CN110214137A - 作为αv整联蛋白拮抗剂的吲唑衍生物 - Google Patents
作为αv整联蛋白拮抗剂的吲唑衍生物 Download PDFInfo
- Publication number
- CN110214137A CN110214137A CN201780082125.5A CN201780082125A CN110214137A CN 110214137 A CN110214137 A CN 110214137A CN 201780082125 A CN201780082125 A CN 201780082125A CN 110214137 A CN110214137 A CN 110214137A
- Authority
- CN
- China
- Prior art keywords
- base
- tetrahydro
- naphthyridines
- indazole
- propionic acid
- 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.)
- Pending
Links
- 108010044426 integrins Proteins 0.000 title abstract description 29
- 102000006495 integrins Human genes 0.000 title abstract description 29
- 239000005557 antagonist Substances 0.000 title abstract description 7
- 125000003453 indazolyl group Chemical class N1N=C(C2=C1C=CC=C2)* 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 144
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 48
- 150000003839 salts Chemical class 0.000 claims abstract description 42
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 23
- 201000010099 disease Diseases 0.000 claims abstract description 20
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 19
- 206010016654 Fibrosis Diseases 0.000 claims abstract description 16
- 230000004761 fibrosis Effects 0.000 claims abstract description 15
- 201000011510 cancer Diseases 0.000 claims abstract description 13
- 230000001575 pathological effect Effects 0.000 claims abstract description 6
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 3
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 3
- 206010052779 Transplant rejections Diseases 0.000 claims abstract 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 332
- -1 cyano, hydroxyl Chemical group 0.000 claims description 187
- 235000019260 propionic acid Nutrition 0.000 claims description 166
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 166
- ZCZVGQCBSJLDDS-UHFFFAOYSA-N 1,2,3,4-tetrahydro-1,8-naphthyridine Chemical class C1=CC=C2CCCNC2=N1 ZCZVGQCBSJLDDS-UHFFFAOYSA-N 0.000 claims description 164
- 125000000217 alkyl group Chemical group 0.000 claims description 107
- 238000000034 method Methods 0.000 claims description 79
- 125000003118 aryl group Chemical group 0.000 claims description 69
- 125000000623 heterocyclic group Chemical group 0.000 claims description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims description 51
- 125000003545 alkoxy group Chemical group 0.000 claims description 49
- 125000001072 heteroaryl group Chemical group 0.000 claims description 47
- 239000001257 hydrogen Substances 0.000 claims description 47
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 31
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 30
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 125000004043 oxo group Chemical group O=* 0.000 claims description 26
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 22
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 22
- 125000004429 atom Chemical group 0.000 claims description 21
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 17
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 16
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 15
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims description 15
- 125000004104 aryloxy group Chemical group 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 14
- 239000004475 Arginine Substances 0.000 claims description 13
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 13
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 13
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 13
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 13
- 150000003254 radicals Chemical class 0.000 claims description 13
- 229940124530 sulfonamide Drugs 0.000 claims description 12
- 150000003456 sulfonamides Chemical class 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 11
- 125000003368 amide group Chemical group 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 11
- 125000002837 carbocyclic group Chemical group 0.000 claims description 10
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 6
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 6
- 210000004185 liver Anatomy 0.000 claims description 6
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 5
- 229910003827 NRaRb Inorganic materials 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 210000003734 kidney Anatomy 0.000 claims description 5
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
- 201000009594 Systemic Scleroderma Diseases 0.000 claims description 4
- 206010042953 Systemic sclerosis Diseases 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- 125000000637 arginyl group Chemical group N[C@@H](CCCNC(N)=N)C(=O)* 0.000 claims description 4
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 4
- 210000004072 lung Anatomy 0.000 claims description 4
- 210000000496 pancreas Anatomy 0.000 claims description 4
- 210000003491 skin Anatomy 0.000 claims description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 3
- 210000004369 blood Anatomy 0.000 claims description 3
- 239000008280 blood Substances 0.000 claims description 3
- 208000020832 chronic kidney disease Diseases 0.000 claims description 3
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 210000003739 neck Anatomy 0.000 claims description 3
- 210000002784 stomach Anatomy 0.000 claims description 3
- 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 2
- 208000000277 Splenic Neoplasms Diseases 0.000 claims description 2
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 2
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 2
- 206010057644 Testis cancer Diseases 0.000 claims description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
- 210000000988 bone and bone Anatomy 0.000 claims description 2
- 210000004556 brain Anatomy 0.000 claims description 2
- 210000003169 central nervous system Anatomy 0.000 claims description 2
- 210000001072 colon Anatomy 0.000 claims description 2
- 210000001508 eye Anatomy 0.000 claims description 2
- 210000000232 gallbladder Anatomy 0.000 claims description 2
- 206010017758 gastric cancer Diseases 0.000 claims description 2
- 210000004392 genitalia Anatomy 0.000 claims description 2
- 210000003128 head Anatomy 0.000 claims description 2
- 210000002216 heart Anatomy 0.000 claims description 2
- 210000002429 large intestine Anatomy 0.000 claims description 2
- 201000011061 large intestine cancer Diseases 0.000 claims description 2
- 210000000867 larynx Anatomy 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 210000001672 ovary Anatomy 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 210000002307 prostate Anatomy 0.000 claims description 2
- 201000000849 skin cancer Diseases 0.000 claims description 2
- 210000000813 small intestine Anatomy 0.000 claims description 2
- 201000002314 small intestine cancer Diseases 0.000 claims description 2
- 210000000952 spleen Anatomy 0.000 claims description 2
- 201000002471 spleen cancer Diseases 0.000 claims description 2
- 201000011549 stomach cancer Diseases 0.000 claims description 2
- 201000003120 testicular cancer Diseases 0.000 claims description 2
- 201000002510 thyroid cancer Diseases 0.000 claims description 2
- 210000003932 urinary bladder Anatomy 0.000 claims description 2
- IWTFOFMTUOBLHG-UHFFFAOYSA-N 2-methoxypyridine Chemical compound COC1=CC=CC=N1 IWTFOFMTUOBLHG-UHFFFAOYSA-N 0.000 claims 24
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 22
- 150000003851 azoles Chemical class 0.000 claims 21
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 14
- XSCHRSMBECNVNS-UHFFFAOYSA-N quinoxaline Chemical compound N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 claims 14
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims 10
- LNJMHEJAYSYZKK-UHFFFAOYSA-N 2-methylpyrimidine Chemical compound CC1=NC=CC=N1 LNJMHEJAYSYZKK-UHFFFAOYSA-N 0.000 claims 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 6
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims 6
- 150000002431 hydrogen Chemical group 0.000 claims 5
- 125000006091 1,3-dioxolane group Chemical class 0.000 claims 4
- YLZYSVYZMDJYOT-UHFFFAOYSA-N 2-methoxypyrimidine Chemical compound COC1=NC=CC=N1 YLZYSVYZMDJYOT-UHFFFAOYSA-N 0.000 claims 4
- QQVXDMFULJVZLA-UHFFFAOYSA-N 3,4-dihydro-2h-pyrido[3,2-b][1,4]oxazine Chemical class C1=CN=C2NCCOC2=C1 QQVXDMFULJVZLA-UHFFFAOYSA-N 0.000 claims 4
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 claims 4
- HBWCJMBLUCNJIS-UHFFFAOYSA-N 7-methyl-1,2,3,4-tetrahydro-1,8-naphthyridine Chemical class C1CCNC2=NC(C)=CC=C21 HBWCJMBLUCNJIS-UHFFFAOYSA-N 0.000 claims 3
- UZVGSSNIUNSOFA-UHFFFAOYSA-N dibenzofuran-1-carboxylic acid Chemical compound O1C2=CC=CC=C2C2=C1C=CC=C2C(=O)O UZVGSSNIUNSOFA-UHFFFAOYSA-N 0.000 claims 3
- 150000002240 furans Chemical class 0.000 claims 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 3
- YEYHFKBVNARCNE-UHFFFAOYSA-N pyrido[2,3-b]pyrazine Chemical compound N1=CC=NC2=CC=CN=C21 YEYHFKBVNARCNE-UHFFFAOYSA-N 0.000 claims 3
- 150000003230 pyrimidines Chemical class 0.000 claims 3
- 150000005058 1,8-naphthyridines Chemical class 0.000 claims 2
- GVLRTOYGRNLSDW-UHFFFAOYSA-N 1h-pyrazolo[3,4-b]pyridine Chemical compound C1=CC=C2C=NNC2=N1 GVLRTOYGRNLSDW-UHFFFAOYSA-N 0.000 claims 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 2
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims 2
- ABADUMLIAZCWJD-UHFFFAOYSA-N 1,3-dioxole Chemical compound C1OC=CO1 ABADUMLIAZCWJD-UHFFFAOYSA-N 0.000 claims 1
- HIZVCIIORGCREW-UHFFFAOYSA-N 1,4-dioxene Chemical compound C1COC=CO1 HIZVCIIORGCREW-UHFFFAOYSA-N 0.000 claims 1
- UKPBWLDHWHLVFV-UHFFFAOYSA-N 1-methyl-3,4-dihydro-2h-pyridine Chemical compound CN1CCCC=C1 UKPBWLDHWHLVFV-UHFFFAOYSA-N 0.000 claims 1
- KRHZROBTVNDYNW-UHFFFAOYSA-N 1-methylimidazo[4,5-b]pyridine Chemical compound C1=CC=C2N(C)C=NC2=N1 KRHZROBTVNDYNW-UHFFFAOYSA-N 0.000 claims 1
- AZWPZEGGNCFEKN-UHFFFAOYSA-N 1-methylpyrazolo[3,4-b]pyridine Chemical compound C1=CN=C2N(C)N=CC2=C1 AZWPZEGGNCFEKN-UHFFFAOYSA-N 0.000 claims 1
- MAJMPAMZRGVCDH-UHFFFAOYSA-N 1-methylpyrazolo[4,3-b]pyridine Chemical compound C1=CC=C2N(C)N=CC2=N1 MAJMPAMZRGVCDH-UHFFFAOYSA-N 0.000 claims 1
- DVVGIUUJYPYENY-UHFFFAOYSA-N 1-methylpyridin-2-one Chemical compound CN1C=CC=CC1=O DVVGIUUJYPYENY-UHFFFAOYSA-N 0.000 claims 1
- BDMFEFZOOOYCKN-UHFFFAOYSA-N 1-propylpyrazole Chemical compound CCCN1C=CC=N1 BDMFEFZOOOYCKN-UHFFFAOYSA-N 0.000 claims 1
- AMFYRKOUWBAGHV-UHFFFAOYSA-N 1h-pyrazolo[4,3-b]pyridine Chemical compound C1=CN=C2C=NNC2=C1 AMFYRKOUWBAGHV-UHFFFAOYSA-N 0.000 claims 1
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical class C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims 1
- PKZOFECOOLMHMG-UHFFFAOYSA-N 2-fluoro-6-methoxypyridine Chemical compound COC1=CC=CC(F)=N1 PKZOFECOOLMHMG-UHFFFAOYSA-N 0.000 claims 1
- DXYYSGDWQCSKKO-UHFFFAOYSA-N 2-methylbenzothiazole Chemical compound C1=CC=C2SC(C)=NC2=C1 DXYYSGDWQCSKKO-UHFFFAOYSA-N 0.000 claims 1
- QLFIVKKMICXCNV-UHFFFAOYSA-N 2-methylpyrazolo[3,4-b]pyridine Chemical compound C1=CC=NC2=NN(C)C=C21 QLFIVKKMICXCNV-UHFFFAOYSA-N 0.000 claims 1
- JACRXWMMHCSSKE-UHFFFAOYSA-N 2-methylpyrazolo[4,3-b]pyridine Chemical compound N1=CC=CC2=NN(C)C=C21 JACRXWMMHCSSKE-UHFFFAOYSA-N 0.000 claims 1
- XXTPHXNBKRVYJI-UHFFFAOYSA-N 2-pyrazol-1-ylpyridine Chemical compound C1=CC=NN1C1=CC=CC=N1 XXTPHXNBKRVYJI-UHFFFAOYSA-N 0.000 claims 1
- SDXAWLJRERMRKF-UHFFFAOYSA-N 3,5-dimethyl-1h-pyrazole Chemical compound CC=1C=C(C)NN=1 SDXAWLJRERMRKF-UHFFFAOYSA-N 0.000 claims 1
- OPBDSRFLAMJZFP-UHFFFAOYSA-N 3-cyclopropylpyridine Chemical compound C1CC1C1=CC=CN=C1 OPBDSRFLAMJZFP-UHFFFAOYSA-N 0.000 claims 1
- XAUBEYHIVLSHOG-UHFFFAOYSA-N 3-methylimidazo[4,5-b]pyridine Chemical compound C1=CN=C2N(C)C=NC2=C1 XAUBEYHIVLSHOG-UHFFFAOYSA-N 0.000 claims 1
- LSBIUXKNVUBKRI-UHFFFAOYSA-N 4,6-dimethylpyrimidine Chemical compound CC1=CC(C)=NC=N1 LSBIUXKNVUBKRI-UHFFFAOYSA-N 0.000 claims 1
- FFSZVTIOFCMLGM-UHFFFAOYSA-N 4-pyrazin-2-ylmorpholine Chemical compound C1COCCN1C1=CN=CC=N1 FFSZVTIOFCMLGM-UHFFFAOYSA-N 0.000 claims 1
- BVQQFKCDQYLYFN-UHFFFAOYSA-N 4-pyrazol-1-ylpyridine Chemical class C1=CC=NN1C1=CC=NC=C1 BVQQFKCDQYLYFN-UHFFFAOYSA-N 0.000 claims 1
- DUIMWXDLDBNUFD-UHFFFAOYSA-N 4-pyrimidin-2-ylmorpholine Chemical compound C1COCCN1C1=NC=CC=N1 DUIMWXDLDBNUFD-UHFFFAOYSA-N 0.000 claims 1
- WJRKNLONLOMALV-UHFFFAOYSA-N 5-chloropyridine Chemical compound ClC1=C=NC=C[CH]1 WJRKNLONLOMALV-UHFFFAOYSA-N 0.000 claims 1
- FZDZPCPNMZUIRW-UHFFFAOYSA-N 5-methoxypyrazine Chemical compound COC1=C=NC=C[N]1 FZDZPCPNMZUIRW-UHFFFAOYSA-N 0.000 claims 1
- GXWNSJYVSIJRLS-UHFFFAOYSA-N 6-bromo-8-methylimidazo[1,2-a]pyrazine Chemical compound CC1=NC(Br)=CN2C=CN=C12 GXWNSJYVSIJRLS-UHFFFAOYSA-N 0.000 claims 1
- BHHMPZQRVWVAAR-UHFFFAOYSA-N 7-bromo-8-methylpyrido[2,3-b]pyrazine Chemical compound C1=CN=C2C(C)=C(Br)C=NC2=N1 BHHMPZQRVWVAAR-UHFFFAOYSA-N 0.000 claims 1
- 206010066786 Diabetic keratopathy Diseases 0.000 claims 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims 1
- WKSXRWSOSLGSTN-UHFFFAOYSA-N Methoxypyrazine Chemical compound COC1=CN=CC=N1 WKSXRWSOSLGSTN-UHFFFAOYSA-N 0.000 claims 1
- UQFQONCQIQEYPJ-UHFFFAOYSA-N N-methylpyrazole Chemical class CN1C=CC=N1 UQFQONCQIQEYPJ-UHFFFAOYSA-N 0.000 claims 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical class C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims 1
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical class C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 1
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 claims 1
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims 1
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims 1
- 210000004696 endometrium Anatomy 0.000 claims 1
- 239000000835 fiber Substances 0.000 claims 1
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims 1
- 210000005075 mammary gland Anatomy 0.000 claims 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims 1
- BQNXHDSGGRTFNX-UHFFFAOYSA-N n-methylpyrimidin-2-amine Chemical compound CNC1=NC=CC=N1 BQNXHDSGGRTFNX-UHFFFAOYSA-N 0.000 claims 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims 1
- 210000001550 testis Anatomy 0.000 claims 1
- 229930192474 thiophene Natural products 0.000 claims 1
- 208000035475 disorder Diseases 0.000 abstract description 27
- 239000012453 solvate Substances 0.000 abstract description 22
- 230000008482 dysregulation Effects 0.000 abstract description 4
- 239000000543 intermediate Substances 0.000 description 276
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 171
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 157
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 142
- 239000000203 mixture Substances 0.000 description 134
- 238000005481 NMR spectroscopy Methods 0.000 description 124
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 91
- 239000000243 solution Substances 0.000 description 90
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 89
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 87
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 81
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 71
- 238000006243 chemical reaction Methods 0.000 description 53
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- 235000019439 ethyl acetate Nutrition 0.000 description 39
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
- 239000003814 drug Substances 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 29
- 125000004432 carbon atom Chemical group C* 0.000 description 29
- 125000000753 cycloalkyl group Chemical group 0.000 description 29
- 239000002904 solvent Substances 0.000 description 28
- 229940124597 therapeutic agent Drugs 0.000 description 27
- 125000005843 halogen group Chemical group 0.000 description 26
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 25
- 238000003818 flash chromatography Methods 0.000 description 25
- 125000001188 haloalkyl group Chemical group 0.000 description 25
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 24
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 23
- 239000005695 Ammonium acetate Substances 0.000 description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 22
- 235000019257 ammonium acetate Nutrition 0.000 description 22
- 229940043376 ammonium acetate Drugs 0.000 description 22
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
- 238000002953 preparative HPLC Methods 0.000 description 21
- 239000000651 prodrug Substances 0.000 description 20
- 229940002612 prodrug Drugs 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 19
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 18
- 238000000746 purification Methods 0.000 description 18
- 125000001424 substituent group Chemical group 0.000 description 18
- 239000012267 brine Substances 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 16
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 150000002148 esters Chemical group 0.000 description 15
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 15
- 239000002245 particle Substances 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 15
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 239000012043 crude product Substances 0.000 description 13
- 239000000377 silicon dioxide Substances 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- 238000003786 synthesis reaction Methods 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 12
- 239000002585 base Substances 0.000 description 12
- 229910052681 coesite Inorganic materials 0.000 description 12
- 229910052906 cristobalite Inorganic materials 0.000 description 12
- 239000003937 drug carrier Substances 0.000 description 12
- 125000005842 heteroatom Chemical group 0.000 description 12
- 239000003112 inhibitor Substances 0.000 description 12
- 125000002950 monocyclic group Chemical group 0.000 description 12
- 125000004433 nitrogen atom Chemical group N* 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- 235000012239 silicon dioxide Nutrition 0.000 description 12
- 229910052682 stishovite Inorganic materials 0.000 description 12
- 229910052905 tridymite Inorganic materials 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- 229910000024 caesium carbonate Inorganic materials 0.000 description 11
- 239000003153 chemical reaction reagent Substances 0.000 description 11
- 125000004438 haloalkoxy group Chemical group 0.000 description 11
- 229910052938 sodium sulfate Inorganic materials 0.000 description 11
- 235000011152 sodium sulphate Nutrition 0.000 description 11
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 10
- 125000002947 alkylene group Chemical group 0.000 description 10
- 238000004128 high performance liquid chromatography Methods 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 9
- 239000007832 Na2SO4 Substances 0.000 description 9
- 238000003556 assay Methods 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 150000001721 carbon Chemical group 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 229910052786 argon Inorganic materials 0.000 description 8
- 238000010511 deprotection reaction Methods 0.000 description 8
- 230000003176 fibrotic effect Effects 0.000 description 8
- 125000004404 heteroalkyl group Chemical group 0.000 description 8
- 230000002062 proliferating effect Effects 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 description 7
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 7
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 7
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 7
- 125000002619 bicyclic group Chemical group 0.000 description 7
- 125000005884 carbocyclylalkyl group Chemical group 0.000 description 7
- 229910052801 chlorine Inorganic materials 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 230000007062 hydrolysis Effects 0.000 description 7
- 238000006460 hydrolysis reaction Methods 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
- RUVAJUODOYPQDW-UHFFFAOYSA-N OC=1C=C2C=NN(C2=CC=1)C(=O)OC(C)(C)C Chemical compound OC=1C=C2C=NN(C2=CC=1)C(=O)OC(C)(C)C RUVAJUODOYPQDW-UHFFFAOYSA-N 0.000 description 6
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 6
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 6
- 150000007513 acids Chemical class 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 6
- 238000007792 addition Methods 0.000 description 6
- 125000004414 alkyl thio group Chemical group 0.000 description 6
- 230000008485 antagonism Effects 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 238000002868 homogeneous time resolved fluorescence Methods 0.000 description 6
- 150000002430 hydrocarbons Chemical class 0.000 description 6
- 230000002757 inflammatory effect Effects 0.000 description 6
- 239000003446 ligand Substances 0.000 description 6
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 238000010898 silica gel chromatography Methods 0.000 description 6
- 238000006467 substitution reaction Methods 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 150000001299 aldehydes Chemical class 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- 235000011114 ammonium hydroxide Nutrition 0.000 description 5
- 125000002618 bicyclic heterocycle group Chemical group 0.000 description 5
- FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 5
- 208000019425 cirrhosis of liver Diseases 0.000 description 5
- 238000001514 detection method Methods 0.000 description 5
- 125000002541 furyl group Chemical group 0.000 description 5
- 125000002971 oxazolyl group Chemical group 0.000 description 5
- 125000003367 polycyclic group Chemical group 0.000 description 5
- 235000015320 potassium carbonate Nutrition 0.000 description 5
- 125000004076 pyridyl group Chemical group 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 5
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 5
- 238000002560 therapeutic procedure Methods 0.000 description 5
- 125000001544 thienyl group Chemical group 0.000 description 5
- 230000009466 transformation Effects 0.000 description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
- 238000007341 Heck reaction Methods 0.000 description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 4
- 102000003816 Interleukin-13 Human genes 0.000 description 4
- 108090000176 Interleukin-13 Proteins 0.000 description 4
- 238000006845 Michael addition reaction Methods 0.000 description 4
- 125000001931 aliphatic group Chemical group 0.000 description 4
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 4
- 239000000908 ammonium hydroxide Substances 0.000 description 4
- 238000006254 arylation reaction Methods 0.000 description 4
- 238000005966 aza-Michael addition reaction Methods 0.000 description 4
- 125000002527 bicyclic carbocyclic group Chemical group 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 125000004093 cyano group Chemical group *C#N 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 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 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000010931 ester hydrolysis Methods 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 208000006454 hepatitis Diseases 0.000 description 4
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 125000002883 imidazolyl group Chemical group 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 125000002757 morpholinyl group Chemical group 0.000 description 4
- 125000000160 oxazolidinyl group Chemical group 0.000 description 4
- 125000004430 oxygen atom Chemical group O* 0.000 description 4
- 239000004033 plastic Substances 0.000 description 4
- 229920003023 plastic Polymers 0.000 description 4
- VVWRJUBEIPHGQF-MDZDMXLPSA-N propan-2-yl (ne)-n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)\N=N\C(=O)OC(C)C VVWRJUBEIPHGQF-MDZDMXLPSA-N 0.000 description 4
- 238000000159 protein binding assay Methods 0.000 description 4
- 125000003226 pyrazolyl group Chemical group 0.000 description 4
- 125000004434 sulfur atom Chemical group 0.000 description 4
- 238000013268 sustained release Methods 0.000 description 4
- 239000012730 sustained-release form Substances 0.000 description 4
- 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 4
- 125000003831 tetrazolyl group Chemical group 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 125000000335 thiazolyl group Chemical group 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 238000000844 transformation Methods 0.000 description 4
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 4
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 3
- 125000004008 6 membered carbocyclic group Chemical group 0.000 description 3
- 102220617587 B1 bradykinin receptor_E13D_mutation Human genes 0.000 description 3
- 102220473808 Beta-adrenergic receptor kinase 1_E14A_mutation Human genes 0.000 description 3
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 102220502369 Golgin subfamily A member 1_E11A_mutation Human genes 0.000 description 3
- 229910004373 HOAc Inorganic materials 0.000 description 3
- 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 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 229910019020 PtO2 Inorganic materials 0.000 description 3
- 208000034189 Sclerosis Diseases 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000003973 alkyl amines Chemical class 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 235000019270 ammonium chloride Nutrition 0.000 description 3
- 125000004658 aryl carbonyl amino group Chemical group 0.000 description 3
- 125000005110 aryl thio group Chemical group 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 3
- 125000005605 benzo group Chemical group 0.000 description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 125000000392 cycloalkenyl group Chemical group 0.000 description 3
- NLUNLVTVUDIHFE-UHFFFAOYSA-N cyclooctylcyclooctane Chemical compound C1CCCCCCC1C1CCCCCCC1 NLUNLVTVUDIHFE-UHFFFAOYSA-N 0.000 description 3
- 238000011033 desalting Methods 0.000 description 3
- 208000033679 diabetic kidney disease Diseases 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 125000002632 imidazolidinyl group Chemical group 0.000 description 3
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 3
- 125000001041 indolyl group Chemical group 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 208000002551 irritable bowel syndrome Diseases 0.000 description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 3
- 125000000842 isoxazolyl group Chemical group 0.000 description 3
- 208000017169 kidney disease Diseases 0.000 description 3
- 208000032839 leukemia Diseases 0.000 description 3
- XIXADJRWDQXREU-UHFFFAOYSA-M lithium acetate Chemical compound [Li+].CC([O-])=O XIXADJRWDQXREU-UHFFFAOYSA-M 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 125000001624 naphthyl group Chemical group 0.000 description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 description 3
- 239000007800 oxidant agent Substances 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 239000000123 paper Substances 0.000 description 3
- 125000004193 piperazinyl group Chemical group 0.000 description 3
- 125000003386 piperidinyl group Chemical group 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 125000003373 pyrazinyl group Chemical group 0.000 description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 3
- 125000000168 pyrrolyl group Chemical group 0.000 description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 238000004007 reversed phase HPLC Methods 0.000 description 3
- 102220287679 rs760609798 Human genes 0.000 description 3
- 102220096711 rs876659744 Human genes 0.000 description 3
- 238000002821 scintillation proximity assay Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 3
- 150000003573 thiols Chemical class 0.000 description 3
- 238000002054 transplantation Methods 0.000 description 3
- 125000004306 triazinyl group Chemical group 0.000 description 3
- 125000001425 triazolyl group Chemical group 0.000 description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 2
- OQJBFFCUFALWQL-BUHFOSPRSA-N (ne)-n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)\N=N\C(=O)N1CCCCC1 OQJBFFCUFALWQL-BUHFOSPRSA-N 0.000 description 2
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 2
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 125000005955 1H-indazolyl group Chemical group 0.000 description 2
- ZHDXWEPRYNHNDC-UHFFFAOYSA-N 1h-indazol-5-ol Chemical compound OC1=CC=C2NN=CC2=C1 ZHDXWEPRYNHNDC-UHFFFAOYSA-N 0.000 description 2
- LWMBPKJYEQGDLN-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;piperazine;hydrate Chemical compound O.C1CNCCN1.C1CNCCN1.C1CNCCN1.OC(=O)CC(O)(C(O)=O)CC(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O LWMBPKJYEQGDLN-UHFFFAOYSA-N 0.000 description 2
- KJIODOACRIRBPB-UHFFFAOYSA-N 4-bromo-1h-indazole Chemical compound BrC1=CC=CC2=C1C=NN2 KJIODOACRIRBPB-UHFFFAOYSA-N 0.000 description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 2
- IRPVABHDSJVBNZ-RTHVDDQRSA-N 5-[1-(cyclopropylmethyl)-5-[(1R,5S)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl]pyrazol-3-yl]-3-(trifluoromethyl)pyridin-2-amine Chemical compound C1=C(C(F)(F)F)C(N)=NC=C1C1=NN(CC2CC2)C(C2[C@@H]3CN(C[C@@H]32)C2COC2)=C1 IRPVABHDSJVBNZ-RTHVDDQRSA-N 0.000 description 2
- XADICJHFELMBGX-UHFFFAOYSA-N 5-bromo-2-methoxypyridine Chemical compound COC1=CC=C(Br)C=N1 XADICJHFELMBGX-UHFFFAOYSA-N 0.000 description 2
- 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 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
- 125000000041 C6-C10 aryl group Chemical group 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 206010008909 Chronic Hepatitis Diseases 0.000 description 2
- 238000006646 Dess-Martin oxidation reaction Methods 0.000 description 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
- 102100037362 Fibronectin Human genes 0.000 description 2
- 108010067306 Fibronectins Proteins 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 208000010412 Glaucoma Diseases 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 108010040765 Integrin alphaV Proteins 0.000 description 2
- 102000004388 Interleukin-4 Human genes 0.000 description 2
- 108090000978 Interleukin-4 Proteins 0.000 description 2
- 208000029523 Interstitial Lung disease Diseases 0.000 description 2
- 108010055717 JNK Mitogen-Activated Protein Kinases Proteins 0.000 description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 description 2
- 206010023421 Kidney fibrosis Diseases 0.000 description 2
- 101800001155 Latency-associated peptide Proteins 0.000 description 2
- 102400000401 Latency-associated peptide Human genes 0.000 description 2
- 239000002841 Lewis acid Substances 0.000 description 2
- 229910013594 LiOAc Inorganic materials 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 102100027159 Membrane primary amine oxidase Human genes 0.000 description 2
- 101710132836 Membrane primary amine oxidase Proteins 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 238000006751 Mitsunobu reaction Methods 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 2
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 2
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- 206010038934 Retinopathy proliferative Diseases 0.000 description 2
- 206010050207 Skin fibrosis Diseases 0.000 description 2
- 238000006069 Suzuki reaction reaction Methods 0.000 description 2
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 102000011016 Type 5 Cyclic Nucleotide Phosphodiesterases Human genes 0.000 description 2
- 108010037581 Type 5 Cyclic Nucleotide Phosphodiesterases Proteins 0.000 description 2
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 description 2
- VSVVREVNVKCKRQ-UHFFFAOYSA-N [Si](C)(C)(C(C)(C)C)OC=1C=C2C=NN(C2=CC=1)C(=O)OC(C)(C)C Chemical compound [Si](C)(C)(C(C)(C)C)OC=1C=C2C=NN(C2=CC=1)C(=O)OC(C)(C)C VSVVREVNVKCKRQ-UHFFFAOYSA-N 0.000 description 2
- 239000000370 acceptor Substances 0.000 description 2
- 231100000354 acute hepatitis Toxicity 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 206010064930 age-related macular degeneration Diseases 0.000 description 2
- 125000005236 alkanoylamino group Chemical group 0.000 description 2
- 125000004450 alkenylene group Chemical group 0.000 description 2
- 125000003282 alkyl amino group Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 125000004419 alkynylene group Chemical group 0.000 description 2
- 125000005129 aryl carbonyl group Chemical group 0.000 description 2
- 125000005160 aryl oxy alkyl group Chemical group 0.000 description 2
- 125000005135 aryl sulfinyl group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000002393 azetidinyl group Chemical group 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 2
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 2
- 125000001589 carboacyl group Chemical group 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 2
- 239000011111 cardboard Substances 0.000 description 2
- 230000009787 cardiac fibrosis Effects 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 238000001023 centrifugal evaporation Methods 0.000 description 2
- 238000012512 characterization method Methods 0.000 description 2
- 238000004296 chiral HPLC Methods 0.000 description 2
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 2
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
- 238000006073 displacement reaction Methods 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- 229940121360 farnesoid X receptor (fxr) agonists Drugs 0.000 description 2
- 229940126864 fibroblast growth factor Drugs 0.000 description 2
- 206010016629 fibroma Diseases 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 235000019256 formaldehyde Nutrition 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 125000005553 heteroaryloxy group Chemical group 0.000 description 2
- 125000005945 imidazopyridyl group Chemical group 0.000 description 2
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 229940028885 interleukin-4 Drugs 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001786 isothiazolyl group Chemical group 0.000 description 2
- 125000000468 ketone group Chemical group 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 150000007517 lewis acids Chemical class 0.000 description 2
- 201000007270 liver cancer Diseases 0.000 description 2
- 208000014018 liver neoplasm Diseases 0.000 description 2
- 208000002780 macular degeneration Diseases 0.000 description 2
- 159000000003 magnesium salts Chemical class 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
- 238000001819 mass spectrum Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 201000000050 myeloid neoplasm Diseases 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 2
- 201000004071 non-specific interstitial pneumonia Diseases 0.000 description 2
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 2
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 230000001590 oxidative effect Effects 0.000 description 2
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- ZHZCYWWNFQUZOR-UHFFFAOYSA-N pent-4-en-2-ol Chemical compound CC(O)CC=C ZHZCYWWNFQUZOR-UHFFFAOYSA-N 0.000 description 2
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 description 2
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 description 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 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
- 229960005141 piperazine Drugs 0.000 description 2
- ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 description 2
- 229960003073 pirfenidone Drugs 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 2
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 2
- 125000002098 pyridazinyl group Chemical group 0.000 description 2
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 201000002793 renal fibrosis Diseases 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 2
- 238000012552 review Methods 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 230000037390 scarring Effects 0.000 description 2
- PEGQOIGYZLJMIB-UHFFFAOYSA-N setogepram Chemical compound CCCCCC1=CC=CC(CC(O)=O)=C1 PEGQOIGYZLJMIB-UHFFFAOYSA-N 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- ARKBPZCITPOGOU-SOFGYWHQSA-N tert-butyl (e)-3-(6-methoxypyridin-3-yl)prop-2-enoate Chemical compound COC1=CC=C(\C=C\C(=O)OC(C)(C)C)C=N1 ARKBPZCITPOGOU-SOFGYWHQSA-N 0.000 description 2
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 2
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
- 125000004525 thiadiazinyl group Chemical group S1NN=C(C=C1)* 0.000 description 2
- 125000001113 thiadiazolyl group Chemical group 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
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
- YCXHGZAPOTVJHZ-VWLOTQADSA-N (2S)-2-(phenylmethoxycarbonylamino)-3-[5-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy]indazol-2-yl]propanoic acid Chemical compound C(C1=CC=CC=C1)OC(=O)N[C@H](C(=O)O)CN1N=C2C=CC(=CC2=C1)OCCC1=NC=2NCCCC=2C=C1 YCXHGZAPOTVJHZ-VWLOTQADSA-N 0.000 description 1
- OUPXSLGGCPUZJJ-SARDKLJWSA-N (2s)-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-n-[(2s)-5-amino-1-[[(2s)-1-[[(2s)-1-[[2-[[(2s)-1-[[(2s)-1-amino-4-methylsulfonyl-1-oxobutan-2-y Chemical compound C([C@@H](C(=O)N(C)CC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCS(C)(=O)=O)C(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 OUPXSLGGCPUZJJ-SARDKLJWSA-N 0.000 description 1
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- IEVJUXBVPRRYJM-VOIUYBSRSA-N (3R)-3-(2-methylpyrimidin-5-yl)-3-[5-[2-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]ethoxy]indazol-1-yl]propanoic acid Chemical compound C[C@@H]1CCC=2C=CC(=NC=2N1)CCOC=1C=C2C=NN(C2=CC=1)[C@H](CC(=O)O)C=1C=NC(=NC=1)C IEVJUXBVPRRYJM-VOIUYBSRSA-N 0.000 description 1
- IEVJUXBVPRRYJM-UPCLLVRISA-N (3R)-3-(2-methylpyrimidin-5-yl)-3-[5-[2-[(7S)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]ethoxy]indazol-1-yl]propanoic acid Chemical compound C[C@H]1CCC=2C=CC(=NC=2N1)CCOC=1C=C2C=NN(C2=CC=1)[C@H](CC(=O)O)C=1C=NC(=NC=1)C IEVJUXBVPRRYJM-UPCLLVRISA-N 0.000 description 1
- IRBNGLACBFFCAF-OAQYLSRUSA-N (3R)-3-[5-[2-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)ethoxy]indazol-1-yl]-3-(6-methoxypyridin-3-yl)propanoic acid Chemical compound O1C2=C(NCC1)N=C(C=C2)CCOC=1C=C2C=NN(C2=CC=1)[C@H](CC(=O)O)C=1C=NC(=CC=1)OC IRBNGLACBFFCAF-OAQYLSRUSA-N 0.000 description 1
- ZHYATRSIDLIEQO-AREMUKBSSA-N (3R)-3-quinoxalin-2-yl-3-[5-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy]indazol-1-yl]propanoic acid Chemical compound N1=C(C=NC2=CC=CC=C12)[C@@H](CC(=O)O)N1N=CC2=CC(=CC=C12)OCCC1=NC=2NCCCC=2C=C1 ZHYATRSIDLIEQO-AREMUKBSSA-N 0.000 description 1
- IEVJUXBVPRRYJM-GYCJOSAFSA-N (3S)-3-(2-methylpyrimidin-5-yl)-3-[5-[2-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]ethoxy]indazol-1-yl]propanoic acid Chemical compound C[C@@H]1CCC=2C=CC(=NC=2N1)CCOC=1C=C2C=NN(C2=CC=1)[C@@H](CC(=O)O)C=1C=NC(=NC=1)C IEVJUXBVPRRYJM-GYCJOSAFSA-N 0.000 description 1
- IEVJUXBVPRRYJM-FYSMJZIKSA-N (3S)-3-(2-methylpyrimidin-5-yl)-3-[5-[2-[(7S)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]ethoxy]indazol-1-yl]propanoic acid Chemical compound C[C@H]1CCC=2C=CC(=NC=2N1)CCOC=1C=C2C=NN(C2=CC=1)[C@@H](CC(=O)O)C=1C=NC(=NC=1)C IEVJUXBVPRRYJM-FYSMJZIKSA-N 0.000 description 1
- IBJMZQSYNARXOG-QHCPKHFHSA-N (3S)-3-(6-methoxypyridin-3-yl)-3-[5-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy]indazol-2-yl]propanoic acid Chemical compound COC1=CC=C(C=N1)[C@H](CC(=O)O)N1N=C2C=CC(=CC2=C1)OCCC1=NC=2NCCCC=2C=C1 IBJMZQSYNARXOG-QHCPKHFHSA-N 0.000 description 1
- SEIOZNXVMKEXMV-QHCPKHFHSA-N (3S)-3-(6-methoxypyridin-3-yl)-3-[6-[(2-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)methyl]indazol-2-yl]propanoic acid Chemical compound COC1=CC=C(C=N1)[C@H](CC(=O)O)N1N=C2C=C(C=CC2=C1)CC=1C(=NC=2NCCCC=2C=1)C SEIOZNXVMKEXMV-QHCPKHFHSA-N 0.000 description 1
- QCJCXKWNJRTCGA-QHCPKHFHSA-N (3S)-3-(6-methoxypyridin-3-yl)-3-[6-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]indazol-2-yl]propanoic acid Chemical compound COC1=CC=C(C=N1)[C@H](CC(=O)O)N1N=C2C=C(C=CC2=C1)CCC1=NC=2NCCCC=2C=C1 QCJCXKWNJRTCGA-QHCPKHFHSA-N 0.000 description 1
- MYPIWCRREWLBQK-DEOSSOPVSA-N (3S)-3-(6-methoxypyridin-3-yl)-3-[6-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl]indazol-2-yl]propanoic acid Chemical compound COC1=CC=C(C=N1)[C@H](CC(=O)O)N1N=C2C=C(C=CC2=C1)CCCC1=NC=2NCCCC=2C=C1 MYPIWCRREWLBQK-DEOSSOPVSA-N 0.000 description 1
- IRBNGLACBFFCAF-NRFANRHFSA-N (3S)-3-[5-[2-(3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl)ethoxy]indazol-1-yl]-3-(6-methoxypyridin-3-yl)propanoic acid Chemical compound O1C2=C(NCC1)N=C(C=C2)CCOC=1C=C2C=NN(C2=CC=1)[C@@H](CC(=O)O)C=1C=NC(=CC=1)OC IRBNGLACBFFCAF-NRFANRHFSA-N 0.000 description 1
- ZHYATRSIDLIEQO-SANMLTNESA-N (3S)-3-quinoxalin-2-yl-3-[5-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy]indazol-1-yl]propanoic acid Chemical compound N1=C(C=NC2=CC=CC=C12)[C@H](CC(=O)O)N1N=CC2=CC(=CC=C12)OCCC1=NC=2NCCCC=2C=C1 ZHYATRSIDLIEQO-SANMLTNESA-N 0.000 description 1
- SCVHJVCATBPIHN-SJCJKPOMSA-N (3s)-3-[[(2s)-2-[[2-(2-tert-butylanilino)-2-oxoacetyl]amino]propanoyl]amino]-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid Chemical compound N([C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)COC=1C(=C(F)C=C(F)C=1F)F)C(=O)C(=O)NC1=CC=CC=C1C(C)(C)C SCVHJVCATBPIHN-SJCJKPOMSA-N 0.000 description 1
- SHKXZIQNFMOPBS-OOMQYRRCSA-N (4r)-4-[(3s,5s,7r,8r,9s,10s,12s,13r,14s,17r)-7,12-dihydroxy-3-(icosanoylamino)-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]pentanoic acid Chemical compound O[C@H]1C[C@@H]2[C@@]3(C)CC[C@H](NC(=O)CCCCCCCCCCCCCCCCCCC)C[C@H]3C[C@@H](O)[C@H]2[C@@H]2CC[C@H]([C@H](C)CCC(O)=O)[C@]21C SHKXZIQNFMOPBS-OOMQYRRCSA-N 0.000 description 1
- YCHYFHOSGQABSW-RTBURBONSA-N (6ar,10ar)-1-hydroxy-6,6-dimethyl-3-(2-methyloctan-2-yl)-6a,7,10,10a-tetrahydrobenzo[c]chromene-9-carboxylic acid Chemical compound C1C(C(O)=O)=CC[C@H]2C(C)(C)OC3=CC(C(C)(C)CCCCCC)=CC(O)=C3[C@@H]21 YCHYFHOSGQABSW-RTBURBONSA-N 0.000 description 1
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 description 1
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- COLOHWPRNRVWPI-UHFFFAOYSA-N 1,1,1-trifluoroethane Chemical compound [CH2]C(F)(F)F COLOHWPRNRVWPI-UHFFFAOYSA-N 0.000 description 1
- FIARMZDBEGVMLV-UHFFFAOYSA-N 1,1,2,2,2-pentafluoroethanolate Chemical group [O-]C(F)(F)C(F)(F)F FIARMZDBEGVMLV-UHFFFAOYSA-N 0.000 description 1
- 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 description 1
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 description 1
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 1
- 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 description 1
- 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 description 1
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 1
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 description 1
- PLCMVACJJSYDFV-UHFFFAOYSA-N 1,3-oxazole-2-carboxamide Chemical class NC(=O)C1=NC=CO1 PLCMVACJJSYDFV-UHFFFAOYSA-N 0.000 description 1
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- GTZJUBQWCWZING-NKUHCKNESA-N 1-o-benzyl 2-o-methyl (2s)-aziridine-1,2-dicarboxylate Chemical compound COC(=O)[C@@H]1CN1C(=O)OCC1=CC=CC=C1 GTZJUBQWCWZING-NKUHCKNESA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- YJKMYHNMBGQQQZ-UHFFFAOYSA-N 1h-indazole-5-carbaldehyde Chemical compound O=CC1=CC=C2NN=CC2=C1 YJKMYHNMBGQQQZ-UHFFFAOYSA-N 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
- PVJZBZSCGJAWNG-UHFFFAOYSA-N 2,4,6-trimethylbenzenesulfonyl chloride Chemical compound CC1=CC(C)=C(S(Cl)(=O)=O)C(C)=C1 PVJZBZSCGJAWNG-UHFFFAOYSA-N 0.000 description 1
- HWERXDRLKHRQJM-UHFFFAOYSA-N 2-(1-methyl-3,4-dihydro-2h-pyrido[2,3-b]pyrazin-6-yl)ethanol Chemical compound OCCC1=CC=C2N(C)CCNC2=N1 HWERXDRLKHRQJM-UHFFFAOYSA-N 0.000 description 1
- QRDYHKLLQVGVNO-UHFFFAOYSA-N 2-(3-iodopropyl)-2-methyl-1,3-dioxolane Chemical compound ICCCC1(C)OCCO1 QRDYHKLLQVGVNO-UHFFFAOYSA-N 0.000 description 1
- HKDFLJPTLIDIRY-UHFFFAOYSA-N 2-(phenylmethoxycarbonylamino)-3-[5-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy]indazol-1-yl]propanoic acid Chemical compound C(C1=CC=CC=C1)OC(=O)NC(C(=O)O)CN1N=CC2=CC(=CC=C12)OCCC1=NC=2NCCCC=2C=C1 HKDFLJPTLIDIRY-UHFFFAOYSA-N 0.000 description 1
- ZZWWXIBKLBMSCS-FQEVSTJZSA-N 2-[1-[(2r)-2-(2-methoxyphenyl)-2-(oxan-4-yloxy)ethyl]-5-methyl-6-(1,3-oxazol-2-yl)-2,4-dioxothieno[2,3-d]pyrimidin-3-yl]-2-methylpropanoic acid Chemical compound COC1=CC=CC=C1[C@@H](OC1CCOCC1)CN1C(=O)N(C(C)(C)C(O)=O)C(=O)C2=C1SC(C=1OC=CN=1)=C2C ZZWWXIBKLBMSCS-FQEVSTJZSA-N 0.000 description 1
- KZSKGLFYQAYZCO-UHFFFAOYSA-N 2-[3-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]-3-hydroxyazetidin-1-yl]pyridine-4-carboxylic acid Chemical compound OC(=O)C1=CC=NC(N2CC(O)(C2)C=2C(=CC(OCC=3C(=NOC=3C3CC3)C=3C(=CC=CC=3Cl)Cl)=CC=2)Cl)=C1 KZSKGLFYQAYZCO-UHFFFAOYSA-N 0.000 description 1
- BVAHPPKGOOJSPU-UHFFFAOYSA-N 2-[[5-chloro-2-[(5-methyl-2-propan-2-ylpyrazol-3-yl)amino]pyridin-4-yl]amino]-n-methoxybenzamide Chemical compound CONC(=O)C1=CC=CC=C1NC1=CC(NC=2N(N=C(C)C=2)C(C)C)=NC=C1Cl BVAHPPKGOOJSPU-UHFFFAOYSA-N 0.000 description 1
- 101710186725 2-acylglycerol O-acyltransferase 2 Proteins 0.000 description 1
- NXMFJCRMSDRXLD-UHFFFAOYSA-N 2-aminopyridine-3-carbaldehyde Chemical compound NC1=NC=CC=C1C=O NXMFJCRMSDRXLD-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- 125000006040 2-hexenyl group Chemical group 0.000 description 1
- FSWRUYCICUXURT-UHFFFAOYSA-N 2-methyl-1,8-naphthyridine Chemical compound C1=CC=NC2=NC(C)=CC=C21 FSWRUYCICUXURT-UHFFFAOYSA-N 0.000 description 1
- 125000006022 2-methyl-2-propenyl group Chemical group 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical class [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 1
- 125000006024 2-pentenyl group Chemical group 0.000 description 1
- KRTGJZMJJVEKRX-UHFFFAOYSA-N 2-phenylethan-1-yl Chemical group [CH2]CC1=CC=CC=C1 KRTGJZMJJVEKRX-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- KQJVDEBWHJRJBT-UHFFFAOYSA-N 3,4-dihydro-1h-1,8-naphthyridin-2-one Chemical compound C1=CN=C2NC(=O)CCC2=C1 KQJVDEBWHJRJBT-UHFFFAOYSA-N 0.000 description 1
- LZNSCTVBCCNNSB-UHFFFAOYSA-N 3-(5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)-3-[5-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy]indazol-1-yl]propanoic acid Chemical compound N1=C(C=CC=2CCCNC1=2)CCOC=1C=C2C=NN(C2=CC=1)C(CC(=O)O)C=1C=NC=2NCCCC=2C=1 LZNSCTVBCCNNSB-UHFFFAOYSA-N 0.000 description 1
- WQDOASZSXXRUQZ-UHFFFAOYSA-N 3-(6-methoxypyridin-3-yl)-3-[4-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy]indazol-1-yl]propanoic acid Chemical compound COC1=CC=C(C=N1)C(CC(=O)O)N1N=CC2=C(C=CC=C12)OCCC1=NC=2NCCCC=2C=C1 WQDOASZSXXRUQZ-UHFFFAOYSA-N 0.000 description 1
- ZMGJXTNJRCUSMZ-UHFFFAOYSA-N 3-(6-methoxypyridin-3-yl)-3-[4-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]indazol-1-yl]propanoic acid Chemical compound COC1=CC=C(C=N1)C(CC(=O)O)N1N=CC2=C(C=CC=C12)CCC1=NC=2NCCCC=2C=C1 ZMGJXTNJRCUSMZ-UHFFFAOYSA-N 0.000 description 1
- DLFAEACDGNDGJR-UHFFFAOYSA-N 3-(6-methoxypyridin-3-yl)-3-[4-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl]indazol-1-yl]propanoic acid Chemical compound COC1=CC=C(C=N1)C(CC(=O)O)N1N=CC2=C(C=CC=C12)CCCC1=NC=2NCCCC=2C=C1 DLFAEACDGNDGJR-UHFFFAOYSA-N 0.000 description 1
- QQVGFIHGWZQKKS-UHFFFAOYSA-N 3-(6-methoxypyridin-3-yl)-3-[5-[2-(1-methyl-3,4-dihydro-2H-pyrido[2,3-b]pyrazin-6-yl)ethoxy]indazol-1-yl]propanoic acid Chemical compound COC1=CC=C(C=N1)C(CC(=O)O)N1N=CC2=CC(=CC=C12)OCCC=1C=CC2=C(NCCN2C)N=1 QQVGFIHGWZQKKS-UHFFFAOYSA-N 0.000 description 1
- BXPMWNWQYVVJET-UHFFFAOYSA-N 3-(6-methoxypyridin-3-yl)-3-[5-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy]pyrazolo[4,3-b]pyridin-1-yl]propanoic acid Chemical compound COC1=CC=C(C=N1)C(CC(=O)O)N1N=CC2=NC(=CC=C21)OCCC1=NC=2NCCCC=2C=C1 BXPMWNWQYVVJET-UHFFFAOYSA-N 0.000 description 1
- XWSAPZZBILUWPA-UHFFFAOYSA-N 3-(6-methoxypyridin-3-yl)-3-[5-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]indazol-1-yl]propanoic acid Chemical compound COC1=CC=C(C=N1)C(CC(=O)O)N1N=CC2=CC(=CC=C12)CCC1=NC=2NCCCC=2C=C1 XWSAPZZBILUWPA-UHFFFAOYSA-N 0.000 description 1
- RZHGYJCHLYTNLF-UHFFFAOYSA-N 3-[5-[2-(4,5-dihydro-1H-imidazol-2-ylamino)ethoxy]indazol-1-yl]-3-(6-methoxypyridin-3-yl)propanoic acid Chemical compound N1C(=NCC1)NCCOC=1C=C2C=NN(C2=CC=1)C(CC(=O)O)C=1C=NC(=CC=1)OC RZHGYJCHLYTNLF-UHFFFAOYSA-N 0.000 description 1
- PTVXEJYPPBQOOR-UHFFFAOYSA-N 3-[5-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy]indazol-1-yl]-2-[(2,4,6-trimethylphenyl)sulfonylamino]propanoic acid Chemical compound N1=C(C=CC=2CCCNC1=2)CCOC=1C=C2C=NN(C2=CC=1)CC(C(=O)O)NS(=O)(=O)C1=C(C=C(C=C1C)C)C PTVXEJYPPBQOOR-UHFFFAOYSA-N 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- 125000006041 3-hexenyl group Chemical group 0.000 description 1
- STMJTKHUFDVBKN-UHFFFAOYSA-N 3-phenyl-3-[5-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propoxy]indazol-1-yl]propanoic acid Chemical compound C1(=CC=CC=C1)C(CC(=O)O)N1N=CC2=CC(=CC=C12)OCCCC1=NC=2NCCCC=2C=C1 STMJTKHUFDVBKN-UHFFFAOYSA-N 0.000 description 1
- ZHYATRSIDLIEQO-UHFFFAOYSA-N 3-quinoxalin-2-yl-3-[5-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy]indazol-1-yl]propanoic acid Chemical compound N1=C(C=NC2=CC=CC=C12)C(CC(=O)O)N1N=CC2=CC(=CC=C12)OCCC1=NC=2NCCCC=2C=C1 ZHYATRSIDLIEQO-UHFFFAOYSA-N 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- OQDQIFQRNZIEEJ-UHFFFAOYSA-N 4-[1-(1,3-benzothiazol-6-ylsulfonyl)-5-chloroindol-2-yl]butanoic acid Chemical compound C1=C2N=CSC2=CC(S(=O)(=O)N2C3=CC=C(Cl)C=C3C=C2CCCC(=O)O)=C1 OQDQIFQRNZIEEJ-UHFFFAOYSA-N 0.000 description 1
- GSXUXSXBEUJRAJ-UHFFFAOYSA-N 4-bromo-2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC(Br)=CC=C1C=O GSXUXSXBEUJRAJ-UHFFFAOYSA-N 0.000 description 1
- LUUMLYXKTPBTQR-UHFFFAOYSA-N 4-chloro-n-[5-methyl-2-(7h-pyrrolo[2,3-d]pyrimidine-4-carbonyl)pyridin-3-yl]-3-(trifluoromethyl)benzenesulfonamide Chemical compound C=1C(C)=CN=C(C(=O)C=2C=3C=CNC=3N=CN=2)C=1NS(=O)(=O)C1=CC=C(Cl)C(C(F)(F)F)=C1 LUUMLYXKTPBTQR-UHFFFAOYSA-N 0.000 description 1
- 125000006042 4-hexenyl group Chemical group 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000003119 4-methyl-3-pentenyl group Chemical group [H]\C(=C(/C([H])([H])[H])C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001054 5 membered carbocyclic group Chemical group 0.000 description 1
- 125000004608 5,6,7,8-tetrahydroquinolinyl group Chemical group N1=C(C=CC=2CCCCC12)* 0.000 description 1
- QWLXNBNVCRSNEX-UHFFFAOYSA-N 5-bromo-1h-pyrazolo[4,3-b]pyridine Chemical compound BrC1=CC=C2NN=CC2=N1 QWLXNBNVCRSNEX-UHFFFAOYSA-N 0.000 description 1
- 125000006043 5-hexenyl group Chemical group 0.000 description 1
- XLYPHUGUKGMURE-UHFFFAOYSA-N 5-hydroxy-2-nitrobenzaldehyde Chemical compound OC1=CC=C([N+]([O-])=O)C(C=O)=C1 XLYPHUGUKGMURE-UHFFFAOYSA-N 0.000 description 1
- 125000006163 5-membered heteroaryl group Chemical group 0.000 description 1
- 125000003627 8 membered carbocyclic group Chemical group 0.000 description 1
- 229940127254 ASK1 inhibitor Drugs 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 208000007082 Alcoholic Fatty Liver Diseases 0.000 description 1
- 102100024296 Alpha-1,6-mannosyl-glycoprotein 2-beta-N-acetylglucosaminyltransferase Human genes 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 241000937413 Axia Species 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical group C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
- 208000009299 Benign Mucous Membrane Pemphigoid Diseases 0.000 description 1
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
- 206010004659 Biliary cirrhosis Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 1
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- 102000001902 CC Chemokines Human genes 0.000 description 1
- 108010040471 CC Chemokines Proteins 0.000 description 1
- 101100421200 Caenorhabditis elegans sep-1 gene Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 201000009030 Carcinoma Diseases 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 208000008964 Chemical and Drug Induced Liver Injury Diseases 0.000 description 1
- 102000006383 Chemokine CCL24 Human genes 0.000 description 1
- 108010083647 Chemokine CCL24 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- AEMZEDNMNLIDSL-YGCVIUNWSA-N Cl.CC(C)(C)NC(=O)C1=CC=C(OC\C(CN)=C\F)C=C1 Chemical compound Cl.CC(C)(C)NC(=O)C1=CC=C(OC\C(CN)=C\F)C=C1 AEMZEDNMNLIDSL-YGCVIUNWSA-N 0.000 description 1
- 102000015225 Connective Tissue Growth Factor Human genes 0.000 description 1
- 108010039419 Connective Tissue Growth Factor Proteins 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- 208000011231 Crohn disease Diseases 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
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 206010072268 Drug-induced liver injury Diseases 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 102100021977 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Human genes 0.000 description 1
- 108050004000 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Proteins 0.000 description 1
- 229940118365 Endothelin receptor antagonist Drugs 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 229940124783 FAK inhibitor Drugs 0.000 description 1
- 229940125634 FPR2 agonist Drugs 0.000 description 1
- 108090000376 Fibroblast growth factor 21 Proteins 0.000 description 1
- 102000003973 Fibroblast growth factor 21 Human genes 0.000 description 1
- 208000007212 Foot-and-Mouth Disease Diseases 0.000 description 1
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 1
- 102100025101 GATA-type zinc finger protein 1 Human genes 0.000 description 1
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 1
- 108010001517 Galectin 3 Proteins 0.000 description 1
- 102100039558 Galectin-3 Human genes 0.000 description 1
- 208000022461 Glomerular disease Diseases 0.000 description 1
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 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(N)=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 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 238000006893 Hayashi rearrangement reaction Methods 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000966782 Homo sapiens Lysophosphatidic acid receptor 1 Proteins 0.000 description 1
- 101001043352 Homo sapiens Lysyl oxidase homolog 2 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 108010023610 IL13-PE38 Proteins 0.000 description 1
- 208000010159 IgA glomerulonephritis Diseases 0.000 description 1
- 206010021263 IgA nephropathy Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000008070 Interferon-gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 208000003618 Intervertebral Disc Displacement Diseases 0.000 description 1
- 208000002260 Keloid Diseases 0.000 description 1
- 206010023330 Keloid scar Diseases 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-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
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)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](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)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=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 1
- 108010019598 Liraglutide Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000012448 Lithium borohydride Substances 0.000 description 1
- 208000005777 Lupus Nephritis Diseases 0.000 description 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102100040607 Lysophosphatidic acid receptor 1 Human genes 0.000 description 1
- 102100021948 Lysyl oxidase homolog 2 Human genes 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- 206010027406 Mesothelioma Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- UCHDWCPVSPXUMX-TZIWLTJVSA-N Montelukast Chemical compound CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC(O)=O)CC1 UCHDWCPVSPXUMX-TZIWLTJVSA-N 0.000 description 1
- 208000012192 Mucous membrane pemphigoid Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 108010082699 NADPH Oxidase 4 Proteins 0.000 description 1
- 102100021872 NADPH oxidase 4 Human genes 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 208000000693 Neurogenic Urinary Bladder Diseases 0.000 description 1
- 206010029279 Neurogenic bladder Diseases 0.000 description 1
- 101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- VYLOOGHLKSNNEK-PIIMJCKOSA-N OC(=O)c1cc(F)c2nc(sc2c1)N1[C@H]2CC[C@@H]1C[C@@H](C2)OCc1c(onc1-c1ccccc1OC(F)(F)F)C1CC1 Chemical compound OC(=O)c1cc(F)c2nc(sc2c1)N1[C@H]2CC[C@@H]1C[C@@H](C2)OCc1c(onc1-c1ccccc1OC(F)(F)F)C1CC1 VYLOOGHLKSNNEK-PIIMJCKOSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 206010034277 Pemphigoid Diseases 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 1
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 229940127472 RNA Synthetase Inhibitors Drugs 0.000 description 1
- 208000032056 Radiation Fibrosis Syndrome Diseases 0.000 description 1
- 108091005682 Receptor kinases Proteins 0.000 description 1
- 108020004511 Recombinant DNA Proteins 0.000 description 1
- GSINGUMRKGRYJP-VZWAGXQNSA-N Remogliflozin Chemical compound C1=CC(OC(C)C)=CC=C1CC1=C(C)N(C(C)C)N=C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 GSINGUMRKGRYJP-VZWAGXQNSA-N 0.000 description 1
- 101100366061 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) SNA2 gene Proteins 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 206010039710 Scleroderma Diseases 0.000 description 1
- DLSWIYLPEUIQAV-UHFFFAOYSA-N Semaglutide Chemical compound CCC(C)C(NC(=O)C(Cc1ccccc1)NC(=O)C(CCC(O)=O)NC(=O)C(CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CCC(NC(=O)CCCCCCCCCCCCCCCCC(O)=O)C(O)=O)NC(=O)C(C)NC(=O)C(C)NC(=O)C(CCC(N)=O)NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(CC(C)C)NC(=O)C(Cc1ccc(O)cc1)NC(=O)C(CO)NC(=O)C(CO)NC(=O)C(NC(=O)C(CC(O)=O)NC(=O)C(CO)NC(=O)C(NC(=O)C(Cc1ccccc1)NC(=O)C(NC(=O)CNC(=O)C(CCC(O)=O)NC(=O)C(C)(C)NC(=O)C(N)Cc1cnc[nH]1)C(C)O)C(C)O)C(C)C)C(=O)NC(C)C(=O)NC(Cc1c[nH]c2ccccc12)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CCCNC(N)=N)C(=O)NCC(O)=O DLSWIYLPEUIQAV-UHFFFAOYSA-N 0.000 description 1
- 201000010208 Seminoma Diseases 0.000 description 1
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 description 1
- 229940123518 Sodium/glucose cotransporter 2 inhibitor Drugs 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 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
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229910052771 Terbium Inorganic materials 0.000 description 1
- KPWYNAGOBXLMSE-UHFFFAOYSA-N Tipelukast Chemical compound CCCC1=C(O)C(C(C)=O)=CC=C1SCCCOC1=CC=C(C(C)=O)C(OCCCC(O)=O)=C1CCC KPWYNAGOBXLMSE-UHFFFAOYSA-N 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 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
- 206010046798 Uterine leiomyoma Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 102100035140 Vitronectin Human genes 0.000 description 1
- 108010031318 Vitronectin Proteins 0.000 description 1
- 238000007239 Wittig reaction Methods 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- BFPLMTPHDFFMTG-UHFFFAOYSA-N [1,3]oxazolo[5,4-b]pyridine Chemical compound C1=CN=C2OC=NC2=C1 BFPLMTPHDFFMTG-UHFFFAOYSA-N 0.000 description 1
- CKUAXEQHGKSLHN-UHFFFAOYSA-N [C].[N] Chemical group [C].[N] CKUAXEQHGKSLHN-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 159000000021 acetate salts Chemical class 0.000 description 1
- 229940121373 acetyl-coa carboxylase inhibitor Drugs 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000614 adrenergic beta-2 receptor agonist Substances 0.000 description 1
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 208000026594 alcoholic fatty liver disease Diseases 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
- 125000002009 alkene group Chemical group 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 150000001345 alkine derivatives Chemical group 0.000 description 1
- 125000005250 alkyl acrylate group Chemical group 0.000 description 1
- 125000006177 alkyl benzyl group Chemical group 0.000 description 1
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 1
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 1
- 150000005215 alkyl ethers Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-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
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003510 anti-fibrotic effect Effects 0.000 description 1
- 230000000843 anti-fungal effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 235000009697 arginine Nutrition 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000005018 aryl alkenyl group Chemical group 0.000 description 1
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 1
- 125000004659 aryl alkyl thio group Chemical group 0.000 description 1
- 125000005100 aryl amino carbonyl group Chemical group 0.000 description 1
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 description 1
- 125000005164 aryl thioalkyl group Chemical group 0.000 description 1
- 125000005325 aryloxy aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004935 benzoxazolinyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- CIZSHMIFOXDHKH-UHFFFAOYSA-N benzyl 2-(phenylmethoxycarbonylamino)-3-[5-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethoxy]indazol-1-yl]propanoate Chemical compound C(C1=CC=CC=C1)OC(=O)NC(C(=O)OCC1=CC=CC=C1)CN1N=CC2=CC(=CC=C12)OCCC1=NC=2NCCCC=2C=C1 CIZSHMIFOXDHKH-UHFFFAOYSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 150000001576 beta-amino acids Chemical class 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 150000001602 bicycloalkyls Chemical group 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000012925 biological evaluation Methods 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000000481 breast Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 229950000771 carlumab Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- PNDKCRDVVKJPKG-WHERJAGFSA-N cenicriviroc Chemical compound C1=CC(OCCOCCCC)=CC=C1C1=CC=C(N(CC(C)C)CCC\C(=C/2)C(=O)NC=3C=CC(=CC=3)[S@@](=O)CC=3N(C=NC=3)CCC)C\2=C1 PNDKCRDVVKJPKG-WHERJAGFSA-N 0.000 description 1
- 229950011033 cenicriviroc Drugs 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 206010008118 cerebral infarction Diseases 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- IBGLGMOPHJQDJB-IHRRRGAJSA-N chembl1950289 Chemical compound C1C[C@@H](O)CC[C@@H]1NC1=NC=C(N=C(NC=2C(=CC(F)=CC=2F)F)N2[C@@H]3COCC3)C2=N1 IBGLGMOPHJQDJB-IHRRRGAJSA-N 0.000 description 1
- 125000003636 chemical group Chemical group 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 1
- 229940106681 chloroacetic acid Drugs 0.000 description 1
- 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 1
- 201000010002 cicatricial pemphigoid Diseases 0.000 description 1
- WCZVZNOTHYJIEI-UHFFFAOYSA-N cinnoline Chemical compound N1=NC=CC2=CC=CC=C21 WCZVZNOTHYJIEI-UHFFFAOYSA-N 0.000 description 1
- 229950010810 cintredekin besudotox Drugs 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000013066 combination product Substances 0.000 description 1
- 229940127555 combination product Drugs 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- XSYZCZPCBXYQTE-UHFFFAOYSA-N cyclodecylcyclodecane Chemical compound C1CCCCCCCCC1C1CCCCCCCCC1 XSYZCZPCBXYQTE-UHFFFAOYSA-N 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000000522 cyclooctenyl group Chemical group C1(=CCCCCCC1)* 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 210000004292 cytoskeleton Anatomy 0.000 description 1
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
- 229910052805 deuterium Inorganic materials 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
- 239000012973 diazabicyclooctane Substances 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 201000008865 drug-induced hepatitis Diseases 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 229950000234 emricasan Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002357 endometrial effect Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000002308 endothelin receptor antagonist Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- UMYZHWLYICNGRQ-UHFFFAOYSA-N ethanol;heptane Chemical compound CCO.CCCCCCC UMYZHWLYICNGRQ-UHFFFAOYSA-N 0.000 description 1
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
- ZUKVIRLUTPQCOS-QMMMGPOBSA-N ethyl (3S)-3-amino-3-(2-methoxypyrimidin-5-yl)propanoate Chemical compound N[C@@H](CC(=O)OCC)C=1C=NC(=NC=1)OC ZUKVIRLUTPQCOS-QMMMGPOBSA-N 0.000 description 1
- ONGSQPYHCQJKPP-JTQLQIEISA-N ethyl (3s)-3-amino-3-(3-fluoro-4-methoxyphenyl)propanoate Chemical compound CCOC(=O)C[C@H](N)C1=CC=C(OC)C(F)=C1 ONGSQPYHCQJKPP-JTQLQIEISA-N 0.000 description 1
- IXTSNOYRNWLAIU-SNAWJCMRSA-N ethyl (e)-3-(2-methoxypyrimidin-5-yl)prop-2-enoate Chemical compound CCOC(=O)\C=C\C1=CN=C(OC)N=C1 IXTSNOYRNWLAIU-SNAWJCMRSA-N 0.000 description 1
- ZUKVIRLUTPQCOS-UHFFFAOYSA-N ethyl 3-amino-3-(2-methoxypyrimidin-5-yl)propanoate Chemical compound C(C)OC(CC(C=1C=NC(=NC=1)OC)N)=O ZUKVIRLUTPQCOS-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229940126374 fipaxalparant Drugs 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000003709 fluoroalkyl group Chemical group 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 229960002714 fluticasone Drugs 0.000 description 1
- MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 231100000852 glomerular disease Toxicity 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 125000004995 haloalkylthio group Chemical group 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004447 heteroarylalkenyl group Chemical group 0.000 description 1
- 125000005114 heteroarylalkoxy group Chemical group 0.000 description 1
- 125000005368 heteroarylthio group Chemical group 0.000 description 1
- 125000004366 heterocycloalkenyl group Chemical group 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 150000004677 hydrates Chemical class 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
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 125000004926 indolenyl group Chemical group 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 230000008611 intercellular interaction Effects 0.000 description 1
- 229960003130 interferon gamma Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 description 1
- 229960001888 ipratropium Drugs 0.000 description 1
- 239000004407 iron oxides and hydroxides Substances 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 125000004936 isatinoyl group Chemical group N1(C(=O)C(=O)C2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000005438 isoindazolyl group Chemical group 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
- 208000011379 keloid formation Diseases 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229950002183 lebrikizumab Drugs 0.000 description 1
- 201000010260 leiomyoma Diseases 0.000 description 1
- 229940065725 leukotriene receptor antagonists for obstructive airway diseases Drugs 0.000 description 1
- 239000003199 leukotriene receptor blocking agent Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229960002701 liraglutide Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 235000018977 lysine Nutrition 0.000 description 1
- JGCMEBMXRHSZKX-UHFFFAOYSA-N macitentan Chemical compound C=1C=C(Br)C=CC=1C=1C(NS(=O)(=O)NCCC)=NC=NC=1OCCOC1=NC=C(Br)C=N1 JGCMEBMXRHSZKX-UHFFFAOYSA-N 0.000 description 1
- 229960001039 macitentan Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 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
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- MMIPFLVOWGHZQD-UHFFFAOYSA-N manganese(3+) Chemical compound [Mn+3] MMIPFLVOWGHZQD-UHFFFAOYSA-N 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000003584 mesangial cell Anatomy 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
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 229960005127 montelukast Drugs 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 239000003149 muscarinic antagonist Substances 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 206010028537 myelofibrosis Diseases 0.000 description 1
- ZUHZZVMEUAUWHY-UHFFFAOYSA-N n,n-dimethylpropan-1-amine Chemical compound CCCN(C)C ZUHZZVMEUAUWHY-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 1
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 description 1
- XZXHXSATPCNXJR-ZIADKAODSA-N nintedanib Chemical compound O=C1NC2=CC(C(=O)OC)=CC=C2\C1=C(C=1C=CC=CC=1)\NC(C=C1)=CC=C1N(C)C(=O)CN1CCN(C)CC1 XZXHXSATPCNXJR-ZIADKAODSA-N 0.000 description 1
- 229960004378 nintedanib Drugs 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 1
- 125000006574 non-aromatic ring group Chemical group 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 238000005016 nuclear Overhauser enhanced spectroscopy Methods 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- ACSQLTBPYZSGBA-GMXVVIOVSA-N olorinab Chemical compound C([C@@H]1C[C@@H]1C=12)C=1C(C(=O)N[C@H](CO)C(C)(C)C)=NN2C1=C[N+]([O-])=CC=N1 ACSQLTBPYZSGBA-GMXVVIOVSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 210000002997 osteoclast Anatomy 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000003566 oxetanyl group Chemical group 0.000 description 1
- 125000005489 p-toluenesulfonic acid group Chemical class 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 102000014187 peptide receptors Human genes 0.000 description 1
- 108010011903 peptide receptors Proteins 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 210000003668 pericyte Anatomy 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
- 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 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
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- KASDHRXLYQOAKZ-ZPSXYTITSA-N pimecrolimus Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](Cl)[C@H](OC)C1 KASDHRXLYQOAKZ-ZPSXYTITSA-N 0.000 description 1
- 229960005330 pimecrolimus Drugs 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 125000004928 piperidonyl group Chemical group 0.000 description 1
- 229960005235 piperonyl butoxide Drugs 0.000 description 1
- 125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 description 1
- LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 description 1
- 210000000557 podocyte Anatomy 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 150000004033 porphyrin derivatives Chemical class 0.000 description 1
- 208000007232 portal hypertension Diseases 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 108010042589 prolyl T RNA synthetase Proteins 0.000 description 1
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 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
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 230000001172 regenerating effect Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229940126844 remogliflozin Drugs 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 102220285764 rs876658288 Human genes 0.000 description 1
- 229960002052 salbutamol Drugs 0.000 description 1
- 229960004017 salmeterol Drugs 0.000 description 1
- MRWFZSLZNUJVQW-DEOSSOPVSA-N saroglitazar Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCN1C(C=2C=CC(SC)=CC=2)=CC=C1C MRWFZSLZNUJVQW-DEOSSOPVSA-N 0.000 description 1
- 229950006544 saroglitazar Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 208000010157 sclerosing cholangitis Diseases 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229950011186 semaglutide Drugs 0.000 description 1
- 108010060325 semaglutide Proteins 0.000 description 1
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 1
- 239000008299 semisolid dosage form Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- RGYQPQARIQKJKH-UHFFFAOYSA-N setanaxib Chemical compound CN(C)C1=CC=CC(C2=C3C(=O)N(C=4C(=CC=CC=4)Cl)NC3=CC(=O)N2C)=C1 RGYQPQARIQKJKH-UHFFFAOYSA-N 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 229950009513 simtuzumab 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
- 229960002930 sirolimus Drugs 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 208000010485 smooth muscle tumor Diseases 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- JEZLFWXSKCTMPN-ILCIQDJASA-M sodium;2-[(2s,3r,4e,6e,10e,12s)-13-(4-fluorophenoxy)-2,3,12-trihydroxytrideca-4,6,10-trien-8-ynoxy]acetate Chemical compound [Na+].[O-]C(=O)COC[C@H](O)[C@H](O)/C=C/C=C/C#C/C=C/[C@H](O)COC1=CC=C(F)C=C1 JEZLFWXSKCTMPN-ILCIQDJASA-M 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 239000002594 sorbent Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 206010062261 spinal cord neoplasm Diseases 0.000 description 1
- 208000005198 spinal stenosis Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
- 239000001648 tannin Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- GZCRRIHWUXGPOV-UHFFFAOYSA-N terbium atom Chemical compound [Tb] GZCRRIHWUXGPOV-UHFFFAOYSA-N 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- NNFABGQUERYRHT-UHFFFAOYSA-N tert-butyl 5-hydroxyindazole-2-carboxylate Chemical compound OC1=CC2=CN(N=C2C=C1)C(=O)OC(C)(C)C NNFABGQUERYRHT-UHFFFAOYSA-N 0.000 description 1
- WSKVZCMVVPXHJR-UHFFFAOYSA-N tert-butyl 6-(2-hydroxyethyl)-2,3-dihydropyrido[3,2-b][1,4]oxazine-4-carboxylate Chemical compound C1=C(CCO)N=C2N(C(=O)OC(C)(C)C)CCOC2=C1 WSKVZCMVVPXHJR-UHFFFAOYSA-N 0.000 description 1
- CVUHKLHGFJLYRY-UHFFFAOYSA-N tert-butyl 7-(2-hydroxyethyl)-2-methyl-3,4-dihydro-2h-1,8-naphthyridine-1-carboxylate Chemical compound C1=C(CCO)N=C2N(C(=O)OC(C)(C)C)C(C)CCC2=C1 CVUHKLHGFJLYRY-UHFFFAOYSA-N 0.000 description 1
- IJHJVBXIXJMORX-UHFFFAOYSA-N tert-butyl 7-(2-methoxy-2-oxoethyl)-3,4-dihydro-2h-1,8-naphthyridine-1-carboxylate Chemical compound C1CCN(C(=O)OC(C)(C)C)C2=NC(CC(=O)OC)=CC=C21 IJHJVBXIXJMORX-UHFFFAOYSA-N 0.000 description 1
- CYPOVXLEGDEOSP-UHFFFAOYSA-N tert-butyl 7-ethenyl-3,4-dihydro-2h-1,8-naphthyridine-1-carboxylate Chemical compound C1=C(C=C)N=C2N(C(=O)OC(C)(C)C)CCCC2=C1 CYPOVXLEGDEOSP-UHFFFAOYSA-N 0.000 description 1
- XGTPDIIFEPTULX-UHFFFAOYSA-N tert-butyl prop-2-ynoate Chemical compound CC(C)(C)OC(=O)C#C XGTPDIIFEPTULX-UHFFFAOYSA-N 0.000 description 1
- TYQUQRGGXWJRAR-UHFFFAOYSA-N tert-butyl-(1h-indazol-5-yloxy)-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OC1=CC=C2NN=CC2=C1 TYQUQRGGXWJRAR-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-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
- 230000002381 testicular Effects 0.000 description 1
- NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- 125000005403 thiohaloalkoxy group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical compound O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 description 1
- 229940110309 tiotropium Drugs 0.000 description 1
- 229950004996 tipelukast Drugs 0.000 description 1
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229950000835 tralokinumab Drugs 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 1
- 229960002117 triamcinolone acetonide Drugs 0.000 description 1
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical group CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- GGUBFICZYGKNTD-UHFFFAOYSA-N triethyl phosphonoacetate Chemical compound CCOC(=O)CP(=O)(OCC)OCC GGUBFICZYGKNTD-UHFFFAOYSA-N 0.000 description 1
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 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
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- REQQVBGILUTQNN-UHFFFAOYSA-N ziritaxestat Chemical compound CCC=1N=C2C(C)=CC(N3CCN(CC(=O)N4CC(O)C4)CC3)=CN2C=1N(C)C(SC=1C#N)=NC=1C1=CC=C(F)C=C1 REQQVBGILUTQNN-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/498—Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5355—Non-condensed oxazines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D498/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Pulmonology (AREA)
- Transplantation (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662418842P | 2016-11-08 | 2016-11-08 | |
| US62/418,842 | 2016-11-08 | ||
| PCT/US2017/060386 WO2018089357A1 (en) | 2016-11-08 | 2017-11-07 | INDAZOLE DERIVATIVES AS αV INTEGRIN ANTAGONISTS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN110214137A true CN110214137A (zh) | 2019-09-06 |
Family
ID=60409436
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201780082125.5A Pending CN110214137A (zh) | 2016-11-08 | 2017-11-07 | 作为αv整联蛋白拮抗剂的吲唑衍生物 |
Country Status (13)
| Country | Link |
|---|---|
| US (2) | US10745384B2 (enExample) |
| EP (1) | EP3538519B1 (enExample) |
| JP (1) | JP7213804B2 (enExample) |
| KR (1) | KR102506327B1 (enExample) |
| CN (1) | CN110214137A (enExample) |
| AU (1) | AU2017359027A1 (enExample) |
| CA (1) | CA3042714A1 (enExample) |
| EA (1) | EA201991123A1 (enExample) |
| ES (1) | ES2886650T3 (enExample) |
| IL (1) | IL266472A (enExample) |
| MA (1) | MA46745A (enExample) |
| MX (1) | MX378565B (enExample) |
| WO (1) | WO2018089357A1 (enExample) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW201823208A (zh) | 2016-09-07 | 2018-07-01 | 美商普萊恩醫療公司 | N－醯基胺基酸化合物及其使用方法 |
| MA46745A (fr) * | 2016-11-08 | 2021-03-31 | Bristol Myers Squibb Co | Dérivés d'indazole en tant qu'antagonistes de l'intégrine alpha v |
| MX2019007797A (es) | 2016-12-29 | 2019-10-21 | Univ Saint Louis | Antagonistas de integrinas. |
| CN116283977A (zh) | 2017-02-28 | 2023-06-23 | 莫菲克医疗股份有限公司 | αvβ6整合蛋白的抑制剂 |
| EP3589285A4 (en) | 2017-02-28 | 2020-08-12 | Morphic Therapeutic, Inc. | INHIBITORS OF INTEGRIN (ALPHA-V) (BETA-6) |
| SG11202101913PA (en) | 2018-08-29 | 2021-03-30 | Morphic Therapeutic Inc | INHIBITING aV ß6 INTEGRIN |
| PL3873605T3 (pl) | 2018-10-30 | 2025-03-03 | Gilead Sciences, Inc. | Związki hamujące integrynę alfa4beta7 |
| DK3873884T3 (da) | 2018-10-30 | 2025-02-17 | Gilead Sciences Inc | 3-(quinolin-8-yl)-1,4-dihydropyrido[3,4-d]pyrimidin-2,4-dion-derivater som alpha4beta7-integrinhæmmere til behandling af inflammatoriske sygdomme |
| EP3873897B1 (en) | 2018-10-30 | 2024-08-14 | Gilead Sciences, Inc. | N-benzoyl-phenylalanine derivatives as alpha4beta7 integrin inhibitors for treating inflammatory diseases |
| WO2020092394A1 (en) | 2018-10-30 | 2020-05-07 | Gilead Sciences, Inc. | Imidazopyridine derivatives as alpha4beta7 integrin inhibitors |
| US11578069B2 (en) | 2019-08-14 | 2023-02-14 | Gilead Sciences, Inc. | Compounds for inhibition of α4 β7 integrin |
| KR102048050B1 (ko) * | 2019-08-29 | 2020-01-22 | 대한민국 | Adb-푸비나카의 대사체 합성 방법 |
| WO2021059023A1 (en) | 2019-09-26 | 2021-04-01 | Abionyx Pharma Sa | Compounds useful for treating liver diseases |
| WO2022189856A1 (en) | 2021-03-08 | 2022-09-15 | Abionyx Pharma Sa | Compounds useful for treating liver diseases |
| WO2022202864A1 (ja) * | 2021-03-24 | 2022-09-29 | 塩野義製薬株式会社 | 縮合環を有するｇｌｐ－１受容体作動薬を含有する医薬組成物 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002060438A1 (en) * | 2001-01-29 | 2002-08-08 | 3-Dimensional Pharmaceuticals, Inc. | Substituted indoles and their use as integrin antagonists |
| WO2006108040A1 (en) * | 2005-04-05 | 2006-10-12 | Janssen Pharmaceutica, N.V. | Substituted indoles and their use as integrin antagonists |
| WO2007141473A1 (en) * | 2006-06-09 | 2007-12-13 | Astrazeneca Ab | N-(benzoyl)-o- [2- (pyridin- 2 -ylamino) ethyl] -l-tyrosine derivatives and related compounds as a5b1 antagonists for the treatment of solid tumors |
| WO2015091426A1 (de) * | 2013-12-19 | 2015-06-25 | Bayer Pharma Aktiengesellschaft | Neue indazolcarboxamide, verfahren zu ihrer herstellung, pharmazeutische präparate die diese enthalten, sowie deren verwendung zur herstellung von arzneimitteln |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5849736A (en) | 1993-11-24 | 1998-12-15 | The Dupont Merck Pharmaceutical Company | Isoxazoline and isoxazole fibrinogen receptor antagonists |
| CA2240439A1 (en) * | 1995-12-22 | 1997-07-03 | The Dupont Merck Pharmaceutical Company | Novel integrin receptor antagonists |
| ZA972195B (en) | 1996-03-15 | 1998-09-14 | Du Pont Merck Pharma | Spirocycle integrin inhibitors |
| IL136267A0 (en) | 1997-11-26 | 2001-05-20 | Du Pont Pharm Co | 1,3,4-THIADIZOLES AND 1,3,4-OXADIAZOLES AS αVβ3 ANTAGONISTS |
| JP2002508323A (ja) | 1997-12-17 | 2002-03-19 | メルク エンド カムパニー インコーポレーテッド | インテグリン受容体拮抗薬 |
| JP2002522540A (ja) | 1998-08-13 | 2002-07-23 | メルク エンド カムパニー インコーポレーテッド | インテグリン受容体拮抗薬 |
| US6921767B2 (en) | 2000-06-15 | 2005-07-26 | Pharmacia Corporation | Cycloalkyl alkanoic acids as integrin receptor antagonists derivatives |
| US6872730B2 (en) * | 2001-04-27 | 2005-03-29 | 3-Dimensional Pharmaceuticals, Inc. | Substituted benzofurans and benzothiophenes, methods of making and methods of use as integrin antagonists |
| RU2311177C2 (ru) * | 2001-08-01 | 2007-11-27 | Мерк Патент Гмбх | Ингибиторы интегрина для лечения заболевания глаз |
| WO2008125811A1 (en) | 2007-04-11 | 2008-10-23 | Astrazeneca Ab | N-[HETEROARYLCARBONYL]-S-THIENYL-L-ALANINE DERIVATIVES AS α5β1 ANTAGONISTS |
| ITFI20100019A1 (it) | 2010-02-12 | 2011-08-13 | Univ Firenze | Inibitori peptidomimetici di integrine basati sull'1,2,3-triazolo per la diagnosi e terapia dei tumori. |
| GB201305668D0 (en) | 2013-03-28 | 2013-05-15 | Glaxosmithkline Ip Dev Ltd | Avs6 Integrin Antagonists |
| JP6387100B2 (ja) | 2014-08-08 | 2018-09-05 | 株式会社Ｆｕｊｉ | スクリーン印刷装置 |
| GB201417011D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201417002D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compound |
| GB201417018D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| GB201417094D0 (en) | 2014-09-26 | 2014-11-12 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
| CA2976634C (en) | 2015-02-19 | 2023-10-17 | Scifluor Life Sciences, Inc | Fluorinated tetrahydronaphthyridinyl nonanoic acid derivatives and uses thereof |
| WO2016145258A1 (en) | 2015-03-10 | 2016-09-15 | The Regents Of The University Of California | Anti-alphavbeta1 integrin inhibitors and methods of use |
| MA46745A (fr) * | 2016-11-08 | 2021-03-31 | Bristol Myers Squibb Co | Dérivés d'indazole en tant qu'antagonistes de l'intégrine alpha v |
-
2017
- 2017-11-07 MA MA046745A patent/MA46745A/fr unknown
- 2017-11-07 ES ES17801234T patent/ES2886650T3/es active Active
- 2017-11-07 CN CN201780082125.5A patent/CN110214137A/zh active Pending
- 2017-11-07 AU AU2017359027A patent/AU2017359027A1/en not_active Abandoned
- 2017-11-07 EA EA201991123A patent/EA201991123A1/ru unknown
- 2017-11-07 EP EP17801234.0A patent/EP3538519B1/en active Active
- 2017-11-07 US US16/347,831 patent/US10745384B2/en active Active
- 2017-11-07 JP JP2019523838A patent/JP7213804B2/ja active Active
- 2017-11-07 KR KR1020197016080A patent/KR102506327B1/ko active Active
- 2017-11-07 MX MX2019005243A patent/MX378565B/es unknown
- 2017-11-07 WO PCT/US2017/060386 patent/WO2018089357A1/en not_active Ceased
- 2017-11-07 CA CA3042714A patent/CA3042714A1/en not_active Abandoned
-
2019
- 2019-05-06 IL IL266472A patent/IL266472A/en unknown
-
2020
- 2020-07-09 US US16/924,346 patent/US11028071B2/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002060438A1 (en) * | 2001-01-29 | 2002-08-08 | 3-Dimensional Pharmaceuticals, Inc. | Substituted indoles and their use as integrin antagonists |
| WO2006108040A1 (en) * | 2005-04-05 | 2006-10-12 | Janssen Pharmaceutica, N.V. | Substituted indoles and their use as integrin antagonists |
| WO2007141473A1 (en) * | 2006-06-09 | 2007-12-13 | Astrazeneca Ab | N-(benzoyl)-o- [2- (pyridin- 2 -ylamino) ethyl] -l-tyrosine derivatives and related compounds as a5b1 antagonists for the treatment of solid tumors |
| WO2015091426A1 (de) * | 2013-12-19 | 2015-06-25 | Bayer Pharma Aktiengesellschaft | Neue indazolcarboxamide, verfahren zu ihrer herstellung, pharmazeutische präparate die diese enthalten, sowie deren verwendung zur herstellung von arzneimitteln |
Non-Patent Citations (2)
| Title |
|---|
| PIERRE RABOISSON: "identification of novel short chain 4-substituted indoles as potent αVβ3 drug design", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 * |
| TOBIAS G KAPP: "Integrin modulators:a patent review", 《EXPERT OPINION ON THERAPEUTIC PATENTS 》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| JP2019536768A (ja) | 2019-12-19 |
| KR20190076033A (ko) | 2019-07-01 |
| MA46745A (fr) | 2021-03-31 |
| US20190256496A1 (en) | 2019-08-22 |
| ES2886650T3 (es) | 2021-12-20 |
| EA201991123A1 (ru) | 2019-11-29 |
| MX378565B (es) | 2025-03-10 |
| US20200339540A1 (en) | 2020-10-29 |
| KR102506327B1 (ko) | 2023-03-03 |
| IL266472A (en) | 2019-07-31 |
| EP3538519A1 (en) | 2019-09-18 |
| AU2017359027A1 (en) | 2019-06-20 |
| JP7213804B2 (ja) | 2023-01-27 |
| US10745384B2 (en) | 2020-08-18 |
| MX2019005243A (es) | 2019-08-05 |
| WO2018089357A1 (en) | 2018-05-17 |
| CA3042714A1 (en) | 2018-05-17 |
| EP3538519B1 (en) | 2021-07-28 |
| US11028071B2 (en) | 2021-06-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11028071B2 (en) | Indazole derivatives as alpha v integrin antagonists | |
| CN110167934B (zh) | 作为αV整联蛋白抑制剂的含有环丁烷和含有氮杂环丁烷的单环和螺环化合物 | |
| CN110167933B (zh) | 作为αV整联蛋白抑制剂的唑酰胺和胺 | |
| CN110139864B (zh) | 作为αV整联蛋白抑制剂的吡咯酰胺 | |
| CN105492444B (zh) | 作为rock抑制剂的三环吡啶-甲酰胺衍生物 | |
| CN110167935B (zh) | 作为αV整合素抑制剂的3-经取代的丙酸 | |
| CN108699038A (zh) | 作为Rock抑制剂的螺环庚烷水杨酸酰胺和相关化合物 | |
| CN111433207B (zh) | 作为αV整合素抑制剂的吡咯并吡嗪衍生物 | |
| JP7223016B2 (ja) | ファルネソイドｘ受容体モジュレーターとしてのアルケンスピロ環化合物 | |
| CN111278817A (zh) | 作为法尼醇x受体调节剂的多环化合物 | |
| CN117242061A (zh) | 用于治疗艰难梭菌的二氮杂卓衍生物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |