CA3087784A1 - C5a receptor modulators - Google Patents

Info

Publication number

CA3087784A1

CA3087784A1 CA3087784A CA3087784A CA3087784A1 CA 3087784 A1 CA3087784 A1 CA 3087784A1 CA 3087784 A CA3087784 A CA 3087784A CA 3087784 A CA3087784 A CA 3087784A CA 3087784 A1 CA3087784 A1 CA 3087784A1

Authority

CA

Canada

Prior art keywords

dihydro

quinazolin

methyl

trifluoromethyl

fluoro

Prior art date

2018-01-19

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

• Espacenet
• Global Dossier
• CIPO
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• 108010059426 Anaphylatoxin C5a Receptor Proteins 0.000 title abstract description 42
• 102000005590 Anaphylatoxin C5a Receptor Human genes 0.000 title abstract description 42
• 150000001875 compounds Chemical class 0.000 claims abstract description 167
• 150000003839 salts Chemical class 0.000 claims abstract description 34
• 239000003814 drug Substances 0.000 claims abstract description 10
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
• 238000002360 preparation method Methods 0.000 claims abstract description 5
• -1 azetidin-1,3-diyl Chemical group 0.000 claims description 158
• 238000000034 method Methods 0.000 claims description 116
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 95
• 125000003545 alkoxy group Chemical group 0.000 claims description 69
• 125000001424 substituent group Chemical group 0.000 claims description 63
• 125000000217 alkyl group Chemical group 0.000 claims description 61
• 201000010099 disease Diseases 0.000 claims description 57
• 238000011282 treatment Methods 0.000 claims description 56
• 208000027866 inflammatory disease Diseases 0.000 claims description 49
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 49
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 38
• 208000035475 disorder Diseases 0.000 claims description 38
• FVACZQHQBKPPMX-UHFFFAOYSA-N quinazolin-2-one Chemical compound C1=C[CH]C2=NC(=O)N=CC2=C1 FVACZQHQBKPPMX-UHFFFAOYSA-N 0.000 claims description 38
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 37
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 32
• 229910052736 halogen Inorganic materials 0.000 claims description 32
• 150000002367 halogens Chemical class 0.000 claims description 32
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 31
• 229910052739 hydrogen Inorganic materials 0.000 claims description 31
• 239000001257 hydrogen Substances 0.000 claims description 31
• WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 26
• 230000002265 prevention Effects 0.000 claims description 26
• 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 25
• 125000001072 heteroaryl group Chemical group 0.000 claims description 25
• 229910052757 nitrogen Inorganic materials 0.000 claims description 25
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 24
• 206010028980 Neoplasm Diseases 0.000 claims description 23
• 208000023275 Autoimmune disease Diseases 0.000 claims description 20
• 208000014674 injury Diseases 0.000 claims description 20
• 230000009467 reduction Effects 0.000 claims description 19
• 201000011510 cancer Diseases 0.000 claims description 18
• 230000000295 complement effect Effects 0.000 claims description 18
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 17
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
• 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 15
• 206010063837 Reperfusion injury Diseases 0.000 claims description 15
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
• 230000001575 pathological effect Effects 0.000 claims description 15
• 125000004076 pyridyl group Chemical group 0.000 claims description 14
• 206010061218 Inflammation Diseases 0.000 claims description 13
• 230000006378 damage Effects 0.000 claims description 13
• 230000004054 inflammatory process Effects 0.000 claims description 13
• 208000010125 myocardial infarction Diseases 0.000 claims description 13
• 230000035939 shock Effects 0.000 claims description 13
• 208000027418 Wounds and injury Diseases 0.000 claims description 12
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 12
• 125000006163 5-membered heteroaryl group Chemical group 0.000 claims description 11
• 208000007536 Thrombosis Diseases 0.000 claims description 11
• 230000002612 cardiopulmonary effect Effects 0.000 claims description 11
• 230000035987 intoxication Effects 0.000 claims description 11
• 231100000566 intoxication Toxicity 0.000 claims description 11
• 230000000302 ischemic effect Effects 0.000 claims description 11
• 208000028867 ischemia Diseases 0.000 claims description 10
• 230000003156 vasculitic effect Effects 0.000 claims description 10
• 210000000265 leukocyte Anatomy 0.000 claims description 9
• 230000004770 neurodegeneration Effects 0.000 claims description 9
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 9
• 238000001356 surgical procedure Methods 0.000 claims description 9
• 206010048554 Endothelial dysfunction Diseases 0.000 claims description 8
• 206010030113 Oedema Diseases 0.000 claims description 8
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 8
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
• 230000004856 capillary permeability Effects 0.000 claims description 8
• 208000010247 contact dermatitis Diseases 0.000 claims description 8
• 230000008694 endothelial dysfunction Effects 0.000 claims description 8
• 230000008595 infiltration Effects 0.000 claims description 8
• 238000001764 infiltration Methods 0.000 claims description 8
• 230000010118 platelet activation Effects 0.000 claims description 8
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
• 238000002054 transplantation Methods 0.000 claims description 8
• 230000008733 trauma Effects 0.000 claims description 8
• 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 claims description 8
• 208000032843 Hemorrhage Diseases 0.000 claims description 7
• 125000000335 thiazolyl group Chemical group 0.000 claims description 7
• 229920006395 saturated elastomer Polymers 0.000 claims description 6
• 230000002939 deleterious effect Effects 0.000 claims description 5
• 150000002431 hydrogen Chemical group 0.000 claims description 5
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 4
• ROULNWHEFOIYHD-UHFFFAOYSA-N 1-[(2-cyclobutyloxyphenyl)methyl]-3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-4H-quinazolin-2-one Chemical compound C1(CCC1)OC1=C(CN2C(N(CC3=CC=CC=C23)C2CCN(CC2)C2=C(C=CC=C2C)F)=O)C=CC=C1 ROULNWHEFOIYHD-UHFFFAOYSA-N 0.000 claims 1
• BQXOWWKUXNMIGH-UHFFFAOYSA-N 1-[(2-cyclopropyloxyphenyl)methyl]-3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-4H-quinazolin-2-one Chemical compound C1(CC1)OC1=C(CN2C(N(CC3=CC=CC=C23)C2CCN(CC2)C2=C(C=CC=C2C)F)=O)C=CC=C1 BQXOWWKUXNMIGH-UHFFFAOYSA-N 0.000 claims 1
• FOBWPBOYCGBEGR-UHFFFAOYSA-N 1-[(2-cyclopropylphenyl)methyl]-3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-4H-quinazolin-2-one Chemical compound C1(CC1)C1=C(CN2C(N(CC3=CC=CC=C23)C2CCN(CC2)C2=C(C=CC=C2C)F)=O)C=CC=C1 FOBWPBOYCGBEGR-UHFFFAOYSA-N 0.000 claims 1
• MFISIQPKTILCSC-UHFFFAOYSA-N 1-[[2-(cyclopropylmethoxy)phenyl]methyl]-3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-4H-quinazolin-2-one Chemical compound C1(CC1)COC1=C(CN2C(N(CC3=CC=CC=C23)C2CCN(CC2)C2=C(C=CC=C2C)F)=O)C=CC=C1 MFISIQPKTILCSC-UHFFFAOYSA-N 0.000 claims 1
• ODEVORZVJQIQDL-UHFFFAOYSA-N 1-[[2-[2-(dimethylamino)ethoxy]phenyl]methyl]-3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-4H-quinazolin-2-one Chemical compound CN(CCOC1=C(CN2C(N(CC3=CC=CC=C23)C2CCN(CC2)C2=C(C=CC=C2C)F)=O)C=CC=C1)C ODEVORZVJQIQDL-UHFFFAOYSA-N 0.000 claims 1
• IUTHEOCJFAFDRT-BNEYPBHNSA-N 1-[[2-deuterio-6-(trifluoromethyl)phenyl]methyl]-3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-4H-quinazolin-2-one Chemical compound FC(C=1C=CC=C(C=1CN1C(N(CC2=CC=CC=C12)C1CCN(CC1)C1=C(C=CC=C1C)F)=O)[2H])(F)F IUTHEOCJFAFDRT-BNEYPBHNSA-N 0.000 claims 1
• IDLDOHAQPIPZJO-LJQANCHMSA-N 3-[(3R)-1-(2,6-difluorophenyl)pyrrolidin-3-yl]-8-methoxy-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)F)N1C[C@@H](CC1)N1C(N(C2=C(C=CC=C2C1)OC)CC1=C(C=CC=C1)C(F)(F)F)=O IDLDOHAQPIPZJO-LJQANCHMSA-N 0.000 claims 1
• ZLKLYTGXTUOQGL-HSZRJFAPSA-N 3-[(3R)-1-(2,6-dimethylphenyl)pyrrolidin-3-yl]-8-methoxy-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound CC1=C(C(=CC=C1)C)N1C[C@@H](CC1)N1C(N(C2=C(C=CC=C2C1)OC)CC1=C(C=CC=C1)C(F)(F)F)=O ZLKLYTGXTUOQGL-HSZRJFAPSA-N 0.000 claims 1
• HRPTYAYGHJGXTP-HXUWFJFHSA-N 3-[(3R)-1-(2-fluoro-6-methoxyphenyl)pyrrolidin-3-yl]-8-methoxy-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)OC)N1C[C@@H](CC1)N1C(N(C2=C(C=CC=C2C1)OC)CC1=C(C=CC=C1)C(F)(F)F)=O HRPTYAYGHJGXTP-HXUWFJFHSA-N 0.000 claims 1
• IXWZFXSOBMYKBS-IBGZPJMESA-N 3-[(3S)-1-(2,6-difluorophenyl)pyrrolidin-3-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)F)N1C[C@H](CC1)N1C(N(C2=CC=CC=C2C1)CC1=C(C=CC=C1)C(F)(F)F)=O IXWZFXSOBMYKBS-IBGZPJMESA-N 0.000 claims 1
• GZXPMBCGRLEEGF-NRFANRHFSA-N 3-[(3S)-1-(2-methoxyphenyl)pyrrolidin-3-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound COC1=C(C=CC=C1)N1C[C@H](CC1)N1C(N(C2=CC=CC=C2C1)CC1=C(C=CC=C1)C(F)(F)F)=O GZXPMBCGRLEEGF-NRFANRHFSA-N 0.000 claims 1
• LMZFFQWZRMWDJL-UHFFFAOYSA-N 3-[1-(2,6-dimethylphenyl)piperidin-4-yl]-8-methoxy-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound CC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=C(C=CC=C2C1)OC)CC1=C(C=CC=C1)C(F)(F)F)=O LMZFFQWZRMWDJL-UHFFFAOYSA-N 0.000 claims 1
• LKWNQRUJDBWFPC-UHFFFAOYSA-N 3-[1-(2-chloro-6-methylphenyl)piperidin-4-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound ClC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1)CC1=C(C=CC=C1)C(F)(F)F)=O LKWNQRUJDBWFPC-UHFFFAOYSA-N 0.000 claims 1
• JSCPXKOAEFZLBG-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methoxyphenyl)piperidin-4-yl]-8-methoxy-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)OC)N1CCC(CC1)N1C(N(C2=C(C=CC=C2C1)OC)CC1=C(C=CC=C1)C(F)(F)F)=O JSCPXKOAEFZLBG-UHFFFAOYSA-N 0.000 claims 1
• YIJVDIMJLAYCLF-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)azepan-4-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CCC(CCC1)N1C(N(C2=CC=CC=C2C1)CC1=C(C=CC=C1)C(F)(F)F)=O YIJVDIMJLAYCLF-UHFFFAOYSA-N 0.000 claims 1
• MKGKQOGGQJXJJF-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)azetidin-3-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CC(C1)N1C(N(C2=CC=CC=C2C1)CC1=C(C=CC=C1)C(F)(F)F)=O MKGKQOGGQJXJJF-UHFFFAOYSA-N 0.000 claims 1
• SEANTEBEHGMFEL-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-1-[(2-propan-2-yloxyphenyl)methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1)CC1=C(C=CC=C1)OC(C)C)=O SEANTEBEHGMFEL-UHFFFAOYSA-N 0.000 claims 1
• JPTMBHWPALEFPA-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-1-[(2-propan-2-ylphenyl)methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1)CC1=C(C=CC=C1)C(C)C)=O JPTMBHWPALEFPA-UHFFFAOYSA-N 0.000 claims 1
• RWPISPUGJCEEFD-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-1-[(3-propan-2-yloxypyrazin-2-yl)methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1)CC1=NC=CN=C1OC(C)C)=O RWPISPUGJCEEFD-UHFFFAOYSA-N 0.000 claims 1
• YFLKLLNVZNVRMO-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-1-[(3-propan-2-ylpyrazin-2-yl)methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1)CC1=NC=CN=C1C(C)C)=O YFLKLLNVZNVRMO-UHFFFAOYSA-N 0.000 claims 1
• JQDVBYRJYFGDIE-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-1-[(4-propan-2-yloxypyridazin-3-yl)methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1)CC=1N=NC=CC=1OC(C)C)=O JQDVBYRJYFGDIE-UHFFFAOYSA-N 0.000 claims 1
• HRJDQETWZVYYRF-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-1-[(4-propan-2-ylpyridin-3-yl)methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1)CC=1C=NC=CC=1C(C)C)=O HRJDQETWZVYYRF-UHFFFAOYSA-N 0.000 claims 1
• ORVGONCZDGTYET-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-1-[(4-propan-2-ylpyrimidin-5-yl)methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1)CC=1C(=NC=NC=1)C(C)C)=O ORVGONCZDGTYET-UHFFFAOYSA-N 0.000 claims 1
• PXXJEJVTIKODSS-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-1-[1-[2-(trifluoromethyl)phenyl]ethyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1)C(C)C1=C(C=CC=C1)C(F)(F)F)=O PXXJEJVTIKODSS-UHFFFAOYSA-N 0.000 claims 1
• SCOUHHPOQXESAN-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-1-[[2-(2-hydroxyethoxy)phenyl]methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1)CC1=C(C=CC=C1)OCCO)=O SCOUHHPOQXESAN-UHFFFAOYSA-N 0.000 claims 1
• GOWOHJGJJOZBMH-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-1-[[2-(oxan-4-yloxy)phenyl]methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1)CC1=C(C=CC=C1)OC1CCOCC1)=O GOWOHJGJJOZBMH-UHFFFAOYSA-N 0.000 claims 1
• QAZUBYJUDOWVQU-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-pteridin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=NC=CN=C2C1)CC1=C(C=CC=C1)C(F)(F)F)=O QAZUBYJUDOWVQU-UHFFFAOYSA-N 0.000 claims 1
• YZDDXLPECVVGKN-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-pyrimido[4,5-d]pyrimidin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=NC=NC=C2C1)CC1=C(C=CC=C1)C(F)(F)F)=O YZDDXLPECVVGKN-UHFFFAOYSA-N 0.000 claims 1
• IUTHEOCJFAFDRT-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1)CC1=C(C=CC=C1)C(F)(F)F)=O IUTHEOCJFAFDRT-UHFFFAOYSA-N 0.000 claims 1
• FMILTLNGCAQTES-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-1-[[2-methyl-4-(trifluoromethyl)-1,3-thiazol-5-yl]methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1)CC1=C(N=C(S1)C)C(F)(F)F)=O FMILTLNGCAQTES-UHFFFAOYSA-N 0.000 claims 1
• ZYCSKCXVVFBZRO-UHFFFAOYSA-N 3-[1-(2-fluoro-6-methylphenyl)piperidin-4-yl]-4-methyl-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)C)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1C)CC1=C(C=CC=C1)C(F)(F)F)=O ZYCSKCXVVFBZRO-UHFFFAOYSA-N 0.000 claims 1
• BGGLOCYWZHWZER-UHFFFAOYSA-N 3-[1-(2-methoxyphenyl)piperidin-4-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound COC1=C(C=CC=C1)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1)CC1=C(C=CC=C1)C(F)(F)F)=O BGGLOCYWZHWZER-UHFFFAOYSA-N 0.000 claims 1
• AAOZPQAOSWHXFD-UHFFFAOYSA-N 3-[1-(4-chloro-2,5-dimethylpyrazol-3-yl)piperidin-4-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound ClC1=C(N(N=C1C)C)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1)CC1=C(C=CC=C1)C(F)(F)F)=O AAOZPQAOSWHXFD-UHFFFAOYSA-N 0.000 claims 1
• MWGMYMISWMJWJX-UHFFFAOYSA-N 3-[1-[2-fluoro-6-(trifluoromethyl)phenyl]piperidin-4-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound FC1=C(C(=CC=C1)C(F)(F)F)N1CCC(CC1)N1C(N(C2=CC=CC=C2C1)CC1=C(C=CC=C1)C(F)(F)F)=O MWGMYMISWMJWJX-UHFFFAOYSA-N 0.000 claims 1
• BYRZQYVIJZFRMQ-OAQYLSRUSA-N 8-methoxy-3-[(3R)-1-(2-methoxyphenyl)pyrrolidin-3-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound COC=1C=CC=C2CN(C(N(C=12)CC1=C(C=CC=C1)C(F)(F)F)=O)[C@H]1CN(CC1)C1=C(C=CC=C1)OC BYRZQYVIJZFRMQ-OAQYLSRUSA-N 0.000 claims 1
• SJJDJFIXXNIVEE-UHFFFAOYSA-N 8-methoxy-3-[1-(2-methoxyphenyl)piperidin-4-yl]-1-[[2-(trifluoromethyl)phenyl]methyl]-4H-quinazolin-2-one Chemical compound COC=1C=CC=C2CN(C(N(C=12)CC1=C(C=CC=C1)C(F)(F)F)=O)C1CCN(CC1)C1=C(C=CC=C1)OC SJJDJFIXXNIVEE-UHFFFAOYSA-N 0.000 claims 1
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 102
• 239000000376 reactant Substances 0.000 description 68
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 63
• 239000002904 solvent Substances 0.000 description 63
• 239000000543 intermediate Substances 0.000 description 62
• 239000011541 reaction mixture Substances 0.000 description 62
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 61
• 238000004440 column chromatography Methods 0.000 description 53
• YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 52
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 51
• 235000019341 magnesium sulphate Nutrition 0.000 description 51
• 239000012267 brine Substances 0.000 description 49
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 49
• 102100031506 Complement C5 Human genes 0.000 description 47
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 description 42
• 230000015572 biosynthetic process Effects 0.000 description 42
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 41
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