BR112018007664B1 - Compostos antagonistas de ep4, composição compreendendo o composto e uso dos mesmos para tratar câncer - Google Patents

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Publication number

BR112018007664B1

BR112018007664B1 BR112018007664-3A BR112018007664A BR112018007664B1 BR 112018007664 B1 BR112018007664 B1 BR 112018007664B1 BR 112018007664 A BR112018007664 A BR 112018007664A BR 112018007664 B1 BR112018007664 B1 BR 112018007664B1

Authority

BR

Brazil

Prior art keywords

trifluoromethyl

imidazo

ethyl

dihydro

pyrazol

Prior art date

2015-10-16

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 237
• 206010028980 Neoplasm Diseases 0.000 title claims abstract description 138
• 201000011510 cancer Diseases 0.000 title claims abstract description 66
• 239000000203 mixture Substances 0.000 title abstract description 150
• 239000005557 antagonist Substances 0.000 title abstract description 5
• 150000003839 salts Chemical class 0.000 claims abstract description 45
• WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 470
• 239000002253 acid Substances 0.000 claims description 361
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 294
• -1 -CH2OH Chemical group 0.000 claims description 183
• 239000005711 Benzoic acid Substances 0.000 claims description 176
• 235000010233 benzoic acid Nutrition 0.000 claims description 176
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 90
• 125000005518 carboxamido group Chemical group 0.000 claims description 30
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 30
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 29
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
• 239000008194 pharmaceutical composition Substances 0.000 claims description 21
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 20
• 229910052799 carbon Inorganic materials 0.000 claims description 19
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 18
• FXCMBRNTTSRLGY-ZDUSSCGKSA-N 4-[(1S)-1-[[6-(trifluoromethyl)-1-[[3-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound FC(C=1C(=C2N(N=1)CCN2CC1=CC(=CC=C1)C(F)(F)F)C(=O)N[C@@H](C)C1=CC=C(C(=O)O)C=C1)(F)F FXCMBRNTTSRLGY-ZDUSSCGKSA-N 0.000 claims description 17
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 14
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
• BEFFDYDYZGETQK-AWEZNQCLSA-N 4-[(1S)-1-[[1-[[3-(chloromethyl)phenyl]methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound ClCC=1C=C(CN2CCN3N=C(C(=C32)C(=O)N[C@@H](C)C2=CC=C(C(=O)O)C=C2)C(F)(F)F)C=CC=1 BEFFDYDYZGETQK-AWEZNQCLSA-N 0.000 claims description 10
• 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 10
• 206010009944 Colon cancer Diseases 0.000 claims description 9
• 201000000459 head and neck squamous cell carcinoma Diseases 0.000 claims description 9
• 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 9
• 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 9
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 9
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 9
• QHGMILBHUDIACW-FHERZECASA-N 4-[(1S)-1-[[1-[[4-(fluoromethyl)cyclohexyl]methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound C[C@H](NC(=O)C1=C2N(CC3CCC(CF)CC3)CCN2N=C1C(F)(F)F)C1=CC=C(C=C1)C(O)=O QHGMILBHUDIACW-FHERZECASA-N 0.000 claims description 7
• 206010005003 Bladder cancer Diseases 0.000 claims description 6
• 206010008342 Cervix carcinoma Diseases 0.000 claims description 6
• 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 claims description 6
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 6
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 6
• 201000010881 cervical cancer Diseases 0.000 claims description 6
• 239000003814 drug Substances 0.000 claims description 6
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 6
• 201000005112 urinary bladder cancer Diseases 0.000 claims description 6
• CBFSANWUGZMIDS-HNNXBMFYSA-N 4-[(1S)-1-[[1-[[4-(3-fluoropropyl)-3-(trifluoromethyl)phenyl]methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound FCCCC1=C(C=C(CN2CCN3N=C(C(=C32)C(=O)N[C@@H](C)C2=CC=C(C(=O)O)C=C2)C(F)(F)F)C=C1)C(F)(F)F CBFSANWUGZMIDS-HNNXBMFYSA-N 0.000 claims description 5
• VTTJSCZIFMDAOP-ZDUSSCGKSA-N 4-[(1S)-1-[[6-(difluoromethyl)-1-[[3-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound FC(C=1C(=C2N(N=1)CCN2CC1=CC(=CC=C1)C(F)(F)F)C(=O)N[C@@H](C)C1=CC=C(C(=O)O)C=C1)F VTTJSCZIFMDAOP-ZDUSSCGKSA-N 0.000 claims description 5
• OQSOZOZUBZYDDB-AWEZNQCLSA-N 4-[(1S)-1-[[6-(hydroxymethyl)-1-[[3-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound C[C@H](NC(=O)c1c(CO)nn2CCN(Cc3cccc(c3)C(F)(F)F)c12)c1ccc(cc1)C(O)=O OQSOZOZUBZYDDB-AWEZNQCLSA-N 0.000 claims description 5
• LLWMHWHDBAYPBB-ZDUSSCGKSA-N 4-[(1S)-1-[[6-(trifluoromethyl)-1-[[2-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound C[C@H](NC(=O)C1=C2N(CC3=C(C=CC=C3)C(F)(F)F)CCN2N=C1C(F)(F)F)C1=CC=C(C=C1)C(O)=O LLWMHWHDBAYPBB-ZDUSSCGKSA-N 0.000 claims description 5
• DGVHXEAJFGVTSE-INIZCTEOSA-N N-[(1S)-1-[4-[(3,4-difluorophenyl)sulfonylcarbamoyl]phenyl]ethyl]-6-(trifluoromethyl)-1-[[3-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxamide Chemical compound FC=1C=C(C=CC=1F)S(=O)(=O)NC(=O)C1=CC=C(C=C1)[C@H](C)NC(=O)C1=C2N(N=C1C(F)(F)F)CCN2CC1=CC(=CC=C1)C(F)(F)F DGVHXEAJFGVTSE-INIZCTEOSA-N 0.000 claims description 5
• 206010033128 Ovarian cancer Diseases 0.000 claims description 5
• HFMRGFYRDGOFSK-HNNXBMFYSA-N 4-[(1S)-1-[[1-[[3-(dimethylamino)phenyl]methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound C[C@H](NC(=O)c1c(nn2CCN(Cc3cccc(c3)N(C)C)c12)C(F)(F)F)c1ccc(cc1)C(O)=O HFMRGFYRDGOFSK-HNNXBMFYSA-N 0.000 claims description 4
• FKJCNFLQSDQIGQ-UHFFFAOYSA-N 4-[1-[[6-methyl-1-[[4-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]cyclopropyl]benzoic acid Chemical compound CC=1C(=C2N(N=1)CCN2CC1=CC=C(C=C1)C(F)(F)F)C(=O)NC1(CC1)C1=CC=C(C(=O)O)C=C1 FKJCNFLQSDQIGQ-UHFFFAOYSA-N 0.000 claims description 4
• DKRFNIRCESYVBB-AWEZNQCLSA-N N-[(1S)-1-[4-(cyanocarbamoyl)phenyl]ethyl]-6-(trifluoromethyl)-1-[[3-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxamide Chemical compound C(#N)NC(=O)C1=CC=C(C=C1)[C@H](C)NC(=O)C1=C2N(N=C1C(F)(F)F)CCN2CC1=CC(=CC=C1)C(F)(F)F DKRFNIRCESYVBB-AWEZNQCLSA-N 0.000 claims 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 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• MYSPBBWKRKFYRR-AWEZNQCLSA-N 4-[(1S)-1-[[1-[(4-chlorophenyl)methyl]-6-methyl-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound C[C@H](NC(=O)C1=C2N(CC3=CC=C(Cl)C=C3)CCN2N=C1C)C1=CC=C(C=C1)C(O)=O MYSPBBWKRKFYRR-AWEZNQCLSA-N 0.000 claims description 3
• FCFYSCJVOKDMAR-HNNXBMFYSA-N 4-[(1S)-1-[[1-[[3-(3-fluoropropyl)-5-(trifluoromethyl)phenyl]methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound C[C@H](NC(=O)C1=C2N(CC3=CC(CCCF)=CC(=C3)C(F)(F)F)CCN2N=C1C(F)(F)F)C1=CC=C(C=C1)C(O)=O FCFYSCJVOKDMAR-HNNXBMFYSA-N 0.000 claims description 3
• LOBZFUUTCRAOIK-ZDUSSCGKSA-N 4-[(1S)-1-[[1-[[3-methylsulfanyl-5-(trifluoromethyl)phenyl]methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound CSc1cc(CN2CCn3nc(c(C(=O)N[C@@H](C)c4ccc(cc4)C(O)=O)c23)C(F)(F)F)cc(c1)C(F)(F)F LOBZFUUTCRAOIK-ZDUSSCGKSA-N 0.000 claims description 3
• YDXGJXMMZFGYHU-AWEZNQCLSA-N 4-[(1S)-1-[[1-benzyl-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound C[C@H](NC(=O)c1c(nn2CCN(Cc3ccccc3)c12)C(F)(F)F)c1ccc(cc1)C(O)=O YDXGJXMMZFGYHU-AWEZNQCLSA-N 0.000 claims description 3
• FJEJVYMWYLLYOU-ZDUSSCGKSA-N 4-[(1S)-1-[[2-(trifluoromethyl)-4-[4-(trifluoromethyl)phenyl]-6,7-dihydro-5H-pyrazolo[1,5-a]pyrimidine-3-carbonyl]amino]ethyl]benzoic acid Chemical compound C[C@H](NC(=O)C1=C2N(CCCN2C2=CC=C(C=C2)C(F)(F)F)N=C1C(F)(F)F)C1=CC=C(C=C1)C(O)=O FJEJVYMWYLLYOU-ZDUSSCGKSA-N 0.000 claims description 3
• RCKMLUHIDNKCJQ-LBPRGKRZSA-N 4-[(1S)-1-[[6-(trifluoromethyl)-1-[3-(trifluoromethyl)phenyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound C[C@H](NC(=O)C1=C2N(CCN2C2=CC(=CC=C2)C(F)(F)F)N=C1C(F)(F)F)C1=CC=C(C=C1)C(O)=O RCKMLUHIDNKCJQ-LBPRGKRZSA-N 0.000 claims description 3
• PQARKUPQWKORDD-LBPRGKRZSA-N 4-[(1S)-1-[[6-(trifluoromethyl)-1-[4-(trifluoromethyl)phenyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound C[C@H](NC(=O)c1c(nn2CCN(c12)c1ccc(cc1)C(F)(F)F)C(F)(F)F)c1ccc(cc1)C(O)=O PQARKUPQWKORDD-LBPRGKRZSA-N 0.000 claims description 3
• UETDGZYHPIKQKO-ZDUSSCGKSA-N 4-[(1S)-1-[[6-(trifluoromethyl)-1-[[4-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound C[C@H](NC(=O)C1=C2N(CC3=CC=C(C=C3)C(F)(F)F)CCN2N=C1C(F)(F)F)C1=CC=C(C=C1)C(O)=O UETDGZYHPIKQKO-ZDUSSCGKSA-N 0.000 claims description 3
• IGYMWRCBBCGCPD-UHFFFAOYSA-N 4-[1-[[1-[(4-chlorophenyl)methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]cyclopropyl]benzoic acid Chemical compound ClC1=CC=C(CN2CCN3N=C(C(=C32)C(=O)NC2(CC2)C2=CC=C(C(=O)O)C=C2)C(F)(F)F)C=C1 IGYMWRCBBCGCPD-UHFFFAOYSA-N 0.000 claims description 3
• QPYVCVOJUUYQRA-UHFFFAOYSA-N 4-[[[1-[(4-chlorophenyl)methyl]-6-methyl-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]methyl]benzoic acid Chemical compound CC1=NN2CCN(CC3=CC=C(Cl)C=C3)C2=C1C(=O)NCC1=CC=C(C=C1)C(O)=O QPYVCVOJUUYQRA-UHFFFAOYSA-N 0.000 claims description 3
• AYCDVHZVHJJZOS-HNNXBMFYSA-N N-[(1S)-1-(4-cyclopropylphenyl)ethyl]-6-(trifluoromethyl)-1-[[4-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxamide Chemical compound C[C@H](NC(=O)C1=C2N(CC3=CC=C(C=C3)C(F)(F)F)CCN2N=C1C(F)(F)F)C1=CC=C(C=C1)C1CC1 AYCDVHZVHJJZOS-HNNXBMFYSA-N 0.000 claims description 3
• GDZONDXTSVPCIJ-AWEZNQCLSA-N N-[(1S)-1-[3-methyl-4-(2H-tetrazol-5-yl)phenyl]ethyl]-6-(trifluoromethyl)-1-[[4-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxamide Chemical compound C[C@H](NC(=O)C1=C2N(CC3=CC=C(C=C3)C(F)(F)F)CCN2N=C1C(F)(F)F)C1=CC(C)=C(C=C1)C1=NNN=N1 GDZONDXTSVPCIJ-AWEZNQCLSA-N 0.000 claims description 3
• ZSUUBVQCONIHAJ-ZDUSSCGKSA-N N-[(1S)-1-[4-(2H-tetrazol-5-yl)phenyl]ethyl]-6-(trifluoromethyl)-1-[[3-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxamide Chemical compound C[C@H](NC(=O)C1=C2N(CC3=CC(=CC=C3)C(F)(F)F)CCN2N=C1C(F)(F)F)C1=CC=C(C=C1)C1=NNN=N1 ZSUUBVQCONIHAJ-ZDUSSCGKSA-N 0.000 claims description 3
• XOFNZIDDFFYOCG-ZDUSSCGKSA-N N-[(1S)-1-[4-(2H-tetrazol-5-yl)phenyl]ethyl]-6-(trifluoromethyl)-1-[[4-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxamide Chemical compound N=1NN=NC=1C1=CC=C(C=C1)[C@H](C)NC(=O)C1=C2N(N=C1C(F)(F)F)CCN2CC1=CC=C(C=C1)C(F)(F)F XOFNZIDDFFYOCG-ZDUSSCGKSA-N 0.000 claims description 3
• ZQYAIENGHRVVNX-SFHVURJKSA-N N-[(1S)-1-[4-(benzenesulfonylcarbamoyl)phenyl]ethyl]-1-[[3-(trifluoromethoxy)phenyl]methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxamide Chemical compound C[C@H](NC(=O)c1c(nn2CCN(Cc3cccc(OC(F)(F)F)c3)c12)C(F)(F)F)c1ccc(cc1)C(=O)NS(=O)(=O)c1ccccc1 ZQYAIENGHRVVNX-SFHVURJKSA-N 0.000 claims description 3
• ZPGSEUYIAIQFOP-HNNXBMFYSA-N N-[(1S)-1-[4-(cyclopropylsulfonylcarbamoyl)phenyl]ethyl]-6-(trifluoromethyl)-1-[[3-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxamide Chemical compound C[C@H](NC(=O)C1=C2N(CC3=CC(=CC=C3)C(F)(F)F)CCN2N=C1C(F)(F)F)C1=CC=C(C=C1)C(=O)NS(=O)(=O)C1CC1 ZPGSEUYIAIQFOP-HNNXBMFYSA-N 0.000 claims description 3
• UTYAZVQWAKJCCB-INIZCTEOSA-N N-[(1S)-1-[4-(furan-3-yl)phenyl]ethyl]-6-(trifluoromethyl)-1-[[4-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxamide Chemical compound O1C=C(C=C1)C1=CC=C(C=C1)[C@H](C)NC(=O)C1=C2N(N=C1C(F)(F)F)CCN2CC1=CC=C(C=C1)C(F)(F)F UTYAZVQWAKJCCB-INIZCTEOSA-N 0.000 claims description 3
• FGAHPKTWBLOGGV-AWEZNQCLSA-N N-[(1S)-1-[4-(methylsulfonylcarbamoyl)phenyl]ethyl]-6-(trifluoromethyl)-1-[[3-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxamide Chemical compound C[C@H](NC(=O)C1=C2N(CC3=CC(=CC=C3)C(F)(F)F)CCN2N=C1C(F)(F)F)C1=CC=C(C=C1)C(=O)NS(C)(=O)=O FGAHPKTWBLOGGV-AWEZNQCLSA-N 0.000 claims description 3
• WPVUUOBTLLUKPA-KRWDZBQOSA-N N-[(1S)-1-[4-[(4-aminophenyl)sulfonylcarbamoyl]phenyl]ethyl]-6-(trifluoromethyl)-1-[[3-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxamide Chemical compound NC1=CC=C(C=C1)S(=O)(=O)NC(=O)C1=CC=C(C=C1)[C@H](C)NC(=O)C1=C2N(N=C1C(F)(F)F)CCN2CC1=CC(=CC=C1)C(F)(F)F WPVUUOBTLLUKPA-KRWDZBQOSA-N 0.000 claims description 3
• 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
• 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
• 208000006265 Renal cell carcinoma Diseases 0.000 claims description 3
• 125000001821 azanediyl group Chemical group [H]N(*)* 0.000 claims description 3
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 3
• 201000002528 pancreatic cancer Diseases 0.000 claims description 3
• 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
• AIXRGUMOSJCSAV-SCLBCKFNSA-N 4-[(1S)-1-[[(3S)-3-(fluoromethyl)-6-(trifluoromethyl)-1-[[3-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound C[C@H](NC(=O)c1c(nn2[C@H](CF)CN(Cc3cccc(c3)C(F)(F)F)c12)C(F)(F)F)c1ccc(cc1)C(O)=O AIXRGUMOSJCSAV-SCLBCKFNSA-N 0.000 claims description 2
• MCXRAALCXZRLBN-UGSOOPFHSA-N 4-[(1S)-1-[[(3S)-3-(hydroxymethyl)-6-(trifluoromethyl)-1-[[3-(trifluoromethyl)phenyl]methyl]-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound OC[C@@H]1CN(C=2N1N=C(C=2C(=O)N[C@@H](C)C1=CC=C(C(=O)O)C=C1)C(F)(F)F)CC1=CC(=CC=C1)C(F)(F)F MCXRAALCXZRLBN-UGSOOPFHSA-N 0.000 claims description 2
• NYHFQQMVQFJALI-AWEZNQCLSA-N 4-[(1S)-1-[[1-[[3-(1,1-difluoro-2-hydroxyethyl)phenyl]methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound C[C@H](NC(=O)C1=C2N(CC3=CC(=CC=C3)C(F)(F)CO)CCN2N=C1C(F)(F)F)C1=CC=C(C=C1)C(O)=O NYHFQQMVQFJALI-AWEZNQCLSA-N 0.000 claims description 2
• ATAAVKLFUSWCPR-AWEZNQCLSA-N 4-[(1S)-1-[[1-[[3-(dimethylamino)-5-(trifluoromethyl)phenyl]methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound CN(C=1C=C(CN2CCN3N=C(C(=C32)C(=O)N[C@@H](C)C2=CC=C(C(=O)O)C=C2)C(F)(F)F)C=C(C=1)C(F)(F)F)C ATAAVKLFUSWCPR-AWEZNQCLSA-N 0.000 claims description 2
• POARJDBPIPHYIJ-AWEZNQCLSA-N 4-[(1S)-1-[[1-[[3-(fluoromethyl)phenyl]methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carbonyl]amino]ethyl]benzoic acid Chemical compound C[C@H](NC(=O)c1c(nn2CCN(Cc3cccc(CF)c3)c12)C(F)(F)F)c1ccc(cc1)C(O)=O POARJDBPIPHYIJ-AWEZNQCLSA-N 0.000 claims description 2
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• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
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• YMGRBFZSBHLOIO-UHFFFAOYSA-N methyl 1-(3-chlorophenyl)-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxylate Chemical compound COC(=O)c1c(nn2CCN(c12)c1cccc(Cl)c1)C(F)(F)F YMGRBFZSBHLOIO-UHFFFAOYSA-N 0.000 description 2
• FYZYITMDSZCPKM-UHFFFAOYSA-N methyl 1-[(2-chlorophenyl)methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxylate Chemical compound COC(=O)c1c(nn2CCN(Cc3ccccc3Cl)c12)C(F)(F)F FYZYITMDSZCPKM-UHFFFAOYSA-N 0.000 description 2
• CHMUBYYOKBWXGJ-UHFFFAOYSA-N methyl 1-[(2-fluorophenyl)methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxylate Chemical compound COC(=O)c1c(nn2CCN(Cc3ccccc3F)c12)C(F)(F)F CHMUBYYOKBWXGJ-UHFFFAOYSA-N 0.000 description 2
• ADLLMNWCKWJKCP-UHFFFAOYSA-N methyl 1-[(2-methylphenyl)methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxylate Chemical compound COC(=O)c1c(nn2CCN(Cc3ccccc3C)c12)C(F)(F)F ADLLMNWCKWJKCP-UHFFFAOYSA-N 0.000 description 2
• PIVWDGJXXIXKLF-UHFFFAOYSA-N methyl 1-[(3,4-dichlorophenyl)methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxylate Chemical compound COC(=O)c1c(nn2CCN(Cc3ccc(Cl)c(Cl)c3)c12)C(F)(F)F PIVWDGJXXIXKLF-UHFFFAOYSA-N 0.000 description 2
• VWBLMUYOIAUFGK-UHFFFAOYSA-N methyl 1-[(3,5-dichlorophenyl)methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxylate Chemical compound COC(=O)c1c(nn2CCN(Cc3cc(Cl)cc(Cl)c3)c12)C(F)(F)F VWBLMUYOIAUFGK-UHFFFAOYSA-N 0.000 description 2
• NDAQFTCFEUCGQM-UHFFFAOYSA-N methyl 1-[(3-chlorophenyl)methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxylate Chemical compound COC(=O)c1c(nn2CCN(Cc3cccc(Cl)c3)c12)C(F)(F)F NDAQFTCFEUCGQM-UHFFFAOYSA-N 0.000 description 2
• JKFVMKQEMXDXGS-UHFFFAOYSA-N methyl 1-[(3-fluorophenyl)methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxylate Chemical compound COC(=O)c1c(nn2CCN(Cc3cccc(F)c3)c12)C(F)(F)F JKFVMKQEMXDXGS-UHFFFAOYSA-N 0.000 description 2
• JWFFLEWOEJYLOE-UHFFFAOYSA-N methyl 1-[(3-methoxyphenyl)methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxylate Chemical compound COC(=O)c1c(nn2CCN(Cc3cccc(OC)c3)c12)C(F)(F)F JWFFLEWOEJYLOE-UHFFFAOYSA-N 0.000 description 2
• NMVLNVZOGLQONP-UHFFFAOYSA-N methyl 1-[(3-methylphenyl)methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxylate Chemical compound COC(=O)c1c(nn2CCN(Cc3cccc(C)c3)c12)C(F)(F)F NMVLNVZOGLQONP-UHFFFAOYSA-N 0.000 description 2
• GFPDRCMARJEVSA-UHFFFAOYSA-N methyl 1-[(4-chlorophenyl)methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxylate Chemical compound COC(=O)c1c(nn2CCN(Cc3ccc(Cl)cc3)c12)C(F)(F)F GFPDRCMARJEVSA-UHFFFAOYSA-N 0.000 description 2
• VJUYDFHVSSLACL-UHFFFAOYSA-N methyl 1-[(4-fluorophenyl)methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxylate Chemical compound COC(=O)c1c(nn2CCN(Cc3ccc(F)cc3)c12)C(F)(F)F VJUYDFHVSSLACL-UHFFFAOYSA-N 0.000 description 2
• SWKRDEKRNNMCQD-UHFFFAOYSA-N methyl 1-[(4-methoxyphenyl)methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxylate Chemical compound COC(=O)c1c(nn2CCN(Cc3ccc(OC)cc3)c12)C(F)(F)F SWKRDEKRNNMCQD-UHFFFAOYSA-N 0.000 description 2
• NBEHXZXELWLCLI-UHFFFAOYSA-N methyl 1-[(4-methylphenyl)methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxylate Chemical compound COC(=O)c1c(nn2CCN(Cc3ccc(C)cc3)c12)C(F)(F)F NBEHXZXELWLCLI-UHFFFAOYSA-N 0.000 description 2
• JVSZMQCRSFFRCO-UHFFFAOYSA-N methyl 1-[[3-(trifluoromethoxy)phenyl]methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxylate Chemical compound COC(=O)c1c(nn2CCN(Cc3cccc(OC(F)(F)F)c3)c12)C(F)(F)F JVSZMQCRSFFRCO-UHFFFAOYSA-N 0.000 description 2
• DTGJQLJJBXFWCO-UHFFFAOYSA-N methyl 1-[[4-(trifluoromethoxy)phenyl]methyl]-6-(trifluoromethyl)-2,3-dihydroimidazo[1,2-b]pyrazole-7-carboxylate Chemical compound COC(=O)c1c(nn2CCN(Cc3ccc(OC(F)(F)F)cc3)c12)C(F)(F)F DTGJQLJJBXFWCO-UHFFFAOYSA-N 0.000 description 2
• VMZAUFRMYFHDBA-UHFFFAOYSA-N methyl 2-(trifluoromethyl)-4-[[4-(trifluoromethyl)phenyl]methyl]-6,7-dihydro-5H-pyrazolo[1,5-a]pyrimidine-3-carboxylate Chemical compound COC(=O)C1=C2N(CCCN2CC2=CC=C(C=C2)C(F)(F)F)N=C1C(F)(F)F VMZAUFRMYFHDBA-UHFFFAOYSA-N 0.000 description 2
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