIXBK-UHFFFAOYSA-N 2-[2-[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]-6-methoxybenzoic acid Chemical compound COC1=CC=CC(OCCN2CCC(CC2)C=2C3=CC=CN=C3N(CC=3SC(Cl)=CC=3)C=2)=C1C(O)=O OHNUPNKFGDIXBK-UHFFFAOYSA-N 0.000 description 2
• CGUKVONCIOEJMC-UHFFFAOYSA-N 2-[2-[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]acetic acid Chemical compound C1CN(CCOCC(=O)O)CCC1C(C1=CC=NC=C11)=CN1CC1=CC=C(Cl)S1 CGUKVONCIOEJMC-UHFFFAOYSA-N 0.000 description 2
• MMWVLKICJQRXEU-UHFFFAOYSA-N 2-[2-[4-[4-chloro-1-(1-thiophen-2-ylethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]acetic acid Chemical compound C1=C(C2CCN(CCOCC(O)=O)CC2)C2=C(Cl)C=NC=C2N1C(C)C1=CC=CS1 MMWVLKICJQRXEU-UHFFFAOYSA-N 0.000 description 2
• HZJOQXYKPWVJDK-UHFFFAOYSA-N 2-[4-[2-[4-(2-methoxy-7h-pyrrolo[2,3-d]pyrimidin-5-yl)piperidin-1-yl]ethyl]phenyl]-2-methylpropanoic acid Chemical compound C=1NC2=NC(OC)=NC=C2C=1C(CC1)CCN1CCC1=CC=C(C(C)(C)C(O)=O)C=C1 HZJOQXYKPWVJDK-UHFFFAOYSA-N 0.000 description 2
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 2
• MQTKXCOGYOYAMW-UHFFFAOYSA-N 2-chloro-5-(chloromethyl)thiophene Chemical compound ClCC1=CC=C(Cl)S1 MQTKXCOGYOYAMW-UHFFFAOYSA-N 0.000 description 2
• 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
• VNRHPBFPPQVSMN-UHFFFAOYSA-N 3-[[4-(1-butylpyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl]methyl]-2,4-dimethoxybenzoic acid Chemical compound C12=CC=CN=C2N(CCCC)C=C1C(CC1)CCN1CC1=C(OC)C=CC(C(O)=O)=C1OC VNRHPBFPPQVSMN-UHFFFAOYSA-N 0.000 description 2
• RLKZHDIYYAMASP-UHFFFAOYSA-N 3-[[4-(1-butylpyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl]methyl]-2-methoxybenzoic acid Chemical compound C12=CC=CN=C2N(CCCC)C=C1C(CC1)CCN1CC1=CC=CC(C(O)=O)=C1OC RLKZHDIYYAMASP-UHFFFAOYSA-N 0.000 description 2
• MQODFSYMAUWWNZ-UHFFFAOYSA-N 3-[[4-(1-butylpyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl]methyl]benzoic acid Chemical compound C12=CC=CN=C2N(CCCC)C=C1C(CC1)CCN1CC1=CC=CC(C(O)=O)=C1 MQODFSYMAUWWNZ-UHFFFAOYSA-N 0.000 description 2
• UHRANEKPMXTRCR-UHFFFAOYSA-N 3-[[4-(1-butylpyrrolo[2,3-c]pyridin-3-yl)piperidin-1-yl]methyl]benzoic acid Chemical compound C12=CC=NC=C2N(CCCC)C=C1C(CC1)CCN1CC1=CC=CC(C(O)=O)=C1 UHRANEKPMXTRCR-UHFFFAOYSA-N 0.000 description 2
• SXSPWXBCQMBESZ-UHFFFAOYSA-N 3-[[4-(1-propan-2-ylpyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl]methyl]benzoic acid Chemical compound C12=CC=CN=C2N(C(C)C)C=C1C(CC1)CCN1CC1=CC=CC(C(O)=O)=C1 SXSPWXBCQMBESZ-UHFFFAOYSA-N 0.000 description 2
• QZYJJCZVXYDPDU-UHFFFAOYSA-N 3-[[4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]-2,4-dimethoxybenzoic acid Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C(CC1)CCN1CC1=C(OC)C=CC(C(O)=O)=C1OC QZYJJCZVXYDPDU-UHFFFAOYSA-N 0.000 description 2
• IVUVZWZUXQGMOX-UHFFFAOYSA-N 3-[[4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]-2-methoxybenzoic acid Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C(CC1)CCN1CC1=CC=CC(C(O)=O)=C1OC IVUVZWZUXQGMOX-UHFFFAOYSA-N 0.000 description 2
• TULHVCNNVBNNDL-UHFFFAOYSA-N 3-[[4-[1-(cyclopropylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(CN2CCC(CC2)C=2C3=CC=CN=C3N(CC3CC3)C=2)=C1 TULHVCNNVBNNDL-UHFFFAOYSA-N 0.000 description 2
• PBTNOOBHZUVLGC-UHFFFAOYSA-N 3-[[4-[1-(furan-2-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(CN2CCC(CC2)C=2C3=CC=CN=C3N(CC=3OC=CC=3)C=2)=C1 PBTNOOBHZUVLGC-UHFFFAOYSA-N 0.000 description 2
• VYKQFACBDTVVOC-UHFFFAOYSA-N 3-[[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]-2,4-dimethoxybenzoic acid Chemical compound COC1=CC=C(C(O)=O)C(OC)=C1CN1CCC(C=2C3=CC=CN=C3N(CC=3SC(Cl)=CC=3)C=2)CC1 VYKQFACBDTVVOC-UHFFFAOYSA-N 0.000 description 2
• IFORIWBPFRVBKM-UHFFFAOYSA-N 3-[[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]-2-methoxybenzoic acid Chemical compound C1=CC=C(C(O)=O)C(OC)=C1CN1CCC(C=2C3=CC=CN=C3N(CC=3SC(Cl)=CC=3)C=2)CC1 IFORIWBPFRVBKM-UHFFFAOYSA-N 0.000 description 2
• FKQBASZURHCTPX-UHFFFAOYSA-N 3-[methyl-[2-[4-[1-(pyridin-2-ylmethyl)pyrrolo[3,2-c]pyridin-3-yl]piperidin-1-yl]ethyl]amino]benzoic acid Chemical compound C=1C=CC(C(O)=O)=CC=1N(C)CCN(CC1)CCC1C(C1=CN=CC=C11)=CN1CC1=CC=CC=N1 FKQBASZURHCTPX-UHFFFAOYSA-N 0.000 description 2
• LULAYUGMBFYYEX-UHFFFAOYSA-N 3-chlorobenzoic acid Chemical compound OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 2
• NEPJEYWHPYJSHE-UHFFFAOYSA-N 3-piperidin-4-yl-1-(pyridin-2-ylmethyl)pyrrolo[2,3-b]pyridine Chemical compound C1=C(C2CCNCC2)C2=CC=CN=C2N1CC1=CC=CC=N1 NEPJEYWHPYJSHE-UHFFFAOYSA-N 0.000 description 2
• UDPHXURFEQSPKO-UHFFFAOYSA-N 3-piperidin-4-yl-1-(thiophen-2-ylmethyl)pyrrolo[2,3-b]pyridine Chemical compound C1=C(C2CCNCC2)C2=CC=CN=C2N1CC1=CC=CS1 UDPHXURFEQSPKO-UHFFFAOYSA-N 0.000 description 2
• IJUKIMJTPYQAES-UHFFFAOYSA-N 3-piperidin-4-yl-1-(thiophen-3-ylmethyl)pyrrolo[2,3-b]pyridine Chemical compound C1=C(C2CCNCC2)C2=CC=CN=C2N1CC=1C=CSC=1 IJUKIMJTPYQAES-UHFFFAOYSA-N 0.000 description 2
• KLSUIMVPRHPHKO-UHFFFAOYSA-N 3-piperidin-4-yl-1-propan-2-ylpyrrolo[2,3-b]pyridine Chemical compound C12=CC=CN=C2N(C(C)C)C=C1C1CCNCC1 KLSUIMVPRHPHKO-UHFFFAOYSA-N 0.000 description 2
• OUNKWLVIJBPPIF-UHFFFAOYSA-N 3-piperidin-4-yl-1h-pyrrolo[2,3-b]pyridine Chemical compound C1CNCCC1C1=CNC2=NC=CC=C12 OUNKWLVIJBPPIF-UHFFFAOYSA-N 0.000 description 2
• OWIIYJJOFGVISF-UHFFFAOYSA-N 4-(1h-pyrrolo[2,3-b]pyridin-3-yl)piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1C1=CNC2=NC=CC=C12 OWIIYJJOFGVISF-UHFFFAOYSA-N 0.000 description 2
• VEBADEJYJGAYLI-UHFFFAOYSA-N 4-[4-[1-(pyridin-2-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]butanoic acid Chemical compound C1CN(CCCC(=O)O)CCC1C(C1=CC=CN=C11)=CN1CC1=CC=CC=N1 VEBADEJYJGAYLI-UHFFFAOYSA-N 0.000 description 2
• AIIMEHWTQIQMNT-UHFFFAOYSA-N 4-[4-[1-[(4-fluorophenyl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]butanoic acid Chemical compound C1CN(CCCC(=O)O)CCC1C(C1=CC=CN=C11)=CN1CC1=CC=C(F)C=C1 AIIMEHWTQIQMNT-UHFFFAOYSA-N 0.000 description 2
• ZDMDZUGMFBEBQW-UHFFFAOYSA-N 4-bromo-3-[[4-(1-butylpyrrolo[2,3-c]pyridin-3-yl)piperidin-1-yl]methyl]benzoic acid Chemical compound C12=CC=NC=C2N(CCCC)C=C1C(CC1)CCN1CC1=CC(C(O)=O)=CC=C1Br ZDMDZUGMFBEBQW-UHFFFAOYSA-N 0.000 description 2
• CNTVQSKWWZUDGL-UHFFFAOYSA-N 4-chloro-2-[2-[4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC(Cl)=CC=C1C(O)=O CNTVQSKWWZUDGL-UHFFFAOYSA-N 0.000 description 2
• ZEYHEAKUIGZSGI-UHFFFAOYSA-M 4-methoxybenzoate Chemical compound COC1=CC=C(C([O-])=O)C=C1 ZEYHEAKUIGZSGI-UHFFFAOYSA-M 0.000 description 2
• VRJHQPZVIGNGMX-UHFFFAOYSA-N 4-piperidinone Chemical compound O=C1CCNCC1 VRJHQPZVIGNGMX-UHFFFAOYSA-N 0.000 description 2
• VWZFJUQNIUEJIH-UHFFFAOYSA-N 5-[[4-(1-butylpyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl]methyl]-2-fluorobenzoic acid Chemical compound C12=CC=CN=C2N(CCCC)C=C1C(CC1)CCN1CC1=CC=C(F)C(C(O)=O)=C1 VWZFJUQNIUEJIH-UHFFFAOYSA-N 0.000 description 2
• KGCJGUHQEZZXQN-UHFFFAOYSA-N 5-[[4-(1-butylpyrrolo[2,3-c]pyridin-3-yl)piperidin-1-yl]methyl]-2-methoxybenzoic acid Chemical compound C12=CC=NC=C2N(CCCC)C=C1C(CC1)CCN1CC1=CC=C(OC)C(C(O)=O)=C1 KGCJGUHQEZZXQN-UHFFFAOYSA-N 0.000 description 2
• OCNQSKBZWWUKJD-UHFFFAOYSA-N 5-[[4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]-2-fluorobenzoic acid Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C(CC1)CCN1CC1=CC=C(F)C(C(O)=O)=C1 OCNQSKBZWWUKJD-UHFFFAOYSA-N 0.000 description 2
• UFGYGDZCCVNMJX-UHFFFAOYSA-N 5-[[4-[1-(furan-2-ylmethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]methyl]-2-methoxybenzoic acid Chemical compound C1=C(C(O)=O)C(OC)=CC=C1CN1CCC(C=2C3=CC=NC=C3N(CC=3OC=CC=3)C=2)CC1 UFGYGDZCCVNMJX-UHFFFAOYSA-N 0.000 description 2
• AEZGRUYZBOYVHR-UHFFFAOYSA-N 5-[[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]-2-fluorobenzoic acid Chemical compound C1=C(F)C(C(=O)O)=CC(CN2CCC(CC2)C=2C3=CC=CN=C3N(CC=3SC(Cl)=CC=3)C=2)=C1 AEZGRUYZBOYVHR-UHFFFAOYSA-N 0.000 description 2
• ONWNWGULGHJQGF-UHFFFAOYSA-N 6-[4-[1-(thiophen-3-ylmethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]hexanoic acid Chemical compound C1CN(CCCCCC(=O)O)CCC1C(C1=CC=NC=C11)=CN1CC1=CSC=C1 ONWNWGULGHJQGF-UHFFFAOYSA-N 0.000 description 2
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
• 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 2
• FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 2
• 229920002785 Croscarmellose sodium Polymers 0.000 description 2
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 2
• NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
• UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
• 235000004443 Ricinus communis Nutrition 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
• 229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
• 150000008041 alkali metal carbonates Chemical class 0.000 description 2
• 125000002947 alkylene group Chemical group 0.000 description 2
• 230000001387 anti-histamine Effects 0.000 description 2
• 239000008346 aqueous phase Substances 0.000 description 2
• 230000004872 arterial blood pressure Effects 0.000 description 2
• 239000004305 biphenyl Substances 0.000 description 2
• 229910052799 carbon Inorganic materials 0.000 description 2
• 210000003169 central nervous system Anatomy 0.000 description 2
• 229960001803 cetirizine Drugs 0.000 description 2
• 239000003610 charcoal Substances 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• 239000000498 cooling water Substances 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
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
• 239000003937 drug carrier Substances 0.000 description 2
• 238000001035 drying Methods 0.000 description 2
• 230000002526 effect on cardiovascular system Effects 0.000 description 2
• MPQNTHDLKHAQBL-UHFFFAOYSA-N ethyl 3-(1-ethoxycarbonyl-3,6-dihydro-2h-pyridin-4-yl)pyrrolo[2,3-b]pyridine-1-carboxylate Chemical compound C1N(C(=O)OCC)CCC(C=2C3=CC=CN=C3N(C(=O)OCC)C=2)=C1 MPQNTHDLKHAQBL-UHFFFAOYSA-N 0.000 description 2
• MQAZVPXJBUFGTK-UHFFFAOYSA-N ethyl 3-(1-ethoxycarbonylpiperidin-4-yl)pyrrolo[2,3-b]pyridine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1C1=CN(C(=O)OCC)C2=NC=CC=C12 MQAZVPXJBUFGTK-UHFFFAOYSA-N 0.000 description 2
• CGURZCDMZJZAEK-UHFFFAOYSA-N ethyl 4-[1-(2-ethoxyethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidine-1-carboxylate Chemical compound C12=CC=NC=C2N(CCOCC)C=C1C1CCN(C(=O)OCC)CC1 CGURZCDMZJZAEK-UHFFFAOYSA-N 0.000 description 2
• ZEJATSKNIRCBIA-UHFFFAOYSA-N ethyl 5-[[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]methyl]-2-methoxybenzoate Chemical compound C1=C(OC)C(C(=O)OCC)=CC(CN2CCC(CC2)C=2C3=CC=NC=C3N(CC=3SC(Cl)=CC=3)C=2)=C1 ZEJATSKNIRCBIA-UHFFFAOYSA-N 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 229960003592 fexofenadine Drugs 0.000 description 2
• 238000009472 formulation Methods 0.000 description 2
• 235000011187 glycerol Nutrition 0.000 description 2
• 230000000004 hemodynamic effect Effects 0.000 description 2
• 150000004678 hydrides Chemical class 0.000 description 2
• 125000002883 imidazolyl group Chemical group 0.000 description 2
• 125000001041 indolyl group Chemical group 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
• 235000019359 magnesium stearate Nutrition 0.000 description 2
• 238000005259 measurement Methods 0.000 description 2
• SNXDSXYLTKYWOR-UHFFFAOYSA-N methyl 2-[2-[4-[1-(2-ethoxyethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoate Chemical compound C12=CC=NC=C2N(CCOCC)C=C1C(CC1)CCN1CCOC1=CC=CC=C1C(=O)OC SNXDSXYLTKYWOR-UHFFFAOYSA-N 0.000 description 2
• MTSTYHKLMUOKBI-UHFFFAOYSA-N methyl 2-[2-[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C=C1OCCN1CCC(C=2C3=CC=CN=C3N(CC3=COC=C3)C=2)CC1 MTSTYHKLMUOKBI-UHFFFAOYSA-N 0.000 description 2
• YRYJVXWCAAIRMQ-UHFFFAOYSA-N methyl 2-[2-[4-[1-(furan-3-ylmethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidin-1-yl]ethoxy]-4-methoxybenzoate Chemical compound COC(=O)C1=CC=C(OC)C=C1OCCN1CCC(C=2C3=CC=NC=C3N(CC3=COC=C3)C=2)CC1 YRYJVXWCAAIRMQ-UHFFFAOYSA-N 0.000 description 2
• YUHSMQQNPRLEEJ-UHFFFAOYSA-N methyl 3-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=CC(CBr)=C1 YUHSMQQNPRLEEJ-UHFFFAOYSA-N 0.000 description 2
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 2
• 239000012299 nitrogen atmosphere Substances 0.000 description 2
• 230000009871 nonspecific binding Effects 0.000 description 2
• 239000003960 organic solvent Substances 0.000 description 2
• ILUJQPXNXACGAN-UHFFFAOYSA-N ortho-methoxybenzoic acid Natural products COC1=CC=CC=C1C(O)=O ILUJQPXNXACGAN-UHFFFAOYSA-N 0.000 description 2
• 125000001715 oxadiazolyl group Chemical group 0.000 description 2
• 125000004430 oxygen atom Chemical group O* 0.000 description 2
• 230000035515 penetration Effects 0.000 description 2
• XNLICIUVMPYHGG-UHFFFAOYSA-N pentan-2-one Chemical compound CCCC(C)=O XNLICIUVMPYHGG-UHFFFAOYSA-N 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 2
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 2
• 125000003386 piperidinyl group Chemical group 0.000 description 2
• 125000003373 pyrazinyl group Chemical group 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 2
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 2
• 125000000714 pyrimidinyl group Chemical group 0.000 description 2
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 235000009518 sodium iodide Nutrition 0.000 description 2
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
• 239000007921 spray Substances 0.000 description 2
• 239000007858 starting material Substances 0.000 description 2
• 238000000967 suction filtration Methods 0.000 description 2
• XROZMXLDMSBVFX-UHFFFAOYSA-N tert-butyl 4-(1h-pyrrolo[2,3-b]pyridin-3-yl)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC(C=2C3=CC=CN=C3NC=2)=C1 XROZMXLDMSBVFX-UHFFFAOYSA-N 0.000 description 2
• 125000001113 thiadiazolyl group Chemical group 0.000 description 2
• 125000000335 thiazolyl group Chemical group 0.000 description 2
• FMCAFXHLMUOIGG-IWFBPKFRSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-IWFBPKFRSA-N 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• SQIWRRMQCSNTHE-UHFFFAOYSA-N 1-[2-[2-[4-[1-[2-(cyclopropylmethoxy)ethyl]-6,7-dimethoxypyrrolo[3,2-b]pyridin-3-yl]piperidin-1-yl]ethylsulfanyl]ethyl]piperidine-2-carboxylic acid Chemical compound C12=C(OC)C(OC)=CN=C2C(C2CCN(CCSCCN3C(CCCC3)C(O)=O)CC2)=CN1CCOCC1CC1 SQIWRRMQCSNTHE-UHFFFAOYSA-N 0.000 description 1
• MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
• XLKDJOPOOHHZAN-UHFFFAOYSA-N 1h-pyrrolo[2,3-c]pyridine Chemical compound C1=NC=C2NC=CC2=C1 XLKDJOPOOHHZAN-UHFFFAOYSA-N 0.000 description 1
• CEFVCNWQCJCMHZ-UHFFFAOYSA-N 2-(bromomethyl)furan Chemical compound BrCC1=CC=CO1 CEFVCNWQCJCMHZ-UHFFFAOYSA-N 0.000 description 1
• QZOBOLDDGXPTBP-UHFFFAOYSA-N 2-(bromomethyl)thiophene Chemical compound BrCC1=CC=CS1 QZOBOLDDGXPTBP-UHFFFAOYSA-N 0.000 description 1
• XGHCXGNPZWLPPF-UHFFFAOYSA-N 2-[2-[4-[7-fluoro-1-(2-methoxyethyl)pyrrolo[3,2-b]pyridin-3-yl]piperidin-1-yl]ethoxy]thiophene-3-carboxylic acid Chemical compound C12=NC=CC(F)=C2N(CCOC)C=C1C(CC1)CCN1CCOC=1SC=CC=1C(O)=O XGHCXGNPZWLPPF-UHFFFAOYSA-N 0.000 description 1
• NAMYKGVDVNBCFQ-UHFFFAOYSA-N 2-bromopropane Chemical compound CC(C)Br NAMYKGVDVNBCFQ-UHFFFAOYSA-N 0.000 description 1
• HNQZRUDJRPSFAU-UHFFFAOYSA-N 2-piperidin-1-yl-1h-indole Chemical group C1CCCCN1C1=CC2=CC=CC=C2N1 HNQZRUDJRPSFAU-UHFFFAOYSA-N 0.000 description 1
• KBWHYRUAHXHHFO-UHFFFAOYSA-N 3-(bromomethyl)thiophene Chemical compound BrCC=1C=CSC=1 KBWHYRUAHXHHFO-UHFFFAOYSA-N 0.000 description 1
• KFTPVHXNHXAMMS-UHFFFAOYSA-N 3-[1-[(2-methylpropan-2-yl)oxycarbonyl]-3,6-dihydro-2h-pyridin-4-yl]pyrrolo[2,3-b]pyridine-1-carboxylic acid Chemical compound C1N(C(=O)OC(C)(C)C)CCC(C=2C3=CC=CN=C3N(C(O)=O)C=2)=C1 KFTPVHXNHXAMMS-UHFFFAOYSA-N 0.000 description 1
• OKGJDWJEWKRFQT-UHFFFAOYSA-N 3-[[4-(1-butylpyrrolo[3,2-c]pyridin-3-yl)piperidin-1-yl]methyl]pyridine-4-carboxylic acid Chemical compound C12=CN=CC=C2N(CCCC)C=C1C(CC1)CCN1CC1=CN=CC=C1C(O)=O OKGJDWJEWKRFQT-UHFFFAOYSA-N 0.000 description 1
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
• MCSXGCZMEPXKIW-UHFFFAOYSA-N 3-hydroxy-4-[(4-methyl-2-nitrophenyl)diazenyl]-N-(3-nitrophenyl)naphthalene-2-carboxamide Chemical compound Cc1ccc(N=Nc2c(O)c(cc3ccccc23)C(=O)Nc2cccc(c2)[N+]([O-])=O)c(c1)[N+]([O-])=O MCSXGCZMEPXKIW-UHFFFAOYSA-N 0.000 description 1
• USRVUBPWYYTBNB-UHFFFAOYSA-N 4-(1-butylpyrrolo[2,3-c]pyridin-3-yl)piperidine-1-carboxylic acid Chemical compound C12=CC=NC=C2N(CCCC)C=C1C1CCN(C(O)=O)CC1 USRVUBPWYYTBNB-UHFFFAOYSA-N 0.000 description 1
• AHGPKEOCUTWCTD-UHFFFAOYSA-N 4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidine-1-carboxylic acid Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C1CCN(C(O)=O)CC1 AHGPKEOCUTWCTD-UHFFFAOYSA-N 0.000 description 1
• HRGSNHHQWTUTGU-UHFFFAOYSA-N 4-[1-(2-methoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidine-1-carboxylic acid Chemical compound C12=CC=CN=C2N(CCOC)C=C1C1CCN(C(O)=O)CC1 HRGSNHHQWTUTGU-UHFFFAOYSA-N 0.000 description 1
• UVPYADGVAZQQEQ-UHFFFAOYSA-N 4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1C(C1=CC=CN=C11)=CN1CC1=COC=C1 UVPYADGVAZQQEQ-UHFFFAOYSA-N 0.000 description 1
• OJRRQPGOBUYIQA-UHFFFAOYSA-N 4-[1-(furan-3-ylmethyl)pyrrolo[2,3-c]pyridin-3-yl]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1C(C1=CC=NC=C11)=CN1CC1=COC=C1 OJRRQPGOBUYIQA-UHFFFAOYSA-N 0.000 description 1
• ORGRTQUGWFTADY-UHFFFAOYSA-N 4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidine-1-carboxylic acid Chemical compound C1CN(C(=O)O)CCC1C(C1=CC=CN=C11)=CN1CC1=CC=C(Cl)S1 ORGRTQUGWFTADY-UHFFFAOYSA-N 0.000 description 1
• VXCAVPWMGVYXAM-UHFFFAOYSA-N 4-chloro-2-[2-[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]ethoxy]benzoic acid Chemical compound OC(=O)C1=CC=C(Cl)C=C1OCCN1CCC(C=2C3=CC=CN=C3N(CC=3SC(Cl)=CC=3)C=2)CC1 VXCAVPWMGVYXAM-UHFFFAOYSA-N 0.000 description 1
• FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical class OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
• HNRLXYNEJIXLGO-UHFFFAOYSA-N 5-(bromomethyl)-2-methoxybenzoic acid Chemical compound COC1=CC=C(CBr)C=C1C(O)=O HNRLXYNEJIXLGO-UHFFFAOYSA-N 0.000 description 1
• FRBHJIIQTCBYOX-UHFFFAOYSA-N 5-[[4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]-2-methoxybenzoic acid Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C(CC1)CCN1CC1=CC=C(OC)C(C(O)=O)=C1 FRBHJIIQTCBYOX-UHFFFAOYSA-N 0.000 description 1
• MQOGVYJNOXKOPG-UHFFFAOYSA-N 5-[[4-[1-[2-(1,4-dioxan-2-yl)ethyl]pyrrolo[3,2-c]pyridin-3-yl]piperidin-1-yl]methyl]-2-fluorobenzoic acid Chemical compound C1=C(F)C(C(=O)O)=CC(CN2CCC(CC2)C=2C3=CN=CC=C3N(CCC3OCCOC3)C=2)=C1 MQOGVYJNOXKOPG-UHFFFAOYSA-N 0.000 description 1
• WKGVVMHURMYJFV-UHFFFAOYSA-N 5-[[4-[7-[2-(4-methoxyphenyl)ethyl]pyrrolo[2,3-d]pyrimidin-5-yl]piperidin-1-yl]methyl]furan-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1CCN1C2=NC=NC=C2C(C2CCN(CC=3OC(=CC=3)C(O)=O)CC2)=C1 WKGVVMHURMYJFV-UHFFFAOYSA-N 0.000 description 1
• FUFZNHHSSMCXCZ-UHFFFAOYSA-N 5-piperidin-4-yl-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C1=CC=CC(C=2N=C(ON=2)C2CCNCC2)=C1 FUFZNHHSSMCXCZ-UHFFFAOYSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 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
• 206010002091 Anaesthesia Diseases 0.000 description 1
• 208000023275 Autoimmune disease Diseases 0.000 description 1
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• 125000000041 C6-C10 aryl group Chemical group 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
• KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
• 108090000613 Cathepsin S Proteins 0.000 description 1
• 102100035654 Cathepsin S Human genes 0.000 description 1
• 241000700199 Cavia porcellus Species 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
• 235000005979 Citrus limon Nutrition 0.000 description 1
• 244000131522 Citrus pyriformis Species 0.000 description 1
• 206010010741 Conjunctivitis Diseases 0.000 description 1
• RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
• QPLDLSVMHZLSFG-UHFFFAOYSA-N Copper oxide Chemical compound [Cu]=O QPLDLSVMHZLSFG-UHFFFAOYSA-N 0.000 description 1
• 239000005751 Copper oxide Substances 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
• 201000004624 Dermatitis Diseases 0.000 description 1
• DBAKFASWICGISY-DASCVMRKSA-N Dexchlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C1([C@H](CCN(C)C)C=2N=CC=CC=2)=CC=C(Cl)C=C1 DBAKFASWICGISY-DASCVMRKSA-N 0.000 description 1
• JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical group CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
• PMVSDNDAUGGCCE-TYYBGVCCSA-L Ferrous fumarate Chemical compound [Fe+2].[O-]C(=O)\C=C\C([O-])=O PMVSDNDAUGGCCE-TYYBGVCCSA-L 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
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• 244000141359 Malus pumila Species 0.000 description 1
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
• FIWILGQIZHDAQG-UHFFFAOYSA-N NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F Chemical compound NC1=C(C(=O)NCC2=CC=C(C=C2)OCC(F)(F)F)C=C(C(=N1)N)N1N=C(N=C1)C1(CC1)C(F)(F)F FIWILGQIZHDAQG-UHFFFAOYSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• 239000005662 Paraffin oil Substances 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 241000700157 Rattus norvegicus Species 0.000 description 1
• 206010039897 Sedation Diseases 0.000 description 1
• 206010040914 Skin reaction Diseases 0.000 description 1
• 208000032140 Sleepiness Diseases 0.000 description 1
• 206010041349 Somnolence Diseases 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-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 239000002671 adjuvant Substances 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 150000001340 alkali metals Chemical class 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001342 alkaline earth metals Chemical class 0.000 description 1
• 150000003973 alkyl amines Chemical class 0.000 description 1
• 239000002168 alkylating agent Substances 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
• 210000000702 aorta abdominal Anatomy 0.000 description 1
• 235000021016 apples Nutrition 0.000 description 1
• 238000013459 approach Methods 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 150000003974 aralkylamines Chemical class 0.000 description 1
• 238000003556 assay Methods 0.000 description 1
• 210000004556 brain Anatomy 0.000 description 1
• CODNYICXDISAEA-UHFFFAOYSA-N bromine monochloride Chemical compound BrCl CODNYICXDISAEA-UHFFFAOYSA-N 0.000 description 1
• AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
• 239000000872 buffer Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
• 210000000748 cardiovascular system Anatomy 0.000 description 1
• 210000001638 cerebellum Anatomy 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 239000008119 colloidal silica Substances 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000009833 condensation Methods 0.000 description 1
• 230000005494 condensation Effects 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 239000010949 copper Substances 0.000 description 1
• 229910000431 copper oxide Inorganic materials 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 238000010511 deprotection reaction Methods 0.000 description 1
• XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 1
• 238000001647 drug administration Methods 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 150000002148 esters Chemical class 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
• APGJWHDAXAURCD-UHFFFAOYSA-N ethyl 3-[1-[(2-methylpropan-2-yl)oxycarbonyl]-3,6-dihydro-2h-pyridin-4-yl]pyrrolo[2,3-b]pyridine-1-carboxylate Chemical compound C12=CC=CN=C2N(C(=O)OCC)C=C1C1=CCN(C(=O)OC(C)(C)C)CC1 APGJWHDAXAURCD-UHFFFAOYSA-N 0.000 description 1
• HCFOWCICLDRGLT-UHFFFAOYSA-N ethyl 4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C1=CCN(C(=O)OCC)CC1 HCFOWCICLDRGLT-UHFFFAOYSA-N 0.000 description 1
• YIFGDDOWHQIQJX-UHFFFAOYSA-N ethyl 4-[1-(2-methoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OCC)CCC1C1=CN(CCOC)C2=NC=CC=C12 YIFGDDOWHQIQJX-UHFFFAOYSA-N 0.000 description 1
• MVPNMAJUKRHQBH-UHFFFAOYSA-N ethyl 5-[[4-(1-butylpyrrolo[2,3-b]pyridin-3-yl)piperidin-1-yl]methyl]-2-methoxybenzoate Chemical compound C12=CC=CN=C2N(CCCC)C=C1C(CC1)CCN1CC1=CC=C(OC)C(C(=O)OCC)=C1 MVPNMAJUKRHQBH-UHFFFAOYSA-N 0.000 description 1
• SBAJBQAKGPXMQK-UHFFFAOYSA-N ethyl 5-[[4-[1-(2-ethoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]-2-methoxybenzoate Chemical compound C12=CC=CN=C2N(CCOCC)C=C1C(CC1)CCN1CC1=CC=C(OC)C(C(=O)OCC)=C1 SBAJBQAKGPXMQK-UHFFFAOYSA-N 0.000 description 1
• RSPUYUYXINLPPI-UHFFFAOYSA-N ethyl 5-[[4-[1-[(5-chlorothiophen-2-yl)methyl]pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]-2-methoxybenzoate Chemical compound C1=C(OC)C(C(=O)OCC)=CC(CN2CCC(CC2)C=2C3=CC=CN=C3N(CC=3SC(Cl)=CC=3)C=2)=C1 RSPUYUYXINLPPI-UHFFFAOYSA-N 0.000 description 1
• 229960003699 evans blue Drugs 0.000 description 1
• 238000011049 filling Methods 0.000 description 1
• 239000012530 fluid Substances 0.000 description 1
• 235000013305 food Nutrition 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
• 238000000589 high-performance liquid chromatography-mass spectrometry Methods 0.000 description 1
• DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
• 238000005984 hydrogenation reaction Methods 0.000 description 1
• 150000004679 hydroxides Chemical class 0.000 description 1
• 230000001631 hypertensive effect Effects 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 238000002513 implantation Methods 0.000 description 1
• 238000000338 in vitro Methods 0.000 description 1
• 238000011534 incubation Methods 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 238000010253 intravenous injection Methods 0.000 description 1
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
• 238000012417 linear regression Methods 0.000 description 1
• JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 1
• 229960003088 loratadine Drugs 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 229960000582 mepyramine Drugs 0.000 description 1
• CHGUCWXJZWEILE-UHFFFAOYSA-N methyl 2-(2-chloroethoxy)-3-methoxybenzoate Chemical compound COC(=O)C1=CC=CC(OC)=C1OCCCl CHGUCWXJZWEILE-UHFFFAOYSA-N 0.000 description 1
• YDUWFOOXVFXHNZ-UHFFFAOYSA-N methyl 3-[[4-[1-(2-methoxyethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidin-1-yl]methyl]benzoate Chemical compound C12=CC=CN=C2N(CCOC)C=C1C(CC1)CCN1CC1=CC=CC(C(=O)OC)=C1 YDUWFOOXVFXHNZ-UHFFFAOYSA-N 0.000 description 1
• IDJNYKMDAYSDPM-UHFFFAOYSA-N methyl 4-chloro-2-(2-chloroethoxy)benzoate Chemical compound COC(=O)C1=CC=C(Cl)C=C1OCCCl IDJNYKMDAYSDPM-UHFFFAOYSA-N 0.000 description 1
• KRCMKUNIILUXPF-UHFFFAOYSA-N methyl 4-hydroxybenzoate;sodium Chemical compound [Na].COC(=O)C1=CC=C(O)C=C1 KRCMKUNIILUXPF-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 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
• 230000004048 modification Effects 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 125000002757 morpholinyl group Chemical group 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
• IOSYSUQITYVOOG-UHFFFAOYSA-N n-[4-(trifluoromethyl)phenyl]pentanamide Chemical compound CCCCC(=O)NC1=CC=C(C(F)(F)F)C=C1 IOSYSUQITYVOOG-UHFFFAOYSA-N 0.000 description 1
• 125000001624 naphthyl group Chemical group 0.000 description 1
• 229920005615 natural polymer Polymers 0.000 description 1
• 229910017604 nitric acid Inorganic materials 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
• 235000005985 organic acids Nutrition 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 239000007800 oxidant agent Substances 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
• 239000012071 phase Substances 0.000 description 1
• 239000008363 phosphate buffer Substances 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 229920000642 polymer Polymers 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
• 239000000843 powder Substances 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 229960003910 promethazine Drugs 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
• 150000003217 pyrazoles Chemical class 0.000 description 1
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• 150000003222 pyridines Chemical class 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 239000002994 raw material Substances 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 206010039083 rhinitis Diseases 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
• 238000009938 salting Methods 0.000 description 1
• 239000012047 saturated solution Substances 0.000 description 1
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
• 230000036280 sedation Effects 0.000 description 1
• 239000000932 sedative agent Substances 0.000 description 1
• 230000001624 sedative effect Effects 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 239000000952 serotonin receptor agonist Substances 0.000 description 1
• 230000035483 skin reaction Effects 0.000 description 1
• 231100000430 skin reaction Toxicity 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 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
• 239000000600 sorbitol Substances 0.000 description 1
• 230000009870 specific binding Effects 0.000 description 1
• 238000004611 spectroscopical analysis Methods 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 239000000126 substance Substances 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
• 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
• HJZBTILRDYMUEY-UHFFFAOYSA-N tert-butyl 2-[3-[3-[4-(2-bromo-7-propan-2-yloxy-1h-pyrrolo[3,2-c]pyridin-3-yl)-2,2-dimethylpiperidin-1-yl]propanoyl]-5-chlorophenoxy]acetate Chemical compound BrC=1NC=2C(OC(C)C)=CN=CC=2C=1C(CC1(C)C)CCN1CCC(=O)C1=CC(Cl)=CC(OCC(=O)OC(C)(C)C)=C1 HJZBTILRDYMUEY-UHFFFAOYSA-N 0.000 description 1
• RYYJEKLQXYGNCD-UHFFFAOYSA-N tert-butyl 4-[1-(furan-3-ylmethyl)pyrrolo[2,3-b]pyridin-3-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(C1=CC=CN=C11)=CN1CC1=COC=C1 RYYJEKLQXYGNCD-UHFFFAOYSA-N 0.000 description 1
• ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
• 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1