NO20023058L - Oks(adi)azolyl-hydroksamsyrer nyttige som prokollagen c- proteinaseinhibitorer - Google Patents

Info

Publication number

NO20023058L

NO20023058L NO20023058A NO20023058A NO20023058L NO 20023058 L NO20023058 L NO 20023058L NO 20023058 A NO20023058 A NO 20023058A NO 20023058 A NO20023058 A NO 20023058A NO 20023058 L NO20023058 L NO 20023058L

Authority

NO

Norway

Prior art keywords

mmol

compound

formula

cyclohexyl

stirred

Prior art date

1999-12-23

Links

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• -1 azolyl hydroxamic acids Chemical class 0.000 title claims description 77
• 108090000654 Bone morphogenetic protein 1 Proteins 0.000 title claims description 47
• 102100028728 Bone morphogenetic protein 1 Human genes 0.000 title claims description 47
• 229940019748 antifibrinolytic proteinase inhibitors Drugs 0.000 title 1
• 239000000137 peptide hydrolase inhibitor Substances 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 308
• 229910052739 hydrogen Inorganic materials 0.000 claims description 307
• 238000004519 manufacturing process Methods 0.000 claims description 98
• 150000003839 salts Chemical class 0.000 claims description 50
• 238000000034 method Methods 0.000 claims description 41
• 229940002612 prodrug Drugs 0.000 claims description 31
• 239000000651 prodrug Substances 0.000 claims description 31
• 239000012453 solvate Substances 0.000 claims description 28
• 239000003112 inhibitor Substances 0.000 claims description 25
• 125000003118 aryl group Chemical group 0.000 claims description 24
• 229910052736 halogen Inorganic materials 0.000 claims description 23
• 102100026802 72 kDa type IV collagenase Human genes 0.000 claims description 20
• 101710151806 72 kDa type IV collagenase Proteins 0.000 claims description 20
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
• 238000006243 chemical reaction Methods 0.000 claims description 17
• 102000000380 Matrix Metalloproteinase 1 Human genes 0.000 claims description 16
• 108010016113 Matrix Metalloproteinase 1 Proteins 0.000 claims description 16
• 102100030412 Matrix metalloproteinase-9 Human genes 0.000 claims description 16
• 108010015302 Matrix metalloproteinase-9 Proteins 0.000 claims description 16
• 125000000217 alkyl group Chemical group 0.000 claims description 16
• 150000002367 halogens Chemical class 0.000 claims description 16
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
• 108010076557 Matrix Metalloproteinase 14 Proteins 0.000 claims description 14
• 102100030216 Matrix metalloproteinase-14 Human genes 0.000 claims description 14
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 13
• 239000003153 chemical reaction reagent Substances 0.000 claims description 13
• 238000011282 treatment Methods 0.000 claims description 13
• 238000010511 deprotection reaction Methods 0.000 claims description 12
• 125000001153 fluoro group Chemical group F* 0.000 claims description 12
• 229910052757 nitrogen Inorganic materials 0.000 claims description 11
• 239000000126 substance Substances 0.000 claims description 11
• 125000001424 substituent group Chemical group 0.000 claims description 11
• VVYVFZRWUJASEV-CQSZACIVSA-N (2r)-5-cyclohexyl-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]pentanoic acid Chemical compound CC(C)(C)OC(=O)C[C@H](C(O)=O)CCCC1CCCCC1 VVYVFZRWUJASEV-CQSZACIVSA-N 0.000 claims description 10
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
• 125000000623 heterocyclic group Chemical group 0.000 claims description 10
• 230000008569 process Effects 0.000 claims description 10
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 9
• 125000005843 halogen group Chemical group 0.000 claims description 9
• 125000006239 protecting group Chemical group 0.000 claims description 9
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 7
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 6
• 229910052799 carbon Inorganic materials 0.000 claims description 6
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• 230000001404 mediated effect Effects 0.000 claims description 6
• 125000006362 methylene amino carbonyl group Chemical group [H]N(C([*:2])=O)C([H])([H])[*:1] 0.000 claims description 6
• ARJCBSRIPGJMAD-LLVKDONJSA-N 5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-1,2,4-oxadiazole-3-carboxamide Chemical compound NC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 ARJCBSRIPGJMAD-LLVKDONJSA-N 0.000 claims description 5
• 238000009833 condensation Methods 0.000 claims description 5
• 230000005494 condensation Effects 0.000 claims description 5
• 125000006661 (C4-C6) heterocyclic group Chemical group 0.000 claims description 4
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 4
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 4
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 150000004677 hydrates Chemical class 0.000 claims description 4
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 4
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
• 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
• 229910052717 sulfur Inorganic materials 0.000 claims description 4
• RDSMOKJZGFXQCT-IBGZPJMESA-N (4s)-4-benzyl-3-(5-cyclohexylpentanoyl)-1,3-oxazolidin-2-one Chemical compound C([C@@H]1CC=2C=CC=CC=2)OC(=O)N1C(=O)CCCCC1CCCCC1 RDSMOKJZGFXQCT-IBGZPJMESA-N 0.000 claims description 3
• HZSBMUWLMGKWMN-SDNWHVSQSA-N (e)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-5-phenylpent-2-enoic acid Chemical compound CC(C)(C)OC(=O)C\C(C(O)=O)=C/CCC1=CC=CC=C1 HZSBMUWLMGKWMN-SDNWHVSQSA-N 0.000 claims description 3
• 125000002947 alkylene group Chemical group 0.000 claims description 3
• 229910002091 carbon monoxide Inorganic materials 0.000 claims description 3
• 125000006355 carbonyl methylene group Chemical group [H]C([H])([*:2])C([*:1])=O 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 2
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 2
• 125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims description 2
• QZHKYOPXQSFVRT-UHFFFAOYSA-N 2-diethoxyphosphoryl-4-[(2-methylpropan-2-yl)oxy]-4-oxobutanoic acid Chemical compound CCOP(=O)(OCC)C(C(O)=O)CC(=O)OC(C)(C)C QZHKYOPXQSFVRT-UHFFFAOYSA-N 0.000 claims description 2
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 2
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
• FRASWKFJOBLAQF-CYBMUJFWSA-N 5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-n,n-dimethyl-1,2,4-oxadiazole-3-carboxamide Chemical compound CN(C)C(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 FRASWKFJOBLAQF-CYBMUJFWSA-N 0.000 claims description 2
• OIXMXOATOMTGIL-GFCCVEGCSA-N 5-[(3r)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-n-methyl-1,2,4-oxadiazole-3-carboxamide Chemical compound CNC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)NO)=N1 OIXMXOATOMTGIL-GFCCVEGCSA-N 0.000 claims description 2
• 150000001204 N-oxides Chemical class 0.000 claims description 2
• OCBFFGCSTGGPSQ-UHFFFAOYSA-N [CH2]CC Chemical compound [CH2]CC OCBFFGCSTGGPSQ-UHFFFAOYSA-N 0.000 claims description 2
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 2
• 125000000638 benzylaminocarbonyl group Chemical group C(C1=CC=CC=C1)NC(=O)* 0.000 claims description 2
• 125000002619 bicyclic group Chemical group 0.000 claims description 2
• 125000002837 carbocyclic group Chemical group 0.000 claims description 2
• 125000004122 cyclic group Chemical group 0.000 claims description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
• 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 2
• 125000002950 monocyclic group Chemical group 0.000 claims description 2
• 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 2
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
• 125000004076 pyridyl group Chemical group 0.000 claims description 2
• 125000006413 ring segment Chemical group 0.000 claims description 2
• ARKLZNKRUULBKN-WCSIJFPASA-N tert-butyl 3-[(4s)-4-benzyl-2-oxo-1,3-oxazolidine-3-carbonyl]-6-cyclohexylhexanoate Chemical compound C([C@@H]1CC=2C=CC=CC=2)OC(=O)N1C(=O)C(CC(=O)OC(C)(C)C)CCCC1CCCCC1 ARKLZNKRUULBKN-WCSIJFPASA-N 0.000 claims description 2
• MEUAVGJWGDPTLF-UHFFFAOYSA-N 4-(5-benzenesulfonylamino-1-methyl-1h-benzoimidazol-2-ylmethyl)-benzamidine Chemical group N=1C2=CC(NS(=O)(=O)C=3C=CC=CC=3)=CC=C2N(C)C=1CC1=CC=C(C(N)=N)C=C1 MEUAVGJWGDPTLF-UHFFFAOYSA-N 0.000 claims 3
• VVYVFZRWUJASEV-UHFFFAOYSA-N 5-cyclohexyl-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]pentanoic acid Chemical compound CC(C)(C)OC(=O)CC(C(O)=O)CCCC1CCCCC1 VVYVFZRWUJASEV-UHFFFAOYSA-N 0.000 claims 1
• 230000003213 activating effect Effects 0.000 claims 1
• 125000006360 carbonyl amino methylene group Chemical group [H]N(C([*:1])=O)C([H])([H])[*:2] 0.000 claims 1
• 238000006356 dehydrogenation reaction Methods 0.000 claims 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 664
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 515
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 376
• 239000000203 mixture Substances 0.000 description 263
• 239000000243 solution Substances 0.000 description 245
• 230000002829 reductive effect Effects 0.000 description 238
• 239000002904 solvent Substances 0.000 description 235
• 238000002360 preparation method Methods 0.000 description 177
• 235000019439 ethyl acetate Nutrition 0.000 description 173
• 238000005160 1H NMR spectroscopy Methods 0.000 description 161
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 132
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 129
• 239000012299 nitrogen atmosphere Substances 0.000 description 116
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 114
• 229910001868 water Inorganic materials 0.000 description 114
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 113
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 111
• 239000000741 silica gel Substances 0.000 description 105
• 229910002027 silica gel Inorganic materials 0.000 description 105
• 238000004440 column chromatography Methods 0.000 description 104
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 97
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 96
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 73
• 239000007787 solid Substances 0.000 description 73
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 70
• 239000012267 brine Substances 0.000 description 69
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 69
• OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 61
• 239000012074 organic phase Substances 0.000 description 61
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 60
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 59
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 51
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 51
• 239000003921 oil Substances 0.000 description 51
• 235000019198 oils Nutrition 0.000 description 51
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 48
• JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 42
• 239000012230 colorless oil Substances 0.000 description 40
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 39
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 37
• 229910021529 ammonia Inorganic materials 0.000 description 36
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 36
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 35
• 238000004458 analytical method Methods 0.000 description 35
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 34
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 33
• WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 32
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
• YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 29
• 108010035532 Collagen Proteins 0.000 description 28
• 102000008186 Collagen Human genes 0.000 description 28
• 229920001436 collagen Polymers 0.000 description 28
• AEKHNNJSMVVESS-UHFFFAOYSA-N o-trimethylsilylhydroxylamine Chemical compound C[Si](C)(C)ON AEKHNNJSMVVESS-UHFFFAOYSA-N 0.000 description 28
• 102000004190 Enzymes Human genes 0.000 description 26
• 108090000790 Enzymes Proteins 0.000 description 26
• 229940088598 enzyme Drugs 0.000 description 26
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 24
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
• 239000012071 phase Substances 0.000 description 22
• 239000008346 aqueous phase Substances 0.000 description 21
• 229920006395 saturated elastomer Polymers 0.000 description 21
• 229960000583 acetic acid Drugs 0.000 description 20
• 239000002253 acid Substances 0.000 description 20
• 238000004128 high performance liquid chromatography Methods 0.000 description 20
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 19
• 239000007864 aqueous solution Substances 0.000 description 19
• ZKEOPGBLILZRRC-MRXNPFEDSA-N ethyl 5-[(3r)-6-cyclohexyl-1-[(2-methylpropan-2-yl)oxy]-1-oxohexan-3-yl]-1,2,4-oxadiazole-3-carboxylate Chemical compound CCOC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)=N1 ZKEOPGBLILZRRC-MRXNPFEDSA-N 0.000 description 19
• 239000006260 foam Substances 0.000 description 18
• 239000000725 suspension Substances 0.000 description 17
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 16
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 16
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 16
• 239000000758 substrate Substances 0.000 description 15
• 230000000694 effects Effects 0.000 description 14
• 230000005764 inhibitory process Effects 0.000 description 14
• 239000011541 reaction mixture Substances 0.000 description 14
• 238000003556 assay Methods 0.000 description 13
• YIHVTLUDAYABNF-CYBMUJFWSA-N (3r)-6-cyclohexyl-3-(3-ethoxycarbonyl-1,2,4-oxadiazol-5-yl)hexanoic acid Chemical compound CCOC(=O)C1=NOC([C@H](CCCC2CCCCC2)CC(O)=O)=N1 YIHVTLUDAYABNF-CYBMUJFWSA-N 0.000 description 12
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• 239000000706 filtrate Substances 0.000 description 11
• 206010016654 Fibrosis Diseases 0.000 description 10
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• 230000004761 fibrosis Effects 0.000 description 9
• GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 9
• 235000017557 sodium bicarbonate Nutrition 0.000 description 9
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
• 238000003756 stirring Methods 0.000 description 9
• PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 8
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 8
• 239000012043 crude product Substances 0.000 description 8
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 8
• FUZZWVXGSFPDMH-UHFFFAOYSA-N n-hexanoic acid Natural products CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 8
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
• 238000010992 reflux Methods 0.000 description 8
• 239000011780 sodium chloride Substances 0.000 description 8
• 238000012360 testing method Methods 0.000 description 8
• 206010052428 Wound Diseases 0.000 description 7
• 208000027418 Wounds and injury Diseases 0.000 description 7
• 235000019270 ammonium chloride Nutrition 0.000 description 7
• 238000003776 cleavage reaction Methods 0.000 description 7
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
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