CA2759162A1 - Derives de benzazole, compositions et methodes d'utilisation des derives comme inhibiteurs de la .beta.-secretase - Google Patents

Derives de benzazole, compositions et methodes d'utilisation des derives comme inhibiteurs de la .beta.-secretase Download PDF

Info

Publication number: CA2759162A1
Authority: CA; Canada
Prior art keywords: carboxylic acid; amide; imidazol; isoquinoline; group
Prior art date: 2005-03-14
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.): Abandoned

Application number

CA2759162A

Other languages

English (en)

Inventor

Adnan M.M. Mjalli

David Jones

Devi Reddy Gohimmukkula

Guoxiang Huang

Jeff Zhu

Mohan Rao

Robert C. Andrews

Tan Ren

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

vTv Therapeutics LLC

Original Assignee

High Point Pharnaceuticals LLC

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

2005-03-14

Filing date

2006-03-14

Publication date

2006-09-21

2005-08-29 Priority claimed from US11/661,349 external-priority patent/US7619424B2/en

2006-03-14 Application filed by High Point Pharnaceuticals LLC filed Critical High Point Pharnaceuticals LLC

2006-03-14 Priority claimed from CA2600570A external-priority patent/CA2600570C/fr

2006-09-21 Publication of CA2759162A1 publication Critical patent/CA2759162A1/fr

Status Abandoned legal-status Critical Current

Links

239000000203 mixture Substances 0.000 title claims abstract description 116
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238000000034 method Methods 0.000 title claims description 144
239000003112 inhibitor Substances 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 232
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 29
102100021257 Beta-secretase 1 Human genes 0.000 claims abstract description 28
101000894895 Homo sapiens Beta-secretase 1 Proteins 0.000 claims abstract description 28
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
201000010099 disease Diseases 0.000 claims abstract description 14
208000024827 Alzheimer disease Diseases 0.000 claims abstract description 12
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-1 heterocyclylene Chemical group 0.000 claims description 840
NDMFETHQFUOIQX-UHFFFAOYSA-N 1-(3-chloropropyl)imidazolidin-2-one Chemical compound ClCCCN1CCNC1=O NDMFETHQFUOIQX-UHFFFAOYSA-N 0.000 claims description 213
125000000217 alkyl group Chemical group 0.000 claims description 123
229910052739 hydrogen Inorganic materials 0.000 claims description 98
239000001257 hydrogen Substances 0.000 claims description 97
DEPDDPLQZYCHOH-UHFFFAOYSA-N 1h-imidazol-2-amine Chemical compound NC1=NC=CN1 DEPDDPLQZYCHOH-UHFFFAOYSA-N 0.000 claims description 87
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 80
125000003118 aryl group Chemical group 0.000 claims description 67
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 61
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 58
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 54
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 52
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125000001424 substituent group Chemical group 0.000 claims description 50
150000002148 esters Chemical class 0.000 claims description 48
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 claims description 43
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 43
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BBUXIKFCXJNYIJ-UHFFFAOYSA-N 2-isoquinolin-3-yl-3h-benzimidazole-5-carboxylic acid Chemical compound C1=CC=C2C=NC(C=3NC4=CC=C(C=C4N=3)C(=O)O)=CC2=C1 BBUXIKFCXJNYIJ-UHFFFAOYSA-N 0.000 claims description 31
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125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 22
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125000004429 atom Chemical group 0.000 claims description 21
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RNYNOBZIVBNYBJ-UHFFFAOYSA-N 2-isoquinolin-3-yl-1h-benzimidazole-4-carboxylic acid Chemical compound C1=CC=C2C=NC(C=3NC=4C=CC=C(C=4N=3)C(=O)O)=CC2=C1 RNYNOBZIVBNYBJ-UHFFFAOYSA-N 0.000 claims description 12
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FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 10
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 10
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125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 7
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RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 claims description 5
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VNHBYKHXBCYPBJ-UHFFFAOYSA-N 5-ethynylimidazo[1,2-a]pyridine Chemical compound C#CC1=CC=CC2=NC=CN12 VNHBYKHXBCYPBJ-UHFFFAOYSA-N 0.000 claims description 4
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PUROHTHWKOSHHR-UHFFFAOYSA-N 2-(isoquinolin-3-ylamino)-n-methyl-1h-benzimidazole-4-carboxamide Chemical compound C1=CC=C2C=NC(NC3=NC=4C=CC=C(C=4N3)C(=O)NC)=CC2=C1 PUROHTHWKOSHHR-UHFFFAOYSA-N 0.000 claims 1
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XNXBQZHJNSDVQM-UHFFFAOYSA-N 2-[(2-fluorobenzoyl)amino]-n-(1h-imidazol-2-yl)-1h-benzimidazole-4-carboxamide Chemical compound FC1=CC=CC=C1C(=O)NC1=NC2=CC=CC(C(=O)NC=3NC=CN=3)=C2N1 XNXBQZHJNSDVQM-UHFFFAOYSA-N 0.000 claims 1
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YYCWDBDINNAQTH-UHFFFAOYSA-N 2-[(3,5-difluorobenzoyl)amino]-n-(1h-imidazol-2-yl)-1h-benzimidazole-4-carboxamide Chemical compound FC1=CC(F)=CC(C(=O)NC=2NC3=C(C(=O)NC=4NC=CN=4)C=CC=C3N=2)=C1 YYCWDBDINNAQTH-UHFFFAOYSA-N 0.000 claims 1
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UEGPDKFYZHJHSK-UHFFFAOYSA-N 2-[(4-fluoro-3-methoxybenzoyl)amino]-n-(1h-imidazol-2-yl)-1h-benzimidazole-4-carboxamide Chemical compound C1=C(F)C(OC)=CC(C(=O)NC=2NC3=C(C(=O)NC=4NC=CN=4)C=CC=C3N=2)=C1 UEGPDKFYZHJHSK-UHFFFAOYSA-N 0.000 claims 1
NRBIGPPBQPOAIW-UHFFFAOYSA-N 2-[(4-fluorobenzoyl)amino]-n-(1h-imidazol-2-yl)-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(F)=CC=C1C(=O)NC1=NC2=CC=CC(C(=O)NC=3NC=CN=3)=C2N1 NRBIGPPBQPOAIW-UHFFFAOYSA-N 0.000 claims 1
MKUUBNAKDGUWGG-UHFFFAOYSA-N 2-[(4-tert-butylbenzoyl)amino]-n-(1h-imidazol-2-yl)-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)NC1=NC2=CC=CC(C(=O)NC=3NC=CN=3)=C2N1 MKUUBNAKDGUWGG-UHFFFAOYSA-N 0.000 claims 1
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KNAXPDGBZIEBTP-UHFFFAOYSA-N n-(1h-benzimidazol-2-yl)-2-naphthalen-2-yl-3h-benzimidazole-5-carboxamide Chemical compound C1=CC=CC2=CC(C=3NC4=CC=C(C=C4N=3)C(NC=3NC4=CC=CC=C4N=3)=O)=CC=C21 KNAXPDGBZIEBTP-UHFFFAOYSA-N 0.000 claims 1
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BHZXBFRORAMRDD-UHFFFAOYSA-N n-(1h-imidazol-2-yl)-2-(1h-indazole-3-carbonylamino)-1h-benzimidazole-4-carboxamide Chemical compound N=1NC2=CC=CC=C2C=1C(=O)NC(NC1=2)=NC1=CC=CC=2C(=O)NC1=NC=CN1 BHZXBFRORAMRDD-UHFFFAOYSA-N 0.000 claims 1
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ADHBNWAYMZEQSF-UHFFFAOYSA-N n-(1h-imidazol-2-yl)-2-(naphthalene-2-carbonylamino)-1h-benzimidazole-4-carboxamide Chemical compound C=1C=C2C=CC=CC2=CC=1C(=O)NC(NC1=CC=C2)=NC1=C2C(=O)NC1=NC=CN1 ADHBNWAYMZEQSF-UHFFFAOYSA-N 0.000 claims 1
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FDISPZPLEREWPS-UHFFFAOYSA-N n-(1h-imidazol-2-yl)-2-[(4-methoxybenzoyl)amino]-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(OC)=CC=C1C(=O)NC1=NC2=CC=CC(C(=O)NC=3NC=CN=3)=C2N1 FDISPZPLEREWPS-UHFFFAOYSA-N 0.000 claims 1
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BZAYJTGSTUVJPM-UHFFFAOYSA-N n-(1h-imidazol-2-yl)-2-[(4-phenoxybenzoyl)amino]-1h-benzimidazole-4-carboxamide Chemical compound C=1C=C(OC=2C=CC=CC=2)C=CC=1C(=O)NC(NC1=CC=C2)=NC1=C2C(=O)NC1=NC=CN1 BZAYJTGSTUVJPM-UHFFFAOYSA-N 0.000 claims 1
NQFWEZBPLUCTPE-UHFFFAOYSA-N n-(1h-imidazol-2-yl)-2-[(4-phenylbenzoyl)amino]-1h-benzimidazole-4-carboxamide Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1C(=O)NC(NC1=CC=C2)=NC1=C2C(=O)NC1=NC=CN1 NQFWEZBPLUCTPE-UHFFFAOYSA-N 0.000 claims 1
NCUWSQJNQBFGQM-UHFFFAOYSA-N n-(1h-imidazol-2-yl)-2-[(4-propan-2-ylbenzoyl)amino]-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(C(C)C)=CC=C1C(=O)NC1=NC2=CC=CC(C(=O)NC=3NC=CN=3)=C2N1 NCUWSQJNQBFGQM-UHFFFAOYSA-N 0.000 claims 1
RPUAYSHJAPTPRI-UHFFFAOYSA-N n-(1h-imidazol-2-yl)-2-[(5-methyl-1h-indole-2-carbonyl)amino]-1h-benzimidazole-4-carboxamide Chemical compound C=1C2=CC(C)=CC=C2NC=1C(=O)NC(NC1=2)=NC1=CC=CC=2C(=O)NC1=NC=CN1 RPUAYSHJAPTPRI-UHFFFAOYSA-N 0.000 claims 1
YPUOEDZEMODXLR-UHFFFAOYSA-N n-(1h-imidazol-2-yl)-2-[(6-phenoxypyridine-2-carbonyl)amino]-1h-benzimidazole-4-carboxamide Chemical compound C=1C=CC(OC=2C=CC=CC=2)=NC=1C(=O)NC(NC1=2)=NC1=CC=CC=2C(=O)NC1=NC=CN1 YPUOEDZEMODXLR-UHFFFAOYSA-N 0.000 claims 1
HFHWSAODUBTRNO-UHFFFAOYSA-N n-(1h-imidazol-2-yl)-2-[[4-(trifluoromethyl)benzoyl]amino]-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(C(F)(F)F)=CC=C1C(=O)NC1=NC2=C(C(=O)NC=3NC=CN=3)C=CC=C2N1 HFHWSAODUBTRNO-UHFFFAOYSA-N 0.000 claims 1
AQNHKYWUTXZGON-UHFFFAOYSA-N n-(3-hydroxypropyl)-2-(isoquinolin-3-ylamino)-1h-benzimidazole-4-carboxamide Chemical compound C1=CC=C2C=NC(NC3=NC=4C=CC=C(C=4N3)C(=O)NCCCO)=CC2=C1 AQNHKYWUTXZGON-UHFFFAOYSA-N 0.000 claims 1
VCMBSXHBEUBPMZ-UHFFFAOYSA-N n-(4-chlorophenyl)-2-(isoquinolin-3-ylamino)-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(Cl)=CC=C1NC(=O)C1=CC=CC2=C1NC(NC=1N=CC3=CC=CC=C3C=1)=N2 VCMBSXHBEUBPMZ-UHFFFAOYSA-N 0.000 claims 1
YEGCIUAOIVAIKE-UHFFFAOYSA-N n-(4-fluorophenyl)-2-(isoquinolin-3-ylamino)-1h-benzimidazole-4-carboxamide Chemical compound C1=CC(F)=CC=C1NC(=O)C1=CC=CC2=C1NC(NC=1N=CC3=CC=CC=C3C=1)=N2 YEGCIUAOIVAIKE-UHFFFAOYSA-N 0.000 claims 1
ITJQOWNKDLAANF-XMMPIXPASA-N n-[(3r)-1-(1h-imidazol-2-ylamino)-1-oxo-5-phenylpentan-3-yl]-2-isoquinolin-3-yl-3h-benzimidazole-5-carboxamide Chemical compound C([C@H](CC(=O)NC=1NC=CN=1)NC(=O)C=1C=C2NC(=NC2=CC=1)C=1N=CC2=CC=CC=C2C=1)CC1=CC=CC=C1 ITJQOWNKDLAANF-XMMPIXPASA-N 0.000 claims 1
VMMZUTOFJGCWNY-UHFFFAOYSA-N n-[1-(1h-imidazol-2-ylamino)-1-oxo-3-(4-phenylphenyl)propan-2-yl]-2-isoquinolin-3-yl-3h-benzimidazole-5-carboxamide Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CC(NC(=O)C=1C=C2N=C(NC2=CC=1)C=1N=CC2=CC=CC=C2C=1)C(=O)NC1=NC=CN1 VMMZUTOFJGCWNY-UHFFFAOYSA-N 0.000 claims 1
BDFRHZITHLDJRC-UHFFFAOYSA-N n-[1-(2-fluorophenyl)-3-(1h-imidazol-2-ylamino)-3-oxopropyl]-2-isoquinolin-3-yl-3h-benzimidazole-5-carboxamide Chemical compound FC1=CC=CC=C1C(NC(=O)C=1C=C2N=C(NC2=CC=1)C=1N=CC2=CC=CC=C2C=1)CC(=O)NC1=NC=CN1 BDFRHZITHLDJRC-UHFFFAOYSA-N 0.000 claims 1
NLHFOYIDOITJGC-UHFFFAOYSA-N n-[1-cyclopropyl-3-(1h-imidazol-2-ylamino)-3-oxopropyl]-2-isoquinolin-3-yl-3h-benzimidazole-5-carboxamide Chemical compound N=1C=CNC=1NC(=O)CC(NC(=O)C=1C=C2N=C(NC2=CC=1)C=1N=CC2=CC=CC=C2C=1)C1CC1 NLHFOYIDOITJGC-UHFFFAOYSA-N 0.000 claims 1
MUVFBDXALDLCRP-UHFFFAOYSA-N n-[3-(1h-imidazol-2-ylamino)-1-(3-methoxyphenyl)-3-oxopropyl]-2-isoquinolin-3-yl-3h-benzimidazole-5-carboxamide Chemical compound COC1=CC=CC(C(CC(=O)NC=2NC=CN=2)NC(=O)C=2C=C3N=C(NC3=CC=2)C=2N=CC3=CC=CC=C3C=2)=C1 MUVFBDXALDLCRP-UHFFFAOYSA-N 0.000 claims 1
VMBPXPDMDKBVFK-UHFFFAOYSA-N n-[3-(1h-imidazol-2-ylamino)-3-oxo-1-(4-phenylphenyl)propyl]-2-isoquinolin-3-yl-3h-benzimidazole-5-carboxamide Chemical compound N=1C=CNC=1NC(=O)CC(NC(=O)C=1C=C2N=C(NC2=CC=1)C=1N=CC2=CC=CC=C2C=1)C(C=C1)=CC=C1C1=CC=CC=C1 VMBPXPDMDKBVFK-UHFFFAOYSA-N 0.000 claims 1
UJYULLKVYDKOPQ-UHFFFAOYSA-N n-[3-(1h-imidazol-2-ylamino)-3-oxo-1-phenylpropyl]-2-isoquinolin-3-yl-3h-benzimidazole-5-carboxamide Chemical compound N=1C=CNC=1NC(=O)CC(NC(=O)C=1C=C2N=C(NC2=CC=1)C=1N=CC2=CC=CC=C2C=1)C1=CC=CC=C1 UJYULLKVYDKOPQ-UHFFFAOYSA-N 0.000 claims 1
QKDXSNFVPLTCCB-UHFFFAOYSA-N n-[4-(1,3,4,9-tetrahydropyrido[3,4-b]indole-2-carbonyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C1=CC=C2C=NC(C(NC=3NC4=CC=CC(=C4N=3)C(=O)N3CC4=C(C5=CC=CC=C5N4)CC3)=O)=CC2=C1 QKDXSNFVPLTCCB-UHFFFAOYSA-N 0.000 claims 1
MERIKJZILNJIHZ-UHFFFAOYSA-N n-[4-(1,3,4-thiadiazol-2-ylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=1C2=CC=CC=C2C=NC=1C(=O)NC(NC1=2)=NC1=CC=CC=2C(=O)NC1=NN=CS1 MERIKJZILNJIHZ-UHFFFAOYSA-N 0.000 claims 1
AXRDWPKFDRECFY-UHFFFAOYSA-N n-[4-(1,3-benzothiazol-2-ylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C1=CC=C2C=NC(C(NC=3NC4=C(C(=O)NC=5SC6=CC=CC=C6N=5)C=CC=C4N=3)=O)=CC2=C1 AXRDWPKFDRECFY-UHFFFAOYSA-N 0.000 claims 1
WMRVTFWEWWRLEY-UHFFFAOYSA-N n-[4-(1,3-benzothiazol-2-ylmethylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C1=CC=C2C=NC(C(=O)NC=3NC=4C=CC=C(C=4N=3)C(NCC=3SC4=CC=CC=C4N=3)=O)=CC2=C1 WMRVTFWEWWRLEY-UHFFFAOYSA-N 0.000 claims 1
GYKZEUJLHHBJEQ-UHFFFAOYSA-N n-[4-(1,3-thiazol-2-ylmethylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=1C=CC=2NC(NC(=O)C=3N=CC4=CC=CC=C4C=3)=NC=2C=1C(=O)NCC1=NC=CS1 GYKZEUJLHHBJEQ-UHFFFAOYSA-N 0.000 claims 1
OIEBPWKAVOFYAU-UHFFFAOYSA-N n-[4-(1h-benzimidazol-2-ylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C1=CC=C2C=NC(C(NC=3NC4=C(C(=O)NC=5NC6=CC=CC=C6N=5)C=CC=C4N=3)=O)=CC2=C1 OIEBPWKAVOFYAU-UHFFFAOYSA-N 0.000 claims 1
DAUWQPHLRJSBQC-UHFFFAOYSA-N n-[4-(1h-benzimidazol-2-ylmethylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C1=CC=C2C=NC(C(=O)NC=3NC=4C=CC=C(C=4N=3)C(NCC=3NC4=CC=CC=C4N=3)=O)=CC2=C1 DAUWQPHLRJSBQC-UHFFFAOYSA-N 0.000 claims 1
OUQIBTHOOXURCE-UHFFFAOYSA-N n-[4-(1h-imidazol-2-ylamino)-4-oxo-1-(4-phenylphenyl)butan-2-yl]-2-isoquinolin-3-yl-3h-benzimidazole-5-carboxamide Chemical compound N=1C=CNC=1NC(=O)CC(NC(=O)C=1C=C2N=C(NC2=CC=1)C=1N=CC2=CC=CC=C2C=1)CC(C=C1)=CC=C1C1=CC=CC=C1 OUQIBTHOOXURCE-UHFFFAOYSA-N 0.000 claims 1
MZUIJJAPJIQJPJ-UHFFFAOYSA-N n-[4-(1h-imidazol-2-ylcarbamoyl)-1h-benzimidazol-2-yl]-1-methylindazole-3-carboxamide Chemical compound C12=CC=CC=C2N(C)N=C1C(=O)NC(NC1=2)=NC1=CC=CC=2C(=O)NC1=NC=CN1 MZUIJJAPJIQJPJ-UHFFFAOYSA-N 0.000 claims 1
SXZDJONZRHFELJ-UHFFFAOYSA-N n-[4-(1h-imidazol-2-ylcarbamoyl)-1h-benzimidazol-2-yl]quinoline-2-carboxamide Chemical compound C=1C=C2C=CC=CC2=NC=1C(=O)NC(NC1=2)=NC1=CC=CC=2C(=O)NC1=NC=CN1 SXZDJONZRHFELJ-UHFFFAOYSA-N 0.000 claims 1
LTBQQTOFJBUZND-UHFFFAOYSA-N n-[4-(1h-imidazol-2-ylcarbamoyl)-1h-benzimidazol-2-yl]quinoline-3-carboxamide Chemical compound C=1N=C2C=CC=CC2=CC=1C(=O)NC(NC1=2)=NC1=CC=CC=2C(=O)NC1=NC=CN1 LTBQQTOFJBUZND-UHFFFAOYSA-N 0.000 claims 1
FHTGDBWLXPSCHI-UHFFFAOYSA-N n-[4-(1h-imidazol-2-ylcarbamoyl)-6-(2-methylpropanoylamino)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=12N=C(NC(=O)C=3N=CC4=CC=CC=C4C=3)NC2=CC(NC(=O)C(C)C)=CC=1C(=O)NC1=NC=CN1 FHTGDBWLXPSCHI-UHFFFAOYSA-N 0.000 claims 1
AVBAIVJQGVVFMH-UHFFFAOYSA-N n-[4-(1h-imidazol-2-ylcarbamoyl)-6-(3-methylbutanoylamino)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=12N=C(NC(=O)C=3N=CC4=CC=CC=C4C=3)NC2=CC(NC(=O)CC(C)C)=CC=1C(=O)NC1=NC=CN1 AVBAIVJQGVVFMH-UHFFFAOYSA-N 0.000 claims 1
BMZUPQXUWTYOGL-UHFFFAOYSA-N n-[4-(1h-imidazol-2-ylcarbamoyl)-6-[(2-phenylacetyl)amino]-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=1C(C(=O)NC=2NC=CN=2)=C2NC(NC(=O)C=3N=CC4=CC=CC=C4C=3)=NC2=CC=1NC(=O)CC1=CC=CC=C1 BMZUPQXUWTYOGL-UHFFFAOYSA-N 0.000 claims 1
RLZKTDLRPMDPTO-UHFFFAOYSA-N n-[4-(1h-indazol-5-ylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C1=CC=C2C=NC(C(NC=3NC4=CC=CC(=C4N=3)C(=O)NC=3C=C4C=NNC4=CC=3)=O)=CC2=C1 RLZKTDLRPMDPTO-UHFFFAOYSA-N 0.000 claims 1
CSAKUQDFNPGOEB-UHFFFAOYSA-N n-[4-(2-phenylethylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=1C=CC=2N=C(NC(=O)C=3N=CC4=CC=CC=C4C=3)NC=2C=1C(=O)NCCC1=CC=CC=C1 CSAKUQDFNPGOEB-UHFFFAOYSA-N 0.000 claims 1
DMTYNHPKHKKDQD-UHFFFAOYSA-N n-[4-(2-thiophen-2-ylethylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=1C=CC=2NC(NC(=O)C=3N=CC4=CC=CC=C4C=3)=NC=2C=1C(=O)NCCC1=CC=CS1 DMTYNHPKHKKDQD-UHFFFAOYSA-N 0.000 claims 1
PHNSNJADDNMQJW-UHFFFAOYSA-N n-[4-(benzylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=1C=CC=2N=C(NC(=O)C=3N=CC4=CC=CC=C4C=3)NC=2C=1C(=O)NCC1=CC=CC=C1 PHNSNJADDNMQJW-UHFFFAOYSA-N 0.000 claims 1
WACZJRXNXSYKDZ-UHFFFAOYSA-N n-[4-(ethylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C1=CC=C2C=NC(C(=O)NC3=NC=4C=CC=C(C=4N3)C(=O)NCC)=CC2=C1 WACZJRXNXSYKDZ-UHFFFAOYSA-N 0.000 claims 1
KUORHYQYKHSDFU-UHFFFAOYSA-N n-[4-(furan-2-ylmethylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=1C=CC=2NC(NC(=O)C=3N=CC4=CC=CC=C4C=3)=NC=2C=1C(=O)NCC1=CC=CO1 KUORHYQYKHSDFU-UHFFFAOYSA-N 0.000 claims 1
RFNCAMTURDEWIF-UHFFFAOYSA-N n-[4-(pyridin-2-ylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=1C2=CC=CC=C2C=NC=1C(=O)NC(NC1=CC=C2)=NC1=C2C(=O)NC1=CC=CC=N1 RFNCAMTURDEWIF-UHFFFAOYSA-N 0.000 claims 1
CHGITINTDUXHFD-UHFFFAOYSA-N n-[4-(pyridin-3-ylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=1C2=CC=CC=C2C=NC=1C(=O)NC(NC1=CC=C2)=NC1=C2C(=O)NC1=CC=CN=C1 CHGITINTDUXHFD-UHFFFAOYSA-N 0.000 claims 1
RLNNYBJZFDUQCH-UHFFFAOYSA-N n-[4-(quinolin-3-ylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C1=CC=C2C=NC(C(NC=3NC4=CC=CC(=C4N=3)C(=O)NC=3C=C4C=CC=CC4=NC=3)=O)=CC2=C1 RLNNYBJZFDUQCH-UHFFFAOYSA-N 0.000 claims 1
IATLOPXMINOGRQ-UHFFFAOYSA-N n-[4-(tert-butylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C1=CC=C2C=NC(C(=O)NC3=NC=4C=CC=C(C=4N3)C(=O)NC(C)(C)C)=CC2=C1 IATLOPXMINOGRQ-UHFFFAOYSA-N 0.000 claims 1
CZZKZQOFHMSSTO-UHFFFAOYSA-N n-[4-(thiophen-2-ylmethylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=1C=CC=2NC(NC(=O)C=3N=CC4=CC=CC=C4C=3)=NC=2C=1C(=O)NCC1=CC=CS1 CZZKZQOFHMSSTO-UHFFFAOYSA-N 0.000 claims 1
WCYICWHNKCTOTN-UHFFFAOYSA-N n-[4-[(2-phenoxyphenyl)carbamoyl]-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=1C2=CC=CC=C2C=NC=1C(=O)NC(NC1=CC=C2)=NC1=C2C(=O)NC1=CC=CC=C1OC1=CC=CC=C1 WCYICWHNKCTOTN-UHFFFAOYSA-N 0.000 claims 1
JERHWDQYRLFGAQ-UHFFFAOYSA-N n-[4-[(3-phenoxyphenyl)carbamoyl]-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=1C2=CC=CC=C2C=NC=1C(=O)NC(NC1=CC=C2)=NC1=C2C(=O)NC(C=1)=CC=CC=1OC1=CC=CC=C1 JERHWDQYRLFGAQ-UHFFFAOYSA-N 0.000 claims 1
OQFKYTKAIOWHKY-UHFFFAOYSA-N n-[4-[(4-phenoxyphenyl)carbamoyl]-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=1C2=CC=CC=C2C=NC=1C(=O)NC(NC1=CC=C2)=NC1=C2C(=O)NC(C=C1)=CC=C1OC1=CC=CC=C1 OQFKYTKAIOWHKY-UHFFFAOYSA-N 0.000 claims 1
PPRCVVWDGGEKON-UHFFFAOYSA-N n-[4-[(5-methylfuran-2-yl)methylcarbamoyl]-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound O1C(C)=CC=C1CNC(=O)C1=CC=CC2=C1N=C(NC(=O)C=1N=CC3=CC=CC=C3C=1)N2 PPRCVVWDGGEKON-UHFFFAOYSA-N 0.000 claims 1
JHHKGIRVOJLSIK-UHFFFAOYSA-N n-[4-[(5-phenyl-1h-imidazol-2-yl)carbamoyl]-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=1C2=CC=CC=C2C=NC=1C(=O)NC(NC1=CC=C2)=NC1=C2C(=O)NC(N1)=NC=C1C1=CC=CC=C1 JHHKGIRVOJLSIK-UHFFFAOYSA-N 0.000 claims 1
GNLMGHOPOUFHPQ-UHFFFAOYSA-N n-[4-[2-(1h-benzimidazol-2-yl)ethylcarbamoyl]-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C1=CC=C2C=NC(C(=O)NC=3NC=4C=CC=C(C=4N=3)C(NCCC=3NC4=CC=CC=C4N=3)=O)=CC2=C1 GNLMGHOPOUFHPQ-UHFFFAOYSA-N 0.000 claims 1
HNZNQMUGPRGXBT-UHFFFAOYSA-N n-[6-(1,3-benzothiazol-2-ylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C1=CC=C2C=NC(C(=O)NC=3NC4=CC=C(C=C4N=3)C(NC=3SC4=CC=CC=C4N=3)=O)=CC2=C1 HNZNQMUGPRGXBT-UHFFFAOYSA-N 0.000 claims 1
KGHOCQCTVAUMKT-UHFFFAOYSA-N n-[6-(1,3-thiazol-2-ylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=1C=C2NC(NC(=O)C=3N=CC4=CC=CC=C4C=3)=NC2=CC=1C(=O)NC1=NC=CS1 KGHOCQCTVAUMKT-UHFFFAOYSA-N 0.000 claims 1
DHLGALGXGWELNN-UHFFFAOYSA-N n-[6-(1h-benzimidazol-2-ylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C1=CC=C2C=NC(C(=O)NC=3NC4=CC=C(C=C4N=3)C(NC=3NC4=CC=CC=C4N=3)=O)=CC2=C1 DHLGALGXGWELNN-UHFFFAOYSA-N 0.000 claims 1
MDXUDGLOFAJZRO-UHFFFAOYSA-N n-[6-benzamido-4-(1h-imidazol-2-ylcarbamoyl)-1h-benzimidazol-2-yl]isoquinoline-3-carboxamide Chemical compound C=1C=CC=CC=1C(=O)NC(C=C1NC(NC(=O)C=2N=CC3=CC=CC=C3C=2)=NC1=1)=CC=1C(=O)NC1=NC=CN1 MDXUDGLOFAJZRO-UHFFFAOYSA-N 0.000 claims 1
JWMDMOYMTPPOQC-UHFFFAOYSA-N n-benzyl-2-(isoquinolin-3-ylamino)-1h-benzimidazole-4-carboxamide Chemical compound C=1C=CC=2N=C(NC=3N=CC4=CC=CC=C4C=3)NC=2C=1C(=O)NCC1=CC=CC=C1 JWMDMOYMTPPOQC-UHFFFAOYSA-N 0.000 claims 1
XXWHWMPUYSVHTN-UHFFFAOYSA-N n-butyl-2-isoquinolin-3-yl-1h-benzimidazole-4-carboxamide Chemical compound C1=CC=C2C=NC(C=3NC=4C=CC=C(C=4N=3)C(=O)NCCCC)=CC2=C1 XXWHWMPUYSVHTN-UHFFFAOYSA-N 0.000 claims 1
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ZJPSDBDQMZSDRN-UHFFFAOYSA-N methyl 2-(isoquinoline-3-carbonylamino)-3h-benzimidazole-5-carboxylate Chemical compound C1=CC=C2C=NC(C(=O)NC=3NC4=CC=C(C=C4N=3)C(=O)OC)=CC2=C1 ZJPSDBDQMZSDRN-UHFFFAOYSA-N 0.000 description 2
VLSIRWMAASEDBN-UHFFFAOYSA-N methyl 2-amino-3-(isoquinoline-3-carbonylamino)benzoate Chemical compound COC(=O)C1=CC=CC(NC(=O)C=2N=CC3=CC=CC=C3C=2)=C1N VLSIRWMAASEDBN-UHFFFAOYSA-N 0.000 description 2
HDCLJQZLTMJECA-UHFFFAOYSA-N methyl 2-amino-3-nitrobenzoate Chemical compound COC(=O)C1=CC=CC([N+]([O-])=O)=C1N HDCLJQZLTMJECA-UHFFFAOYSA-N 0.000 description 2
GQGHONNAHNVQRB-UHFFFAOYSA-N methyl 2-amino-6-nitro-1h-benzimidazole-4-carboxylate Chemical compound COC(=O)C1=CC([N+]([O-])=O)=CC2=C1N=C(N)N2 GQGHONNAHNVQRB-UHFFFAOYSA-N 0.000 description 2
IOPLHGOSNCJOOO-UHFFFAOYSA-N methyl 3,4-diaminobenzoate Chemical compound COC(=O)C1=CC=C(N)C(N)=C1 IOPLHGOSNCJOOO-UHFFFAOYSA-N 0.000 description 2
QLIFFWAKDJIXOQ-UHFFFAOYSA-N methyl 3-(3,5-difluorophenyl)-2-[(2-isoquinolin-3-yl-1h-benzimidazole-4-carbonyl)amino]propanoate Chemical compound C=1C=CC=2NC(C=3N=CC4=CC=CC=C4C=3)=NC=2C=1C(=O)NC(C(=O)OC)CC1=CC(F)=CC(F)=C1 QLIFFWAKDJIXOQ-UHFFFAOYSA-N 0.000 description 2
KJJSHOHQQHACLE-UHFFFAOYSA-N methyl 5-hydroxypyridine-3-carboxylate Chemical compound COC(=O)C1=CN=CC(O)=C1 KJJSHOHQQHACLE-UHFFFAOYSA-N 0.000 description 2
UFBYZIGTTYMVBM-UHFFFAOYSA-N methyl 6-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate Chemical compound OC1=CC=C2CNC(C(=O)OC)CC2=C1 UFBYZIGTTYMVBM-UHFFFAOYSA-N 0.000 description 2
TWUXCAUSLKZBEK-UHFFFAOYSA-N methyl 6-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate;hydrochloride Chemical compound Cl.COC1=CC=C2CNC(C(=O)OC)CC2=C1 TWUXCAUSLKZBEK-UHFFFAOYSA-N 0.000 description 2
GKRQHGXMVRSJTJ-UHFFFAOYSA-N methyl 6-methoxyisoquinoline-3-carboxylate Chemical compound COC1=CC=C2C=NC(C(=O)OC)=CC2=C1 GKRQHGXMVRSJTJ-UHFFFAOYSA-N 0.000 description 2
XACDATAIJLJUHQ-UHFFFAOYSA-N methyl 7-nitroisoquinoline-3-carboxylate Chemical compound C1=C([N+]([O-])=O)C=C2C=NC(C(=O)OC)=CC2=C1 XACDATAIJLJUHQ-UHFFFAOYSA-N 0.000 description 2
BOUGJCYRFNCTHP-UHFFFAOYSA-N methyl 8-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate Chemical compound C1=CC(O)=C2CNC(C(=O)OC)CC2=C1 BOUGJCYRFNCTHP-UHFFFAOYSA-N 0.000 description 2
OMHFOSBIKXILAU-UHFFFAOYSA-N methyl 8-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate;hydrochloride Chemical compound Cl.C1=CC(OC)=C2CNC(C(=O)OC)CC2=C1 OMHFOSBIKXILAU-UHFFFAOYSA-N 0.000 description 2
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
FHPJRPZJOWONDO-UHFFFAOYSA-N n-(5-phenyl-1h-imidazol-2-yl)acetamide Chemical compound N1C(NC(=O)C)=NC=C1C1=CC=CC=C1 FHPJRPZJOWONDO-UHFFFAOYSA-N 0.000 description 2
NGGXACLSAZXJGM-UHFFFAOYSA-N n-(diaminomethylidene)acetamide Chemical compound CC(=O)N=C(N)N NGGXACLSAZXJGM-UHFFFAOYSA-N 0.000 description 2
QLONNRBYSGYEQQ-UHFFFAOYSA-N n-[4-[(2-aminophenyl)carbamoyl]-1h-benzimidazol-2-yl]isoquinoline-1-carboxamide Chemical compound NC1=CC=CC=C1NC(=O)C1=CC=CC2=C1NC(NC(=O)C=1C3=CC=CC=C3C=CN=1)=N2 QLONNRBYSGYEQQ-UHFFFAOYSA-N 0.000 description 2
230000000802 nitrating effect Effects 0.000 description 2
229910017604 nitric acid Inorganic materials 0.000 description 2
239000000346 nonvolatile oil Substances 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
239000010452 phosphate Substances 0.000 description 2
125000003367 polycyclic group Chemical group 0.000 description 2
239000011591 potassium Substances 0.000 description 2
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239000000843 powder Substances 0.000 description 2
VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 2
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229920005989 resin Polymers 0.000 description 2
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BMLHPGOMLGKYIJ-UHFFFAOYSA-N tert-butyl 2-amino-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC2=C1SC(N)=N2 BMLHPGOMLGKYIJ-UHFFFAOYSA-N 0.000 description 2
DAWIOUOJDZILGE-UHFFFAOYSA-N tert-butyl 6-[(4-methoxycarbonyl-1h-benzimidazol-2-yl)carbamoyl]-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCC2=CC(C(=O)NC=3NC=4C=CC=C(C=4N=3)C(=O)OC)=CC=C21 DAWIOUOJDZILGE-UHFFFAOYSA-N 0.000 description 2
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PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
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238000002955 isolation Methods 0.000 description 1
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
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125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
XOYMAJLARWXZBA-UHFFFAOYSA-N isoquinoline-3-carbaldehyde Chemical compound C1=CC=C2C=NC(C=O)=CC2=C1 XOYMAJLARWXZBA-UHFFFAOYSA-N 0.000 description 1
KVMMIDQDXZOPAB-UHFFFAOYSA-N isoquinoline-3-carboxylic acid Chemical compound C1=CC=C2C=NC(C(=O)O)=CC2=C1 KVMMIDQDXZOPAB-UHFFFAOYSA-N 0.000 description 1
IXFLTVWYYQIVRB-UHFFFAOYSA-N isoquinoline-3-carboxylic acid;hydrate Chemical compound O.C1=CC=C2C=NC(C(=O)O)=CC2=C1 IXFLTVWYYQIVRB-UHFFFAOYSA-N 0.000 description 1
ZIPLFLRGHZAXSJ-UHFFFAOYSA-N isoquinoline-5-carboxylic acid Chemical compound N1=CC=C2C(C(=O)O)=CC=CC2=C1 ZIPLFLRGHZAXSJ-UHFFFAOYSA-N 0.000 description 1
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
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238000005304 joining Methods 0.000 description 1
NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
229940001447 lactate Drugs 0.000 description 1
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JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
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239000007788 liquid Substances 0.000 description 1
229940040692 lithium hydroxide monohydrate Drugs 0.000 description 1
GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229940049920 malate Drugs 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
OGOVUFLIQYXZKW-UHFFFAOYSA-N methyl 2-(1h-imidazol-5-yl)acetate;hydrochloride Chemical compound Cl.COC(=O)CC1=CNC=N1 OGOVUFLIQYXZKW-UHFFFAOYSA-N 0.000 description 1
YHFHKDRUMQAVCW-UHFFFAOYSA-N methyl 2-(2-amino-1h-imidazol-5-yl)acetate Chemical compound COC(=O)CC1=CNC(N)=N1 YHFHKDRUMQAVCW-UHFFFAOYSA-N 0.000 description 1
CCBGBHKDLYDFLV-UHFFFAOYSA-N methyl 2-(2-amino-1h-imidazol-5-yl)acetate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COC(=O)CC1=CNC(N)=N1 CCBGBHKDLYDFLV-UHFFFAOYSA-N 0.000 description 1
LPDRADRDQIXUPC-UHFFFAOYSA-N methyl 2-(isoquinolin-3-ylamino)-1h-benzimidazole-4-carboxylate Chemical compound C1=CC=C2C=NC(NC3=NC=4C=CC=C(C=4N3)C(=O)OC)=CC2=C1 LPDRADRDQIXUPC-UHFFFAOYSA-N 0.000 description 1
KRWOSURKBWGVKD-UHFFFAOYSA-N methyl 2-(isoquinoline-3-carbonylamino)-1h-benzimidazole-4-carboxylate Chemical compound C1=CC=C2C=NC(C(=O)NC=3NC=4C=CC=C(C=4N=3)C(=O)OC)=CC2=C1 KRWOSURKBWGVKD-UHFFFAOYSA-N 0.000 description 1
NZDFXVADWKUPIW-UHFFFAOYSA-N methyl 2-(isoquinoline-3-carbonylamino)-6-nitro-1h-benzimidazole-4-carboxylate Chemical compound C1=CC=C2C=NC(C(=O)NC=3NC=4C=C(C=C(C=4N=3)C(=O)OC)[N+]([O-])=O)=CC2=C1 NZDFXVADWKUPIW-UHFFFAOYSA-N 0.000 description 1
CZTGJWJPHRFMKB-UHFFFAOYSA-N methyl 2-[(7-phenylmethoxyisoquinoline-3-carbonyl)amino]-1h-benzimidazole-4-carboxylate Chemical compound N=1C=2C(C(=O)OC)=CC=CC=2NC=1NC(=O)C(N=CC1=C2)=CC1=CC=C2OCC1=CC=CC=C1 CZTGJWJPHRFMKB-UHFFFAOYSA-N 0.000 description 1
GYHQKXLMJWHGOR-UHFFFAOYSA-N methyl 2-[[6-[2-(3-methylsulfonylphenyl)ethynyl]pyridine-2-carbonyl]amino]-1h-benzimidazole-4-carboxylate Chemical compound N=1C=2C(C(=O)OC)=CC=CC=2NC=1NC(=O)C(N=1)=CC=CC=1C#CC1=CC=CC(S(C)(=O)=O)=C1 GYHQKXLMJWHGOR-UHFFFAOYSA-N 0.000 description 1
CIPXQNRKZSYYSB-UHFFFAOYSA-N methyl 2-amino-1-benzylbenzimidazole-4-carboxylate Chemical compound NC1=NC=2C(C(=O)OC)=CC=CC=2N1CC1=CC=CC=C1 CIPXQNRKZSYYSB-UHFFFAOYSA-N 0.000 description 1
FBJMQPGFNQWPNN-UHFFFAOYSA-N methyl 2-amino-3-(isoquinolin-3-ylcarbamothioylamino)benzoate Chemical compound COC(=O)C1=CC=CC(NC(=S)NC=2N=CC3=CC=CC=C3C=2)=C1N FBJMQPGFNQWPNN-UHFFFAOYSA-N 0.000 description 1
WHVPFOLJDWVLSZ-UHFFFAOYSA-N methyl 2-amino-3h-benzimidazole-5-carboxylate Chemical compound COC(=O)C1=CC=C2N=C(N)NC2=C1 WHVPFOLJDWVLSZ-UHFFFAOYSA-N 0.000 description 1
LJHAPRKTPAREGO-UHFFFAOYSA-N methyl 2-dimethoxyphosphoryl-2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate Chemical compound COC(=O)C(P(=O)(OC)OC)NC(=O)OC(C)(C)C LJHAPRKTPAREGO-UHFFFAOYSA-N 0.000 description 1
YRMODRRGEUGHTF-UHFFFAOYSA-N methyl 2-formylbenzoate Chemical compound COC(=O)C1=CC=CC=C1C=O YRMODRRGEUGHTF-UHFFFAOYSA-N 0.000 description 1
ZHNXSEBPEYJFRS-UHFFFAOYSA-N methyl 2-isoquinolin-3-yl-1h-benzimidazole-4-carboxylate Chemical compound C1=CC=C2C=NC(C=3NC=4C=CC=C(C=4N=3)C(=O)OC)=CC2=C1 ZHNXSEBPEYJFRS-UHFFFAOYSA-N 0.000 description 1
RFUGMFSGSVNAMY-UHFFFAOYSA-N methyl 4-[[5-(2-methoxy-2-oxoethyl)-1H-imidazol-2-yl]diazenyl]benzoate Chemical compound COC(=O)CC1=CNC(N=NC=2C=CC(=CC=2)C(=O)OC)=N1 RFUGMFSGSVNAMY-UHFFFAOYSA-N 0.000 description 1
LZXXNPOYQCLXRS-UHFFFAOYSA-N methyl 4-aminobenzoate Chemical compound COC(=O)C1=CC=C(N)C=C1 LZXXNPOYQCLXRS-UHFFFAOYSA-N 0.000 description 1
HYGYYOAEKJNITG-UHFFFAOYSA-N methyl 5-phenoxypyridine-3-carboxylate Chemical compound COC(=O)C1=CN=CC(OC=2C=CC=CC=2)=C1 HYGYYOAEKJNITG-UHFFFAOYSA-N 0.000 description 1
ALFRUJCNWFGWTG-UHFFFAOYSA-N methyl 5-phenylmethoxypyridine-3-carboxylate Chemical compound COC(=O)C1=CN=CC(OCC=2C=CC=CC=2)=C1 ALFRUJCNWFGWTG-UHFFFAOYSA-N 0.000 description 1
WIVUCFHAFWZWON-UHFFFAOYSA-N methyl 6-[[4-(1h-imidazol-2-ylcarbamoyl)-1h-benzimidazol-2-yl]carbamoyl]-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C=1C=C2CN(C(=O)OC)CCC2=CC=1C(=O)NC(NC1=CC=C2)=NC1=C2C(=O)NC1=NC=CN1 WIVUCFHAFWZWON-UHFFFAOYSA-N 0.000 description 1
CADJOWXRLMBQQU-UHFFFAOYSA-N methyl 7-(methanesulfonamido)isoquinoline-3-carboxylate Chemical compound C1=C(NS(C)(=O)=O)C=C2C=NC(C(=O)OC)=CC2=C1 CADJOWXRLMBQQU-UHFFFAOYSA-N 0.000 description 1
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SZYSYNRTQKWQIU-UHFFFAOYSA-N methyl 7-chloro-8-methoxyisoquinoline-3-carboxylate Chemical compound C1=C(Cl)C(OC)=C2C=NC(C(=O)OC)=CC2=C1 SZYSYNRTQKWQIU-UHFFFAOYSA-N 0.000 description 1
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DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 description 1
150000003248 quinolines Chemical class 0.000 description 1
UPUZGXILYFKSGE-UHFFFAOYSA-N quinoxaline-2-carboxylic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CN=C21 UPUZGXILYFKSGE-UHFFFAOYSA-N 0.000 description 1
238000009790 rate-determining step (RDS) Methods 0.000 description 1
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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
230000007017 scission Effects 0.000 description 1
230000003248 secreting effect Effects 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
239000004328 sodium tetraborate Substances 0.000 description 1
235000010339 sodium tetraborate Nutrition 0.000 description 1
ABBQHOQBGMUPJH-UHFFFAOYSA-N sodium;2-hydroxybenzoic acid Chemical compound [Na+].OC(=O)C1=CC=CC=C1O ABBQHOQBGMUPJH-UHFFFAOYSA-N 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
241000894007 species Species 0.000 description 1
239000007921 spray Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
230000003637 steroidlike Effects 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical compound [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
125000004646 sulfenyl group Chemical group S(*)* 0.000 description 1
150000003457 sulfones Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000002459 sustained effect Effects 0.000 description 1
239000000454 talc Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229950002757 teoclate Drugs 0.000 description 1
GFJCZDJPSXKGSF-UHFFFAOYSA-N tert-butyl 1,3,4,9-tetrahydropyrido[3,4-b]indole-2-carboxylate Chemical compound N1C2=CC=CC=C2C2=C1CN(C(=O)OC(C)(C)C)CC2 GFJCZDJPSXKGSF-UHFFFAOYSA-N 0.000 description 1
OTAYALZGFGCDRY-UHFFFAOYSA-N tert-butyl 1-[[4-(1h-imidazol-2-ylcarbamoyl)-1h-benzimidazol-2-yl]carbamoyl]-6,7-dimethoxy-3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C(=O)OC(C)(C)C)C1C(=O)NC(NC1=CC=C2)=NC1=C2C(=O)NC1=NC=CN1 OTAYALZGFGCDRY-UHFFFAOYSA-N 0.000 description 1
LJNMREZVRQKMPX-UHFFFAOYSA-N tert-butyl 2-[[2-(isoquinoline-3-carbonylamino)-1h-benzimidazole-4-carbonyl]amino]-6,7-dihydro-4h-[1,3]thiazolo[5,4-c]pyridine-5-carboxylate Chemical compound C1=CC=C2C=NC(C(=O)NC3=NC=4C=CC=C(C=4N3)C(=O)NC3=NC=4CCN(CC=4S3)C(=O)OC(C)(C)C)=CC2=C1 LJNMREZVRQKMPX-UHFFFAOYSA-N 0.000 description 1
HTDOHIVUPFBSNR-UHFFFAOYSA-N tert-butyl 3,4-dihydro-1h-isoquinoline-2-carboxylate Chemical compound C1=CC=C2CN(C(=O)OC(C)(C)C)CCC2=C1 HTDOHIVUPFBSNR-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
FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
230000004797 therapeutic response Effects 0.000 description 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
239000002562 thickening agent Substances 0.000 description 1
RIIAHEIBOHZBED-UHFFFAOYSA-N thieno[2,3-c]pyridine-5-carboxylic acid Chemical compound C1=NC(C(=O)O)=CC2=C1SC=C2 RIIAHEIBOHZBED-UHFFFAOYSA-N 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
WSEJZRIZDQWMKQ-UHFFFAOYSA-N thiophene-2,3-dicarbaldehyde Chemical compound O=CC=1C=CSC=1C=O WSEJZRIZDQWMKQ-UHFFFAOYSA-N 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
WBYWAXJHAXSJNI-VOTSOKGWSA-M trans-cinnamate Chemical compound [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
229940066528 trichloroacetate Drugs 0.000 description 1
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical compound C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
229910052722 tritium Inorganic materials 0.000 description 1
229940070710 valerate Drugs 0.000 description 1
NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1

Landscapes

Nitrogen Condensed Heterocyclic Rings (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA2759162A 2005-03-14 2006-03-14 Derives de benzazole, compositions et methodes d'utilisation des derives comme inhibiteurs de la .beta.-secretase Abandoned CA2759162A1 (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US60/661,349		2005-03-14
US11/661,349 US7619424B2 (en)	2004-08-30	2005-08-29	Probe needle, method for manufacturing the probe needle and method for constructing a three-dimensional structure
CA2600570A CA2600570C (fr)	2005-03-14	2006-03-14	Derives de benzazole, compositions et methodes d'utilisation des derives comme inhibiteurs de la .beta.-secretase
PCT/US2006/009049 WO2006099379A2 (fr)	2005-03-14	2006-03-14	Derives de benzazole, compositions et methodes d'utilisation des derives comme inhibiteurs de la b-secretase

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2600570A Division CA2600570C (fr)	2005-03-14	2006-03-14	Derives de benzazole, compositions et methodes d'utilisation des derives comme inhibiteurs de la .beta.-secretase

Publications (1)

Publication Number	Publication Date
CA2759162A1 true CA2759162A1 (fr)	2006-09-21

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CA2759162A Abandoned CA2759162A1 (fr)	2005-03-14	2006-03-14	Derives de benzazole, compositions et methodes d'utilisation des derives comme inhibiteurs de la .beta.-secretase

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Country	Link
CA (1)	CA2759162A1 (fr)

2006
- 2006-03-14 CA CA2759162A patent/CA2759162A1/fr not_active Abandoned

Legal Events

Date	Code	Title	Description
2011-11-17	EEER	Examination request
2014-05-12	FZDE	Dead	Effective date: 20140314

Publication	Publication Date	Title
CA2600570C (fr)	2011-12-06	Derives de benzazole, compositions et methodes d'utilisation des derives comme inhibiteurs de la .beta.-secretase
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US6465484B1 (en)	2002-10-15	Angiogenesis inhibitors
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AU744939B2 (en)	2002-03-07	Novel angiogenesis inhibitors
EP2590950B1 (fr)	2014-10-15	Dérivés de n-cyclyl-3-(cyclylcarbonylaminométhyl)benzamide comme inhibiteurs de rho kinase
CA2758958A1 (fr)	2010-11-04	Derives imidazo[1,2-a]pyridine substitues, compositions pharmaceutiques, et procedes d'utilisation comme inhibiteurs de la.beta.-secretase
WO2004087053A2 (fr)	2004-10-14	Inhibiteurs de dipeptidyle peptidase
AU2012247455A1 (en)	2013-10-24	Novel ROCK inhibitors
CA2759162A1 (fr)	2006-09-21	Derives de benzazole, compositions et methodes d'utilisation des derives comme inhibiteurs de la .beta.-secretase
AU2011244844A1 (en)	2011-11-24	Benzazole derivatives, compositions, and methods of use as B-secretase inhibitors
HK1115752B (en)	2013-03-22	BENZAZOLE DERIVATIVES, COMPOSITIONS, AND METHODS OF USE AS β-SECRETASE INHIBITORS