CA2612893A1

CA2612893A1 - Composes de pyridyle et de pyridonyle stereoisomeriques et methodes de traitement des troubles gastro-intestinaux et des troubles du systeme nerveux central

Composes de pyridyle et de pyridonyle stereoisomeriques et methodes de traitement des troubles gastro-intestinaux et des troubles du systeme nerveux central Download PDF

Info

Publication number: CA2612893A1
Authority: CA; Canada
Prior art keywords: amino; chloro; methoxypiperidin; oxo; dihydropyridine
Prior art date: 2005-07-05
Legal status : Abandoned

Application number

CA002612893A

Other languages

English (en)

Inventor

Pascal Druzgala

Current Assignee

ARYx Therapeutics Inc

Original Assignee

Individual

Priority date

2005-07-05

Filing date

2006-07-05

Publication date

2007-01-11

2006-07-05 Application filed by Individual filed Critical Individual

2007-01-11 Publication of CA2612893A1 publication Critical patent/CA2612893A1/fr

Status Abandoned legal-status Critical Current

Links

238000011282 treatment Methods 0.000 title claims abstract description 31
238000000034 method Methods 0.000 title claims description 40
125000004076 pyridyl group Chemical group 0.000 title claims description 25
125000005494 pyridonyl group Chemical group 0.000 title claims description 14
230000002496 gastric effect Effects 0.000 title description 7
208000015114 central nervous system disease Diseases 0.000 title description 4
208000010643 digestive system disease Diseases 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 252
239000000203 mixture Substances 0.000 claims abstract description 43
208000021302 gastroesophageal reflux disease Diseases 0.000 claims abstract description 22
206010021518 Impaired gastric emptying Diseases 0.000 claims abstract description 17
208000001288 gastroparesis Diseases 0.000 claims abstract description 16
-1 hydroxy-C1-C4-alkyl Chemical group 0.000 claims description 434
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 135
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 117
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 92
125000000217 alkyl group Chemical group 0.000 claims description 91
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 88
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims description 62
125000003386 piperidinyl group Chemical group 0.000 claims description 61
229910052736 halogen Inorganic materials 0.000 claims description 56
150000002367 halogens Chemical class 0.000 claims description 51
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 51
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 48
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 48
229910052757 nitrogen Inorganic materials 0.000 claims description 47
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 43
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 40
150000003839 salts Chemical class 0.000 claims description 38
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 37
125000002757 morpholinyl group Chemical group 0.000 claims description 36
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 34
125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 claims description 32
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 26
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 25
125000001309 chloro group Chemical group Cl* 0.000 claims description 23
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
125000001072 heteroaryl group Chemical group 0.000 claims description 18
125000004193 piperazinyl group Chemical group 0.000 claims description 16
239000002904 solvent Substances 0.000 claims description 16
125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 15
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 15
125000003118 aryl group Chemical group 0.000 claims description 15
206010010774 Constipation Diseases 0.000 claims description 14
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
125000005843 halogen group Chemical group 0.000 claims description 14
206010052105 Gastrointestinal hypomotility Diseases 0.000 claims description 12
201000005081 Intestinal Pseudo-Obstruction Diseases 0.000 claims description 12
206010047700 Vomiting Diseases 0.000 claims description 12
201000006549 dyspepsia Diseases 0.000 claims description 12
206010054048 Postoperative ileus Diseases 0.000 claims description 11
125000006579 5 or 6-membered monocyclic heterocycloalkyl group Chemical group 0.000 claims description 10
125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 9
125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 9
XOWCADXWOIONSA-FSSWDIPSSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 6-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound N([C@@H]1CCN(CCCCCC(=O)O[C@@H]2C3CCN(CC3)C2)C[C@@H]1OC)C(=O)C1=CC(Cl)=C(N)N=C1OC XOWCADXWOIONSA-FSSWDIPSSA-N 0.000 claims description 8
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 6
229910052799 carbon Inorganic materials 0.000 claims description 6
125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 5
125000002877 alkyl aryl group Chemical group 0.000 claims description 5
229940124530 sulfonamide Drugs 0.000 claims description 5
HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 claims description 5
125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 4
125000004122 cyclic group Chemical group 0.000 claims description 4
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
239000002671 adjuvant Substances 0.000 claims description 3
239000000546 pharmaceutical excipient Substances 0.000 claims description 3
125000006282 2-chlorobenzyl group Chemical group [H]C1=C([H])C(Cl)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
125000005213 alkyl heteroaryl group Chemical group 0.000 claims description 2
KSMYWQOYXMCRDC-CVEARBPZSA-N 1-[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]piperidine-4-carboxylic acid Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)N1CCC(C(O)=O)CC1 KSMYWQOYXMCRDC-CVEARBPZSA-N 0.000 claims 2
ULHGIQHCZJKHSH-CABCVRRESA-N 1-[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]piperidine-4-carboxylic acid Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)N1CCC(C(O)=O)CC1 ULHGIQHCZJKHSH-CABCVRRESA-N 0.000 claims 2
IKMCDNUFNABDGU-MNOVXSKESA-N 2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetic acid Chemical compound CO[C@H]1CN(CC(O)=O)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC IKMCDNUFNABDGU-MNOVXSKESA-N 0.000 claims 2
ABCKQMSSZCBQQY-MOPGFXCFSA-N 2-methoxyethyl 1-[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCCOC)CCN1C(=O)CN1C[C@H](OC)[C@H](NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)CC1 ABCKQMSSZCBQQY-MOPGFXCFSA-N 0.000 claims 2
YXTBHDWBLMCOQM-MSOLQXFVSA-N 2-methoxyethyl 1-[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCCOC)CCN1C(=O)CN1C[C@H](OC)[C@H](NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)CC1 YXTBHDWBLMCOQM-MSOLQXFVSA-N 0.000 claims 2
YFLRJCAHPISZHD-DLBZAZTESA-N 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoic acid Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC1=CC=C(C(O)=O)C=C1 YFLRJCAHPISZHD-DLBZAZTESA-N 0.000 claims 2
FVDCMWXWXYADHH-JKSUJKDBSA-N 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoic acid Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)NC1=CC=C(C(O)=O)C=C1 FVDCMWXWXYADHH-JKSUJKDBSA-N 0.000 claims 2
YFLRJCAHPISZHD-SJORKVTESA-N 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoic acid Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC1=CC=C(C(O)=O)C=C1 YFLRJCAHPISZHD-SJORKVTESA-N 0.000 claims 2
FVDCMWXWXYADHH-CVEARBPZSA-N 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoic acid Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)NC1=CC=C(C(O)=O)C=C1 FVDCMWXWXYADHH-CVEARBPZSA-N 0.000 claims 2
XOWCADXWOIONSA-BHDDXSALSA-N [(3s)-1-azabicyclo[2.2.2]octan-3-yl] 6-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound N([C@H]1CCN(CCCCCC(=O)O[C@H]2C3CCN(CC3)C2)C[C@H]1OC)C(=O)C1=CC(Cl)=C(N)N=C1OC XOWCADXWOIONSA-BHDDXSALSA-N 0.000 claims 2
239000003937 drug carrier Substances 0.000 claims 2
XDMGUEWFGXYKSL-MSOLQXFVSA-N ethyl 1-[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(=O)CN1C[C@H](OC)[C@H](NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)CC1 XDMGUEWFGXYKSL-MSOLQXFVSA-N 0.000 claims 2
KNPAPYAAVXYGOQ-SJORKVTESA-N ethyl 1-[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCC)CCN1C(=O)CN1C[C@H](OC)[C@H](NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)CC1 KNPAPYAAVXYGOQ-SJORKVTESA-N 0.000 claims 2
PMDKOLJBYMIHRV-SJORKVTESA-N methyl 1-[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]piperidine-4-carboxylate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)N1CCC(C(=O)OC)CC1 PMDKOLJBYMIHRV-SJORKVTESA-N 0.000 claims 2
LUKDOSNEWQTSDX-CVEARBPZSA-N methyl 1-[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]piperidine-4-carboxylate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)N1CCC(C(=O)OC)CC1 LUKDOSNEWQTSDX-CVEARBPZSA-N 0.000 claims 2
BISVTBCEFWVTSA-XZOQPEGZSA-N (1,4-dimethylpiperidin-4-yl) 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC(C=C1)=CC=C1C(=O)OC1(C)CCN(C)CC1 BISVTBCEFWVTSA-XZOQPEGZSA-N 0.000 claims 1
BISVTBCEFWVTSA-PKTZIBPZSA-N (1,4-dimethylpiperidin-4-yl) 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC(C=C1)=CC=C1C(=O)OC1(C)CCN(C)CC1 BISVTBCEFWVTSA-PKTZIBPZSA-N 0.000 claims 1
WJZSASGPPVIDCR-YADHBBJMSA-N (1,4-dimethylpiperidin-4-yl) 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)NC(C=C1)=CC=C1C(=O)OC1(C)CCN(C)CC1 WJZSASGPPVIDCR-YADHBBJMSA-N 0.000 claims 1
NAIAPWTYBAKBNB-YPFKAFGZSA-N (1-methylpiperidin-3-yl) 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)NC(C=C1)=CC=C1C(=O)OC1CCCN(C)C1 NAIAPWTYBAKBNB-YPFKAFGZSA-N 0.000 claims 1
NTCZGYOEIDZULC-RPWUZVMVSA-N (1-methylpiperidin-4-yl) 2-[4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]phenyl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC(C=C1)=CC=C1CC(=O)OC1CCN(C)CC1 NTCZGYOEIDZULC-RPWUZVMVSA-N 0.000 claims 1
IGXJIIVWWFGJMV-RPBOFIJWSA-N (1-methylpiperidin-4-yl) 4-[3-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propyl]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCCC(C=C1)=CC=C1C(=O)OC1CCN(C)CC1 IGXJIIVWWFGJMV-RPBOFIJWSA-N 0.000 claims 1
VBQXXLUIWZZIDR-XZOQPEGZSA-N (1-methylpiperidin-4-yl) 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC(C=C1)=CC=C1C(=O)OC1CCN(C)CC1 VBQXXLUIWZZIDR-XZOQPEGZSA-N 0.000 claims 1
FNMNXRASLRLHGW-FCHUYYIVSA-N (1-methylpiperidin-4-yl) 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)NC(C=C1)=CC=C1C(=O)OC1CCN(C)CC1 FNMNXRASLRLHGW-FCHUYYIVSA-N 0.000 claims 1
JSZMAWSWGLUFPQ-FTJBHMTQSA-N (1-methylpiperidin-4-yl) 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethyl-methylamino]methyl]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCN(C)CC(C=C1)=CC=C1C(=O)OC1CCN(C)CC1 JSZMAWSWGLUFPQ-FTJBHMTQSA-N 0.000 claims 1
FNMNXRASLRLHGW-YADHBBJMSA-N (1-methylpiperidin-4-yl) 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)NC(C=C1)=CC=C1C(=O)OC1CCN(C)CC1 FNMNXRASLRLHGW-YADHBBJMSA-N 0.000 claims 1
WXMXBIBYVXVKOC-PKOBYXMFSA-N (2,3,4-trimethoxyphenyl)methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=C(OC)C(OC)=C1OC WXMXBIBYVXVKOC-PKOBYXMFSA-N 0.000 claims 1
MXWFRPOVFBBTKF-FUHWJXTLSA-N (2,3,4-trimethoxyphenyl)methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=C(OC)C(OC)=C1OC MXWFRPOVFBBTKF-FUHWJXTLSA-N 0.000 claims 1
JIDIWBZEPQVEJJ-PKOBYXMFSA-N (2,3-dimethoxyphenyl)methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=CC(OC)=C1OC JIDIWBZEPQVEJJ-PKOBYXMFSA-N 0.000 claims 1
GVQMTJHIXHFDDU-FUHWJXTLSA-N (2,3-dimethoxyphenyl)methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=CC(OC)=C1OC GVQMTJHIXHFDDU-FUHWJXTLSA-N 0.000 claims 1
LHDVPYFXJAIUBG-MSOLQXFVSA-N (2-amino-2-oxoethyl) 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC1=CC=C(C(=O)OCC(N)=O)C=C1 LHDVPYFXJAIUBG-MSOLQXFVSA-N 0.000 claims 1
SWZHMIRHRBJRQA-MOPGFXCFSA-N (2-fluoro-6-methylphenyl)methyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=C(C)C=CC=C1F SWZHMIRHRBJRQA-MOPGFXCFSA-N 0.000 claims 1
HEHJGTTWSHWIGA-MSOLQXFVSA-N (2-fluoro-6-methylphenyl)methyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=C(C)C=CC=C1F HEHJGTTWSHWIGA-MSOLQXFVSA-N 0.000 claims 1
JYPGEKSWXZCYBM-ZWKOTPCHSA-N (2-fluorophenyl)methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=CC=C1F JYPGEKSWXZCYBM-ZWKOTPCHSA-N 0.000 claims 1
MBFYGWFEYCRVSF-DLBZAZTESA-N (2-fluorophenyl)methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=CC=C1F MBFYGWFEYCRVSF-DLBZAZTESA-N 0.000 claims 1
QUORWJQKBKFDSD-MJGOQNOKSA-N (2-methoxyphenyl)methyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=CC=C1OC QUORWJQKBKFDSD-MJGOQNOKSA-N 0.000 claims 1
BBUZNEBKQOWILK-AEFFLSMTSA-N (2-methoxyphenyl)methyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=CC=C1OC BBUZNEBKQOWILK-AEFFLSMTSA-N 0.000 claims 1
VMLCTKXSLYRVNW-JIMOISOXSA-N (2r)-3-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]-2-methylpropanoic acid Chemical compound CO[C@@H]1CN(C[C@@H](C)C(O)=O)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC VMLCTKXSLYRVNW-JIMOISOXSA-N 0.000 claims 1
UVZSPMOMPYECCG-JFUSQASVSA-N (2r)-3-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]-2-methylpropanoic acid Chemical compound CO[C@@H]1CN(C[C@@H](C)C(O)=O)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O UVZSPMOMPYECCG-JFUSQASVSA-N 0.000 claims 1
VMLCTKXSLYRVNW-TVYUQYBPSA-N (2s)-3-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]-2-methylpropanoic acid Chemical compound CO[C@@H]1CN(C[C@H](C)C(O)=O)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC VMLCTKXSLYRVNW-TVYUQYBPSA-N 0.000 claims 1
UVZSPMOMPYECCG-KPXOXKRLSA-N (2s)-3-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]-2-methylpropanoic acid Chemical compound CO[C@@H]1CN(C[C@H](C)C(O)=O)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O UVZSPMOMPYECCG-KPXOXKRLSA-N 0.000 claims 1
LKIVOJHHDRWQMK-ZWKOTPCHSA-N (3-chlorophenyl)methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=CC(Cl)=C1 LKIVOJHHDRWQMK-ZWKOTPCHSA-N 0.000 claims 1
FACITQWYVCBQPW-DLBZAZTESA-N (3-chlorophenyl)methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=CC(Cl)=C1 FACITQWYVCBQPW-DLBZAZTESA-N 0.000 claims 1
DSHDXCRVMKPTPC-MOPGFXCFSA-N (3-fluoro-4-methylphenyl)methyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=C(C)C(F)=C1 DSHDXCRVMKPTPC-MOPGFXCFSA-N 0.000 claims 1
CEWNIRDEDUGHLJ-MSOLQXFVSA-N (3-fluoro-4-methylphenyl)methyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=C(C)C(F)=C1 CEWNIRDEDUGHLJ-MSOLQXFVSA-N 0.000 claims 1
OJSRRMYJSWXISA-ZWKOTPCHSA-N (3-fluorophenyl)methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=CC(F)=C1 OJSRRMYJSWXISA-ZWKOTPCHSA-N 0.000 claims 1
ASZUJLORAFOSRL-DLBZAZTESA-N (3-fluorophenyl)methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=CC(F)=C1 ASZUJLORAFOSRL-DLBZAZTESA-N 0.000 claims 1
WEPHYQICXDJRIV-RBUKOAKNSA-N (3-methoxyphenyl)methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=CC(OC)=C1 WEPHYQICXDJRIV-RBUKOAKNSA-N 0.000 claims 1
CMSVNGZGOWWMEW-ZWKOTPCHSA-N (3-methoxyphenyl)methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=CC(OC)=C1 CMSVNGZGOWWMEW-ZWKOTPCHSA-N 0.000 claims 1
KOPVBWZTINFKDZ-RBUKOAKNSA-N (3-methylphenyl)methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=CC(C)=C1 KOPVBWZTINFKDZ-RBUKOAKNSA-N 0.000 claims 1
WYOJHMMEZAXOQZ-ZWKOTPCHSA-N (3-methylphenyl)methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=CC(C)=C1 WYOJHMMEZAXOQZ-ZWKOTPCHSA-N 0.000 claims 1
NWPLETYDHNYVMA-MSOLQXFVSA-N (4-chlorophenyl)methyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=C(Cl)C=C1 NWPLETYDHNYVMA-MSOLQXFVSA-N 0.000 claims 1
SYWVIUOXUULPNU-SJORKVTESA-N (4-chlorophenyl)methyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=C(Cl)C=C1 SYWVIUOXUULPNU-SJORKVTESA-N 0.000 claims 1
CXAXQQBVQSIFBT-MOPGFXCFSA-N (4-fluoro-3-methylphenyl)methyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=C(F)C(C)=C1 CXAXQQBVQSIFBT-MOPGFXCFSA-N 0.000 claims 1
QBUPTTIFSWKLIM-MSOLQXFVSA-N (4-fluorophenyl)methyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=C(F)C=C1 QBUPTTIFSWKLIM-MSOLQXFVSA-N 0.000 claims 1
RILWLAKNUUHGAB-SJORKVTESA-N (4-fluorophenyl)methyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=C(F)C=C1 RILWLAKNUUHGAB-SJORKVTESA-N 0.000 claims 1
JVFFJVRUGGOIGD-OKQVYOHESA-N (4-fluorophenyl)methyl 3-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]-2-methylpropanoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(C)C(=O)OCC1=CC=C(F)C=C1 JVFFJVRUGGOIGD-OKQVYOHESA-N 0.000 claims 1
PPLXLYFLGLIDNY-WFELRXAXSA-N (4-fluorophenyl)methyl 3-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]-2-methylpropanoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(C)C(=O)OCC1=CC=C(F)C=C1 PPLXLYFLGLIDNY-WFELRXAXSA-N 0.000 claims 1
KBRVROSVILAWAQ-YADHBBJMSA-N (4-fluorophenyl)methyl 6-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCCCCC(=O)OCC1=CC=C(F)C=C1 KBRVROSVILAWAQ-YADHBBJMSA-N 0.000 claims 1
NJPYSXOEMABLRO-RTWAWAEBSA-N (4-fluorophenyl)methyl 6-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCCCCC(=O)OCC1=CC=C(F)C=C1 NJPYSXOEMABLRO-RTWAWAEBSA-N 0.000 claims 1
QNHASTXZMACOHA-RTBURBONSA-N (4-methoxyphenyl)methyl 2-[(3r,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=C(OC)C=C1 QNHASTXZMACOHA-RTBURBONSA-N 0.000 claims 1
HUMCYLXDIWTWKH-QZTJIDSGSA-N (4-methoxyphenyl)methyl 2-[(3r,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=C(OC)C=C1 HUMCYLXDIWTWKH-QZTJIDSGSA-N 0.000 claims 1
CENMETLAAILGEL-VQTJNVASSA-N (4-methoxyphenyl)methyl 3-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propanoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCC(=O)OCC1=CC=C(OC)C=C1 CENMETLAAILGEL-VQTJNVASSA-N 0.000 claims 1
RCRGDDCLLFJTIF-RBUKOAKNSA-N (4-methoxyphenyl)methyl 3-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propanoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCC(=O)OCC1=CC=C(OC)C=C1 RCRGDDCLLFJTIF-RBUKOAKNSA-N 0.000 claims 1
UQQASGNZRLZGBP-MOPGFXCFSA-N (4-methylphenyl)methyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=C(C)C=C1 UQQASGNZRLZGBP-MOPGFXCFSA-N 0.000 claims 1
MSYLFQGDEWFSEI-MSOLQXFVSA-N (4-methylphenyl)methyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=C(C)C=C1 MSYLFQGDEWFSEI-MSOLQXFVSA-N 0.000 claims 1
OGROBDWNZGJEGX-ONGXBYRLSA-N (4-methylsulfonylphenyl)methyl (2s)-3-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]-2-methylpropanoate Chemical compound O=C([C@@H](C)CN1C[C@H]([C@H](CC1)NC(=O)C=1C(=NC(N)=C(Cl)C=1)OC)OC)OCC1=CC=C(S(C)(=O)=O)C=C1 OGROBDWNZGJEGX-ONGXBYRLSA-N 0.000 claims 1
OGROBDWNZGJEGX-JDGCJKAJSA-N (4-methylsulfonylphenyl)methyl 3-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]-2-methylpropanoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(C)C(=O)OCC1=CC=C(S(C)(=O)=O)C=C1 OGROBDWNZGJEGX-JDGCJKAJSA-N 0.000 claims 1
JROQQVWFAXHUOX-VQTJNVASSA-N (4-methylsulfonylphenyl)methyl 3-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propanoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCC(=O)OCC1=CC=C(S(C)(=O)=O)C=C1 JROQQVWFAXHUOX-VQTJNVASSA-N 0.000 claims 1
TZHFBEDGICWJNL-RBUKOAKNSA-N (4-methylsulfonylphenyl)methyl 3-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propanoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCC(=O)OCC1=CC=C(S(C)(=O)=O)C=C1 TZHFBEDGICWJNL-RBUKOAKNSA-N 0.000 claims 1
SHKBNAXTTNJQJH-CZJYWYEMSA-N (8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 6-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound N([C@@H]1CCN(CCCCCC(=O)OC2CC3CCC(N3C)C2)C[C@@H]1OC)C(=O)C1=CC(Cl)=C(N)N=C1OC SHKBNAXTTNJQJH-CZJYWYEMSA-N 0.000 claims 1
TUZKFGAVHGPNCC-WFELRXAXSA-N 1-(4-fluorophenyl)ethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OC(C)C1=CC=C(F)C=C1 TUZKFGAVHGPNCC-WFELRXAXSA-N 0.000 claims 1
OWVYIJLKWZIYMO-OTLVQASYSA-N 1-(4-fluorophenyl)ethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OC(C)C1=CC=C(F)C=C1 OWVYIJLKWZIYMO-OTLVQASYSA-N 0.000 claims 1
ULHGIQHCZJKHSH-LSDHHAIUSA-N 1-[2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]piperidine-4-carboxylic acid Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)N1CCC(C(O)=O)CC1 ULHGIQHCZJKHSH-LSDHHAIUSA-N 0.000 claims 1
KNSUZPRROAEJTI-RINPGJGPSA-N 1-adamantylmethyl 6-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound N([C@@H]1CCN(CCCCCC(=O)OCC23CC4CC(CC(C4)C2)C3)C[C@@H]1OC)C(=O)C1=CC(Cl)=C(N)N=C1OC KNSUZPRROAEJTI-RINPGJGPSA-N 0.000 claims 1
ALNFNSAGILNKLJ-PPCJQXESSA-N 1-azabicyclo[2.2.2]octan-3-yl 2-[4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]phenyl]acetate Chemical compound N([C@@H]1CCN(CC(=O)NC=2C=CC(CC(=O)OC3C4CCN(CC4)C3)=CC=2)C[C@@H]1OC)C(=O)C1=CC(Cl)=C(N)N=C1OC ALNFNSAGILNKLJ-PPCJQXESSA-N 0.000 claims 1
MWIUONWRNRJSET-BGTNVORWSA-N 1-azabicyclo[2.2.2]octan-3-yl 2-[4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]phenyl]acetate Chemical compound N([C@@H]1CCN(CC(=O)NC=2C=CC(CC(=O)OC3C4CCN(CC4)C3)=CC=2)C[C@@H]1OC)C(=O)C1=CC(Cl)=C(N)NC1=O MWIUONWRNRJSET-BGTNVORWSA-N 0.000 claims 1
GLSNCSQZIOHOIM-YUIIUQSRSA-N 1-methoxypropan-2-yl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@@H]1CN(CC(=O)OC(C)COC)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC GLSNCSQZIOHOIM-YUIIUQSRSA-N 0.000 claims 1
DVQCDBAJOKACLD-INPHSSGZSA-N 1-methoxypropan-2-yl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@@H]1CN(CC(=O)OC(C)COC)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O DVQCDBAJOKACLD-INPHSSGZSA-N 0.000 claims 1
FVDNXQPAMTVFEE-CABCVRRESA-N 2,2-dimethylpropyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@H]1CN(CC(=O)OCC(C)(C)C)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC FVDNXQPAMTVFEE-CABCVRRESA-N 0.000 claims 1
CHFKQPAZNYUHPW-KGLIPLIRSA-N 2,2-dimethylpropyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@H]1CN(CC(=O)OCC(C)(C)C)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O CHFKQPAZNYUHPW-KGLIPLIRSA-N 0.000 claims 1
BTDHPILKRRRBGN-CVEARBPZSA-N 2,2-dimethylpropyl 3-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propanoate Chemical compound CO[C@H]1CN(CCC(=O)OCC(C)(C)C)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC BTDHPILKRRRBGN-CVEARBPZSA-N 0.000 claims 1
LXPKKZIHPXVFBM-CABCVRRESA-N 2,2-dimethylpropyl 3-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propanoate Chemical compound CO[C@H]1CN(CCC(=O)OCC(C)(C)C)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O LXPKKZIHPXVFBM-CABCVRRESA-N 0.000 claims 1
FXMUPDXVMULESV-MOPGFXCFSA-N 2,2-dimethylpropyl 6-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound CO[C@H]1CN(CCCCCC(=O)OCC(C)(C)C)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC FXMUPDXVMULESV-MOPGFXCFSA-N 0.000 claims 1
GSVPFFRRECXSAQ-MSOLQXFVSA-N 2,2-dimethylpropyl 6-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound CO[C@H]1CN(CCCCCC(=O)OCC(C)(C)C)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O GSVPFFRRECXSAQ-MSOLQXFVSA-N 0.000 claims 1
ITFFBVHEKYOEBC-JKSUJKDBSA-N 2-(2-methoxyethoxy)ethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@@H]1CN(CC(=O)OCCOCCOC)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC ITFFBVHEKYOEBC-JKSUJKDBSA-N 0.000 claims 1
XTLGJQMJQXIQJT-LSDHHAIUSA-N 2-(2-methoxyethoxy)ethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@@H]1CN(CC(=O)OCCOCCOC)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O XTLGJQMJQXIQJT-LSDHHAIUSA-N 0.000 claims 1
WJTYKUYYVYXNIK-LEWJYISDSA-N 2-(dimethylamino)ethyl 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC1=CC=C(C(=O)OCCN(C)C)C=C1 WJTYKUYYVYXNIK-LEWJYISDSA-N 0.000 claims 1
WJTYKUYYVYXNIK-RTWAWAEBSA-N 2-(dimethylamino)ethyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC1=CC=C(C(=O)OCCN(C)C)C=C1 WJTYKUYYVYXNIK-RTWAWAEBSA-N 0.000 claims 1
BPMNLPPAFJCLQX-MSOLQXFVSA-N 2-(dimethylamino)ethyl 6-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound CO[C@H]1CN(CCCCCC(=O)OCCN(C)C)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O BPMNLPPAFJCLQX-MSOLQXFVSA-N 0.000 claims 1
KYMDBQYSEXBLFT-ZJUUUORDSA-N 2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetic acid Chemical compound CO[C@H]1CN(CC(O)=O)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O KYMDBQYSEXBLFT-ZJUUUORDSA-N 0.000 claims 1
VZAKJDZOQYASKR-ZWKOTPCHSA-N 2-[2-(2-methoxyethoxy)ethoxy]ethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@@H]1CN(CC(=O)OCCOCCOCCOC)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC VZAKJDZOQYASKR-ZWKOTPCHSA-N 0.000 claims 1
UBOGWRFJWUVDEM-DLBZAZTESA-N 2-[2-(2-methoxyethoxy)ethoxy]ethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@@H]1CN(CC(=O)OCCOCCOCCOC)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O UBOGWRFJWUVDEM-DLBZAZTESA-N 0.000 claims 1
DKNXXWWKJBKWTG-OLZOCXBDSA-N 2-[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethoxy]acetic acid Chemical compound CO[C@H]1CN(CCOCC(O)=O)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC DKNXXWWKJBKWTG-OLZOCXBDSA-N 0.000 claims 1
HEIWDWPGHZIVRV-NEPJUHHUSA-N 2-[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethoxy]acetic acid Chemical compound CO[C@H]1CN(CCOCC(O)=O)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O HEIWDWPGHZIVRV-NEPJUHHUSA-N 0.000 claims 1
IZDJDSSWEASBQJ-MSOLQXFVSA-N 2-[4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]phenyl]acetic acid Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC1=CC=C(CC(O)=O)C=C1 IZDJDSSWEASBQJ-MSOLQXFVSA-N 0.000 claims 1
OGQCATSQPCUYPW-SJORKVTESA-N 2-[4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]phenyl]acetic acid Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)NC1=CC=C(CC(O)=O)C=C1 OGQCATSQPCUYPW-SJORKVTESA-N 0.000 claims 1
NSGDFAZOQBJZHU-QAUTWBHQSA-N 2-adamantyl 6-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound N([C@@H]1CCN(CCCCCC(=O)OC2C3CC4CC(C3)CC2C4)C[C@@H]1OC)C(=O)C1=CC(Cl)=C(N)N=C1OC NSGDFAZOQBJZHU-QAUTWBHQSA-N 0.000 claims 1
JCPWZVJVCQKQQV-OLZOCXBDSA-N 2-hydroxyethyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@H]1CN(CC(=O)OCCO)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC JCPWZVJVCQKQQV-OLZOCXBDSA-N 0.000 claims 1
UYPNWPJANUUTML-NEPJUHHUSA-N 2-hydroxyethyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@H]1CN(CC(=O)OCCO)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O UYPNWPJANUUTML-NEPJUHHUSA-N 0.000 claims 1
BORIKMGVVWRALP-MOPGFXCFSA-N 2-hydroxyethyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC1=CC=C(C(=O)OCCO)C=C1 BORIKMGVVWRALP-MOPGFXCFSA-N 0.000 claims 1
ABCKQMSSZCBQQY-RBUKOAKNSA-N 2-methoxyethyl 1-[2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]piperidine-4-carboxylate Chemical compound C1CC(C(=O)OCCOC)CCN1C(=O)CN1C[C@@H](OC)[C@@H](NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)CC1 ABCKQMSSZCBQQY-RBUKOAKNSA-N 0.000 claims 1
NNSWXDRWMIYJSA-KGLIPLIRSA-N 2-methoxyethyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@H]1CN(CC(=O)OCCOC)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC NNSWXDRWMIYJSA-KGLIPLIRSA-N 0.000 claims 1
HXVUOVZEORQYLR-OLZOCXBDSA-N 2-methoxyethyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@H]1CN(CC(=O)OCCOC)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O HXVUOVZEORQYLR-OLZOCXBDSA-N 0.000 claims 1
XIQBUFJMIWWWEU-RBUKOAKNSA-N 2-methoxyethyl 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C1=CC(C(=O)OCCOC)=CC=C1NC(=O)CN1C[C@@H](OC)[C@@H](NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)CC1 XIQBUFJMIWWWEU-RBUKOAKNSA-N 0.000 claims 1
GLIQUMZIVHERGI-UXHICEINSA-N 2-methoxyethyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C1=CC(C(=O)OCCOC)=CC=C1NC(=O)CN1C[C@H](OC)[C@H](NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)CC1 GLIQUMZIVHERGI-UXHICEINSA-N 0.000 claims 1
XIQBUFJMIWWWEU-MOPGFXCFSA-N 2-methoxyethyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C1=CC(C(=O)OCCOC)=CC=C1NC(=O)CN1C[C@H](OC)[C@H](NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)CC1 XIQBUFJMIWWWEU-MOPGFXCFSA-N 0.000 claims 1
QITWYHCGUFIFTM-MSOLQXFVSA-N 2-methoxyethyl 6-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound CO[C@H]1CN(CCCCCC(=O)OCCOC)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC QITWYHCGUFIFTM-MSOLQXFVSA-N 0.000 claims 1
NGUJCJBOEZVUEG-SJORKVTESA-N 2-methoxyethyl 6-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound CO[C@H]1CN(CCCCCC(=O)OCCOC)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O NGUJCJBOEZVUEG-SJORKVTESA-N 0.000 claims 1
ZAMAOFXKRNXOFC-UONOGXRCSA-N 2-methylsulfonylethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@@H]1CN(CC(=O)OCCS(C)(=O)=O)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC ZAMAOFXKRNXOFC-UONOGXRCSA-N 0.000 claims 1
DVESRZOBXNMWGI-QWHCGFSZSA-N 2-methylsulfonylethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@@H]1CN(CC(=O)OCCS(C)(=O)=O)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O DVESRZOBXNMWGI-QWHCGFSZSA-N 0.000 claims 1
UWWIYVZWWLCHOH-DLBZAZTESA-N 2-morpholin-4-ylethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCCN1CCOCC1 UWWIYVZWWLCHOH-DLBZAZTESA-N 0.000 claims 1
CQSAZCSUUBKWGK-RPBOFIJWSA-N 2-morpholin-4-ylethyl 4-[3-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propyl]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCCC(C=C1)=CC=C1C(=O)OCCN1CCOCC1 CQSAZCSUUBKWGK-RPBOFIJWSA-N 0.000 claims 1
WJPFVXKJZQUGRH-FTJBHMTQSA-N 2-morpholin-4-ylethyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethyl-methylamino]methyl]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCN(C)CC(C=C1)=CC=C1C(=O)OCCN1CCOCC1 WJPFVXKJZQUGRH-FTJBHMTQSA-N 0.000 claims 1
MWAHLZCFMSBRBI-RPBOFIJWSA-N 2-morpholin-4-ylethyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethyl-methylamino]methyl]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCN(C)CC(C=C1)=CC=C1C(=O)OCCN1CCOCC1 MWAHLZCFMSBRBI-RPBOFIJWSA-N 0.000 claims 1
MGXDFMNVHHBRDQ-PKTZIBPZSA-N 2-piperazin-1-ylethyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC(C=C1)=CC=C1C(=O)OCCN1CCNCC1 MGXDFMNVHHBRDQ-PKTZIBPZSA-N 0.000 claims 1
HGFYJLHHGBCLLT-YADHBBJMSA-N 2-piperazin-1-ylethyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)NC(C=C1)=CC=C1C(=O)OCCN1CCNCC1 HGFYJLHHGBCLLT-YADHBBJMSA-N 0.000 claims 1
UFKHDPZCKWNHJN-BHDTVMLSSA-N 2-piperazin-1-ylethyl 6-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate;hydrochloride Chemical compound Cl.C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCCCCC(=O)OCCN1CCNCC1 UFKHDPZCKWNHJN-BHDTVMLSSA-N 0.000 claims 1
IGLMDEMNLCXOHW-FDOHDBATSA-N 2-piperazin-1-ylethyl 6-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate;hydrochloride Chemical compound Cl.C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCCCCC(=O)OCCN1CCNCC1 IGLMDEMNLCXOHW-FDOHDBATSA-N 0.000 claims 1
LTEMFDWACHBDHB-IIZJFRANSA-N 2-piperazin-2-ylethyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCCC1CNCCN1 LTEMFDWACHBDHB-IIZJFRANSA-N 0.000 claims 1
KESSINPWADJSCC-AGIABQAESA-N 2-piperazin-2-ylethyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCCC1CNCCN1 KESSINPWADJSCC-AGIABQAESA-N 0.000 claims 1
MCMWCGBOKRKAFE-ZWKOTPCHSA-N 2-pyridin-2-ylethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCCC1=CC=CC=N1 MCMWCGBOKRKAFE-ZWKOTPCHSA-N 0.000 claims 1
ZSHVBLIJNUCDBQ-DLBZAZTESA-N 2-pyridin-2-ylethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCCC1=CC=CC=N1 ZSHVBLIJNUCDBQ-DLBZAZTESA-N 0.000 claims 1
BFEOLJKPIJZQRU-XZOQPEGZSA-N 2-pyridin-2-ylethyl 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)NC(C=C1)=CC=C1C(=O)OCCC1=CC=CC=N1 BFEOLJKPIJZQRU-XZOQPEGZSA-N 0.000 claims 1
BFEOLJKPIJZQRU-PKTZIBPZSA-N 2-pyridin-2-ylethyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)NC(C=C1)=CC=C1C(=O)OCCC1=CC=CC=N1 BFEOLJKPIJZQRU-PKTZIBPZSA-N 0.000 claims 1
HOSGWXOXDFIOSK-RPBOFIJWSA-N 2-pyrrolidin-1-ylethyl 4-[3-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propyl]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCCC(C=C1)=CC=C1C(=O)OCCN1CCCC1 HOSGWXOXDFIOSK-RPBOFIJWSA-N 0.000 claims 1
QEDXVPGQNGEAFN-XZOQPEGZSA-N 2-pyrrolidin-1-ylethyl 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC(C=C1)=CC=C1C(=O)OCCN1CCCC1 QEDXVPGQNGEAFN-XZOQPEGZSA-N 0.000 claims 1
RAOPYWXOGNVNDN-FCHUYYIVSA-N 2-pyrrolidin-1-ylethyl 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)NC(C=C1)=CC=C1C(=O)OCCN1CCCC1 RAOPYWXOGNVNDN-FCHUYYIVSA-N 0.000 claims 1
VMCMGZPTCBHMIH-FTJBHMTQSA-N 2-pyrrolidin-1-ylethyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethyl-methylamino]methyl]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCN(C)CC(C=C1)=CC=C1C(=O)OCCN1CCCC1 VMCMGZPTCBHMIH-FTJBHMTQSA-N 0.000 claims 1
ZMGFCLASROHVQI-RPBOFIJWSA-N 2-pyrrolidin-1-ylethyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethyl-methylamino]methyl]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCN(C)CC(C=C1)=CC=C1C(=O)OCCN1CCCC1 ZMGFCLASROHVQI-RPBOFIJWSA-N 0.000 claims 1
OFRBSBANHSVYMC-VQTJNVASSA-N 3-(4-fluorophenoxy)propyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCCCOC1=CC=C(F)C=C1 OFRBSBANHSVYMC-VQTJNVASSA-N 0.000 claims 1
KDXDEPIBOWWBML-RBUKOAKNSA-N 3-(4-fluorophenoxy)propyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCCCOC1=CC=C(F)C=C1 KDXDEPIBOWWBML-RBUKOAKNSA-N 0.000 claims 1
XIFCLQRCORBITB-QXYKUJRHSA-N 3-bicyclo[2.2.1]heptanyl 6-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound N([C@@H]1CCN(CCCCCC(=O)OC2C3CCC(C3)C2)C[C@@H]1OC)C(=O)C1=CC(Cl)=C(N)N=C1OC XIFCLQRCORBITB-QXYKUJRHSA-N 0.000 claims 1
QYHKWLNAHUELBN-RTWAWAEBSA-N 3-hydroxypropyl 2-[4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]phenyl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC1=CC=C(CC(=O)OCCCO)C=C1 QYHKWLNAHUELBN-RTWAWAEBSA-N 0.000 claims 1
WNHQIDZNVFSJJR-YADHBBJMSA-N 3-hydroxypropyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethylamino]methyl]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCNCC1=CC=C(C(=O)OCCCO)C=C1 WNHQIDZNVFSJJR-YADHBBJMSA-N 0.000 claims 1
HLOGADAYNIXPDR-RTWAWAEBSA-N 3-hydroxypropyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethylamino]methyl]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCNCC1=CC=C(C(=O)OCCCO)C=C1 HLOGADAYNIXPDR-RTWAWAEBSA-N 0.000 claims 1
NPDLAEOYQDPPIW-QWHCGFSZSA-N 4-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]butanoic acid Chemical compound CO[C@@H]1CN(CCCC(O)=O)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC NPDLAEOYQDPPIW-QWHCGFSZSA-N 0.000 claims 1
CNFZZAAOXUGRHF-NWDGAFQWSA-N 4-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]butanoic acid Chemical compound CO[C@@H]1CN(CCCC(O)=O)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O CNFZZAAOXUGRHF-NWDGAFQWSA-N 0.000 claims 1
QEBYKLJWHPEZOG-MSOLQXFVSA-N 4-[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethylcarbamoyl]benzoic acid Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCNC(=O)C1=CC=C(C(O)=O)C=C1 QEBYKLJWHPEZOG-MSOLQXFVSA-N 0.000 claims 1
FENHYSCOFKXSKE-SJORKVTESA-N 4-[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethylcarbamoyl]benzoic acid Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCNC(=O)C1=CC=C(C(O)=O)C=C1 FENHYSCOFKXSKE-SJORKVTESA-N 0.000 claims 1
AREIZHHMMNRMEI-MOPGFXCFSA-N 4-[3-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propyl]benzoic acid Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCCC1=CC=C(C(O)=O)C=C1 AREIZHHMMNRMEI-MOPGFXCFSA-N 0.000 claims 1
AYYGQGQNRQYOTO-MSOLQXFVSA-N 4-[3-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propyl]benzoic acid Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCCC1=CC=C(C(O)=O)C=C1 AYYGQGQNRQYOTO-MSOLQXFVSA-N 0.000 claims 1
VRJWNKJVQJWAPZ-RBUKOAKNSA-N 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethyl-methylamino]methyl]benzoic acid Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCN(C)CC1=CC=C(C(O)=O)C=C1 VRJWNKJVQJWAPZ-RBUKOAKNSA-N 0.000 claims 1
ADXWZEIZYQDDJA-UXHICEINSA-N 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethyl-methylamino]methyl]benzoic acid Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCN(C)CC1=CC=C(C(O)=O)C=C1 ADXWZEIZYQDDJA-UXHICEINSA-N 0.000 claims 1
YFODVZSJMNVYOB-MOPGFXCFSA-N 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethylamino]methyl]benzoic acid Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCNCC1=CC=C(C(O)=O)C=C1 YFODVZSJMNVYOB-MOPGFXCFSA-N 0.000 claims 1
VRJWNKJVQJWAPZ-MOPGFXCFSA-N 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethyl-methylamino]methyl]benzoic acid Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCN(C)CC1=CC=C(C(O)=O)C=C1 VRJWNKJVQJWAPZ-MOPGFXCFSA-N 0.000 claims 1
ICCRGMLWNWLJMK-MSOLQXFVSA-N 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethylamino]methyl]benzoic acid Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCNCC1=CC=C(C(O)=O)C=C1 ICCRGMLWNWLJMK-MSOLQXFVSA-N 0.000 claims 1
VVMXEZZGVVYURE-UONOGXRCSA-N 6-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoic acid Chemical compound CO[C@@H]1CN(CCCCCC(O)=O)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O VVMXEZZGVVYURE-UONOGXRCSA-N 0.000 claims 1
JPMFKPRJZZDLGO-CABCVRRESA-N 6-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoic acid Chemical group CO[C@H]1CN(CCCCCC(O)=O)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC JPMFKPRJZZDLGO-CABCVRRESA-N 0.000 claims 1
VVMXEZZGVVYURE-KGLIPLIRSA-N 6-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoic acid Chemical compound CO[C@H]1CN(CCCCCC(O)=O)CC[C@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O VVMXEZZGVVYURE-KGLIPLIRSA-N 0.000 claims 1
FZYUDXHZDATMEM-VHSXEESVSA-N 6-amino-5-chloro-2-methoxy-n-[(3r,4s)-3-methoxypiperidin-4-yl]pyridine-3-carboxamide Chemical compound CO[C@@H]1CNCC[C@@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC FZYUDXHZDATMEM-VHSXEESVSA-N 0.000 claims 1
YVVRXZYIZAHNCZ-NWDGAFQWSA-N 6-amino-5-chloro-n-[(3r,4s)-1-(2-hydroxyethyl)-3-methoxypiperidin-4-yl]-2-methoxypyridine-3-carboxamide Chemical compound CO[C@@H]1CN(CCO)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC YVVRXZYIZAHNCZ-NWDGAFQWSA-N 0.000 claims 1
IJPCCCFJNYJYBL-WDEREUQCSA-N 6-amino-5-chloro-n-[(3r,4s)-1-(2-hydroxyethyl)-3-methoxypiperidin-4-yl]-2-oxo-1h-pyridine-3-carboxamide Chemical compound CO[C@@H]1CN(CCO)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O IJPCCCFJNYJYBL-WDEREUQCSA-N 0.000 claims 1
UQOMRPDOJMSZKF-RBUKOAKNSA-N 6-amino-5-chloro-n-[(3r,4s)-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-yl]-2-methoxypyridine-3-carboxamide Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCCOC1=CC=C(F)C=C1 UQOMRPDOJMSZKF-RBUKOAKNSA-N 0.000 claims 1
WDLFPAPKZZLSPM-ZWKOTPCHSA-N 6-amino-5-chloro-n-[(3r,4s)-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidin-4-yl]-2-oxo-1h-pyridine-3-carboxamide Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCCOC1=CC=C(F)C=C1 WDLFPAPKZZLSPM-ZWKOTPCHSA-N 0.000 claims 1
XCAKZYSSUFGLLS-SJORKVTESA-N 6-amino-5-chloro-n-[(3s,4r)-1-[2-(4-hydroxyanilino)-2-oxoethyl]-3-methoxypiperidin-4-yl]-2-methoxypyridine-3-carboxamide Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC1=CC=C(O)C=C1 XCAKZYSSUFGLLS-SJORKVTESA-N 0.000 claims 1
ZZQNGGXZUPCSTH-CVEARBPZSA-N 6-amino-5-chloro-n-[(3s,4r)-1-[2-(4-hydroxyanilino)-2-oxoethyl]-3-methoxypiperidin-4-yl]-2-oxo-1h-pyridine-3-carboxamide Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)NC1=CC=C(O)C=C1 ZZQNGGXZUPCSTH-CVEARBPZSA-N 0.000 claims 1
HNWLEAHVPSUOAY-MOPGFXCFSA-N NC1=C(C=C(C(N1)=O)C(=O)N[C@H]1[C@H](CN(CC1)CCNCC1=CC=C(C(=O)OC)C=C1)OC)Cl Chemical compound NC1=C(C=C(C(N1)=O)C(=O)N[C@H]1[C@H](CN(CC1)CCNCC1=CC=C(C(=O)OC)C=C1)OC)Cl HNWLEAHVPSUOAY-MOPGFXCFSA-N 0.000 claims 1
KDUXLIXIEIXGDF-ZWKOTPCHSA-N [2-(trifluoromethyl)phenyl]methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=CC=C1C(F)(F)F KDUXLIXIEIXGDF-ZWKOTPCHSA-N 0.000 claims 1
GOTVRQLCDCYCRO-DLBZAZTESA-N [2-(trifluoromethyl)phenyl]methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=CC=C1C(F)(F)F GOTVRQLCDCYCRO-DLBZAZTESA-N 0.000 claims 1
OJDDVKFMLSMEJU-XZOQPEGZSA-N [2-oxo-2-(piperidin-4-ylamino)ethyl] 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC(C=C1)=CC=C1C(=O)OCC(=O)NC1CCNCC1 OJDDVKFMLSMEJU-XZOQPEGZSA-N 0.000 claims 1
OJDDVKFMLSMEJU-PKTZIBPZSA-N [2-oxo-2-(piperidin-4-ylamino)ethyl] 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC(C=C1)=CC=C1C(=O)OCC(=O)NC1CCNCC1 OJDDVKFMLSMEJU-PKTZIBPZSA-N 0.000 claims 1
WTJIKTRLAKHYMS-ZWKOTPCHSA-N [4-(trifluoromethyl)phenyl]methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=C(C(F)(F)F)C=C1 WTJIKTRLAKHYMS-ZWKOTPCHSA-N 0.000 claims 1
ALJDUMLRLJBKON-DLBZAZTESA-N [4-(trifluoromethyl)phenyl]methyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=C(C(F)(F)F)C=C1 ALJDUMLRLJBKON-DLBZAZTESA-N 0.000 claims 1
BPDIYCJARDGBPQ-MOPGFXCFSA-N [4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]phenyl] acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)NC1=CC=C(OC(C)=O)C=C1 BPDIYCJARDGBPQ-MOPGFXCFSA-N 0.000 claims 1
NQPSXERBRXJTFC-MSOLQXFVSA-N [4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]phenyl] acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)NC1=CC=C(OC(C)=O)C=C1 NQPSXERBRXJTFC-MSOLQXFVSA-N 0.000 claims 1
NRWHAZJFVDKWCH-MSOLQXFVSA-N benzyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=CC=C1 NRWHAZJFVDKWCH-MSOLQXFVSA-N 0.000 claims 1
OLFIERBSXTYMEU-SJORKVTESA-N benzyl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=CC=C1 OLFIERBSXTYMEU-SJORKVTESA-N 0.000 claims 1
FYPQYMDRLQJSIP-MOPGFXCFSA-N benzyl 3-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propanoate Chemical group C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCC(=O)OCC1=CC=CC=C1 FYPQYMDRLQJSIP-MOPGFXCFSA-N 0.000 claims 1
FJMRZLPLXHXBJA-MSOLQXFVSA-N benzyl 3-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propanoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCC(=O)OCC1=CC=CC=C1 FJMRZLPLXHXBJA-MSOLQXFVSA-N 0.000 claims 1
XHCZLZZVJUVKIF-DLBZAZTESA-N cyclohexyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OC1CCCCC1 XHCZLZZVJUVKIF-DLBZAZTESA-N 0.000 claims 1
ZDJGIQGRXVNJKG-RBUKOAKNSA-N cyclohexyl 2-[2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethoxy]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCOCC(=O)OC1CCCCC1 ZDJGIQGRXVNJKG-RBUKOAKNSA-N 0.000 claims 1
HNSQWLLHFDPODS-ZWKOTPCHSA-N cyclohexyl 2-[2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethoxy]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCOCC(=O)OC1CCCCC1 HNSQWLLHFDPODS-ZWKOTPCHSA-N 0.000 claims 1
ZDJGIQGRXVNJKG-MOPGFXCFSA-N cyclohexyl 2-[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethoxy]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCOCC(=O)OC1CCCCC1 ZDJGIQGRXVNJKG-MOPGFXCFSA-N 0.000 claims 1
HNSQWLLHFDPODS-MSOLQXFVSA-N cyclohexyl 2-[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethoxy]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCOCC(=O)OC1CCCCC1 HNSQWLLHFDPODS-MSOLQXFVSA-N 0.000 claims 1
YDYARJACLICYCX-ZWKOTPCHSA-N cyclohexyl 3-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propanoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCC(=O)OC1CCCCC1 YDYARJACLICYCX-ZWKOTPCHSA-N 0.000 claims 1
CCKPLZLIVMXDQM-DLBZAZTESA-N cyclohexyl 3-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propanoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCC(=O)OC1CCCCC1 CCKPLZLIVMXDQM-DLBZAZTESA-N 0.000 claims 1
AGCLHPBGZRCYFW-RTWAWAEBSA-N cyclohexyl 6-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCCCCC(=O)OC1CCCCC1 AGCLHPBGZRCYFW-RTWAWAEBSA-N 0.000 claims 1
HGMCFCUIOUONBD-UXHICEINSA-N cyclohexyl 6-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCCCCC(=O)OC1CCCCC1 HGMCFCUIOUONBD-UXHICEINSA-N 0.000 claims 1
SNCWXAZYLHERBS-QWHCGFSZSA-N ethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@@H]1CN(CC(=O)OCC)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC SNCWXAZYLHERBS-QWHCGFSZSA-N 0.000 claims 1
RTZYXGBIPBTABP-NWDGAFQWSA-N ethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@@H]1CN(CC(=O)OCC)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O RTZYXGBIPBTABP-NWDGAFQWSA-N 0.000 claims 1
ZMHNELFAWOWRFZ-UXHICEINSA-N ethyl 2-[4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1NC(=O)CN1C[C@H](OC)[C@H](NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)CC1 ZMHNELFAWOWRFZ-UXHICEINSA-N 0.000 claims 1
KRDVYTGCCZUPTM-MOPGFXCFSA-N ethyl 2-[4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]phenyl]acetate Chemical compound C1=CC(CC(=O)OCC)=CC=C1NC(=O)CN1C[C@H](OC)[C@H](NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)CC1 KRDVYTGCCZUPTM-MOPGFXCFSA-N 0.000 claims 1
JZZUWGIVCKRWMN-RBUKOAKNSA-N ethyl 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1NC(=O)CN1C[C@@H](OC)[C@@H](NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)CC1 JZZUWGIVCKRWMN-RBUKOAKNSA-N 0.000 claims 1
LDSGLCFYMPTYEA-ZWKOTPCHSA-N ethyl 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1NC(=O)CN1C[C@@H](OC)[C@@H](NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)CC1 LDSGLCFYMPTYEA-ZWKOTPCHSA-N 0.000 claims 1
JZZUWGIVCKRWMN-MOPGFXCFSA-N ethyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1NC(=O)CN1C[C@H](OC)[C@H](NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)CC1 JZZUWGIVCKRWMN-MOPGFXCFSA-N 0.000 claims 1
LDSGLCFYMPTYEA-MSOLQXFVSA-N ethyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C1=CC(C(=O)OCC)=CC=C1NC(=O)CN1C[C@H](OC)[C@H](NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)CC1 LDSGLCFYMPTYEA-MSOLQXFVSA-N 0.000 claims 1
XBFQSFXUEOLPPH-DDTOSNHZSA-N methyl (2r)-3-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]-2-methylpropanoate Chemical compound CO[C@@H]1CN(C[C@@H](C)C(=O)OC)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC XBFQSFXUEOLPPH-DDTOSNHZSA-N 0.000 claims 1
FBUOEKXUAFDVRL-JIMOISOXSA-N methyl (2r)-3-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]-2-methylpropanoate Chemical compound CO[C@@H]1CN(C[C@@H](C)C(=O)OC)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O FBUOEKXUAFDVRL-JIMOISOXSA-N 0.000 claims 1
XBFQSFXUEOLPPH-LEWSCRJBSA-N methyl (2s)-3-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]-2-methylpropanoate Chemical compound CO[C@@H]1CN(C[C@H](C)C(=O)OC)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC XBFQSFXUEOLPPH-LEWSCRJBSA-N 0.000 claims 1
FBUOEKXUAFDVRL-TVYUQYBPSA-N methyl (2s)-3-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]-2-methylpropanoate Chemical compound CO[C@@H]1CN(C[C@H](C)C(=O)OC)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O FBUOEKXUAFDVRL-TVYUQYBPSA-N 0.000 claims 1
PMDKOLJBYMIHRV-DLBZAZTESA-N methyl 1-[2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]piperidine-4-carboxylate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)N1CCC(C(=O)OC)CC1 PMDKOLJBYMIHRV-DLBZAZTESA-N 0.000 claims 1
GIQGHDOHCWPGLD-UONOGXRCSA-N methyl 2-[2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethoxy]acetate Chemical compound CO[C@@H]1CN(CCOCC(=O)OC)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC GIQGHDOHCWPGLD-UONOGXRCSA-N 0.000 claims 1
JUALVVVKKSCGRH-QWHCGFSZSA-N methyl 2-[2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethoxy]acetate Chemical compound CO[C@@H]1CN(CCOCC(=O)OC)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O JUALVVVKKSCGRH-QWHCGFSZSA-N 0.000 claims 1
CNLDWWHSYMAXMB-LEWJYISDSA-N methyl 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethyl-methylamino]methyl]benzoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCN(C)CC1=CC=C(C(=O)OC)C=C1 CNLDWWHSYMAXMB-LEWJYISDSA-N 0.000 claims 1
LGJPZELNTNOCIZ-VQTJNVASSA-N methyl 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethylamino]methyl]benzoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCNCC1=CC=C(C(=O)OC)C=C1 LGJPZELNTNOCIZ-VQTJNVASSA-N 0.000 claims 1
HKXLIQCOJGJPAM-VQTJNVASSA-N methyl 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethyl-methylamino]methyl]benzoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCN(C)CC1=CC=C(C(=O)OC)C=C1 HKXLIQCOJGJPAM-VQTJNVASSA-N 0.000 claims 1
HNWLEAHVPSUOAY-RBUKOAKNSA-N methyl 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethylamino]methyl]benzoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCNCC1=CC=C(C(=O)OC)C=C1 HNWLEAHVPSUOAY-RBUKOAKNSA-N 0.000 claims 1
CNLDWWHSYMAXMB-RTWAWAEBSA-N methyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethyl-methylamino]methyl]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCN(C)CC1=CC=C(C(=O)OC)C=C1 CNLDWWHSYMAXMB-RTWAWAEBSA-N 0.000 claims 1
LGJPZELNTNOCIZ-UXHICEINSA-N methyl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethylamino]methyl]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCNCC1=CC=C(C(=O)OC)C=C1 LGJPZELNTNOCIZ-UXHICEINSA-N 0.000 claims 1
GGFBJBYOUMWWBZ-ZMKYACIDSA-N oxan-2-ylmethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1CCCCO1 GGFBJBYOUMWWBZ-ZMKYACIDSA-N 0.000 claims 1
VJEPTBONXNAYOF-FFPFEORLSA-N oxan-2-ylmethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1CCCCO1 VJEPTBONXNAYOF-FFPFEORLSA-N 0.000 claims 1
PNXJJPSKYBLPTK-CXRLMVSZSA-N oxan-2-ylmethyl 3-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propanoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCC(=O)OCC1CCCCO1 PNXJJPSKYBLPTK-CXRLMVSZSA-N 0.000 claims 1
KOYFWXHKRBGBCQ-ZMKYACIDSA-N oxan-2-ylmethyl 3-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propanoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCC(=O)OCC1CCCCO1 KOYFWXHKRBGBCQ-ZMKYACIDSA-N 0.000 claims 1
IZUXEZSYLBRGTL-JKSUJKDBSA-N oxan-4-yl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OC1CCOCC1 IZUXEZSYLBRGTL-JKSUJKDBSA-N 0.000 claims 1
CMUJEGGRKWLHQF-LSDHHAIUSA-N oxan-4-yl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OC1CCOCC1 CMUJEGGRKWLHQF-LSDHHAIUSA-N 0.000 claims 1
LERBDOPQPSQWTG-FFPFEORLSA-N piperidin-3-ylmethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1CCCNC1 LERBDOPQPSQWTG-FFPFEORLSA-N 0.000 claims 1
GNAAPGMNDNTRCW-CABCVRRESA-N piperidin-4-yl 2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OC1CCNCC1 GNAAPGMNDNTRCW-CABCVRRESA-N 0.000 claims 1
ICUQRERGHQFLTL-CJRXIRLBSA-N piperidin-4-yl 2-[2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethoxy]acetate;hydrochloride Chemical compound Cl.C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCOCC(=O)OC1CCNCC1 ICUQRERGHQFLTL-CJRXIRLBSA-N 0.000 claims 1
XRPBQQMSGLQTCW-MCJVGQIASA-N piperidin-4-yl 2-[2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethoxy]acetate;hydrochloride Chemical compound Cl.C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCOCC(=O)OC1CCNCC1 XRPBQQMSGLQTCW-MCJVGQIASA-N 0.000 claims 1
BBAVZVCRKCUUEC-PKTZIBPZSA-N piperidin-4-yl 4-[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethylcarbamoyl]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCNC(=O)C(C=C1)=CC=C1C(=O)OC1CCNCC1 BBAVZVCRKCUUEC-PKTZIBPZSA-N 0.000 claims 1
XEKMKEHOAMEVTR-YADHBBJMSA-N piperidin-4-yl 4-[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethylcarbamoyl]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCNC(=O)C(C=C1)=CC=C1C(=O)OC1CCNCC1 XEKMKEHOAMEVTR-YADHBBJMSA-N 0.000 claims 1
NUZBVCPGYAGIMR-RPWUZVMVSA-N piperidin-4-yl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethylamino]methyl]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCNCC(C=C1)=CC=C1C(=O)OC1CCNCC1 NUZBVCPGYAGIMR-RPWUZVMVSA-N 0.000 claims 1
CLZOSRPROCJLOC-PKTZIBPZSA-N piperidin-4-yl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethylamino]methyl]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCNCC(C=C1)=CC=C1C(=O)OC1CCNCC1 CLZOSRPROCJLOC-PKTZIBPZSA-N 0.000 claims 1
STIVEQWEFOLAFW-UONOGXRCSA-N propan-2-yl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@@H]1CN(CC(=O)OC(C)C)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC STIVEQWEFOLAFW-UONOGXRCSA-N 0.000 claims 1
PZHZSZGMCRYVEV-QWHCGFSZSA-N propan-2-yl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound CO[C@@H]1CN(CC(=O)OC(C)C)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O PZHZSZGMCRYVEV-QWHCGFSZSA-N 0.000 claims 1
BFGVXTXHVHJBIW-LSDHHAIUSA-N propan-2-yl 3-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propanoate Chemical compound CO[C@@H]1CN(CCC(=O)OC(C)C)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC BFGVXTXHVHJBIW-LSDHHAIUSA-N 0.000 claims 1
HTKDKWMWQCUDET-UONOGXRCSA-N propan-2-yl 3-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propanoate Chemical compound CO[C@@H]1CN(CCC(=O)OC(C)C)CC[C@@H]1NC(=O)C1=CC(Cl)=C(N)NC1=O HTKDKWMWQCUDET-UONOGXRCSA-N 0.000 claims 1
ZECKRFYNXUGMHQ-LEWJYISDSA-N propan-2-yl 4-[[2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]ethylamino]methyl]benzoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCNCC1=CC=C(C(=O)OC(C)C)C=C1 ZECKRFYNXUGMHQ-LEWJYISDSA-N 0.000 claims 1
OFJXRZISDZQWCO-MOPGFXCFSA-N propan-2-yl 4-[[2-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetyl]amino]benzoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)NC1=CC=C(C(=O)OC(C)C)C=C1 OFJXRZISDZQWCO-MOPGFXCFSA-N 0.000 claims 1
ILVYRBILMKBFCQ-JKSUJKDBSA-N pyridin-2-ylmethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=CC=N1 ILVYRBILMKBFCQ-JKSUJKDBSA-N 0.000 claims 1
ZNIQBTXCKKJYNO-RTWAWAEBSA-N pyridin-2-ylmethyl 6-[(3s,4r)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCCCCC(=O)OCC1=CC=CC=N1 ZNIQBTXCKKJYNO-RTWAWAEBSA-N 0.000 claims 1
YOSLKZNVBFNNBP-UXHICEINSA-N pyridin-2-ylmethyl 6-[(3s,4r)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCCCCC(=O)OCC1=CC=CC=N1 YOSLKZNVBFNNBP-UXHICEINSA-N 0.000 claims 1
RFUVXAFWFVCRLS-DLBZAZTESA-N pyridin-3-ylmethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=CN=C1 RFUVXAFWFVCRLS-DLBZAZTESA-N 0.000 claims 1
JJFNUFCMTCCTKQ-JKSUJKDBSA-N pyridin-3-ylmethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CC(=O)OCC1=CC=CN=C1 JJFNUFCMTCCTKQ-JKSUJKDBSA-N 0.000 claims 1
FDLMTCAKLNFYSG-DLBZAZTESA-N pyridin-4-ylmethyl 2-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]acetate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CC(=O)OCC1=CC=NC=C1 FDLMTCAKLNFYSG-DLBZAZTESA-N 0.000 claims 1
LASZNNQRTHAMPY-ZWKOTPCHSA-N pyridin-4-ylmethyl 3-[(3r,4s)-4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propanoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(=NC(N)=C(Cl)C=2)OC)OC)N1CCC(=O)OCC1=CC=NC=C1 LASZNNQRTHAMPY-ZWKOTPCHSA-N 0.000 claims 1
LGWRJDXMZBNSQD-DLBZAZTESA-N pyridin-4-ylmethyl 3-[(3r,4s)-4-[(6-amino-5-chloro-2-oxo-1h-pyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]propanoate Chemical compound C([C@H]([C@H](CC1)NC(=O)C=2C(NC(N)=C(Cl)C=2)=O)OC)N1CCC(=O)OCC1=CC=NC=C1 LGWRJDXMZBNSQD-DLBZAZTESA-N 0.000 claims 1
210000003169 central nervous system Anatomy 0.000 abstract description 7
208000018522 Gastrointestinal disease Diseases 0.000 abstract description 4
WPYMKLBDIGXBTP-UHFFFAOYSA-M benzoate Chemical compound [O-]C(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-M 0.000 description 86
125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 74
DCSUBABJRXZOMT-IRLDBZIGSA-N cisapride Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)OC)N1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-IRLDBZIGSA-N 0.000 description 57
229960005132 cisapride Drugs 0.000 description 55
DCSUBABJRXZOMT-UHFFFAOYSA-N cisapride Natural products C1CC(NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)C(OC)CN1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-UHFFFAOYSA-N 0.000 description 53
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
125000003545 alkoxy group Chemical group 0.000 description 32
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
125000001589 carboacyl group Chemical group 0.000 description 30
230000000694 effects Effects 0.000 description 29
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
238000006243 chemical reaction Methods 0.000 description 25
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 25
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 25
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 24
239000000047 product Substances 0.000 description 24
229940079593 drug Drugs 0.000 description 22
239000003814 drug Substances 0.000 description 22
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 22
229910001868 water Inorganic materials 0.000 description 22
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 19
239000002253 acid Substances 0.000 description 19
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
230000002411 adverse Effects 0.000 description 18
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 18
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 17
230000001225 therapeutic effect Effects 0.000 description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
125000006273 (C1-C3) alkyl group Chemical group 0.000 description 16
108090000371 Esterases Proteins 0.000 description 16
241000124008 Mammalia Species 0.000 description 16
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 15
229910052739 hydrogen Inorganic materials 0.000 description 15
238000003786 synthesis reaction Methods 0.000 description 15
SRJOCJYGOFTFLH-UHFFFAOYSA-M piperidine-4-carboxylate Chemical compound [O-]C(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-M 0.000 description 14
239000000243 solution Substances 0.000 description 14
208000035475 disorder Diseases 0.000 description 13
230000015572 biosynthetic process Effects 0.000 description 12
201000010099 disease Diseases 0.000 description 12
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 12
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 12
229940076279 serotonin Drugs 0.000 description 12
FZYUDXHZDATMEM-UHFFFAOYSA-N 6-amino-5-chloro-2-methoxy-n-(3-methoxypiperidin-4-yl)pyridine-3-carboxamide Chemical compound COC1CNCCC1NC(=O)C1=CC(Cl)=C(N)N=C1OC FZYUDXHZDATMEM-UHFFFAOYSA-N 0.000 description 11
150000003936 benzamides Chemical class 0.000 description 11
230000015556 catabolic process Effects 0.000 description 11
230000004060 metabolic process Effects 0.000 description 11
238000002360 preparation method Methods 0.000 description 11
239000005711 Benzoic acid Substances 0.000 description 10
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
235000010233 benzoic acid Nutrition 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 9
230000009471 action Effects 0.000 description 9
WXBLLCUINBKULX-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1.OC(=O)C1=CC=CC=C1 WXBLLCUINBKULX-UHFFFAOYSA-N 0.000 description 9
KQNPFQTWMSNSAP-UHFFFAOYSA-M isobutyrate Chemical compound CC(C)C([O-])=O KQNPFQTWMSNSAP-UHFFFAOYSA-M 0.000 description 9
229910000027 potassium carbonate Inorganic materials 0.000 description 9
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
102000005962 receptors Human genes 0.000 description 9
108020003175 receptors Proteins 0.000 description 9
239000007787 solid Substances 0.000 description 9
150000002148 esters Chemical group 0.000 description 8
235000019439 ethyl acetate Nutrition 0.000 description 8
239000002207 metabolite Substances 0.000 description 8
239000000725 suspension Substances 0.000 description 8
125000004890 (C1-C6) alkylamino group Chemical group 0.000 description 7
108091005482 5-HT4 receptors Proteins 0.000 description 7
102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 7
108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 7
239000002585 base Substances 0.000 description 7
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 7
230000000968 intestinal effect Effects 0.000 description 7
238000002560 therapeutic procedure Methods 0.000 description 7
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 6
239000007832 Na2SO4 Substances 0.000 description 6
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 6
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
230000003474 anti-emetic effect Effects 0.000 description 6
239000002111 antiemetic agent Substances 0.000 description 6
230000008901 benefit Effects 0.000 description 6
238000005859 coupling reaction Methods 0.000 description 6
238000001914 filtration Methods 0.000 description 6
229910052731 fluorine Inorganic materials 0.000 description 6
230000001965 increasing effect Effects 0.000 description 6
239000000463 material Substances 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
229910052938 sodium sulfate Inorganic materials 0.000 description 6
235000011152 sodium sulphate Nutrition 0.000 description 6
239000003826 tablet Substances 0.000 description 6
125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 5
125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 5
WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 5
RLFVFTCMGPYXAW-SQNIBIBYSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 6-[(3s,4r)-4-amino-3-methoxypiperidin-1-yl]hexanoate Chemical compound C1C[C@@H](N)[C@@H](OC)CN1CCCCCC(=O)O[C@@H]1C(CC2)CCN2C1 RLFVFTCMGPYXAW-SQNIBIBYSA-N 0.000 description 5
125000003282 alkyl amino group Chemical group 0.000 description 5
GONOPSZTUGRENK-UHFFFAOYSA-N benzyl(trichloro)silane Chemical compound Cl[Si](Cl)(Cl)CC1=CC=CC=C1 GONOPSZTUGRENK-UHFFFAOYSA-N 0.000 description 5
239000012267 brine Substances 0.000 description 5
239000002775 capsule Substances 0.000 description 5
229940125890 compound Ia Drugs 0.000 description 5
238000001816 cooling Methods 0.000 description 5
238000006731 degradation reaction Methods 0.000 description 5
238000001784 detoxification Methods 0.000 description 5
230000004064 dysfunction Effects 0.000 description 5
DXBULVYHTICWKT-UHFFFAOYSA-N ethyl 6-bromohexanoate Chemical compound CCOC(=O)CCCCCBr DXBULVYHTICWKT-UHFFFAOYSA-N 0.000 description 5
125000004494 ethyl ester group Chemical group 0.000 description 5
230000005176 gastrointestinal motility Effects 0.000 description 5
125000004438 haloalkoxy group Chemical group 0.000 description 5
125000002632 imidazolidinyl group Chemical group 0.000 description 5
125000001041 indolyl group Chemical group 0.000 description 5
229910052740 iodine Inorganic materials 0.000 description 5
238000004519 manufacturing process Methods 0.000 description 5
230000002503 metabolic effect Effects 0.000 description 5
235000005152 nicotinamide Nutrition 0.000 description 5
239000011570 nicotinamide Substances 0.000 description 5
229960003966 nicotinamide Drugs 0.000 description 5
229910052760 oxygen Inorganic materials 0.000 description 5
230000008569 process Effects 0.000 description 5
238000010992 reflux Methods 0.000 description 5
210000002460 smooth muscle Anatomy 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
239000007858 starting material Substances 0.000 description 5
208000024891 symptom Diseases 0.000 description 5
125000004568 thiomorpholinyl group Chemical group 0.000 description 5
FSNYTEYOTCTPSO-SSDOTTSWSA-N (2r)-1-azabicyclo[2.2.2]octan-2-ol Chemical compound C1CN2[C@H](O)CC1CC2 FSNYTEYOTCTPSO-SSDOTTSWSA-N 0.000 description 4
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 4
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 4
102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 4
HJGMRAKQWLKWMH-UHFFFAOYSA-N 8-methyl-8-azabicyclo[3.2.1]octan-3-amine Chemical compound C1C(N)CC2CCC1N2C HJGMRAKQWLKWMH-UHFFFAOYSA-N 0.000 description 4
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
206010012735 Diarrhoea Diseases 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
230000003187 abdominal effect Effects 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
230000001154 acute effect Effects 0.000 description 4
125000002029 aromatic hydrocarbon group Chemical group 0.000 description 4
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
239000003153 chemical reaction reagent Substances 0.000 description 4
230000008878 coupling Effects 0.000 description 4
238000010168 coupling process Methods 0.000 description 4
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 4
KOUAQOCYMAENKN-UHFFFAOYSA-N ethyl 2-bromohexanoate Chemical compound CCCCC(Br)C(=O)OCC KOUAQOCYMAENKN-UHFFFAOYSA-N 0.000 description 4
DQFZUSUSVFTCQN-UHFFFAOYSA-N ethyl 4-(dibenzylamino)-3-methoxypiperidine-1-carboxylate Chemical compound COC1CN(C(=O)OCC)CCC1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 DQFZUSUSVFTCQN-UHFFFAOYSA-N 0.000 description 4
238000009472 formulation Methods 0.000 description 4
210000001035 gastrointestinal tract Anatomy 0.000 description 4
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 4
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
210000000111 lower esophageal sphincter Anatomy 0.000 description 4
230000001404 mediated effect Effects 0.000 description 4
210000003205 muscle Anatomy 0.000 description 4
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
OMLDMGPCWMBPAN-YPMHNXCESA-N norcisapride Chemical compound CO[C@H]1CNCC[C@H]1NC(=O)C1=CC(Cl)=C(N)C=C1OC OMLDMGPCWMBPAN-YPMHNXCESA-N 0.000 description 4
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
125000000714 pyrimidinyl group Chemical group 0.000 description 4
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 4
230000004044 response Effects 0.000 description 4
210000002966 serum Anatomy 0.000 description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
210000002784 stomach Anatomy 0.000 description 4
238000003860 storage Methods 0.000 description 4
239000010936 titanium Substances 0.000 description 4
JMXKSZRRTHPKDL-UHFFFAOYSA-N titanium ethoxide Chemical compound [Ti+4].CC[O-].CC[O-].CC[O-].CC[O-] JMXKSZRRTHPKDL-UHFFFAOYSA-N 0.000 description 4
IVLICPVPXWEGCA-ZETCQYMHSA-N (3r)-1-azabicyclo[2.2.2]octan-3-ol Chemical compound C1CC2[C@@H](O)CN1CC2 IVLICPVPXWEGCA-ZETCQYMHSA-N 0.000 description 3
NJQRAAHKQQPUIT-UHFFFAOYSA-N 1,2-dihydropyridine-3-carboxamide Chemical compound NC(=O)C1=CC=CNC1 NJQRAAHKQQPUIT-UHFFFAOYSA-N 0.000 description 3
IVLICPVPXWEGCA-UHFFFAOYSA-N 3-quinuclidinol Chemical group C1C[C@@H]2C(O)C[N@]1CC2 IVLICPVPXWEGCA-UHFFFAOYSA-N 0.000 description 3
125000000882 C2-C6 alkenyl group Chemical group 0.000 description 3
206010028980 Neoplasm Diseases 0.000 description 3
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
208000018452 Torsade de pointes Diseases 0.000 description 3
208000002363 Torsades de Pointes Diseases 0.000 description 3
IBISNRFYBNEIBT-RTOKGZNSSA-N [(3r)-1-azabicyclo[2.2.2]octan-3-yl] 6-[(3s,4r)-4-(dibenzylamino)-3-methoxypiperidin-1-yl]hexanoate Chemical compound C=1C=CC=CC=1CN([C@@H]1CCN(CCCCCC(=O)O[C@@H]2C3CCN(CC3)C2)C[C@@H]1OC)CC1=CC=CC=C1 IBISNRFYBNEIBT-RTOKGZNSSA-N 0.000 description 3
230000003542 behavioural effect Effects 0.000 description 3
201000011510 cancer Diseases 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
238000002512 chemotherapy Methods 0.000 description 3
238000004296 chiral HPLC Methods 0.000 description 3
230000001684 chronic effect Effects 0.000 description 3
230000021615 conjugation Effects 0.000 description 3
230000001086 cytosolic effect Effects 0.000 description 3
230000034994 death Effects 0.000 description 3
231100000517 death Toxicity 0.000 description 3
206010012601 diabetes mellitus Diseases 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
238000001035 drying Methods 0.000 description 3
210000003238 esophagus Anatomy 0.000 description 3
125000004185 ester group Chemical group 0.000 description 3
JTSYONJBXBFDSY-SXOMAYOGSA-N ethyl 6-[(3s,4r)-4-(dibenzylamino)-3-methoxypiperidin-1-yl]hexanoate Chemical compound CO[C@H]1CN(CCCCCC(=O)OCC)CC[C@H]1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 JTSYONJBXBFDSY-SXOMAYOGSA-N 0.000 description 3
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
230000006870 function Effects 0.000 description 3
125000001188 haloalkyl group Chemical group 0.000 description 3
125000005842 heteroatom Chemical group 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 3
230000003993 interaction Effects 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 description 3
239000007788 liquid Substances 0.000 description 3
125000001624 naphthyl group Chemical group 0.000 description 3
230000001537 neural effect Effects 0.000 description 3
235000001968 nicotinic acid Nutrition 0.000 description 3
239000011664 nicotinic acid Substances 0.000 description 3
229960003512 nicotinic acid Drugs 0.000 description 3
230000001590 oxidative effect Effects 0.000 description 3
239000001301 oxygen Substances 0.000 description 3
230000036961 partial effect Effects 0.000 description 3
239000008194 pharmaceutical composition Substances 0.000 description 3
235000011181 potassium carbonates Nutrition 0.000 description 3
239000000843 powder Substances 0.000 description 3
230000000069 prophylactic effect Effects 0.000 description 3
238000000746 purification Methods 0.000 description 3
125000000168 pyrrolyl group Chemical group 0.000 description 3
229940044601 receptor agonist Drugs 0.000 description 3
239000000018 receptor agonist Substances 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
230000004936 stimulating effect Effects 0.000 description 3
239000000126 substance Substances 0.000 description 3
238000006467 substitution reaction Methods 0.000 description 3
230000001988 toxicity Effects 0.000 description 3
231100000419 toxicity Toxicity 0.000 description 3
238000003828 vacuum filtration Methods 0.000 description 3
230000008673 vomiting Effects 0.000 description 3
YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 description 2
UERXJDUECXDWNN-UXHICEINSA-N (3s,4r)-n,n-dibenzyl-3-methoxypiperidin-4-amine Chemical compound CO[C@H]1CNCC[C@H]1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 UERXJDUECXDWNN-UXHICEINSA-N 0.000 description 2
QWVOLCQYBXARGY-UHFFFAOYSA-N 1-chloropyridin-2-one Chemical compound ClN1C=CC=CC1=O QWVOLCQYBXARGY-UHFFFAOYSA-N 0.000 description 2
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 2
125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 2
WVKPYYLOFMTDHB-UHFFFAOYSA-N 2-norbornyl radical Chemical group C1CC2[CH]CC1C2 WVKPYYLOFMTDHB-UHFFFAOYSA-N 0.000 description 2
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 2
125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 2
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 2
125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 2
108091005477 5-HT3 receptors Proteins 0.000 description 2
102000035037 5-HT3 receptors Human genes 0.000 description 2
PHOSWLARCIBBJZ-UHFFFAOYSA-N 6-bromohexanenitrile Chemical compound BrCCCCCC#N PHOSWLARCIBBJZ-UHFFFAOYSA-N 0.000 description 2
208000004998 Abdominal Pain Diseases 0.000 description 2
208000000103 Anorexia Nervosa Diseases 0.000 description 2
206010003011 Appendicitis Diseases 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
125000003601 C2-C6 alkynyl group Chemical group 0.000 description 2
241000283707 Capra Species 0.000 description 2
201000003066 Diffuse Scleroderma Diseases 0.000 description 2
206010013710 Drug interaction Diseases 0.000 description 2
208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 2
241000282326 Felis catus Species 0.000 description 2
241000282412 Homo Species 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
208000002720 Malnutrition Diseases 0.000 description 2
208000008238 Muscle Spasticity Diseases 0.000 description 2
206010068871 Myotonic dystrophy Diseases 0.000 description 2
241000283973 Oryctolagus cuniculus Species 0.000 description 2
101100350457 Oryza sativa subsp. japonica RR24 gene Proteins 0.000 description 2
206010033799 Paralysis Diseases 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
201000009594 Systemic Scleroderma Diseases 0.000 description 2
206010042953 Systemic sclerosis Diseases 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
206010070863 Toxicity to various agents Diseases 0.000 description 2
230000005856 abnormality Effects 0.000 description 2
IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 2
OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
229960004373 acetylcholine Drugs 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
229940125683 antiemetic agent Drugs 0.000 description 2
238000007262 aromatic hydroxylation reaction Methods 0.000 description 2
206010003119 arrhythmia Diseases 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
230000037424 autonomic function Effects 0.000 description 2
230000004888 barrier function Effects 0.000 description 2
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
125000004600 benzothiopyranyl group Chemical group S1C(C=CC2=C1C=CC=C2)* 0.000 description 2
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
239000011230 binding agent Substances 0.000 description 2
239000004305 biphenyl Substances 0.000 description 2
235000010290 biphenyl Nutrition 0.000 description 2
239000000969 carrier Substances 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
238000005356 chiral GC Methods 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
208000027742 colicky pain Diseases 0.000 description 2
239000013058 crude material Substances 0.000 description 2
238000006900 dealkylation reaction Methods 0.000 description 2
230000006735 deficit Effects 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
238000010511 deprotection reaction Methods 0.000 description 2
230000029087 digestion Effects 0.000 description 2
HDRXZJPWHTXQRI-BHDTVMLSSA-N diltiazem hydrochloride Chemical compound [Cl-].C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CC[NH+](C)C)C2=CC=CC=C2S1 HDRXZJPWHTXQRI-BHDTVMLSSA-N 0.000 description 2
239000003085 diluting agent Substances 0.000 description 2
230000036267 drug metabolism Effects 0.000 description 2
230000000095 emetic effect Effects 0.000 description 2
210000002322 enterochromaffin cell Anatomy 0.000 description 2
210000003608 fece Anatomy 0.000 description 2
125000002541 furyl group Chemical group 0.000 description 2
210000000232 gallbladder Anatomy 0.000 description 2
230000030136 gastric emptying Effects 0.000 description 2
210000003736 gastrointestinal content Anatomy 0.000 description 2
230000007160 gastrointestinal dysfunction Effects 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
125000000623 heterocyclic group Chemical group 0.000 description 2
238000007327 hydrogenolysis reaction Methods 0.000 description 2
125000002883 imidazolyl group Chemical group 0.000 description 2
230000001771 impaired effect Effects 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
210000000936 intestine Anatomy 0.000 description 2
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 2
239000003446 ligand Substances 0.000 description 2
230000000670 limiting effect Effects 0.000 description 2
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
210000004185 liver Anatomy 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
230000001071 malnutrition Effects 0.000 description 2
235000000824 malnutrition Nutrition 0.000 description 2
239000012528 membrane Substances 0.000 description 2
230000011987 methylation Effects 0.000 description 2
238000007069 methylation reaction Methods 0.000 description 2
230000004048 modification Effects 0.000 description 2
238000012986 modification Methods 0.000 description 2
210000004877 mucosa Anatomy 0.000 description 2
UERXJDUECXDWNN-UHFFFAOYSA-N n,n-dibenzyl-3-methoxypiperidin-4-amine Chemical compound COC1CNCCC1N(CC=1C=CC=CC=1)CC1=CC=CC=C1 UERXJDUECXDWNN-UHFFFAOYSA-N 0.000 description 2
239000002858 neurotransmitter agent Substances 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
208000015380 nutritional deficiency disease Diseases 0.000 description 2
230000008506 pathogenesis Effects 0.000 description 2
230000008855 peristalsis Effects 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
229940049953 phenylacetate Drugs 0.000 description 2
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
235000015320 potassium carbonate Nutrition 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
230000002265 prevention Effects 0.000 description 2
239000002325 prokinetic agent Substances 0.000 description 2
238000011321 prophylaxis Methods 0.000 description 2
AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
238000001959 radiotherapy Methods 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
230000009467 reduction Effects 0.000 description 2
238000006722 reduction reaction Methods 0.000 description 2
238000002390 rotary evaporation Methods 0.000 description 2
238000010583 slow cooling Methods 0.000 description 2
208000018198 spasticity Diseases 0.000 description 2
238000003756 stirring Methods 0.000 description 2
239000011593 sulfur Chemical group 0.000 description 2
229910052717 sulfur Chemical group 0.000 description 2
238000001356 surgical procedure Methods 0.000 description 2
230000002194 synthesizing effect Effects 0.000 description 2
230000035488 systolic blood pressure Effects 0.000 description 2
235000002906 tartaric acid Nutrition 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 2
125000005958 tetrahydrothienyl group Chemical group 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
238000005809 transesterification reaction Methods 0.000 description 2
230000009466 transformation Effects 0.000 description 2
238000000844 transformation Methods 0.000 description 2
210000002700 urine Anatomy 0.000 description 2
208000003663 ventricular fibrillation Diseases 0.000 description 2
206010047302 ventricular tachycardia Diseases 0.000 description 2
SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 1
FSNYTEYOTCTPSO-ZETCQYMHSA-N (2s)-1-azabicyclo[2.2.2]octan-2-ol Chemical compound C1CN2[C@@H](O)CC1CC2 FSNYTEYOTCTPSO-ZETCQYMHSA-N 0.000 description 1
125000006274 (C1-C3)alkoxy group Chemical group 0.000 description 1
XOWCADXWOIONSA-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-yl 6-[4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoate Chemical compound COC1CN(CCCCCC(=O)OC2C3CCN(CC3)C2)CCC1NC(=O)C1=CC(Cl)=C(N)N=C1OC XOWCADXWOIONSA-UHFFFAOYSA-N 0.000 description 1
WYAPDFWEFUDKDF-UHFFFAOYSA-N 1-benzyl-3-bromopiperidin-4-one Chemical compound C1CC(=O)C(Br)CN1CC1=CC=CC=C1 WYAPDFWEFUDKDF-UHFFFAOYSA-N 0.000 description 1
BNRNKZZNINUCEE-UHFFFAOYSA-N 1-benzyl-3-methoxypiperidin-4-amine Chemical compound C1CC(N)C(OC)CN1CC1=CC=CC=C1 BNRNKZZNINUCEE-UHFFFAOYSA-N 0.000 description 1
ANEFKQJYRFOSON-UHFFFAOYSA-N 1-benzyl-4,4-dimethoxypiperidin-3-ol Chemical compound C1C(O)C(OC)(OC)CCN1CC1=CC=CC=C1 ANEFKQJYRFOSON-UHFFFAOYSA-N 0.000 description 1
SJZKULRDWHPHGG-UHFFFAOYSA-N 1-benzylpiperidin-4-one Chemical compound C1CC(=O)CCN1CC1=CC=CC=C1 SJZKULRDWHPHGG-UHFFFAOYSA-N 0.000 description 1
QDKWLJJOYIFEBS-UHFFFAOYSA-N 1-fluoro-4-$l^{1}-oxidanylbenzene Chemical group [O]C1=CC=C(F)C=C1 QDKWLJJOYIFEBS-UHFFFAOYSA-N 0.000 description 1
125000004486 1-methylpiperidin-3-yl group Chemical group CN1CC(CCC1)* 0.000 description 1
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
ZDLILMQNLSEPLK-UHFFFAOYSA-N 2-chloro-5-methoxy-n-piperidin-4-ylpyrimidin-4-amine Chemical compound COC1=CN=C(Cl)N=C1NC1CCNCC1 ZDLILMQNLSEPLK-UHFFFAOYSA-N 0.000 description 1
125000004847 2-fluorobenzyl group Chemical group [H]C1=C([H])C(F)=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
YNJXVWIPWJKJJD-UHFFFAOYSA-N 2-methoxypyridine-3-carboxamide Chemical compound COC1=NC=CC=C1C(N)=O YNJXVWIPWJKJJD-UHFFFAOYSA-N 0.000 description 1
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 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
125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 description 1
125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 description 1
125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 1
125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 description 1
229960000549 4-dimethylaminophenol Drugs 0.000 description 1
OZJPLYNZGCXSJM-UHFFFAOYSA-N 5-valerolactone Chemical compound O=C1CCCCO1 OZJPLYNZGCXSJM-UHFFFAOYSA-N 0.000 description 1
JPMFKPRJZZDLGO-UHFFFAOYSA-N 6-[4-[(6-amino-5-chloro-2-methoxypyridine-3-carbonyl)amino]-3-methoxypiperidin-1-yl]hexanoic acid Chemical compound COC1CN(CCCCCC(O)=O)CCC1NC(=O)C1=CC(Cl)=C(N)N=C1OC JPMFKPRJZZDLGO-UHFFFAOYSA-N 0.000 description 1
FZYUDXHZDATMEM-ZJUUUORDSA-N 6-amino-5-chloro-2-methoxy-n-[(3s,4r)-3-methoxypiperidin-4-yl]pyridine-3-carboxamide Chemical compound CO[C@H]1CNCC[C@H]1NC(=O)C1=CC(Cl)=C(N)N=C1OC FZYUDXHZDATMEM-ZJUUUORDSA-N 0.000 description 1
QKOVEUOBKSBZOB-UHFFFAOYSA-N 6-amino-5-chloro-2-methoxypyridine-3-carboxylic acid Chemical compound COC1=NC(N)=C(Cl)C=C1C(O)=O QKOVEUOBKSBZOB-UHFFFAOYSA-N 0.000 description 1
ABFBIMWKJXQTMV-UHFFFAOYSA-N 6-amino-5-chloro-n-(3-methoxypiperidin-4-yl)-2-oxo-1h-pyridine-3-carboxamide Chemical compound COC1CNCCC1NC(=O)C1=CC(Cl)=C(N)NC1=O ABFBIMWKJXQTMV-UHFFFAOYSA-N 0.000 description 1
RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 1
208000024827 Alzheimer disease Diseases 0.000 description 1
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
239000005695 Ammonium acetate Substances 0.000 description 1
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
208000019901 Anxiety disease Diseases 0.000 description 1
229930003347 Atropine Natural products 0.000 description 1
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical group NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 1
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
108010009685 Cholinergic Receptors Proteins 0.000 description 1
LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
208000007530 Essential hypertension Diseases 0.000 description 1
206010019233 Headaches Diseases 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
108090000604 Hydrolases Proteins 0.000 description 1
102000004157 Hydrolases Human genes 0.000 description 1
RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
206010026749 Mania Diseases 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
208000019022 Mood disease Diseases 0.000 description 1
206010028813 Nausea Diseases 0.000 description 1
208000012902 Nervous system disease Diseases 0.000 description 1
208000025966 Neurological disease Diseases 0.000 description 1
LUZWXMGSPXIQHB-UHFFFAOYSA-N OC(=O)CC(C1=CC=C(C=C1)[N+]([O-])=O)C1=C(O)C2=C(OC1=O)C=CC=C2 Chemical compound OC(=O)CC(C1=CC=C(C=C1)[N+]([O-])=O)C1=C(O)C2=C(OC1=O)C=CC=C2 LUZWXMGSPXIQHB-UHFFFAOYSA-N 0.000 description 1
208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
108010052164 Sodium Channels Proteins 0.000 description 1
102000018674 Sodium Channels Human genes 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
208000001871 Tachycardia Diseases 0.000 description 1
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
238000010521 absorption reaction Methods 0.000 description 1
229960002054 acenocoumarol Drugs 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
150000001241 acetals Chemical class 0.000 description 1
230000021736 acetylation Effects 0.000 description 1
238000006640 acetylation reaction Methods 0.000 description 1
102000034337 acetylcholine receptors Human genes 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
125000003670 adamantan-2-yl group Chemical group [H]C1([H])C(C2([H])[H])([H])C([H])([H])C3([H])C([*])([H])C1([H])C([H])([H])C2([H])C3([H])[H] 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
230000008484 agonism Effects 0.000 description 1
239000000556 agonist Substances 0.000 description 1
239000003570 air Substances 0.000 description 1
230000001476 alcoholic effect Effects 0.000 description 1
125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
125000005037 alkyl phenyl group Chemical group 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
235000019257 ammonium acetate Nutrition 0.000 description 1
229940043376 ammonium acetate Drugs 0.000 description 1
235000011114 ammonium hydroxide Nutrition 0.000 description 1
239000003708 ampul Substances 0.000 description 1
230000003466 anti-cipated effect Effects 0.000 description 1
230000000151 anti-reflux effect Effects 0.000 description 1
230000036506 anxiety Effects 0.000 description 1
210000003818 area postrema Anatomy 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
230000006793 arrhythmia Effects 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
229960000396 atropine Drugs 0.000 description 1
230000003190 augmentative effect Effects 0.000 description 1
IUKQLMGVFMDQDP-UHFFFAOYSA-N azane;piperidine Chemical compound N.C1CCNCC1 IUKQLMGVFMDQDP-UHFFFAOYSA-N 0.000 description 1
229940054066 benzamide antipsychotics Drugs 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
125000005605 benzo group Chemical group 0.000 description 1
125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
125000004622 benzoxazinyl group Chemical group O1NC(=CC2=C1C=CC=C2)* 0.000 description 1
125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
210000000941 bile Anatomy 0.000 description 1
ZDZHCHYQNPQSGG-UHFFFAOYSA-N binaphthyl group Chemical group C1(=CC=CC2=CC=CC=C12)C1=CC=CC2=CC=CC=C12 ZDZHCHYQNPQSGG-UHFFFAOYSA-N 0.000 description 1
230000000975 bioactive effect Effects 0.000 description 1
230000005540 biological transmission Effects 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
230000036765 blood level Effects 0.000 description 1
230000036772 blood pressure Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002837 carbocyclic group Chemical group 0.000 description 1
150000003857 carboxamides Chemical class 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
108091008690 chemoreceptors Proteins 0.000 description 1
229940112822 chewing gum Drugs 0.000 description 1
235000015218 chewing gum Nutrition 0.000 description 1
125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 description 1
229960001380 cimetidine Drugs 0.000 description 1
CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 description 1
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
229960004316 cisplatin Drugs 0.000 description 1
208000010877 cognitive disease Diseases 0.000 description 1
230000001149 cognitive effect Effects 0.000 description 1
229940125773 compound 10 Drugs 0.000 description 1
229940126543 compound 14 Drugs 0.000 description 1
230000001268 conjugating effect Effects 0.000 description 1
230000008602 contraction Effects 0.000 description 1
230000001595 contractor effect Effects 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
239000010779 crude oil Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
230000006378 damage Effects 0.000 description 1
230000020335 dealkylation Effects 0.000 description 1
238000006264 debenzylation reaction Methods 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
238000012217 deletion Methods 0.000 description 1
230000037430 deletion Effects 0.000 description 1
AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
229960003529 diazepam Drugs 0.000 description 1
LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 description 1
229960005156 digoxin Drugs 0.000 description 1
LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 description 1
125000005992 dihydrobenzisothiazinyl group Chemical group 0.000 description 1
125000005993 dihydrobenzisoxazinyl group Chemical group 0.000 description 1
125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
125000005046 dihydronaphthyl group Chemical group 0.000 description 1
125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 description 1
125000005051 dihydropyrazinyl group Chemical group N1(CC=NC=C1)* 0.000 description 1
125000005052 dihydropyrazolyl group Chemical group N1(NCC=C1)* 0.000 description 1
125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
125000005053 dihydropyrimidinyl group Chemical group N1(CN=CC=C1)* 0.000 description 1
125000005054 dihydropyrrolyl group Chemical group [H]C1=C([H])C([H])([H])C([H])([H])N1* 0.000 description 1
125000005044 dihydroquinolinyl group Chemical group N1(CC=CC2=CC=CC=C12)* 0.000 description 1
238000007865 diluting Methods 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
238000004821 distillation Methods 0.000 description 1
238000009509 drug development Methods 0.000 description 1
238000002651 drug therapy Methods 0.000 description 1
230000008406 drug-drug interaction Effects 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
230000002708 enhancing effect Effects 0.000 description 1
229960004756 ethanol Drugs 0.000 description 1
FIIGTSPAEONQHZ-UHFFFAOYSA-N ethyl 4-amino-3-methoxypiperidine-1-carboxylate Chemical compound CCOC(=O)N1CCC(N)C(OC)C1 FIIGTSPAEONQHZ-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
230000029142 excretion Effects 0.000 description 1
239000000284 extract Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
239000012458 free base Substances 0.000 description 1
230000030135 gastric motility Effects 0.000 description 1
210000005095 gastrointestinal system Anatomy 0.000 description 1
230000023611 glucuronidation Effects 0.000 description 1
239000008187 granular material Substances 0.000 description 1
239000003979 granulating agent Substances 0.000 description 1
231100000869 headache Toxicity 0.000 description 1
230000010240 hepatic drug metabolism Effects 0.000 description 1
230000002440 hepatic effect Effects 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 1
125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
230000000977 initiatory effect Effects 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
229910003480 inorganic solid Inorganic materials 0.000 description 1
210000001153 interneuron Anatomy 0.000 description 1
230000008991 intestinal motility Effects 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
125000005994 isobenzotetrahydrofuranyl group Chemical group 0.000 description 1
125000005995 isobenzotetrahydrothienyl group Chemical group 0.000 description 1
125000005990 isobenzothienyl group Chemical group 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
125000005956 isoquinolyl group Chemical group 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000000842 isoxazolyl group Chemical group 0.000 description 1
ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
230000003907 kidney function Effects 0.000 description 1
239000010410 layer Substances 0.000 description 1
230000003908 liver function Effects 0.000 description 1
208000030208 low-grade fever Diseases 0.000 description 1
239000007937 lozenge Substances 0.000 description 1
238000007726 management method Methods 0.000 description 1
210000004379 membrane Anatomy 0.000 description 1
230000037323 metabolic rate Effects 0.000 description 1
RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 description 1
TTWJBBZEZQICBI-UHFFFAOYSA-N metoclopramide Chemical compound CCN(CC)CCNC(=O)C1=CC(Cl)=C(N)C=C1OC TTWJBBZEZQICBI-UHFFFAOYSA-N 0.000 description 1
229960004503 metoclopramide Drugs 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
150000007522 mineralic acids Chemical class 0.000 description 1
230000036651 mood Effects 0.000 description 1
230000004899 motility Effects 0.000 description 1
239000003149 muscarinic antagonist Substances 0.000 description 1
230000004118 muscle contraction Effects 0.000 description 1
210000003249 myenteric plexus Anatomy 0.000 description 1
WWECJGLXBSQKRF-UHFFFAOYSA-N n,n-dimethylformamide;methanol Chemical compound OC.CN(C)C=O WWECJGLXBSQKRF-UHFFFAOYSA-N 0.000 description 1
UANSQQFYKHHDJM-KRWDZBQOSA-N n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]naphthalene-1-carboxamide Chemical compound C1=CC=C2C(C(N[C@@H]3C4CCN(CC4)C3)=O)=CC=CC2=C1 UANSQQFYKHHDJM-KRWDZBQOSA-N 0.000 description 1
ORRXNPKJTGGJNV-UHFFFAOYSA-N n-ethyl-n'-(3-methylbutyl)methanediimine Chemical compound CCN=C=NCCC(C)C ORRXNPKJTGGJNV-UHFFFAOYSA-N 0.000 description 1
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
230000008693 nausea Effects 0.000 description 1
210000004126 nerve fiber Anatomy 0.000 description 1
230000000926 neurological effect Effects 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
125000006574 non-aromatic ring group Chemical group 0.000 description 1
239000003921 oil Substances 0.000 description 1
229940127240 opiate Drugs 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
210000000056 organ Anatomy 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
239000003960 organic solvent Substances 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
229960005489 paracetamol Drugs 0.000 description 1
210000005037 parasympathetic nerve Anatomy 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
230000002572 peristaltic effect Effects 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
239000006187 pill Substances 0.000 description 1
239000004033 plastic Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
230000002028 premature Effects 0.000 description 1
238000000039 preparative column chromatography Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
229960003712 propranolol Drugs 0.000 description 1
125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
230000000541 pulsatile effect Effects 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000003373 pyrazinyl 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
UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
125000001422 pyrrolinyl group Chemical group 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000004620 quinolinyl-N-oxide group Chemical group 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 description 1
229960000620 ranitidine Drugs 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
230000000246 remedial effect Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
201000000980 schizophrenia Diseases 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000000926 separation method Methods 0.000 description 1
230000000862 serotonergic effect Effects 0.000 description 1
208000019116 sleep disease Diseases 0.000 description 1
210000000813 small intestine Anatomy 0.000 description 1
150000003384 small molecules Chemical group 0.000 description 1
210000000329 smooth muscle myocyte Anatomy 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
239000007909 solid dosage form Substances 0.000 description 1
235000021055 solid food Nutrition 0.000 description 1
239000011343 solid material Substances 0.000 description 1
210000005070 sphincter Anatomy 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
208000011117 substance-related disease Diseases 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
230000006794 tachycardia Effects 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000012360 testing method Methods 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 description 1
229950010357 tetrodotoxin Drugs 0.000 description 1
CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 1
238000011287 therapeutic dose Methods 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
230000003867 tiredness Effects 0.000 description 1
208000016255 tiredness Diseases 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
230000001515 vagal effect Effects 0.000 description 1
230000002792 vascular Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1