CA2880523A1 - Aryl lactam kinase inhibitors - Google Patents
Aryl lactam kinase inhibitors Download PDFInfo
- Publication number
- CA2880523A1 CA2880523A1 CA2880523A CA2880523A CA2880523A1 CA 2880523 A1 CA2880523 A1 CA 2880523A1 CA 2880523 A CA2880523 A CA 2880523A CA 2880523 A CA2880523 A CA 2880523A CA 2880523 A1 CA2880523 A1 CA 2880523A1
- Authority
- CA
- Canada
- Prior art keywords
- naphthyridin
- amino
- oxy
- mmol
- methylpentyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- -1 Aryl lactam Chemical class 0.000 title claims description 130
- 229940043355 kinase inhibitor Drugs 0.000 title description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 3
- 238000000034 method Methods 0.000 claims abstract description 393
- 239000000203 mixture Substances 0.000 claims abstract description 149
- 150000001875 compounds Chemical class 0.000 claims abstract description 130
- 102100038079 AP2-associated protein kinase 1 Human genes 0.000 claims abstract description 8
- 101710148635 AP2-associated protein kinase 1 Proteins 0.000 claims abstract description 8
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 6
- 125000005843 halogen group Chemical group 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 239000001257 hydrogen Substances 0.000 claims description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 38
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 35
- 150000002431 hydrogen Chemical group 0.000 claims description 33
- 229910052757 nitrogen Inorganic materials 0.000 claims description 30
- 201000010099 disease Diseases 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 208000035475 disorder Diseases 0.000 claims description 14
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 208000002193 Pain Diseases 0.000 claims description 11
- 230000000694 effects Effects 0.000 claims description 9
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 201000000980 schizophrenia Diseases 0.000 claims description 8
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 208000004296 neuralgia Diseases 0.000 claims description 6
- 208000021722 neuropathic pain Diseases 0.000 claims description 6
- 125000001769 aryl amino group Chemical group 0.000 claims description 5
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- ZSCOHFKAMHDAOA-UHFFFAOYSA-N 8-(2-amino-5,5,5-trifluoropentoxy)-6-methyl-5-oxobenzo[c][2,7]naphthyridine-9-carbonitrile Chemical compound C1=NC=C2C(=O)N(C)C3=CC(OCC(N)CCC(F)(F)F)=C(C#N)C=C3C2=C1 ZSCOHFKAMHDAOA-UHFFFAOYSA-N 0.000 claims description 3
- OFNHFLZBMXWFJV-AWEZNQCLSA-N 8-[(2s)-2-amino-4-methylpentoxy]-6-methyl-5-oxobenzo[c][2,7]naphthyridine-9-carbonitrile Chemical compound CN1C(=O)C2=CN=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(C#N)=C2 OFNHFLZBMXWFJV-AWEZNQCLSA-N 0.000 claims description 3
- VBKPIQDGHTZSFR-LBPRGKRZSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-hydroxy-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=CN=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(O)=C2 VBKPIQDGHTZSFR-LBPRGKRZSA-N 0.000 claims description 3
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 208000020925 Bipolar disease Diseases 0.000 claims description 3
- MCBJOMAHTKEJOM-UHFFFAOYSA-N 6-methyl-8-(piperidin-2-ylmethoxy)benzo[c][2,7]naphthyridin-5-one Chemical compound C=1C=C2C3=CC=NC=C3C(=O)N(C)C2=CC=1OCC1CCCCN1 MCBJOMAHTKEJOM-UHFFFAOYSA-N 0.000 claims description 2
- RXVZYVSEPCPLIQ-INIZCTEOSA-N 8-[(2s)-2-(dimethylamino)-4-methylpentoxy]-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@H](CC(C)C)N(C)C)C=C3N(C)C(=O)C2=C1C RXVZYVSEPCPLIQ-INIZCTEOSA-N 0.000 claims description 2
- HRMGBYSRWUAWIG-AWEZNQCLSA-N 8-[(2s)-2-amino-4-methylpentoxy]-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@@H](N)CC(C)C)C=C3N(C)C(=O)C2=C1C HRMGBYSRWUAWIG-AWEZNQCLSA-N 0.000 claims description 2
- JOCMZPAMMJDEEF-IBGZPJMESA-N 8-[(2s)-2-amino-4-methylpentoxy]-6-benzylbenzo[c][2,7]naphthyridin-5-one Chemical compound C=1C(OC[C@@H](N)CC(C)C)=CC=C(C2=CC=NC=C2C2=O)C=1N2CC1=CC=CC=C1 JOCMZPAMMJDEEF-IBGZPJMESA-N 0.000 claims description 2
- ATCROYCGFZTPSQ-LBPRGKRZSA-N 8-[(2s)-2-amino-4-methylpentoxy]-6h-benzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@@H](N)CC(C)C)C=C3NC(=O)C2=C1 ATCROYCGFZTPSQ-LBPRGKRZSA-N 0.000 claims description 2
- OMEXFLHXDATQQV-NSHDSACASA-N 8-[(2s)-2-amino-4-methylpentoxy]-7,9-dichloro-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC=C2C(=O)N(C)C3=C(Cl)C(OC[C@@H](N)CC(C)C)=C(Cl)C=C3C2=C1 OMEXFLHXDATQQV-NSHDSACASA-N 0.000 claims description 2
- AXHQXXMTZWZPDS-ZDUSSCGKSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-(difluoromethyl)-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(C(F)F)=C2 AXHQXXMTZWZPDS-ZDUSSCGKSA-N 0.000 claims description 2
- 208000001640 Fibromyalgia Diseases 0.000 claims description 2
- 230000001404 mediated effect Effects 0.000 claims description 2
- WMPDMMUFIRDMPA-AWEZNQCLSA-N n-[8-[(2s)-2-amino-4-methylpentoxy]-6-methyl-5-oxobenzo[c][2,7]naphthyridin-2-yl]acetamide Chemical compound N1=C(NC(C)=O)C=C2C3=CC=C(OC[C@@H](N)CC(C)C)C=C3N(C)C(=O)C2=C1 WMPDMMUFIRDMPA-AWEZNQCLSA-N 0.000 claims description 2
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 11
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims 10
- 125000006699 (C1-C3) hydroxyalkyl group Chemical group 0.000 claims 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 2
- XCKUSTFLSTVTCR-AWEZNQCLSA-N 8-[(2s)-2-amino-4-methylpentoxy]-2,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=C(C)C=C2C3=CC=C(OC[C@@H](N)CC(C)C)C=C3N(C)C(=O)C2=C1 XCKUSTFLSTVTCR-AWEZNQCLSA-N 0.000 claims 2
- HSHQEKUILXZVHT-ZDUSSCGKSA-N 8-[(2s)-2-amino-4-methylpentoxy]-4,6-dimethyl-9-(trifluoromethyl)benzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(C(F)(F)F)=C2 HSHQEKUILXZVHT-ZDUSSCGKSA-N 0.000 claims 2
- 125000006576 di-(C1-C3-alkyl)-aminocarbonyl group Chemical group 0.000 claims 2
- LOZLKDVGPQCIRZ-INIZCTEOSA-N 4,6-dimethyl-8-[(2s)-4-methyl-2-(methylamino)pentoxy]-5-oxobenzo[c][2,7]naphthyridine-9-carbonitrile Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](NC)CC(C)C)C(C#N)=C2 LOZLKDVGPQCIRZ-INIZCTEOSA-N 0.000 claims 1
- WWWKOVDRVDVLRG-HNNXBMFYSA-N 4,6-dimethyl-8-[(2s)-4-methyl-2-(methylamino)pentoxy]benzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@@H](NC)CC(C)C)C=C3N(C)C(=O)C2=C1C WWWKOVDRVDVLRG-HNNXBMFYSA-N 0.000 claims 1
- GIJACGNPPUYZEJ-LBPRGKRZSA-N 4-amino-8-[(2s)-2-amino-4-methylpentoxy]-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@@H](N)CC(C)C)C=C3N(C)C(=O)C2=C1N GIJACGNPPUYZEJ-LBPRGKRZSA-N 0.000 claims 1
- FCBKDNGEEHZOJJ-NSHDSACASA-N 4-amino-8-[(2s)-2-amino-4-methylpentoxy]-9-fluoro-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=C(N)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(F)=C2 FCBKDNGEEHZOJJ-NSHDSACASA-N 0.000 claims 1
- OAGROMXPCACYDF-AWEZNQCLSA-N 6-methyl-8-[(2s)-4-methyl-2-(methylamino)pentoxy]benzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@@H](NC)CC(C)C)C=C3N(C)C(=O)C2=C1 OAGROMXPCACYDF-AWEZNQCLSA-N 0.000 claims 1
- KLLKJQSKBGRMFP-UHFFFAOYSA-N 8-(2-amino-2,4-dimethylpentoxy)-1-fluoro-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC(F)=C2C3=CC=C(OCC(C)(N)CC(C)C)C=C3N(C)C(=O)C2=C1 KLLKJQSKBGRMFP-UHFFFAOYSA-N 0.000 claims 1
- KAXLZTZBXHYOSC-UHFFFAOYSA-N 8-(2-amino-2,4-dimethylpentoxy)-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OCC(C)(N)CC(C)C)C=C3N(C)C(=O)C2=C1C KAXLZTZBXHYOSC-UHFFFAOYSA-N 0.000 claims 1
- NBHCBBXZBQCGBZ-UHFFFAOYSA-N 8-(2-amino-2,4-dimethylpentoxy)-7-fluoro-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC(C)=C2C(=O)N(C)C3=C(F)C(OCC(C)(N)CC(C)C)=CC=C3C2=C1 NBHCBBXZBQCGBZ-UHFFFAOYSA-N 0.000 claims 1
- KMUIQNNSUSDHKH-UHFFFAOYSA-N 8-(2-amino-2,4-dimethylpentoxy)-7-fluoro-4-methyl-6h-benzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC(C)=C2C(=O)NC3=C(F)C(OCC(C)(N)CC(C)C)=CC=C3C2=C1 KMUIQNNSUSDHKH-UHFFFAOYSA-N 0.000 claims 1
- CMHHZVVLJLNEHM-UHFFFAOYSA-N 8-(2-amino-2,4-dimethylpentoxy)-9-chloro-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OCC(C)(N)CC(C)C)C(Cl)=C2 CMHHZVVLJLNEHM-UHFFFAOYSA-N 0.000 claims 1
- XKLGKAZUFOBXOV-UHFFFAOYSA-N 8-(2-amino-2,4-dimethylpentoxy)-9-fluoro-4-methyl-6h-benzo[c][2,7]naphthyridin-5-one Chemical compound N1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OCC(C)(N)CC(C)C)C(F)=C2 XKLGKAZUFOBXOV-UHFFFAOYSA-N 0.000 claims 1
- STLIWKILGDSCFT-UHFFFAOYSA-N 8-(2-amino-2,4-dimethylpentoxy)-9-methoxy-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OCC(C)(N)CC(C)C)C(OC)=C2 STLIWKILGDSCFT-UHFFFAOYSA-N 0.000 claims 1
- HZWYAONXPMPCBU-UHFFFAOYSA-N 8-(2-amino-4,4,4-trifluorobutoxy)-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC=C2C(=O)N(C)C3=CC(OCC(N)CC(F)(F)F)=CC=C3C2=C1 HZWYAONXPMPCBU-UHFFFAOYSA-N 0.000 claims 1
- FXZTVDZYBASRIS-UHFFFAOYSA-N 8-(2-amino-5,5,5-trifluoropentoxy)-4,6-dimethyl-5-oxobenzo[c][2,7]naphthyridine-9-carbonitrile Chemical compound C12=CC(C#N)=C(OCC(N)CCC(F)(F)F)C=C2N(C)C(=O)C2=C1C=CN=C2C FXZTVDZYBASRIS-UHFFFAOYSA-N 0.000 claims 1
- XWZXCIPLOWRHAC-UHFFFAOYSA-N 8-(2-amino-5,5,5-trifluoropentoxy)-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC=C2C(=O)N(C)C3=CC(OCC(N)CCC(F)(F)F)=CC=C3C2=C1 XWZXCIPLOWRHAC-UHFFFAOYSA-N 0.000 claims 1
- YRGHZZQVZHUGHW-LLVKDONJSA-N 8-[(2r)-2-amino-4,4,4-trifluorobutoxy]-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound C12=CC=C(OC[C@H](N)CC(F)(F)F)C=C2N(C)C(=O)C2=C1C=CN=C2C YRGHZZQVZHUGHW-LLVKDONJSA-N 0.000 claims 1
- NQXBZPJVVGIFBJ-OAHLLOKOSA-N 8-[(2r)-2-amino-4-methylpentoxy]-4,6-dimethyl-5-oxobenzo[c][2,7]naphthyridine-9-carbonitrile Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@H](N)CC(C)C)C(C#N)=C2 NQXBZPJVVGIFBJ-OAHLLOKOSA-N 0.000 claims 1
- HRMGBYSRWUAWIG-CQSZACIVSA-N 8-[(2r)-2-amino-4-methylpentoxy]-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@H](N)CC(C)C)C=C3N(C)C(=O)C2=C1C HRMGBYSRWUAWIG-CQSZACIVSA-N 0.000 claims 1
- GSMCIADOCFDNFO-HNNXBMFYSA-N 8-[(2s)-2-(dimethylamino)-4-methylpentoxy]-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@H](CC(C)C)N(C)C)C=C3N(C)C(=O)C2=C1 GSMCIADOCFDNFO-HNNXBMFYSA-N 0.000 claims 1
- KAXLZTZBXHYOSC-NRFANRHFSA-N 8-[(2s)-2-amino-2,4-dimethylpentoxy]-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@@](C)(N)CC(C)C)C=C3N(C)C(=O)C2=C1C KAXLZTZBXHYOSC-NRFANRHFSA-N 0.000 claims 1
- OOOPDKTUMJEDEK-INIZCTEOSA-N 8-[(2s)-2-amino-3-cyclobutylpropoxy]-4,6,9-trimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound C([C@H](N)COC1=CC2=C(C3=CC=NC(C)=C3C(=O)N2C)C=C1C)C1CCC1 OOOPDKTUMJEDEK-INIZCTEOSA-N 0.000 claims 1
- SPLKFCCVHVFPQH-HNNXBMFYSA-N 8-[(2s)-2-amino-3-cyclobutylpropoxy]-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound C([C@H](N)COC1=CC=C2C=3C=CN=C(C=3C(=O)N(C)C2=C1)C)C1CCC1 SPLKFCCVHVFPQH-HNNXBMFYSA-N 0.000 claims 1
- SNEOIKHHDVLVOX-AWEZNQCLSA-N 8-[(2s)-2-amino-3-cyclobutylpropoxy]-9-chloro-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound C([C@H](N)COC1=C(Cl)C=C2C=3C=CN=C(C=3C(=O)N(C)C2=C1)C)C1CCC1 SNEOIKHHDVLVOX-AWEZNQCLSA-N 0.000 claims 1
- QWYVFLDYWGJEQU-HNNXBMFYSA-N 8-[(2s)-2-amino-3-cyclopropylpropoxy]-4,6,9-trimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound C([C@H](N)COC1=CC2=C(C3=CC=NC(C)=C3C(=O)N2C)C=C1C)C1CC1 QWYVFLDYWGJEQU-HNNXBMFYSA-N 0.000 claims 1
- NJUOJAQINHVMBT-AWEZNQCLSA-N 8-[(2s)-2-amino-3-cyclopropylpropoxy]-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound C([C@H](N)COC1=CC=C2C=3C=CN=C(C=3C(=O)N(C)C2=C1)C)C1CC1 NJUOJAQINHVMBT-AWEZNQCLSA-N 0.000 claims 1
- UVIQIJWVZHLOOF-ZDUSSCGKSA-N 8-[(2s)-2-amino-3-cyclopropylpropoxy]-9-chloro-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound C([C@H](N)COC1=C(Cl)C=C2C=3C=CN=C(C=3C(=O)N(C)C2=C1)C)C1CC1 UVIQIJWVZHLOOF-ZDUSSCGKSA-N 0.000 claims 1
- LXWGNKPGJXVYCC-NSHDSACASA-N 8-[(2s)-2-amino-3-methoxypropoxy]-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@@H](N)COC)C=C3N(C)C(=O)C2=C1 LXWGNKPGJXVYCC-NSHDSACASA-N 0.000 claims 1
- YGIQORZXXQTXBN-ZDUSSCGKSA-N 8-[(2s)-2-amino-3-propan-2-yloxypropoxy]-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@@H](N)COC(C)C)C=C3N(C)C(=O)C2=C1 YGIQORZXXQTXBN-ZDUSSCGKSA-N 0.000 claims 1
- YRGHZZQVZHUGHW-NSHDSACASA-N 8-[(2s)-2-amino-4,4,4-trifluorobutoxy]-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound C12=CC=C(OC[C@@H](N)CC(F)(F)F)C=C2N(C)C(=O)C2=C1C=CN=C2C YRGHZZQVZHUGHW-NSHDSACASA-N 0.000 claims 1
- WHQDGHKLJVQMRP-NSHDSACASA-N 8-[(2s)-2-amino-4,4-difluoropentoxy]-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC=C2C(=O)N(C)C3=CC(OC[C@@H](N)CC(C)(F)F)=CC=C3C2=C1 WHQDGHKLJVQMRP-NSHDSACASA-N 0.000 claims 1
- NLRSBHGTESEGQM-LBPRGKRZSA-N 8-[(2s)-2-amino-4-methylpentoxy]-1-fluoro-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC(F)=C2C3=CC=C(OC[C@@H](N)CC(C)C)C=C3N(C)C(=O)C2=C1 NLRSBHGTESEGQM-LBPRGKRZSA-N 0.000 claims 1
- XVIGNJJPLOWARI-ZDUSSCGKSA-N 8-[(2s)-2-amino-4-methylpentoxy]-1-methoxy-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound C12=CC=C(OC[C@@H](N)CC(C)C)C=C2N(C)C(=O)C2=C1C(OC)=CN=C2 XVIGNJJPLOWARI-ZDUSSCGKSA-N 0.000 claims 1
- VKDHJNPPKCHVLP-HNNXBMFYSA-N 8-[(2s)-2-amino-4-methylpentoxy]-4,6,9-trimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(C)=C2 VKDHJNPPKCHVLP-HNNXBMFYSA-N 0.000 claims 1
- NQXBZPJVVGIFBJ-HNNXBMFYSA-N 8-[(2s)-2-amino-4-methylpentoxy]-4,6-dimethyl-5-oxobenzo[c][2,7]naphthyridine-9-carbonitrile Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(C#N)=C2 NQXBZPJVVGIFBJ-HNNXBMFYSA-N 0.000 claims 1
- BLTIFWQUIKJLLO-ZDUSSCGKSA-N 8-[(2s)-2-amino-4-methylpentoxy]-4,6-dimethyl-5-oxobenzo[c][2,7]naphthyridine-9-carboxamide Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(C(N)=O)=C2 BLTIFWQUIKJLLO-ZDUSSCGKSA-N 0.000 claims 1
- PBOYTVVOMMRCKA-HNNXBMFYSA-N 8-[(2s)-2-amino-4-methylpentoxy]-4,6-dimethyl-9-(1,3-oxazol-5-yl)benzo[c][2,7]naphthyridin-5-one Chemical compound CC(C)C[C@H](N)COC1=CC=2N(C)C(=O)C3=C(C)N=CC=C3C=2C=C1C1=CN=CO1 PBOYTVVOMMRCKA-HNNXBMFYSA-N 0.000 claims 1
- WVWZWEDZULHZHM-HNNXBMFYSA-N 8-[(2s)-2-amino-4-methylpentoxy]-4,6-dimethyl-9-(1,3-thiazol-5-yl)benzo[c][2,7]naphthyridin-5-one Chemical compound CC(C)C[C@H](N)COC1=CC=2N(C)C(=O)C3=C(C)N=CC=C3C=2C=C1C1=CN=CS1 WVWZWEDZULHZHM-HNNXBMFYSA-N 0.000 claims 1
- VNYWTAUYKHVQTO-AWEZNQCLSA-N 8-[(2s)-2-amino-4-methylpentoxy]-4,6-dimethyl-9-methylsulfonylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(S(C)(=O)=O)=C2 VNYWTAUYKHVQTO-AWEZNQCLSA-N 0.000 claims 1
- CJYBTGCGPOINHK-KRWDZBQOSA-N 8-[(2s)-2-amino-4-methylpentoxy]-4,6-dimethyl-9-pyridin-2-ylbenzo[c][2,7]naphthyridin-5-one Chemical compound CC(C)C[C@H](N)COC1=CC=2N(C)C(=O)C3=C(C)N=CC=C3C=2C=C1C1=CC=CC=N1 CJYBTGCGPOINHK-KRWDZBQOSA-N 0.000 claims 1
- BGLUCWKQMAHNGQ-LBPRGKRZSA-N 8-[(2s)-2-amino-4-methylpentoxy]-4-(difluoromethyl)-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@@H](N)CC(C)C)C=C3N(C)C(=O)C2=C1C(F)F BGLUCWKQMAHNGQ-LBPRGKRZSA-N 0.000 claims 1
- SVROKGXYLBYIMC-IBGZPJMESA-N 8-[(2s)-2-amino-4-methylpentoxy]-4-[(4-methoxyphenyl)methylamino]-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound C1=CC(OC)=CC=C1CNC1=NC=CC2=C1C(=O)N(C)C1=CC(OC[C@@H](N)CC(C)C)=CC=C12 SVROKGXYLBYIMC-IBGZPJMESA-N 0.000 claims 1
- LBECDWCCXFEOTO-ZDUSSCGKSA-N 8-[(2s)-2-amino-4-methylpentoxy]-4-methoxy-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound C12=CC=C(OC[C@@H](N)CC(C)C)C=C2N(C)C(=O)C2=C1C=CN=C2OC LBECDWCCXFEOTO-ZDUSSCGKSA-N 0.000 claims 1
- KVRKKRBPFCLMMG-ZDUSSCGKSA-N 8-[(2s)-2-amino-4-methylpentoxy]-4-methyl-6h-benzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@@H](N)CC(C)C)C=C3NC(=O)C2=C1C KVRKKRBPFCLMMG-ZDUSSCGKSA-N 0.000 claims 1
- YPEZYWFTKZJJJZ-AWEZNQCLSA-N 8-[(2s)-2-amino-4-methylpentoxy]-6,9-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=CN=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(C)=C2 YPEZYWFTKZJJJZ-AWEZNQCLSA-N 0.000 claims 1
- ZLWTXUUWGKBYQB-ZDUSSCGKSA-N 8-[(2s)-2-amino-4-methylpentoxy]-6-(2,2,2-trifluoroethyl)benzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@@H](N)CC(C)C)C=C3N(CC(F)(F)F)C(=O)C2=C1 ZLWTXUUWGKBYQB-ZDUSSCGKSA-N 0.000 claims 1
- HRNXRDKJFHAEEN-AWEZNQCLSA-N 8-[(2s)-2-amino-4-methylpentoxy]-6-(2-hydroxyethyl)benzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@@H](N)CC(C)C)C=C3N(CCO)C(=O)C2=C1 HRNXRDKJFHAEEN-AWEZNQCLSA-N 0.000 claims 1
- IHAGWGCKKJXHRG-INIZCTEOSA-N 8-[(2s)-2-amino-4-methylpentoxy]-6-(2-methoxyethyl)-4-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC(C)=C2C(=O)N(CCOC)C3=CC(OC[C@@H](N)CC(C)C)=CC=C3C2=C1 IHAGWGCKKJXHRG-INIZCTEOSA-N 0.000 claims 1
- ODUGXJAXPWAZJC-HNNXBMFYSA-N 8-[(2s)-2-amino-4-methylpentoxy]-6-(2-methoxyethyl)benzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC=C2C(=O)N(CCOC)C3=CC(OC[C@@H](N)CC(C)C)=CC=C3C2=C1 ODUGXJAXPWAZJC-HNNXBMFYSA-N 0.000 claims 1
- APIXEYSCHSPEJC-INIZCTEOSA-N 8-[(2s)-2-amino-4-methylpentoxy]-6-(cyclopropylmethyl)benzo[c][2,7]naphthyridin-5-one Chemical compound C=1C(OC[C@@H](N)CC(C)C)=CC=C(C2=CC=NC=C2C2=O)C=1N2CC1CC1 APIXEYSCHSPEJC-INIZCTEOSA-N 0.000 claims 1
- FGATYYWDIQMZBZ-AWEZNQCLSA-N 8-[(2s)-2-amino-4-methylpentoxy]-6-methyl-9-(1,3-oxazol-5-yl)benzo[c][2,7]naphthyridin-5-one Chemical compound CC(C)C[C@H](N)COC1=CC=2N(C)C(=O)C3=CN=CC=C3C=2C=C1C1=CN=CO1 FGATYYWDIQMZBZ-AWEZNQCLSA-N 0.000 claims 1
- QLTHRQXGSXPWOS-HNNXBMFYSA-N 8-[(2s)-2-amino-4-methylpentoxy]-6-methyl-9-propan-2-ylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=CN=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(C(C)C)=C2 QLTHRQXGSXPWOS-HNNXBMFYSA-N 0.000 claims 1
- WWGYWTPSBKHRKT-HNNXBMFYSA-N 8-[(2s)-2-amino-4-methylpentoxy]-6-prop-2-enylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@@H](N)CC(C)C)C=C3N(CC=C)C(=O)C2=C1 WWGYWTPSBKHRKT-HNNXBMFYSA-N 0.000 claims 1
- AQOSFDACVBCBQG-HNNXBMFYSA-N 8-[(2s)-2-amino-4-methylpentoxy]-6-propan-2-ylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@@H](N)CC(C)C)C=C3N(C(C)C)C(=O)C2=C1 AQOSFDACVBCBQG-HNNXBMFYSA-N 0.000 claims 1
- OYOIIDJCDNWRLV-ZDUSSCGKSA-N 8-[(2s)-2-amino-4-methylpentoxy]-7-chloro-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC(C)=C2C(=O)N(C)C3=C(Cl)C(OC[C@@H](N)CC(C)C)=CC=C3C2=C1 OYOIIDJCDNWRLV-ZDUSSCGKSA-N 0.000 claims 1
- WSKQQUBBBVNHFA-ZDUSSCGKSA-N 8-[(2s)-2-amino-4-methylpentoxy]-7-fluoro-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC(C)=C2C(=O)N(C)C3=C(F)C(OC[C@@H](N)CC(C)C)=CC=C3C2=C1 WSKQQUBBBVNHFA-ZDUSSCGKSA-N 0.000 claims 1
- IBOVYPMCAGZYGE-LBPRGKRZSA-N 8-[(2s)-2-amino-4-methylpentoxy]-7-fluoro-4-methyl-6h-benzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC(C)=C2C(=O)NC3=C(F)C(OC[C@@H](N)CC(C)C)=CC=C3C2=C1 IBOVYPMCAGZYGE-LBPRGKRZSA-N 0.000 claims 1
- CRIWGRHBFYLTLV-ZDUSSCGKSA-N 8-[(2s)-2-amino-4-methylpentoxy]-7-methoxy-4-methyl-6h-benzo[c][2,7]naphthyridin-5-one Chemical compound C12=CC=NC(C)=C2C(=O)NC2=C1C=CC(OC[C@@H](N)CC(C)C)=C2OC CRIWGRHBFYLTLV-ZDUSSCGKSA-N 0.000 claims 1
- UDYNBTZVRFJLDX-LOACHALJSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-(1-hydroxyethyl)-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(C(C)O)=C2 UDYNBTZVRFJLDX-LOACHALJSA-N 0.000 claims 1
- USAMSFVGHFFXCT-HNNXBMFYSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-(2-hydroxypropan-2-yl)-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(C(C)(C)O)=C2 USAMSFVGHFFXCT-HNNXBMFYSA-N 0.000 claims 1
- CUYXOTOYPMKKDG-SFHVURJKSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-(4-fluorophenyl)-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound CC(C)C[C@H](N)COC1=CC=2N(C)C(=O)C3=CN=CC=C3C=2C=C1C1=CC=C(F)C=C1 CUYXOTOYPMKKDG-SFHVURJKSA-N 0.000 claims 1
- ORQYAHOYSVQHFF-ZDUSSCGKSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-(difluoromethoxy)-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(OC(F)F)=C2 ORQYAHOYSVQHFF-ZDUSSCGKSA-N 0.000 claims 1
- NWYXJWAMZICQET-HNNXBMFYSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-(hydroxymethyl)-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(CO)=C2 NWYXJWAMZICQET-HNNXBMFYSA-N 0.000 claims 1
- BJNSPVVEWIIBBR-INIZCTEOSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-(methoxymethyl)-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(COC)=C2 BJNSPVVEWIIBBR-INIZCTEOSA-N 0.000 claims 1
- CCHPJDYBRNVSFQ-LBPRGKRZSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-bromo-4-methyl-6h-benzo[c][2,7]naphthyridin-5-one Chemical compound N1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(Br)=C2 CCHPJDYBRNVSFQ-LBPRGKRZSA-N 0.000 claims 1
- DNJVIWQGOSPTGR-LBPRGKRZSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-bromo-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=CN=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(Br)=C2 DNJVIWQGOSPTGR-LBPRGKRZSA-N 0.000 claims 1
- KAPLDTONLWMQIE-NSHDSACASA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-bromo-7-fluoro-4-methyl-6h-benzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC(C)=C2C(=O)NC3=C(F)C(OC[C@@H](N)CC(C)C)=C(Br)C=C3C2=C1 KAPLDTONLWMQIE-NSHDSACASA-N 0.000 claims 1
- DWWYXDNMFIWINY-ZDUSSCGKSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-chloro-2,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=CN=C(C)C=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(Cl)=C2 DWWYXDNMFIWINY-ZDUSSCGKSA-N 0.000 claims 1
- URECUINDIIRBJP-ZDUSSCGKSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-chloro-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(Cl)=C2 URECUINDIIRBJP-ZDUSSCGKSA-N 0.000 claims 1
- HYRWSXHWUJUTDU-HNNXBMFYSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-chloro-6-(2-methoxyethyl)-4-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC(C)=C2C(=O)N(CCOC)C3=CC(OC[C@@H](N)CC(C)C)=C(Cl)C=C3C2=C1 HYRWSXHWUJUTDU-HNNXBMFYSA-N 0.000 claims 1
- IOELABXSEUZEQB-LBPRGKRZSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-chloro-7-fluoro-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC(C)=C2C(=O)N(C)C3=C(F)C(OC[C@@H](N)CC(C)C)=C(Cl)C=C3C2=C1 IOELABXSEUZEQB-LBPRGKRZSA-N 0.000 claims 1
- MYZKGWHBHRHHHC-NSHDSACASA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-chloro-7-fluoro-4-methyl-6h-benzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC(C)=C2C(=O)NC3=C(F)C(OC[C@@H](N)CC(C)C)=C(Cl)C=C3C2=C1 MYZKGWHBHRHHHC-NSHDSACASA-N 0.000 claims 1
- JKZORRCCLSIZMM-HNNXBMFYSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-cyclopropyl-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound CC(C)C[C@H](N)COC1=CC=2N(C)C(=O)C3=CN=CC=C3C=2C=C1C1CC1 JKZORRCCLSIZMM-HNNXBMFYSA-N 0.000 claims 1
- JXAKSJXCPHGYPY-INIZCTEOSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-ethyl-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(CC)=C2 JXAKSJXCPHGYPY-INIZCTEOSA-N 0.000 claims 1
- SYTLAGDWFIULBR-ZDUSSCGKSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-fluoro-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(F)=C2 SYTLAGDWFIULBR-ZDUSSCGKSA-N 0.000 claims 1
- BVYQOYUERGMZOR-LBPRGKRZSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-fluoro-4-methyl-6h-benzo[c][2,7]naphthyridin-5-one Chemical compound N1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(F)=C2 BVYQOYUERGMZOR-LBPRGKRZSA-N 0.000 claims 1
- UIIOSLHEZNMKMF-LBPRGKRZSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-fluoro-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=CN=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(F)=C2 UIIOSLHEZNMKMF-LBPRGKRZSA-N 0.000 claims 1
- PWXKBOZXLHEXHI-AWEZNQCLSA-N 8-[(2s)-2-amino-4-methylpentoxy]-9-methoxy-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(OC)=C2 PWXKBOZXLHEXHI-AWEZNQCLSA-N 0.000 claims 1
- CPDCVAWWRJBIEE-HNNXBMFYSA-N 8-[(2s)-2-amino-4-methylpentoxy]-n,n,4,6-tetramethyl-5-oxobenzo[c][2,7]naphthyridine-9-carboxamide Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(C(=O)N(C)C)=C2 CPDCVAWWRJBIEE-HNNXBMFYSA-N 0.000 claims 1
- DRXIVOBMZNQSMK-YUZLPWPTSA-N 8-[(2s)-2-amino-5,5,5-trifluoro-4-methylpentoxy]-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@@H](N)CC(C)C(F)(F)F)C=C3N(C)C(=O)C2=C1C DRXIVOBMZNQSMK-YUZLPWPTSA-N 0.000 claims 1
- UDIIMGJDZJDIMZ-ZDUSSCGKSA-N 8-[(2s)-2-amino-5,5-difluoropent-4-enoxy]-4,6-dimethyl-5-oxobenzo[c][2,7]naphthyridine-9-carbonitrile Chemical compound C12=CC(C#N)=C(OC[C@@H](N)CC=C(F)F)C=C2N(C)C(=O)C2=C1C=CN=C2C UDIIMGJDZJDIMZ-ZDUSSCGKSA-N 0.000 claims 1
- JTJPHTSXEWEQPY-KSSFIOAISA-N 8-[(2s,3s)-3-amino-5-methylhexan-2-yl]oxy-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(O[C@@H](C)[C@@H](N)CC(C)C)C=C3N(C)C(=O)C2=C1C JTJPHTSXEWEQPY-KSSFIOAISA-N 0.000 claims 1
- MGSGDLOSBWIMAZ-AWEZNQCLSA-N methyl 8-[(2s)-2-amino-4-methylpentoxy]-4,6-dimethyl-5-oxobenzo[c][2,7]naphthyridine-9-carboxylate Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](N)CC(C)C)C(C(=O)OC)=C2 MGSGDLOSBWIMAZ-AWEZNQCLSA-N 0.000 claims 1
- PCUUDYSYXFBLDS-RUZDIDTESA-N tert-butyl n-[(2r)-2,4-dimethyl-1-(6-methyl-5-oxobenzo[c][2,7]naphthyridin-8-yl)oxypentan-2-yl]carbamate Chemical compound N1=CC=C2C3=CC=C(OC[C@@](C)(CC(C)C)NC(=O)OC(C)(C)C)C=C3N(C)C(=O)C2=C1 PCUUDYSYXFBLDS-RUZDIDTESA-N 0.000 claims 1
- PCUUDYSYXFBLDS-VWLOTQADSA-N tert-butyl n-[(2s)-2,4-dimethyl-1-(6-methyl-5-oxobenzo[c][2,7]naphthyridin-8-yl)oxypentan-2-yl]carbamate Chemical compound N1=CC=C2C3=CC=C(OC[C@](C)(CC(C)C)NC(=O)OC(C)(C)C)C=C3N(C)C(=O)C2=C1 PCUUDYSYXFBLDS-VWLOTQADSA-N 0.000 claims 1
- PCUUDYSYXFBLDS-UHFFFAOYSA-N tert-butyl n-[2,4-dimethyl-1-(6-methyl-5-oxobenzo[c][2,7]naphthyridin-8-yl)oxypentan-2-yl]carbamate Chemical compound N1=CC=C2C3=CC=C(OCC(C)(CC(C)C)NC(=O)OC(C)(C)C)C=C3N(C)C(=O)C2=C1 PCUUDYSYXFBLDS-UHFFFAOYSA-N 0.000 claims 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 420
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 403
- 230000014759 maintenance of location Effects 0.000 description 328
- 239000011541 reaction mixture Substances 0.000 description 204
- 239000000243 solution Substances 0.000 description 189
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 183
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 180
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 177
- 230000002829 reductive effect Effects 0.000 description 177
- 239000007787 solid Substances 0.000 description 167
- 238000004128 high performance liquid chromatography Methods 0.000 description 141
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 139
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 120
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 105
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 102
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 100
- 229910052938 sodium sulfate Inorganic materials 0.000 description 95
- 235000011152 sodium sulphate Nutrition 0.000 description 95
- 238000005160 1H NMR spectroscopy Methods 0.000 description 92
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 81
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 77
- 239000012044 organic layer Substances 0.000 description 74
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 60
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 60
- 239000012267 brine Substances 0.000 description 56
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 56
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 53
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 52
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 51
- 238000000746 purification Methods 0.000 description 51
- 238000006243 chemical reaction Methods 0.000 description 50
- 239000007832 Na2SO4 Substances 0.000 description 49
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 44
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 42
- 239000000543 intermediate Substances 0.000 description 40
- 239000002904 solvent Substances 0.000 description 39
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 36
- 239000012043 crude product Substances 0.000 description 34
- 239000000047 product Substances 0.000 description 34
- 239000005909 Kieselgur Substances 0.000 description 33
- 229910000024 caesium carbonate Inorganic materials 0.000 description 33
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 32
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 32
- 239000010410 layer Substances 0.000 description 32
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 31
- 125000005605 benzo group Chemical group 0.000 description 30
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 29
- 238000003786 synthesis reaction Methods 0.000 description 29
- 238000011282 treatment Methods 0.000 description 27
- 239000000706 filtrate Substances 0.000 description 26
- 239000000463 material Substances 0.000 description 26
- 239000003921 oil Substances 0.000 description 26
- 238000003756 stirring Methods 0.000 description 25
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 235000019198 oils Nutrition 0.000 description 24
- 125000006239 protecting group Chemical group 0.000 description 24
- 238000010898 silica gel chromatography Methods 0.000 description 24
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 23
- 235000017557 sodium bicarbonate Nutrition 0.000 description 23
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 23
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 22
- 239000003208 petroleum Substances 0.000 description 21
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
- 239000012071 phase Substances 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 19
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 18
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 18
- 238000007792 addition Methods 0.000 description 17
- 239000003153 chemical reaction reagent Substances 0.000 description 17
- 229910000104 sodium hydride Inorganic materials 0.000 description 17
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 16
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 16
- 238000001816 cooling Methods 0.000 description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 16
- 150000003951 lactams Chemical class 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 15
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 15
- 125000000217 alkyl group Chemical group 0.000 description 15
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 14
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 14
- 239000008194 pharmaceutical composition Substances 0.000 description 14
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 13
- 238000010511 deprotection reaction Methods 0.000 description 13
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 13
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 239000003795 chemical substances by application Substances 0.000 description 12
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 12
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 238000004007 reversed phase HPLC Methods 0.000 description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 11
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 11
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 11
- 125000003277 amino group Chemical group 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 11
- 238000002953 preparative HPLC Methods 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 229960001866 silicon dioxide Drugs 0.000 description 11
- LQTMEOSBXTVYRM-VIFPVBQESA-N tert-butyl n-[(2s)-1-hydroxy-4-methylpentan-2-yl]carbamate Chemical compound CC(C)C[C@@H](CO)NC(=O)OC(C)(C)C LQTMEOSBXTVYRM-VIFPVBQESA-N 0.000 description 11
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 10
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
- 239000000872 buffer Substances 0.000 description 10
- 239000012230 colorless oil Substances 0.000 description 10
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- 239000012312 sodium hydride Substances 0.000 description 10
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 9
- 239000005695 Ammonium acetate Substances 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 229940043376 ammonium acetate Drugs 0.000 description 9
- 235000019257 ammonium acetate Nutrition 0.000 description 9
- 235000019270 ammonium chloride Nutrition 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- 230000008878 coupling Effects 0.000 description 9
- 238000010168 coupling process Methods 0.000 description 9
- 238000005859 coupling reaction Methods 0.000 description 9
- 239000013058 crude material Substances 0.000 description 9
- 150000002170 ethers Chemical class 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 230000001225 therapeutic effect Effects 0.000 description 9
- VCLJNXICBACRBN-UHFFFAOYSA-N 4-(4-chloro-2-fluorophenyl)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC=C1C1=CC=C(Cl)C=C1F VCLJNXICBACRBN-UHFFFAOYSA-N 0.000 description 8
- 102100020870 La-related protein 6 Human genes 0.000 description 8
- 108050008265 La-related protein 6 Proteins 0.000 description 8
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 238000006069 Suzuki reaction reaction Methods 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 8
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 8
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- 235000017550 sodium carbonate Nutrition 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 7
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 229910052802 copper Inorganic materials 0.000 description 7
- 239000010949 copper Substances 0.000 description 7
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 7
- 239000007819 coupling partner Substances 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- 239000012285 osmium tetroxide Substances 0.000 description 7
- 229910000489 osmium tetroxide Inorganic materials 0.000 description 7
- 229910052763 palladium Inorganic materials 0.000 description 7
- 238000012746 preparative thin layer chromatography Methods 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- GBBSAMQTQCPOBF-UHFFFAOYSA-N 2,4,6-trimethyl-1,3,5,2,4,6-trioxatriborinane Chemical compound CB1OB(C)OB(C)O1 GBBSAMQTQCPOBF-UHFFFAOYSA-N 0.000 description 6
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 6
- 238000004296 chiral HPLC Methods 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
- 239000003112 inhibitor Substances 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- PMWJYAHNDINWIY-UHFFFAOYSA-N methyl 4-chloro-2-methylpyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)N=CC=C1Cl PMWJYAHNDINWIY-UHFFFAOYSA-N 0.000 description 6
- 229960001238 methylnicotinate Drugs 0.000 description 6
- 239000012299 nitrogen atmosphere Substances 0.000 description 6
- 235000011181 potassium carbonates Nutrition 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000011369 resultant mixture Substances 0.000 description 6
- 239000011877 solvent mixture Substances 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- VFMXZOSZIRYSGH-UHFFFAOYSA-N tert-butyl n-(1-hydroxy-2,4-dimethylpentan-2-yl)carbamate Chemical compound CC(C)CC(C)(CO)NC(=O)OC(C)(C)C VFMXZOSZIRYSGH-UHFFFAOYSA-N 0.000 description 6
- 239000003039 volatile agent Substances 0.000 description 6
- YBNDRTRLXPEWKQ-UHFFFAOYSA-N (4-chloro-2-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Cl)C=C1F YBNDRTRLXPEWKQ-UHFFFAOYSA-N 0.000 description 5
- APOYTRAZFJURPB-UHFFFAOYSA-N 2-methoxy-n-(2-methoxyethyl)-n-(trifluoro-$l^{4}-sulfanyl)ethanamine Chemical compound COCCN(S(F)(F)F)CCOC APOYTRAZFJURPB-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N 2-propanol Substances CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 241000400611 Eucalyptus deanei Species 0.000 description 5
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 229910052786 argon Inorganic materials 0.000 description 5
- 235000010290 biphenyl Nutrition 0.000 description 5
- 229910001873 dinitrogen Inorganic materials 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 5
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- 235000001968 nicotinic acid Nutrition 0.000 description 5
- 239000011664 nicotinic acid Substances 0.000 description 5
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 5
- 230000008569 process Effects 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Substances ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 5
- 229940086542 triethylamine Drugs 0.000 description 5
- 239000003643 water by type Substances 0.000 description 5
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 4
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 4
- JAOINXWEFKZYIL-UHFFFAOYSA-N 4-(1-methyl-2-oxoquinolin-4-yl)oxy-n-(4-methylpyridin-2-yl)butanamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CC1=CC=NC(NC(=O)CCCOC=2C3=CC=CC=C3N(C)C(=O)C=2)=C1 JAOINXWEFKZYIL-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 101150041968 CDC13 gene Proteins 0.000 description 4
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 4
- 102000048238 Neuregulin-1 Human genes 0.000 description 4
- 108090000556 Neuregulin-1 Proteins 0.000 description 4
- 229910021120 PdC12 Inorganic materials 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 4
- 239000012346 acetyl chloride Substances 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000000556 agonist Substances 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 125000001188 haloalkyl group Chemical group 0.000 description 4
- 230000026030 halogenation Effects 0.000 description 4
- 238000005658 halogenation reaction Methods 0.000 description 4
- 239000003018 immunosuppressive agent Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 238000007726 management method Methods 0.000 description 4
- IBZIEMCFERTPNR-UHFFFAOYSA-N methyl 2,4-dichloropyridine-3-carboxylate Chemical compound COC(=O)C1=C(Cl)C=CN=C1Cl IBZIEMCFERTPNR-UHFFFAOYSA-N 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000003880 polar aprotic solvent Substances 0.000 description 4
- 235000015320 potassium carbonate Nutrition 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- CFOAUYCPAUGDFF-UHFFFAOYSA-N tosmic Chemical compound CC1=CC=C(S(=O)(=O)C[N+]#[C-])C=C1 CFOAUYCPAUGDFF-UHFFFAOYSA-N 0.000 description 4
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 description 3
- ZFGZNVSNOJPGDV-UHFFFAOYSA-N 2,4-dichloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=C(Cl)C=CN=C1Cl ZFGZNVSNOJPGDV-UHFFFAOYSA-N 0.000 description 3
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- KFVIQMJAIMIKSX-UHFFFAOYSA-N 4-(4-chloro-2,5-difluorophenyl)pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC=C1C1=CC(F)=C(Cl)C=C1F KFVIQMJAIMIKSX-UHFFFAOYSA-N 0.000 description 3
- OSARGZPDYZSHAH-UHFFFAOYSA-N 4-(4-chloro-2-fluorophenyl)pyridine-3-carboxamide Chemical compound NC(=O)C1=CN=CC=C1C1=CC=C(Cl)C=C1F OSARGZPDYZSHAH-UHFFFAOYSA-N 0.000 description 3
- RQMWVVBHJMUJNZ-UHFFFAOYSA-N 4-chloropyridin-2-amine Chemical compound NC1=CC(Cl)=CC=N1 RQMWVVBHJMUJNZ-UHFFFAOYSA-N 0.000 description 3
- YRXRZBPEGLIKRH-UHFFFAOYSA-N 5,5,5-trifluoro-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CC(C)(C)OC(=O)NC(C(O)=O)CCC(F)(F)F YRXRZBPEGLIKRH-UHFFFAOYSA-N 0.000 description 3
- HPFOEWJXDNWCTH-UHFFFAOYSA-N 6h-benzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC=C2C(=O)NC3=CC=CC=C3C2=C1 HPFOEWJXDNWCTH-UHFFFAOYSA-N 0.000 description 3
- KYQYYKHSIPMOTF-UHFFFAOYSA-N 8-chloro-6h-benzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(Cl)C=C3NC(=O)C2=C1 KYQYYKHSIPMOTF-UHFFFAOYSA-N 0.000 description 3
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 3
- 102000020897 Formins Human genes 0.000 description 3
- 108091022623 Formins Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 3
- 229930182821 L-proline Natural products 0.000 description 3
- 239000012448 Lithium borohydride Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000003472 antidiabetic agent Substances 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 239000004305 biphenyl Substances 0.000 description 3
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 239000006184 cosolvent Substances 0.000 description 3
- 238000007333 cyanation reaction Methods 0.000 description 3
- WLVKDFJTYKELLQ-UHFFFAOYSA-N cyclopropylboronic acid Chemical compound OB(O)C1CC1 WLVKDFJTYKELLQ-UHFFFAOYSA-N 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000006196 drop Substances 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- YFXCNIVBAVFOBX-UHFFFAOYSA-N ethenylboronic acid Chemical compound OB(O)C=C YFXCNIVBAVFOBX-UHFFFAOYSA-N 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 238000003818 flash chromatography Methods 0.000 description 3
- VNWHJJCHHGPAEO-UHFFFAOYSA-N fluoroboronic acid Chemical compound OB(O)F VNWHJJCHHGPAEO-UHFFFAOYSA-N 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 230000014509 gene expression Effects 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 229960003444 immunosuppressant agent Drugs 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 238000011813 knockout mouse model Methods 0.000 description 3
- 239000012280 lithium aluminium hydride Substances 0.000 description 3
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 3
- BITKFESLEDFJMG-QMMMGPOBSA-N methyl (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-oxopentanoate Chemical compound COC(=O)[C@H](CC(C)=O)NC(=O)OC(C)(C)C BITKFESLEDFJMG-QMMMGPOBSA-N 0.000 description 3
- XDDHRHFKTNUBLQ-ZETCQYMHSA-N methyl (2s)-4,4-difluoro-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentanoate Chemical compound COC(=O)[C@H](CC(C)(F)F)NC(=O)OC(C)(C)C XDDHRHFKTNUBLQ-ZETCQYMHSA-N 0.000 description 3
- HDCNZMXVOIZXPD-VIFPVBQESA-N methyl (2s)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pent-4-enoate Chemical compound COC(=O)[C@H](CC(C)=C)NC(=O)OC(C)(C)C HDCNZMXVOIZXPD-VIFPVBQESA-N 0.000 description 3
- AWIZTSGUZYZVCC-UHFFFAOYSA-N methyl 4-(4-chloro-2,5-difluorophenyl)pyridine-3-carboxylate Chemical compound COC(=O)C1=CN=CC=C1C1=CC(F)=C(Cl)C=C1F AWIZTSGUZYZVCC-UHFFFAOYSA-N 0.000 description 3
- MYYVAUGLIUDCHG-UHFFFAOYSA-N methyl 4-(4-chloro-2-fluorophenyl)pyridine-3-carboxylate Chemical compound COC(=O)C1=CN=CC=C1C1=CC=C(Cl)C=C1F MYYVAUGLIUDCHG-UHFFFAOYSA-N 0.000 description 3
- VAKBQHRUUZLSLW-UHFFFAOYSA-N methyl 4-chloro-6-methylpyridine-3-carboxylate Chemical compound COC(=O)C1=CN=C(C)C=C1Cl VAKBQHRUUZLSLW-UHFFFAOYSA-N 0.000 description 3
- OGYJYEPICBLYRQ-UHFFFAOYSA-N methyl 4-iodo-2-methylpyridine-3-carboxylate Chemical compound COC(=O)C1=C(C)N=CC=C1I OGYJYEPICBLYRQ-UHFFFAOYSA-N 0.000 description 3
- UIGOMFDGHINZOC-UHFFFAOYSA-N n-(4-chloro-5-ethenylpyridin-2-yl)acetamide Chemical compound CC(=O)NC1=CC(Cl)=C(C=C)C=N1 UIGOMFDGHINZOC-UHFFFAOYSA-N 0.000 description 3
- AEQIKYQIJKUJFG-UHFFFAOYSA-N n-(4-chloro-5-formylpyridin-2-yl)acetamide Chemical compound CC(=O)NC1=CC(Cl)=C(C=O)C=N1 AEQIKYQIJKUJFG-UHFFFAOYSA-N 0.000 description 3
- AJORAFCTYBOMAV-UHFFFAOYSA-N n-(5-bromo-4-chloropyridin-2-yl)acetamide Chemical compound CC(=O)NC1=CC(Cl)=C(Br)C=N1 AJORAFCTYBOMAV-UHFFFAOYSA-N 0.000 description 3
- WZMRSIYAYHFIGX-UHFFFAOYSA-N n-(8-chloro-6-methylbenzo[c][2,7]naphthyridin-6-ium-2-yl)acetamide;fluoride Chemical compound [F-].C1=[N+](C)C2=CC(Cl)=CC=C2C2=C1C=NC(NC(=O)C)=C2 WZMRSIYAYHFIGX-UHFFFAOYSA-N 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 125000004430 oxygen atom Chemical group O* 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 229960002429 proline Drugs 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 3
- 229910000080 stannane Inorganic materials 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- XVSQOLAOMZHRGM-UHFFFAOYSA-N tert-butyl 2-(benzhydrylideneamino)-5,5,5-trifluoropentanoate Chemical compound C=1C=CC=CC=1C(=NC(CCC(F)(F)F)C(=O)OC(C)(C)C)C1=CC=CC=C1 XVSQOLAOMZHRGM-UHFFFAOYSA-N 0.000 description 3
- FPJFJKWJLFKRCO-UHFFFAOYSA-N tert-butyl n-(8-chloro-6-methylbenzo[f][2,7]naphthyridin-6-ium-4-yl)carbamate;fluoride Chemical compound [F-].C1=C(Cl)C=C2[N+](C)=CC3=C(NC(=O)OC(C)(C)C)N=CC=C3C2=C1 FPJFJKWJLFKRCO-UHFFFAOYSA-N 0.000 description 3
- GZFXVYZYBWQWIQ-UHFFFAOYSA-O tert-butyl n-(8-chloro-9-fluoro-6-methylbenzo[f][2,7]naphthyridin-6-ium-4-yl)carbamate Chemical compound FC1=C(Cl)C=C2[N+](C)=CC3=C(NC(=O)OC(C)(C)C)N=CC=C3C2=C1 GZFXVYZYBWQWIQ-UHFFFAOYSA-O 0.000 description 3
- RQSBRFZHUKLKNO-VIFPVBQESA-N tert-butyl n-[(2s)-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound CC(C)C[C@@H](C=O)NC(=O)OC(C)(C)C RQSBRFZHUKLKNO-VIFPVBQESA-N 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- RQLCJLJVSWUYSK-UHFFFAOYSA-N 2-amino-5,5,5-trifluoropentanoic acid;hydrochloride Chemical compound Cl.OC(=O)C(N)CCC(F)(F)F RQLCJLJVSWUYSK-UHFFFAOYSA-N 0.000 description 2
- KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical compound C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- ZZLCFHIKESPLTH-UHFFFAOYSA-N 4-Methylbiphenyl Chemical compound C1=CC(C)=CC=C1C1=CC=CC=C1 ZZLCFHIKESPLTH-UHFFFAOYSA-N 0.000 description 2
- HLPGDZOFTVZOHC-HNNXBMFYSA-N 4-[2-fluoro-4-[(2s)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pentoxy]phenyl]pyridine-3-carboxylic acid Chemical compound FC1=CC(OC[C@H](CC(C)C)NC(=O)OC(C)(C)C)=CC=C1C1=CC=NC=C1C(O)=O HLPGDZOFTVZOHC-HNNXBMFYSA-N 0.000 description 2
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 description 2
- IMRGVWZLCZERSQ-UHFFFAOYSA-N 4-chloropyridine-3-carboxylic acid Chemical compound OC(=O)C1=CN=CC=C1Cl IMRGVWZLCZERSQ-UHFFFAOYSA-N 0.000 description 2
- DDOFUMWLNSICHU-UHFFFAOYSA-N 5-bromo-4-chloropyridin-2-amine Chemical compound NC1=CC(Cl)=C(Br)C=N1 DDOFUMWLNSICHU-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- RBZXYCOQPBVLCD-UHFFFAOYSA-N 8-chloro-9-(difluoromethyl)-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound C12=CC(C(F)F)=C(Cl)C=C2N(C)C(=O)C2=C1C=CN=C2C RBZXYCOQPBVLCD-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 229940123208 Biguanide Drugs 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- 244000166102 Eucalyptus leucoxylon Species 0.000 description 2
- 235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 2
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 2
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 2
- 108010081348 HRT1 protein Hairy Proteins 0.000 description 2
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- 108010016731 PPAR gamma Proteins 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229940125708 antidiabetic agent Drugs 0.000 description 2
- 239000003524 antilipemic agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 210000004556 brain Anatomy 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- YKPUWZUDDOIDPM-SOFGYWHQSA-N capsaicin Chemical compound COC1=CC(CNC(=O)CCCC\C=C\C(C)C)=CC=C1O YKPUWZUDDOIDPM-SOFGYWHQSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- XMPZTFVPEKAKFH-UHFFFAOYSA-P ceric ammonium nitrate Chemical compound [NH4+].[NH4+].[Ce+4].[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O.[O-][N+]([O-])=O XMPZTFVPEKAKFH-UHFFFAOYSA-P 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 238000004891 communication Methods 0.000 description 2
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 239000010779 crude oil Substances 0.000 description 2
- 125000006254 cycloalkyl carbonyl group Chemical group 0.000 description 2
- NXQGGXCHGDYOHB-UHFFFAOYSA-L cyclopenta-1,4-dien-1-yl(diphenyl)phosphane;dichloropalladium;iron(2+) Chemical compound [Fe+2].Cl[Pd]Cl.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1.[CH-]1C=CC(P(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 NXQGGXCHGDYOHB-UHFFFAOYSA-L 0.000 description 2
- 230000002939 deleterious effect Effects 0.000 description 2
- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 229960004580 glibenclamide Drugs 0.000 description 2
- 239000003862 glucocorticoid Substances 0.000 description 2
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 2
- 125000004692 haloalkylcarbonyl group Chemical group 0.000 description 2
- 125000001475 halogen functional group Chemical group 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 150000004678 hydrides Chemical class 0.000 description 2
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 238000005805 hydroxylation reaction Methods 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 2
- 229960000485 methotrexate Drugs 0.000 description 2
- SNZRPPBWRSEVIU-UHFFFAOYSA-N methyl 4-chloropyridine-3-carboxylate Chemical compound COC(=O)C1=CN=CC=C1Cl SNZRPPBWRSEVIU-UHFFFAOYSA-N 0.000 description 2
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 2
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 238000004305 normal phase HPLC Methods 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 239000005022 packaging material Substances 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- YLHJACXHRQQNQR-UHFFFAOYSA-N pyridine;2,4,6-tris(ethenyl)-1,3,5,2,4,6-trioxatriborinane Chemical compound C1=CC=NC=C1.C=CB1OB(C=C)OB(C=C)O1 YLHJACXHRQQNQR-UHFFFAOYSA-N 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- WVYADZUPLLSGPU-UHFFFAOYSA-N salsalate Chemical compound OC(=O)C1=CC=CC=C1OC(=O)C1=CC=CC=C1O WVYADZUPLLSGPU-UHFFFAOYSA-N 0.000 description 2
- 238000007127 saponification reaction Methods 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 238000009097 single-agent therapy Methods 0.000 description 2
- 238000009491 slugging Methods 0.000 description 2
- 239000002002 slurry Substances 0.000 description 2
- MRTAVLDNYYEJHK-UHFFFAOYSA-M sodium;2-chloro-2,2-difluoroacetate Chemical compound [Na+].[O-]C(=O)C(F)(F)Cl MRTAVLDNYYEJHK-UHFFFAOYSA-M 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 229940037128 systemic glucocorticoids Drugs 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 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
- PZTAGFCBNDBBFZ-UHFFFAOYSA-N tert-butyl 2-(hydroxymethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1CO PZTAGFCBNDBBFZ-UHFFFAOYSA-N 0.000 description 2
- BBVWKZYPGJJDEK-UHFFFAOYSA-N tert-butyl n-(5,5,5-trifluoro-1-hydroxypentan-2-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC(CO)CCC(F)(F)F BBVWKZYPGJJDEK-UHFFFAOYSA-N 0.000 description 2
- WYCWRSAXISKSTL-ZETCQYMHSA-N tert-butyl n-[(2s)-4,4-difluoro-1-hydroxypentan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](CO)CC(C)(F)F WYCWRSAXISKSTL-ZETCQYMHSA-N 0.000 description 2
- XLUYGQSBFHQKOG-HNNXBMFYSA-N tert-butyl n-[(2s)-4-methyl-1-[(5-oxo-6h-benzo[c][2,7]naphthyridin-8-yl)oxy]pentan-2-yl]carbamate Chemical compound N1=CC=C2C3=CC=C(OC[C@H](CC(C)C)NC(=O)OC(C)(C)C)C=C3NC(=O)C2=C1 XLUYGQSBFHQKOG-HNNXBMFYSA-N 0.000 description 2
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- ONDSBJMLAHVLMI-UHFFFAOYSA-N trimethylsilyldiazomethane Chemical compound C[Si](C)(C)[CH-][N+]#N ONDSBJMLAHVLMI-UHFFFAOYSA-N 0.000 description 2
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 2
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
- 239000002691 unilamellar liposome Substances 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 1
- GUHPRPJDBZHYCJ-SECBINFHSA-N (2s)-2-(5-benzoylthiophen-2-yl)propanoic acid Chemical compound S1C([C@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CC=C1 GUHPRPJDBZHYCJ-SECBINFHSA-N 0.000 description 1
- MDKGKXOCJGEUJW-VIFPVBQESA-N (2s)-2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CS1 MDKGKXOCJGEUJW-VIFPVBQESA-N 0.000 description 1
- YHWOMLAFEJVSSA-QMMMGPOBSA-N (2s)-4-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]pent-4-enoic acid Chemical compound CC(=C)C[C@@H](C(O)=O)NC(=O)OC(C)(C)C YHWOMLAFEJVSSA-QMMMGPOBSA-N 0.000 description 1
- QKDRXGFQVGOQKS-CRSSMBPESA-N (2s,3r,4r,5s,6r)-2-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6-methylsulfanyloxane-3,4,5-triol Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](SC)O2)O)=CC=C1Cl QKDRXGFQVGOQKS-CRSSMBPESA-N 0.000 description 1
- OQANPHBRHBJGNZ-FYJGNVAPSA-N (3e)-6-oxo-3-[[4-(pyridin-2-ylsulfamoyl)phenyl]hydrazinylidene]cyclohexa-1,4-diene-1-carboxylic acid Chemical compound C1=CC(=O)C(C(=O)O)=C\C1=N\NC1=CC=C(S(=O)(=O)NC=2N=CC=CC=2)C=C1 OQANPHBRHBJGNZ-FYJGNVAPSA-N 0.000 description 1
- CUTKSWXGYLUSCY-UHFFFAOYSA-N (4-bromo-2,3-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC=C(Br)C(F)=C1F CUTKSWXGYLUSCY-UHFFFAOYSA-N 0.000 description 1
- HMLGSIZOMSVISS-ONJSNURVSA-N (7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2,2-dimethylpropanoyloxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(C=C)CSC21)C(O)=O)=O)C(=O)\C(=N/OCOC(=O)C(C)(C)C)C1=CSC(N)=N1 HMLGSIZOMSVISS-ONJSNURVSA-N 0.000 description 1
- HVNFWZZTYRGCTB-UHFFFAOYSA-N (8-chloro-6-methyl-5-oxobenzo[f][2,7]naphthyridin-4-yl)carbamic acid Chemical compound C1=NC(NC(O)=O)=C2C(=O)N(C)C3=CC(Cl)=CC=C3C2=C1 HVNFWZZTYRGCTB-UHFFFAOYSA-N 0.000 description 1
- ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 description 1
- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 1
- QVXGDUWCYGGRHC-UHFFFAOYSA-N 1-bromo-4-chloro-2,5-difluorobenzene Chemical compound FC1=CC(Br)=C(F)C=C1Cl QVXGDUWCYGGRHC-UHFFFAOYSA-N 0.000 description 1
- VSTXCZGEEVFJES-UHFFFAOYSA-N 1-cycloundecyl-1,5-diazacycloundec-5-ene Chemical compound C1CCCCCC(CCCC1)N1CCCCCC=NCCC1 VSTXCZGEEVFJES-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- JUXCXIKESGMNHC-UHFFFAOYSA-N 1-methyl-6h-benzo[c][2,7]naphthyridin-5-one Chemical compound C12=CC=CC=C2NC(=O)C2=C1C(C)=CN=C2 JUXCXIKESGMNHC-UHFFFAOYSA-N 0.000 description 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- ZESRJSPZRDMNHY-YFWFAHHUSA-N 11-deoxycorticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 ZESRJSPZRDMNHY-YFWFAHHUSA-N 0.000 description 1
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 1
- 238000004293 19F NMR spectroscopy Methods 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 description 1
- LXFQSRIDYRFTJW-UHFFFAOYSA-M 2,4,6-trimethylbenzenesulfonate Chemical compound CC1=CC(C)=C(S([O-])(=O)=O)C(C)=C1 LXFQSRIDYRFTJW-UHFFFAOYSA-M 0.000 description 1
- TYPVHTOETJVYIV-UHFFFAOYSA-N 2,4-dichloropyridine Chemical compound ClC1=CC=NC(Cl)=C1 TYPVHTOETJVYIV-UHFFFAOYSA-N 0.000 description 1
- NBYLBWHHTUWMER-UHFFFAOYSA-N 2-Methylquinolin-8-ol Chemical compound C1=CC=C(O)C2=NC(C)=CC=C21 NBYLBWHHTUWMER-UHFFFAOYSA-N 0.000 description 1
- CWDOPTSHRUOSOF-JTQLQIEISA-N 2-[(2s)-1-hydroxy-4-methylpentan-2-yl]isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N([C@H](CO)CC(C)C)C(=O)C2=C1 CWDOPTSHRUOSOF-JTQLQIEISA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- NXFFJDQHYLNEJK-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1h-cyclopenta[b]indol-3-yl]acetic acid Chemical compound C1=2C(S(=O)(=O)C)=CC(F)=CC=2C=2CCC(CC(O)=O)C=2N1CC1=CC=C(Cl)C=C1 NXFFJDQHYLNEJK-UHFFFAOYSA-N 0.000 description 1
- KTZZIDWVKLDWBF-UHFFFAOYSA-N 2-azaniumyl-5,5,5-trifluoropentanoate Chemical compound OC(=O)C(N)CCC(F)(F)F KTZZIDWVKLDWBF-UHFFFAOYSA-N 0.000 description 1
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical class O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
- 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 1
- CFROLHNCACAAOW-UHFFFAOYSA-N 3,3,3-trifluoropropyl trifluoromethanesulfonate Chemical compound FC(F)(F)CCOS(=O)(=O)C(F)(F)F CFROLHNCACAAOW-UHFFFAOYSA-N 0.000 description 1
- JHUUPUMBZGWODW-UHFFFAOYSA-N 3,6-dihydro-1,2-dioxine Chemical compound C1OOCC=C1 JHUUPUMBZGWODW-UHFFFAOYSA-N 0.000 description 1
- SWLAMJPTOQZTAE-UHFFFAOYSA-N 4-[2-[(5-chloro-2-methoxybenzoyl)amino]ethyl]benzoic acid Chemical class COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(C(O)=O)C=C1 SWLAMJPTOQZTAE-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- WCLAIJOYSIJIIR-UHFFFAOYSA-N 4-amino-8-chloro-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC(N)=C2C(=O)N(C)C3=CC(Cl)=CC=C3C2=C1 WCLAIJOYSIJIIR-UHFFFAOYSA-N 0.000 description 1
- TVZGACDUOSZQKY-LBPRGKRZSA-N 4-aminofolic acid Chemical compound C1=NC2=NC(N)=NC(N)=C2N=C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 TVZGACDUOSZQKY-LBPRGKRZSA-N 0.000 description 1
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- LBUNNMJLXWQQBY-UHFFFAOYSA-N 4-fluorophenylboronic acid Chemical compound OB(O)C1=CC=C(F)C=C1 LBUNNMJLXWQQBY-UHFFFAOYSA-N 0.000 description 1
- PJJGZPJJTHBVMX-UHFFFAOYSA-N 5,7-Dihydroxyisoflavone Chemical compound C=1C(O)=CC(O)=C(C2=O)C=1OC=C2C1=CC=CC=C1 PJJGZPJJTHBVMX-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- UVIHYWTURRDUAZ-ZDUSSCGKSA-N 8-[(2s)-2-amino-4-methylpentoxy]-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound N1=CC=C2C3=CC=C(OC[C@@H](N)CC(C)C)C=C3N(C)C(=O)C2=C1 UVIHYWTURRDUAZ-ZDUSSCGKSA-N 0.000 description 1
- APMVKNUGMWPJEU-UHFFFAOYSA-N 8-chloro-2,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound C12=CC=C(Cl)C=C2N(C)C(=O)C2=C1C=C(C)N=C2 APMVKNUGMWPJEU-UHFFFAOYSA-N 0.000 description 1
- IKLCTUGDLJSEPW-UHFFFAOYSA-N 8-chloro-6-cyclopropylbenzo[c][2,7]naphthyridin-5-one Chemical compound C=1C(Cl)=CC=C(C2=CC=NC=C2C2=O)C=1N2C1CC1 IKLCTUGDLJSEPW-UHFFFAOYSA-N 0.000 description 1
- DKUZJXWZIANASE-UHFFFAOYSA-N 8-chloro-6-methyl-3-oxidobenzo[c][2,7]naphthyridin-3-ium-5-one Chemical compound C1=[N+]([O-])C=C2C(=O)N(C)C3=CC(Cl)=CC=C3C2=C1 DKUZJXWZIANASE-UHFFFAOYSA-N 0.000 description 1
- SMQBXCCDTIHBEP-UHFFFAOYSA-N 8-chloro-6-methyl-5-oxobenzo[f][2,7]naphthyridine-4-carbaldehyde Chemical compound C1=NC(C=O)=C2C(=O)N(C)C3=CC(Cl)=CC=C3C2=C1 SMQBXCCDTIHBEP-UHFFFAOYSA-N 0.000 description 1
- FLMJPJIXMFKKRI-UHFFFAOYSA-N 8-chloro-6-methylbenzo[c][2,7]naphthyridin-5-one Chemical compound C1=NC=C2C(=O)N(C)C3=CC(Cl)=CC=C3C2=C1 FLMJPJIXMFKKRI-UHFFFAOYSA-N 0.000 description 1
- YHAFJWDMWZHBGH-UHFFFAOYSA-N 8-chloro-9-iodo-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound C12=CC(I)=C(Cl)C=C2N(C)C(=O)C2=C1C=CN=C2C YHAFJWDMWZHBGH-UHFFFAOYSA-N 0.000 description 1
- FIMSBRGXBGVHEF-UHFFFAOYSA-N 9-bromo-8-chloro-4,6-dimethylbenzo[c][2,7]naphthyridin-5-one Chemical compound C12=CC(Br)=C(Cl)C=C2N(C)C(=O)C2=C1C=CN=C2C FIMSBRGXBGVHEF-UHFFFAOYSA-N 0.000 description 1
- PQSUYGKTWSAVDQ-ZVIOFETBSA-N Aldosterone Chemical compound C([C@@]1([C@@H](C(=O)CO)CC[C@H]1[C@@H]1CC2)C=O)[C@H](O)[C@@H]1[C@]1(C)C2=CC(=O)CC1 PQSUYGKTWSAVDQ-ZVIOFETBSA-N 0.000 description 1
- PQSUYGKTWSAVDQ-UHFFFAOYSA-N Aldosterone Natural products C1CC2C3CCC(C(=O)CO)C3(C=O)CC(O)C2C2(C)C1=CC(=O)CC2 PQSUYGKTWSAVDQ-UHFFFAOYSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
- MNIPYSSQXLZQLJ-UHFFFAOYSA-N Biofenac Chemical compound OC(=O)COC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl MNIPYSSQXLZQLJ-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- 101100268665 Caenorhabditis elegans acc-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical compound CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 description 1
- JVHXJTBJCFBINQ-ADAARDCZSA-N Dapagliflozin Chemical compound C1=CC(OCC)=CC=C1CC1=CC([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)=CC=C1Cl JVHXJTBJCFBINQ-ADAARDCZSA-N 0.000 description 1
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- 101100224482 Drosophila melanogaster PolE1 gene Proteins 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- 108010008165 Etanercept Proteins 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 102000030914 Fatty Acid-Binding Human genes 0.000 description 1
- 241000982822 Ficus obtusifolia Species 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 241000237858 Gastropoda Species 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- 102000007446 Glucagon-Like Peptide-1 Receptor Human genes 0.000 description 1
- 108010086246 Glucagon-Like Peptide-1 Receptor Proteins 0.000 description 1
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000004366 Glucosidases Human genes 0.000 description 1
- 108010056771 Glucosidases Proteins 0.000 description 1
- 102000007390 Glycogen Phosphorylase Human genes 0.000 description 1
- 108010046163 Glycogen Phosphorylase Proteins 0.000 description 1
- 239000007818 Grignard reagent Substances 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 1
- 101001059454 Homo sapiens Serine/threonine-protein kinase MARK2 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 206010065390 Inflammatory pain Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 229940122199 Insulin secretagogue Drugs 0.000 description 1
- 229940122355 Insulin sensitizer Drugs 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 1
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 1
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- MQHWFIOJQSCFNM-UHFFFAOYSA-L Magnesium salicylate Chemical compound [Mg+2].OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O MQHWFIOJQSCFNM-UHFFFAOYSA-L 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 description 1
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 1
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 238000006411 Negishi coupling reaction Methods 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108010028924 PPAR alpha Proteins 0.000 description 1
- 102000023984 PPAR alpha Human genes 0.000 description 1
- 102000000536 PPAR gamma Human genes 0.000 description 1
- 102100038831 Peroxisome proliferator-activated receptor alpha Human genes 0.000 description 1
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 1
- 102100028904 Serine/threonine-protein kinase MARK2 Human genes 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 238000006619 Stille reaction Methods 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- 229940123464 Thiazolidinedione Drugs 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 1
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 1
- 229960003697 abatacept Drugs 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229960004420 aceclofenac Drugs 0.000 description 1
- 229960004892 acemetacin Drugs 0.000 description 1
- FSQKKOOTNAMONP-UHFFFAOYSA-N acemetacin Chemical compound CC1=C(CC(=O)OCC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 FSQKKOOTNAMONP-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 229960002964 adalimumab Drugs 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229960002478 aldosterone Drugs 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 229960003896 aminopterin Drugs 0.000 description 1
- 229960004238 anakinra Drugs 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 239000000883 anti-obesity agent Substances 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 229940111133 antiinflammatory and antirheumatic drug oxicams Drugs 0.000 description 1
- 229940125710 antiobesity agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000002830 appetite depressant Substances 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229960001671 azapropazone Drugs 0.000 description 1
- WOIIIUDZSOLAIW-NSHDSACASA-N azapropazone Chemical compound C1=C(C)C=C2N3C(=O)[C@H](CC=C)C(=O)N3C(N(C)C)=NC2=C1 WOIIIUDZSOLAIW-NSHDSACASA-N 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- ZZCNKSMCIZCVDR-UHFFFAOYSA-N barium(2+);dioxido(dioxo)manganese Chemical compound [Ba+2].[O-][Mn]([O-])(=O)=O ZZCNKSMCIZCVDR-UHFFFAOYSA-N 0.000 description 1
- 229960004495 beclometasone Drugs 0.000 description 1
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- 229960004277 benorilate Drugs 0.000 description 1
- FEJKLNWAOXSSNR-UHFFFAOYSA-N benorilate Chemical compound C1=CC(NC(=O)C)=CC=C1OC(=O)C1=CC=CC=C1OC(C)=O FEJKLNWAOXSSNR-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- 229940077388 benzenesulfonate 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
- 229940050390 benzoate Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- JVMCONIXUJMNOB-MDWMIUADSA-N benzyl N-[(2R)-1-hydroxy-3-propan-2-yloxypropan-2-yl]carbamate methyl (2S)-2-(phenylmethoxycarbonylamino)-3-propan-2-yloxypropanoate Chemical compound C(C1=CC=CC=C1)OC(=O)N[C@H](C(=O)OC)COC(C)C.OC[C@H](COC(C)C)NC(OCC1=CC=CC=C1)=O JVMCONIXUJMNOB-MDWMIUADSA-N 0.000 description 1
- AFLHSVCECVKLKI-CYBMUJFWSA-N benzyl n-[(2r)-1-hydroxy-3-propan-2-yloxypropan-2-yl]carbamate Chemical compound CC(C)OC[C@@H](CO)NC(=O)OCC1=CC=CC=C1 AFLHSVCECVKLKI-CYBMUJFWSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 1
- JFIOVJDNOJYLKP-UHFFFAOYSA-N bithionol Chemical compound OC1=C(Cl)C=C(Cl)C=C1SC1=CC(Cl)=CC(Cl)=C1O JFIOVJDNOJYLKP-UHFFFAOYSA-N 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 229960003655 bromfenac Drugs 0.000 description 1
- ZBPLOVFIXSTCRZ-UHFFFAOYSA-N bromfenac Chemical compound NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=C(Br)C=C1 ZBPLOVFIXSTCRZ-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
- 229960001713 canagliflozin Drugs 0.000 description 1
- VHOFTEAWFCUTOS-TUGBYPPCSA-N canagliflozin hydrate Chemical compound O.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1.CC1=CC=C([C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C=C1CC(S1)=CC=C1C1=CC=C(F)C=C1 VHOFTEAWFCUTOS-TUGBYPPCSA-N 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 235000017663 capsaicin Nutrition 0.000 description 1
- 229960002504 capsaicin Drugs 0.000 description 1
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
- 229960000623 carbamazepine Drugs 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 229960003184 carprofen Drugs 0.000 description 1
- IVUMCTKHWDRRMH-UHFFFAOYSA-N carprofen Chemical compound C1=CC(Cl)=C[C]2C3=CC=C(C(C(O)=O)C)C=C3N=C21 IVUMCTKHWDRRMH-UHFFFAOYSA-N 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 229960003115 certolizumab pegol Drugs 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960001761 chlorpropamide Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 229940127204 compound 29 Drugs 0.000 description 1
- 229940126540 compound 41 Drugs 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 238000003350 crude synaptosomal preparation Methods 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- 125000006310 cycloalkyl amino group Chemical group 0.000 description 1
- 125000005169 cycloalkylcarbonylamino group Chemical group 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 229960003834 dapagliflozin Drugs 0.000 description 1
- ZESRJSPZRDMNHY-UHFFFAOYSA-N de-oxy corticosterone Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 ZESRJSPZRDMNHY-UHFFFAOYSA-N 0.000 description 1
- 229940119740 deoxycorticosterone Drugs 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- CPELXLSAUQHCOX-DYCDLGHISA-N deuterium bromide Chemical compound [2H]Br CPELXLSAUQHCOX-DYCDLGHISA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 1
- 229960000616 diflunisal Drugs 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 229940120889 dipyrone Drugs 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000000221 dopamine uptake inhibitor Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 229960002866 duloxetine Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002121 endocytic effect Effects 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 229960000403 etanercept Drugs 0.000 description 1
- 229960005293 etodolac Drugs 0.000 description 1
- XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 description 1
- 229960004945 etoricoxib Drugs 0.000 description 1
- MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical compound C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 108091022862 fatty acid binding Proteins 0.000 description 1
- ZPAKPRAICRBAOD-UHFFFAOYSA-N fenbufen Chemical compound C1=CC(C(=O)CCC(=O)O)=CC=C1C1=CC=CC=C1 ZPAKPRAICRBAOD-UHFFFAOYSA-N 0.000 description 1
- 229960001395 fenbufen Drugs 0.000 description 1
- 229960001419 fenoprofen Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 150000004673 fluoride salts Chemical class 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 229960002870 gabapentin Drugs 0.000 description 1
- 229960000346 gliclazide Drugs 0.000 description 1
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
- 229960004346 glimepiride Drugs 0.000 description 1
- ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 1
- 229960001381 glipizide Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 150000002343 gold Chemical class 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000005221 halo alkyl carbonyl amino group Chemical group 0.000 description 1
- 125000004438 haloalkoxy group Chemical group 0.000 description 1
- 125000004992 haloalkylamino group Chemical group 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 description 1
- 229960004171 hydroxychloroquine Drugs 0.000 description 1
- 230000000055 hyoplipidemic effect Effects 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000002348 inosinate dehydrogenase inhibitor Substances 0.000 description 1
- 239000004026 insulin derivative Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 1
- 229960000991 ketoprofen Drugs 0.000 description 1
- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 1
- 229960004752 ketorolac Drugs 0.000 description 1
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
- 229960000681 leflunomide Drugs 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 1
- OXROWJKCGCOJDO-JLHYYAGUSA-N lornoxicam Chemical compound O=C1C=2SC(Cl)=CC=2S(=O)(=O)N(C)\C1=C(\O)NC1=CC=CC=N1 OXROWJKCGCOJDO-JLHYYAGUSA-N 0.000 description 1
- 229960002202 lornoxicam Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229960002373 loxoprofen Drugs 0.000 description 1
- BAZQYVYVKYOAGO-UHFFFAOYSA-M loxoprofen sodium hydrate Chemical compound O.O.[Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 BAZQYVYVKYOAGO-UHFFFAOYSA-M 0.000 description 1
- 229960000994 lumiracoxib Drugs 0.000 description 1
- KHPKQFYUPIUARC-UHFFFAOYSA-N lumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1Cl KHPKQFYUPIUARC-UHFFFAOYSA-N 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229940072082 magnesium salicylate Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- LVKCSZQWLOVUGB-UHFFFAOYSA-M magnesium;propane;bromide Chemical compound [Mg+2].[Br-].C[CH-]C LVKCSZQWLOVUGB-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960003803 meclofenamic acid Drugs 0.000 description 1
- 229960003464 mefenamic acid Drugs 0.000 description 1
- 229950004994 meglitinide Drugs 0.000 description 1
- 229960001929 meloxicam Drugs 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000006263 metalation reaction Methods 0.000 description 1
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- 238000006198 methoxylation reaction Methods 0.000 description 1
- JPPAYRZURRWOMP-ZDUSSCGKSA-N methyl (2s)-2-(phenylmethoxycarbonylamino)-3-propan-2-yloxypropanoate Chemical compound CC(C)OC[C@@H](C(=O)OC)NC(=O)OCC1=CC=CC=C1 JPPAYRZURRWOMP-ZDUSSCGKSA-N 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
- JEJMDUMJSZTJTI-UHFFFAOYSA-N methyl 4,6-dichloropyridine-3-carboxylate Chemical compound COC(=O)C1=CN=C(Cl)C=C1Cl JEJMDUMJSZTJTI-UHFFFAOYSA-N 0.000 description 1
- TVYIWWPHTKGXRU-UHFFFAOYSA-N methyl 4-(4-chloro-2-fluorophenyl)pyridine-3-carboxylate methyl 4-chloropyridine-3-carboxylate Chemical compound ClC1=CC=NC=C1C(=O)OC.ClC1=CC(=C(C=C1)C1=CC=NC=C1C(=O)OC)F TVYIWWPHTKGXRU-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 229960001047 methyl salicylate Drugs 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229960004584 methylprednisolone Drugs 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 229960001110 miglitol Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 description 1
- 229960004023 minocycline Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
- 229960004866 mycophenolate mofetil Drugs 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- UQEIFYRRSNJVDO-UHFFFAOYSA-N n,n-dibenzyl-2-phenylethanamine Chemical compound C=1C=CC=CC=1CN(CC=1C=CC=CC=1)CCC1=CC=CC=C1 UQEIFYRRSNJVDO-UHFFFAOYSA-N 0.000 description 1
- DOYGLPIATUEFFH-UHFFFAOYSA-N n-(6-chloro-4-trimethylstannylpyridin-2-yl)acetamide Chemical compound CC(=O)NC1=CC([Sn](C)(C)C)=CC(Cl)=N1 DOYGLPIATUEFFH-UHFFFAOYSA-N 0.000 description 1
- ZPIDLGSMBZCKGX-UHFFFAOYSA-N n-(8-chloro-6-methyl-5-oxobenzo[c][2,7]naphthyridin-2-yl)acetamide Chemical compound C12=CC=C(Cl)C=C2N(C)C(=O)C2=C1C=C(NC(=O)C)N=C2 ZPIDLGSMBZCKGX-UHFFFAOYSA-N 0.000 description 1
- YBYSYASPLZEJPO-UHFFFAOYSA-N n-(8-chloro-6-methyl-5h-benzo[c][2,7]naphthyridin-2-yl)acetamide Chemical compound C1=C(Cl)C=C2N(C)CC3=CN=C(NC(C)=O)C=C3C2=C1 YBYSYASPLZEJPO-UHFFFAOYSA-N 0.000 description 1
- 229960004270 nabumetone Drugs 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-M naproxen(1-) Chemical compound C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-M 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 230000014511 neuron projection development Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 229960000965 nimesulide Drugs 0.000 description 1
- HYWYRSMBCFDLJT-UHFFFAOYSA-N nimesulide Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1=CC=CC=C1 HYWYRSMBCFDLJT-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002767 noradrenalin uptake inhibitor Substances 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229940046781 other immunosuppressants in atc Drugs 0.000 description 1
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
- 229960002739 oxaprozin Drugs 0.000 description 1
- 150000002916 oxazoles Chemical class 0.000 description 1
- 238000007248 oxidative elimination reaction Methods 0.000 description 1
- 229940105606 oxycontin Drugs 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Chemical group 0.000 description 1
- 229960000649 oxyphenbutazone Drugs 0.000 description 1
- HFHZKZSRXITVMK-UHFFFAOYSA-N oxyphenbutazone Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=C(O)C=C1 HFHZKZSRXITVMK-UHFFFAOYSA-N 0.000 description 1
- YTXAYGAYACWVGD-UHFFFAOYSA-N palladium;hydrate Chemical compound O.[Pd] YTXAYGAYACWVGD-UHFFFAOYSA-N 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229960004662 parecoxib Drugs 0.000 description 1
- TZRHLKRLEZJVIJ-UHFFFAOYSA-N parecoxib Chemical compound C1=CC(S(=O)(=O)NC(=O)CC)=CC=C1C1=C(C)ON=C1C1=CC=CC=C1 TZRHLKRLEZJVIJ-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 229960001639 penicillamine Drugs 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 description 1
- 229960003243 phenformin Drugs 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 229960002895 phenylbutazone Drugs 0.000 description 1
- VYMDGNCVAMGZFE-UHFFFAOYSA-N phenylbutazonum Chemical compound O=C1C(CCCC)C(=O)N(C=2C=CC=CC=2)N1C1=CC=CC=C1 VYMDGNCVAMGZFE-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- PRAYXGYYVXRDDW-UHFFFAOYSA-N piperidin-2-ylmethanol Chemical compound OCC1CCCCN1 PRAYXGYYVXRDDW-UHFFFAOYSA-N 0.000 description 1
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-M pivalate Chemical compound CC(C)(C)C([O-])=O IUGYQRQAERSCNH-UHFFFAOYSA-M 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920002721 polycyanoacrylate Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 description 1
- 229960001233 pregabalin Drugs 0.000 description 1
- GCYXWQUSHADNBF-AAEALURTSA-N preproglucagon 78-108 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 GCYXWQUSHADNBF-AAEALURTSA-N 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000011253 protective coating Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 150000003218 pyrazolidines Chemical class 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 229960002354 repaglinide Drugs 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229960004641 rituximab Drugs 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 150000003902 salicylic acid esters Chemical class 0.000 description 1
- 229960000953 salsalate Drugs 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- LYPGDCWPTHTUDO-UHFFFAOYSA-M sodium;methanesulfinate Chemical compound [Na+].CS([O-])=O LYPGDCWPTHTUDO-UHFFFAOYSA-M 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229960001940 sulfasalazine Drugs 0.000 description 1
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
- 229910052717 sulfur Chemical group 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 229960000894 sulindac Drugs 0.000 description 1
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 229960004492 suprofen Drugs 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 210000002504 synaptic vesicle Anatomy 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- WZWYJBNHTWCXIM-UHFFFAOYSA-N tenoxicam Chemical compound O=C1C=2SC=CC=2S(=O)(=O)N(C)C1=C(O)NC1=CC=CC=N1 WZWYJBNHTWCXIM-UHFFFAOYSA-N 0.000 description 1
- 229960002871 tenoxicam Drugs 0.000 description 1
- YSHDPXQDVKNPKA-UHFFFAOYSA-N tert-butyl 2-(benzhydrylideneamino)acetate Chemical compound C=1C=CC=CC=1C(=NCC(=O)OC(C)(C)C)C1=CC=CC=C1 YSHDPXQDVKNPKA-UHFFFAOYSA-N 0.000 description 1
- NWJFFODDOCUGJT-UHFFFAOYSA-N tert-butyl n-(4-bromo-3-formylpyridin-2-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=NC=CC(Br)=C1C=O NWJFFODDOCUGJT-UHFFFAOYSA-N 0.000 description 1
- QWVXQYZWGQFXPU-UHFFFAOYSA-N tert-butyl n-(4-chloro-3-formylpyridin-2-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=NC=CC(Cl)=C1C=O QWVXQYZWGQFXPU-UHFFFAOYSA-N 0.000 description 1
- XBNCQZKFFSZFBC-MRXNPFEDSA-N tert-butyl n-[(2r)-1-(9-chloro-4,6-dimethyl-5-oxobenzo[c][2,7]naphthyridin-8-yl)oxy-4-methylpentan-2-yl]carbamate Chemical compound CN1C(=O)C2=C(C)N=CC=C2C2=C1C=C(OC[C@@H](CC(C)C)NC(=O)OC(C)(C)C)C(Cl)=C2 XBNCQZKFFSZFBC-MRXNPFEDSA-N 0.000 description 1
- LQTMEOSBXTVYRM-SECBINFHSA-N tert-butyl n-[(2r)-1-hydroxy-4-methylpentan-2-yl]carbamate Chemical compound CC(C)C[C@H](CO)NC(=O)OC(C)(C)C LQTMEOSBXTVYRM-SECBINFHSA-N 0.000 description 1
- KZHQXDJMPXHAQD-SFHVURJKSA-N tert-butyl n-[(2s)-1-(9-ethyl-6-methyl-5-oxobenzo[c][2,7]naphthyridin-8-yl)oxy-4-methylpentan-2-yl]carbamate Chemical compound CN1C(=O)C2=CN=CC=C2C2=C1C=C(OC[C@H](CC(C)C)NC(=O)OC(C)(C)C)C(CC)=C2 KZHQXDJMPXHAQD-SFHVURJKSA-N 0.000 description 1
- YPLXEXQBWUZRJV-QFIPXVFZSA-N tert-butyl n-[(2s)-1-[4-[(4-methoxyphenyl)methylamino]-6-methyl-5-oxobenzo[c][2,7]naphthyridin-8-yl]oxy-4-methylpentan-2-yl]carbamate Chemical compound C1=CC(OC)=CC=C1CNC1=NC=CC2=C1C(=O)N(C)C1=CC(OC[C@H](CC(C)C)NC(=O)OC(C)(C)C)=CC=C12 YPLXEXQBWUZRJV-QFIPXVFZSA-N 0.000 description 1
- GDHLFRCMOIXMKQ-KRWDZBQOSA-N tert-butyl n-[(2s)-1-[6-(2-hydroxyethyl)-5-oxobenzo[c][2,7]naphthyridin-8-yl]oxy-4-methylpentan-2-yl]carbamate Chemical compound N1=CC=C2C3=CC=C(OC[C@H](CC(C)C)NC(=O)OC(C)(C)C)C=C3N(CCO)C(=O)C2=C1 GDHLFRCMOIXMKQ-KRWDZBQOSA-N 0.000 description 1
- PAPDVMYJOYERBZ-IBGZPJMESA-N tert-butyl n-[(2s)-1-[6-(cyclopropylmethyl)-5-oxobenzo[c][2,7]naphthyridin-8-yl]oxy-4-methylpentan-2-yl]carbamate Chemical compound C=1C(OC[C@H](CC(C)C)NC(=O)OC(C)(C)C)=CC=C(C2=CC=NC=C2C2=O)C=1N2CC1CC1 PAPDVMYJOYERBZ-IBGZPJMESA-N 0.000 description 1
- VVCQWEYZOQUNBX-UHFFFAOYSA-N tert-butyl n-[1-(4,6-dimethyl-5-oxobenzo[c][2,7]naphthyridin-8-yl)oxy-2,4-dimethylpentan-2-yl]carbamate Chemical compound N1=CC=C2C3=CC=C(OCC(C)(CC(C)C)NC(=O)OC(C)(C)C)C=C3N(C)C(=O)C2=C1C VVCQWEYZOQUNBX-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 150000001467 thiazolidinediones Chemical class 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229960001312 tiaprofenic acid Drugs 0.000 description 1
- 229960001017 tolmetin Drugs 0.000 description 1
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 229940066528 trichloroacetate Drugs 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- 238000006692 trifluoromethylation reaction Methods 0.000 description 1
- MWKJTNBSKNUMFN-UHFFFAOYSA-N trifluoromethyltrimethylsilane Chemical compound C[Si](C)(C)C(F)(F)F MWKJTNBSKNUMFN-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- FQCQGOZEWWPOKI-UHFFFAOYSA-K trisalicylate-choline Chemical compound [Mg+2].C[N+](C)(C)CCO.OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O.OC1=CC=CC=C1C([O-])=O FQCQGOZEWWPOKI-UHFFFAOYSA-K 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 229960002004 valdecoxib Drugs 0.000 description 1
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- GTLDTDOJJJZVBW-UHFFFAOYSA-N zinc cyanide Chemical compound [Zn+2].N#[C-].N#[C-] GTLDTDOJJJZVBW-UHFFFAOYSA-N 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261677856P | 2012-07-31 | 2012-07-31 | |
| US61/677,856 | 2012-07-31 | ||
| US13/946,344 US8901305B2 (en) | 2012-07-31 | 2013-07-19 | Aryl lactam kinase inhibitors |
| US13/946,344 | 2013-07-19 | ||
| PCT/US2013/051831 WO2014022167A1 (en) | 2012-07-31 | 2013-07-24 | Aryl lactam kinase inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2880523A1 true CA2880523A1 (en) | 2014-02-06 |
Family
ID=50026068
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2880523A Abandoned CA2880523A1 (en) | 2012-07-31 | 2013-07-24 | Aryl lactam kinase inhibitors |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US8901305B2 (enExample) |
| EP (1) | EP2880032B1 (enExample) |
| JP (1) | JP2015528018A (enExample) |
| CN (1) | CN104507941A (enExample) |
| AR (1) | AR093758A1 (enExample) |
| BR (1) | BR112015001890A2 (enExample) |
| CA (1) | CA2880523A1 (enExample) |
| EA (1) | EA201590268A1 (enExample) |
| ES (1) | ES2602965T3 (enExample) |
| MX (1) | MX2015000980A (enExample) |
| TW (1) | TW201410676A (enExample) |
| WO (1) | WO2014022167A1 (enExample) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2016509066A (ja) | 2013-02-22 | 2016-03-24 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | アダプター関連キナーゼ１（ａａｋ１）の阻害剤としての５ｈ−クロメノ［３，４−ｃ］ピリジン |
| WO2015006100A1 (en) | 2013-07-08 | 2015-01-15 | Bristol-Myers Squibb Company | Aryl amide kinase inhibitors |
| ES2678877T3 (es) | 2013-10-11 | 2018-08-20 | Bristol-Myers Squibb Company | Inhibidores de pirrolotriazina quinasa |
| EP3099300B1 (en) * | 2014-01-29 | 2018-09-05 | Bristol-Myers Squibb Company | Aryl lactam kinase inhibitors |
| KR102379518B1 (ko) * | 2014-04-02 | 2022-03-25 | 브리스톨-마이어스 스큅 컴퍼니 | 비아릴 키나제 억제제 |
| EP3292124B1 (en) * | 2015-04-10 | 2019-05-22 | Bristol-Myers Squibb Company | 6h-isochromeno[3,4-c]pyridines and benzo[c][1,7]naphthyridin-6-(5h)-ones as adaptor associated kinase 1 (aak1) inhibitors |
| ES2767776T3 (es) * | 2015-10-01 | 2020-06-18 | Bristol Myers Squibb Co | Inhibidores de biaril cinasa |
| US10544120B2 (en) | 2015-10-01 | 2020-01-28 | Bristol-Myers Squibb Company | Biaryl kinase inhibitors |
| US20230011378A1 (en) * | 2019-08-08 | 2023-01-12 | Institute For Cancer Research D/B/A The Research Institute Of Fox Chase Cancer Center | Combination Therapy For Treatment Of Cancer |
| CN114853664B (zh) * | 2022-06-02 | 2023-09-29 | 河南大学 | 一种钯催化条件下合成α,β-不饱和杂环己基酮类化合物的方法 |
| CN116102542A (zh) * | 2023-02-15 | 2023-05-12 | 如东众意化工有限公司 | 环丙唑醇精制母液中环丙唑醇的回收方法 |
Family Cites Families (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5464764A (en) | 1989-08-22 | 1995-11-07 | University Of Utah Research Foundation | Positive-negative selection methods and vectors |
| WO1993004169A1 (en) | 1991-08-20 | 1993-03-04 | Genpharm International, Inc. | Gene targeting in animal cells using isogenic dna constructs |
| EP0672031B1 (en) | 1992-12-02 | 2003-03-12 | Pfizer Inc. | Catechol diethers as selective pde iv inhibitors |
| US5709861A (en) | 1993-04-22 | 1998-01-20 | Emisphere Technologies, Inc. | Compositions for the delivery of antigens |
| AUPS137402A0 (en) * | 2002-03-26 | 2002-05-09 | Fujisawa Pharmaceutical Co., Ltd. | Novel tricyclic compounds |
| EP1495009B1 (en) | 2002-04-05 | 2008-03-12 | Boehringer Ingelheim Pharmaceuticals Inc. | Cyanamides useful as reversible inhibitors of cysteine proteases |
| WO2004056744A1 (en) | 2002-12-23 | 2004-07-08 | Janssen Pharmaceutica N.V. | Adamantyl acetamides as hydroxysteroid dehydrogenase inhibitors |
| WO2004072018A1 (ja) | 2003-02-12 | 2004-08-26 | Takeda Pharmaceutical Company Limited | アミン誘導体 |
| WO2005000309A2 (en) | 2003-06-27 | 2005-01-06 | Ionix Pharmaceuticals Limited | Chemical compounds |
| RU2006133265A (ru) * | 2004-02-18 | 2008-04-10 | Ф.Хоффманн-Ля Рош Аг (Ch) | Гетероциклические модуляторы, селективные в отношении подтипа рецептора гамка |
| WO2006012227A2 (en) | 2004-06-24 | 2006-02-02 | Incyte Corporation | Amido compounds and their use as pharmaceuticals |
| CN100494167C (zh) | 2005-08-02 | 2009-06-03 | 天津大学 | 抗乙肝病毒的叔胺氧化物及制备方法和制备药物的应用 |
| AU2006326247A1 (en) * | 2005-12-15 | 2007-06-21 | F. Hoffmann-La Roche Ag | Tricyclic lactam derivatives, their manufacture and use as pharmaceutical agents |
| JP2007217408A (ja) | 2006-01-19 | 2007-08-30 | Tanabe Seiyaku Co Ltd | 医薬組成物 |
| EA200801945A1 (ru) * | 2006-03-07 | 2009-02-27 | Бристол-Маерс Сквибб Компани | Пирролотриазинанилиновые пролекарственные соединения, полезные в качестве ингибиторов киназы |
| ES2882684T3 (es) | 2006-04-07 | 2021-12-02 | Vertex Pharma | Preparación de moduladores de transportadores del casete de unión a ATP |
| US20080039535A1 (en) | 2006-08-14 | 2008-02-14 | Wyeth | Methods of identifying agents for treating neurological disorders |
| WO2008079933A2 (en) * | 2006-12-22 | 2008-07-03 | Novartis Ag | Heteroaryl-heteroaryl compounds as cdk inhibitors for the treatment of cancer, inflammation and viral infections |
| US20100292281A1 (en) * | 2009-05-15 | 2010-11-18 | The University Of Kentucky Research Foundation | Treatment of mci and alzheimer's disease |
| FR2955109B1 (fr) * | 2010-01-08 | 2012-09-07 | Sanofi Aventis | Derives de 5-oxo-5,8-dihydro-pyrido[2, 3-d]pyrimidine, leur preparation et leur application en therapeutique |
| CN102918045A (zh) * | 2010-03-31 | 2013-02-06 | 百时美施贵宝公司 | 作为蛋白激酶抑制剂的取代的吡咯并三嗪 |
| PL2834243T3 (pl) | 2012-03-09 | 2018-09-28 | Lexicon Pharmaceuticals, Inc. | Związki na bazie pirazolo[1,5-a]pirymidyny, zawierające je kompozycje i sposoby ich zastosowania |
| WO2013134219A1 (en) | 2012-03-09 | 2013-09-12 | Lexicon Pharmaceuticals, Inc. | Imidazo [1, 2 - b] pyridazine - based compounds, compositions comprising them, and uses thereof |
| US8703953B2 (en) | 2012-03-09 | 2014-04-22 | Bristol-Myers Squibb Company | Aryl ether-base kinase inhibitors |
| HUE036040T2 (hu) | 2012-03-09 | 2018-06-28 | Lexicon Pharmaceuticals Inc | Adaptor-asszociált kináz 1 gátlása fájdalom kezelésére |
-
2013
- 2013-07-19 US US13/946,344 patent/US8901305B2/en active Active
- 2013-07-24 JP JP2015525460A patent/JP2015528018A/ja not_active Withdrawn
- 2013-07-24 CA CA2880523A patent/CA2880523A1/en not_active Abandoned
- 2013-07-24 EA EA201590268A patent/EA201590268A1/ru unknown
- 2013-07-24 MX MX2015000980A patent/MX2015000980A/es unknown
- 2013-07-24 ES ES13744927.8T patent/ES2602965T3/es active Active
- 2013-07-24 EP EP13744927.8A patent/EP2880032B1/en active Active
- 2013-07-24 WO PCT/US2013/051831 patent/WO2014022167A1/en not_active Ceased
- 2013-07-24 BR BR112015001890A patent/BR112015001890A2/pt not_active Application Discontinuation
- 2013-07-24 CN CN201380041073.9A patent/CN104507941A/zh active Pending
- 2013-07-30 TW TW102127296A patent/TW201410676A/zh unknown
- 2013-07-31 AR ARP130102716A patent/AR093758A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN104507941A (zh) | 2015-04-08 |
| TW201410676A (zh) | 2014-03-16 |
| WO2014022167A1 (en) | 2014-02-06 |
| MX2015000980A (es) | 2015-04-10 |
| BR112015001890A2 (pt) | 2017-07-04 |
| US8901305B2 (en) | 2014-12-02 |
| ES2602965T3 (es) | 2017-02-23 |
| EP2880032B1 (en) | 2016-10-05 |
| AR093758A1 (es) | 2015-06-24 |
| EP2880032A1 (en) | 2015-06-10 |
| JP2015528018A (ja) | 2015-09-24 |
| EA201590268A1 (ru) | 2015-05-29 |
| US20140038999A1 (en) | 2014-02-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8901305B2 (en) | Aryl lactam kinase inhibitors | |
| JP7754846B2 (ja) | ミエロイド細胞に発現するトリガー受容体２アゴニストとしてのヘテロ環化合物及び使用方法 | |
| JP6276865B2 (ja) | アリールラクタムキナーゼ阻害剤 | |
| EP2822952B1 (en) | Aryl ether-base kinase inhibitors | |
| EP3044226B1 (en) | Aryl ether-base kinase inhibitors | |
| EP3099673B1 (en) | Quinoline-based kinase inhibitors | |
| EP3200797A1 (en) | Quinazoline-based kinase inhibitors | |
| WO2017059080A1 (en) | Biaryl kinase inhibitors | |
| EP2958924B1 (en) | 5h-chromeno[3,4-c]pyridines as inhibitors of adaptor associated kinase 1 (aak1) | |
| CA3002930A1 (en) | Pyranodipyridine compound | |
| EP3292124B1 (en) | 6h-isochromeno[3,4-c]pyridines and benzo[c][1,7]naphthyridin-6-(5h)-ones as adaptor associated kinase 1 (aak1) inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20160722 |
|
| FZDE | Discontinued |
Effective date: 20180724 |