DE60310767T2 - PYRAZOL-3,4-d-PYRIMIDINDERIVATE UND IHRE VERWENDUNG BEI DER BEHANDLUNG VON H.PYLORI-INFEKTIONEN - Google Patents

Info

Publication number

DE60310767T2

DE60310767T2 DE60310767T DE60310767T DE60310767T2 DE 60310767 T2 DE60310767 T2 DE 60310767T2 DE 60310767 T DE60310767 T DE 60310767T DE 60310767 T DE60310767 T DE 60310767T DE 60310767 T2 DE60310767 T2 DE 60310767T2

Authority

DE

Germany

Prior art keywords

alkyl

het

methyl

optionally substituted

pyrazolo

Prior art date

2002-12-20

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.)

Expired - Fee Related

Links

• Espacenet
• Global Dossier
• DPMA
• Discuss

• 208000015181 infectious disease Diseases 0.000 title claims abstract description 19
• 238000011282 treatment Methods 0.000 title claims abstract description 12
• KEUDMLLLHGLIGH-LHVCLSMISA-N N1=CN=CC=C1.N1N=C(C(=C1)[2H])[2H] Chemical class N1=CN=CC=C1.N1N=C(C(=C1)[2H])[2H] KEUDMLLLHGLIGH-LHVCLSMISA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 120
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
• 238000011321 prophylaxis Methods 0.000 claims abstract description 4
• 125000000217 alkyl group Chemical group 0.000 claims description 319
• -1 hydroxy, amino Chemical group 0.000 claims description 210
• 125000000623 heterocyclic group Chemical group 0.000 claims description 106
• 229910052760 oxygen Inorganic materials 0.000 claims description 102
• 229910052717 sulfur Inorganic materials 0.000 claims description 101
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 95
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 80
• 229920006395 saturated elastomer Polymers 0.000 claims description 69
• 125000005842 heteroatom Chemical group 0.000 claims description 64
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 63
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 56
• 229910052736 halogen Inorganic materials 0.000 claims description 52
• 150000002367 halogens Chemical class 0.000 claims description 52
• 125000001424 substituent group Chemical group 0.000 claims description 51
• 229910052757 nitrogen Inorganic materials 0.000 claims description 50
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 47
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 42
• 125000004122 cyclic group Chemical group 0.000 claims description 40
• 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 39
• 229910052799 carbon Inorganic materials 0.000 claims description 38
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 36
• 125000005843 halogen group Chemical group 0.000 claims description 33
• 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 32
• 150000003839 salts Chemical class 0.000 claims description 32
• 229910052739 hydrogen Inorganic materials 0.000 claims description 30
• 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 28
• 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 25
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 25
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 25
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 24
• 125000005017 substituted alkenyl group Chemical group 0.000 claims description 22
• 125000005415 substituted alkoxy group Chemical group 0.000 claims description 22
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 22
• 125000004426 substituted alkynyl group Chemical group 0.000 claims description 22
• 125000003107 substituted aryl group Chemical group 0.000 claims description 22
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 22
• 125000003545 alkoxy group Chemical group 0.000 claims description 20
• 125000000304 alkynyl group Chemical group 0.000 claims description 18
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 16
• 125000004423 acyloxy group Chemical group 0.000 claims description 16
• 125000003342 alkenyl group Chemical group 0.000 claims description 16
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 16
• 125000002619 bicyclic group Chemical group 0.000 claims description 16
• 125000005518 carboxamido group Chemical group 0.000 claims description 16
• 125000002950 monocyclic group Chemical group 0.000 claims description 16
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 15
• 238000006467 substitution reaction Methods 0.000 claims description 14
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
• 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims description 11
• 125000001188 haloalkyl group Chemical group 0.000 claims description 11
• 239000001257 hydrogen Substances 0.000 claims description 10
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 9
• 125000004486 1-methylpiperidin-3-yl group Chemical group CN1CC(CCC1)* 0.000 claims description 8
• 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 8
• 125000006413 ring segment Chemical group 0.000 claims description 8
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
• 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 7
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 6
• 239000003814 drug Substances 0.000 claims description 6
• 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 6
• VKIQPLVVCDWMHD-UHFFFAOYSA-N 5-[6-amino-2-[(6-chloroquinolin-4-yl)methyl]-5-methyl-4-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound CN1C=C(C#N)C=C1C1=C2C(=O)N(C)C(N)=NC2=NN1CC1=CC=NC2=CC=C(Cl)C=C12 VKIQPLVVCDWMHD-UHFFFAOYSA-N 0.000 claims description 5
• OLLUIQZCXQBQSK-UHFFFAOYSA-N n-[2-[(6-chloroquinolin-4-yl)methyl]-3-(4-cyano-1-methylpyrrol-2-yl)-5-methyl-4-oxopyrazolo[3,4-d]pyrimidin-6-yl]-3-methylbutanamide Chemical compound C=12C(=O)N(C)C(NC(=O)CC(C)C)=NC2=NN(CC=2C3=CC(Cl)=CC=C3N=CC=2)C=1C1=CC(C#N)=CN1C OLLUIQZCXQBQSK-UHFFFAOYSA-N 0.000 claims description 5
• 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims description 5
• FOSBPPDZQFIBKJ-UHFFFAOYSA-N 2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-5-methyl-3-(3-methylimidazol-4-yl)-4-sulfanylidenepyrazolo[3,4-d]pyrimidin-6-one Chemical compound CN1C=NC=C1C1=C2C(=S)N(C)C(=O)N(CC3CC3)C2=NN1CC1=CC=NC2=CC=C(Cl)C=C12 FOSBPPDZQFIBKJ-UHFFFAOYSA-N 0.000 claims description 4
• ZBYRJOXGXSUWSZ-UHFFFAOYSA-N 4-amino-2-[(6-chloroquinolin-4-yl)methyl]-7-(2-methylpropyl)-3-(1-methylpyrrol-2-yl)pyrazolo[3,4-d]pyrimidin-6-one Chemical compound C=12C(N)=NC(=O)N(CC(C)C)C2=NN(CC=2C3=CC(Cl)=CC=C3N=CC=2)C=1C1=CC=CN1C ZBYRJOXGXSUWSZ-UHFFFAOYSA-N 0.000 claims description 4
• RCMLFJBVAMYCKS-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-4-(dimethylamino)-7-(2-methylpropyl)-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound C=12C(N(C)C)=NC(=O)N(CC(C)C)C2=NN(CC=2C3=CC(Cl)=CC=C3N=CC=2)C=1C1=CC(C#N)=CN1C RCMLFJBVAMYCKS-UHFFFAOYSA-N 0.000 claims description 4
• GYDJJDMTXJIGHU-UHFFFAOYSA-N 4-(4-methylpiperazin-1-yl)-7-(2-methylpropyl)-2-(naphthalen-1-ylmethyl)-3-pyridin-4-ylpyrazolo[3,4-d]pyrimidin-6-one Chemical compound C=12C(N3CCN(C)CC3)=NC(=O)N(CC(C)C)C2=NN(CC=2C3=CC=CC=C3C=CC=2)C=1C1=CC=NC=C1 GYDJJDMTXJIGHU-UHFFFAOYSA-N 0.000 claims description 3
• HKDAAJOOEJJXGO-UHFFFAOYSA-N 4-(methylamino)-7-(2-methylpropyl)-2-(naphthalen-1-ylmethyl)-3-pyridin-4-ylpyrazolo[3,4-d]pyrimidin-6-one Chemical compound C=12C(NC)=NC(=O)N(CC(C)C)C2=NN(CC=2C3=CC=CC=C3C=CC=2)C=1C1=CC=NC=C1 HKDAAJOOEJJXGO-UHFFFAOYSA-N 0.000 claims description 3
• RIQCRMGKJGSOKL-UHFFFAOYSA-N 4-amino-7-(2-methylpropyl)-2-(naphthalen-1-ylmethyl)-3-pyridin-4-ylpyrazolo[3,4-d]pyrimidin-6-one Chemical compound C=12C(N)=NC(=O)N(CC(C)C)C2=NN(CC=2C3=CC=CC=C3C=CC=2)C=1C1=CC=NC=C1 RIQCRMGKJGSOKL-UHFFFAOYSA-N 0.000 claims description 3
• OONJOMXXMJPXMB-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-4-(hydroxyamino)-7-(2-methylpropyl)-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound C=12C(NO)=NC(=O)N(CC(C)C)C2=NN(CC=2C3=CC(Cl)=CC=C3N=CC=2)C=1C1=CC(C#N)=CN1C OONJOMXXMJPXMB-UHFFFAOYSA-N 0.000 claims description 3
• HPRPWZCZFAHUEA-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-4-(methylamino)-7-(2-methylpropyl)-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound C=12C(NC)=NC(=O)N(CC(C)C)C2=NN(CC=2C3=CC(Cl)=CC=C3N=CC=2)C=1C1=CC(C#N)=CN1C HPRPWZCZFAHUEA-UHFFFAOYSA-N 0.000 claims description 3
• XUIUADSSDASZOS-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-4-hydrazinyl-7-(2-methylpropyl)-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound C=12C(NN)=NC(=O)N(CC(C)C)C2=NN(CC=2C3=CC(Cl)=CC=C3N=CC=2)C=1C1=CC(C#N)=CN1C XUIUADSSDASZOS-UHFFFAOYSA-N 0.000 claims description 3
• UOITUYIRMJPNFW-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-7-(2-methylpropyl)-6-oxo-4-(propylamino)pyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound C=12C(NCCC)=NC(=O)N(CC(C)C)C2=NN(CC=2C3=CC(Cl)=CC=C3N=CC=2)C=1C1=CC(C#N)=CN1C UOITUYIRMJPNFW-UHFFFAOYSA-N 0.000 claims description 3
• UZALJGJBYXBJQM-MRXNPFEDSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-4-[[(2r)-2-hydroxypropyl]amino]-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound C12=NN(CC=3C4=CC(Cl)=CC=C4N=CC=3)C(C=3N(C=C(C=3)C#N)C)=C2C(NC[C@H](O)C)=NC(=O)N1CC1CC1 UZALJGJBYXBJQM-MRXNPFEDSA-N 0.000 claims description 3
• XNTNMXMOVZGZBX-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-6-imino-5-methyl-4-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound CN1C=C(C#N)C=C1C1=C2C(=O)N(C)C(=N)N(CC3CC3)C2=NN1CC1=CC=NC2=CC=C(Cl)C=C12 XNTNMXMOVZGZBX-UHFFFAOYSA-N 0.000 claims description 3
• YEHALFCBJLQGOY-UHFFFAOYSA-N 5-[4-amino-2-[(6-chloroquinolin-4-yl)methyl]-7-(2-methylpropyl)-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound C=12C(N)=NC(=O)N(CC(C)C)C2=NN(CC=2C3=CC(Cl)=CC=C3N=CC=2)C=1C1=CC(C#N)=CN1C YEHALFCBJLQGOY-UHFFFAOYSA-N 0.000 claims description 3
• 239000003937 drug carrier Substances 0.000 claims description 3
• 238000004519 manufacturing process Methods 0.000 claims description 3
• SAYQYUMGGZFXHF-UHFFFAOYSA-N n'-[2-[(6-chloroquinolin-4-yl)methyl]-3-(4-cyano-1-methylpyrrol-2-yl)-5-methyl-4-oxopyrazolo[3,4-d]pyrimidin-6-yl]-n,n-dimethylmethanimidamide Chemical compound C=12C(=O)N(C)C(N=CN(C)C)=NC2=NN(CC=2C3=CC(Cl)=CC=C3N=CC=2)C=1C1=CC(C#N)=CN1C SAYQYUMGGZFXHF-UHFFFAOYSA-N 0.000 claims description 3
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
• WMHFDKFVTVNHQC-UHFFFAOYSA-N 1-[2-[(6-chloroquinolin-4-yl)methyl]-3-(4-cyano-1-methylpyrrol-2-yl)-5-methyl-4-oxopyrazolo[3,4-d]pyrimidin-6-yl]-3-ethylurea Chemical compound C=12C(=O)N(C)C(NC(=O)NCC)=NC2=NN(CC=2C3=CC(Cl)=CC=C3N=CC=2)C=1C1=CC(C#N)=CN1C WMHFDKFVTVNHQC-UHFFFAOYSA-N 0.000 claims description 2
• CNCXFTXRDGKTDR-UHFFFAOYSA-N 4-(dimethylamino)-7-(2-methylpropyl)-2-(naphthalen-1-ylmethyl)-3-pyridin-4-ylpyrazolo[3,4-d]pyrimidin-6-one Chemical compound C=12C(N(C)C)=NC(=O)N(CC(C)C)C2=NN(CC=2C3=CC=CC=C3C=CC=2)C=1C1=CC=NC=C1 CNCXFTXRDGKTDR-UHFFFAOYSA-N 0.000 claims description 2
• DDUJQRINUUSATH-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-4-(2-hydroxyethylamino)-7-(2-methylpropyl)-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound C=12C(NCCO)=NC(=O)N(CC(C)C)C2=NN(CC=2C3=CC(Cl)=CC=C3N=CC=2)C=1C1=CC(C#N)=CN1C DDUJQRINUUSATH-UHFFFAOYSA-N 0.000 claims description 2
• KQYJNBWOWUEIDW-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-4-(cyclopropylamino)-7-(2-methylpropyl)-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound C=12C(NC3CC3)=NC(=O)N(CC(C)C)C2=NN(CC=2C3=CC(Cl)=CC=C3N=CC=2)C=1C1=CC(C#N)=CN1C KQYJNBWOWUEIDW-UHFFFAOYSA-N 0.000 claims description 2
• GHDFCCXMBSVWFI-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-6-(cyclopropylmethylamino)-4-(methylamino)pyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound N=1C2=NN(CC=3C4=CC(Cl)=CC=C4N=CC=3)C(C=3N(C=C(C=3)C#N)C)=C2C(NC)=NC=1NCC1CC1 GHDFCCXMBSVWFI-UHFFFAOYSA-N 0.000 claims description 2
• LMYKGRJFOBBZBB-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-6-(cyclopropylmethylamino)-5-methyl-4-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound CN1C=C(C#N)C=C1C1=C2C(=O)N(C)C(NCC3CC3)=NC2=NN1CC1=CC=NC2=CC=C(Cl)C=C12 LMYKGRJFOBBZBB-UHFFFAOYSA-N 0.000 claims description 2
• MAVXHEFSRYLRFP-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-6-[cyclopropylmethyl(methyl)amino]-5-methyl-4-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound N=1C2=NN(CC=3C4=CC(Cl)=CC=C4N=CC=3)C(C=3N(C=C(C=3)C#N)C)=C2C(=O)N(C)C=1N(C)CC1CC1 MAVXHEFSRYLRFP-UHFFFAOYSA-N 0.000 claims description 2
• YVUPPRFJSQNAJX-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-4-(2-hydroxybutylamino)-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound C12=NN(CC=3C4=CC(Cl)=CC=C4N=CC=3)C(C=3N(C=C(C=3)C#N)C)=C2C(NCC(O)CC)=NC(=O)N1CC1CC1 YVUPPRFJSQNAJX-UHFFFAOYSA-N 0.000 claims description 2
• XGIZVGCQMGYMPF-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-4-imino-5-methyl-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound CN1C=C(C#N)C=C1C1=C2C(=N)N(C)C(=O)N(CC3CC3)C2=NN1CC1=CC=NC2=CC=C(Cl)C=C12 XGIZVGCQMGYMPF-UHFFFAOYSA-N 0.000 claims description 2
• HUTVYDIPILCFEP-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-4-methoxy-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound C12=NN(CC=3C4=CC(Cl)=CC=C4N=CC=3)C(C=3N(C=C(C=3)C#N)C)=C2C(OC)=NC(=O)N1CC1CC1 HUTVYDIPILCFEP-UHFFFAOYSA-N 0.000 claims description 2
• RYPUXSXXVALVJC-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-4-methylsulfanyl-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound C12=NN(CC=3C4=CC(Cl)=CC=C4N=CC=3)C(C=3N(C=C(C=3)C#N)C)=C2C(SC)=NC(=O)N1CC1CC1 RYPUXSXXVALVJC-UHFFFAOYSA-N 0.000 claims description 2
• DHSMICAQRHZYBK-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-5-methyl-4-oxo-6-sulfanylidenepyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound CN1C=C(C#N)C=C1C1=C2C(=O)N(C)C(=S)N(CC3CC3)C2=NN1CC1=CC=NC2=CC=C(Cl)C=C12 DHSMICAQRHZYBK-UHFFFAOYSA-N 0.000 claims description 2
• NNRQVFYFIZONSL-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-5-methyl-6-oxo-4h-pyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound C1CC1CN1C(=O)N(C)CC=2C1=NN(CC=1C3=CC(Cl)=CC=C3N=CC=1)C=2C1=CC(C#N)=CN1C NNRQVFYFIZONSL-UHFFFAOYSA-N 0.000 claims description 2
• GZQUXGIBGNJIEG-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-6-oxo-4,5-dihydropyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound CN1C=C(C#N)C=C1C1=C(CNC(=O)N2CC3CC3)C2=NN1CC1=CC=NC2=CC=C(Cl)C=C12 GZQUXGIBGNJIEG-UHFFFAOYSA-N 0.000 claims description 2
• MUCRNTHMLXWZDJ-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-6-oxo-4-pyrrol-1-ylpyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound CN1C=C(C#N)C=C1C1=C2C(N3C=CC=C3)=NC(=O)N(CC3CC3)C2=NN1CC1=CC=NC2=CC=C(Cl)C=C12 MUCRNTHMLXWZDJ-UHFFFAOYSA-N 0.000 claims description 2
• GXSSXOZLPJPIFB-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound CN1C=C(C#N)C=C1C1=C2C=NC(=O)N(CC3CC3)C2=NN1CC1=CC=NC2=CC=C(Cl)C=C12 GXSSXOZLPJPIFB-UHFFFAOYSA-N 0.000 claims description 2
• ZHRCOUHOXZWJOL-VYIQYICTSA-N C12=NN(CC=3C4=CC(Cl)=CC=C4N=CC=3)C(C=3N(C=NC=3)C)=C2C(=N/C)/N(C)C(=O)N1CC1CC1 Chemical compound C12=NN(CC=3C4=CC(Cl)=CC=C4N=CC=3)C(C=3N(C=NC=3)C)=C2C(=N/C)/N(C)C(=O)N1CC1CC1 ZHRCOUHOXZWJOL-VYIQYICTSA-N 0.000 claims description 2
• MLLHFHURWWJCAE-KDJFERLWSA-N C=1C=NC2=CC=C(Cl)C=C2C=1CN1N=C2N(CC3CC3)C(=N/C)/N(C)C(=O)C2=C1C1=CC(C#N)=CN1C Chemical compound C=1C=NC2=CC=C(Cl)C=C2C=1CN1N=C2N(CC3CC3)C(=N/C)/N(C)C(=O)C2=C1C1=CC(C#N)=CN1C MLLHFHURWWJCAE-KDJFERLWSA-N 0.000 claims description 2
• JCEMODISQYSBEB-BXVZCJGGSA-N N=1C2=NN(CC=3C4=CC(Cl)=CC=C4N=CC=3)C(C=3N(C=C(C=3)C#N)C)=C2C(=N/C)/N(C)C=1NCC1CC1 Chemical compound N=1C2=NN(CC=3C4=CC(Cl)=CC=C4N=CC=3)C(C=3N(C=C(C=3)C#N)C)=C2C(=N/C)/N(C)C=1NCC1CC1 JCEMODISQYSBEB-BXVZCJGGSA-N 0.000 claims description 2
• HEUUPWDHDBGQPN-JVCXMKTPSA-N c12c(=N/C)/n(C)c(=O)n(CC3CC3)c2nn(Cc2ccnc3ccc(Cl)cc32)c1-c1n(C)cc(C#N)c1 Chemical compound c12c(=N/C)/n(C)c(=O)n(CC3CC3)c2nn(Cc2ccnc3ccc(Cl)cc32)c1-c1n(C)cc(C#N)c1 HEUUPWDHDBGQPN-JVCXMKTPSA-N 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• WYNIUVFTTPVXHN-UHFFFAOYSA-N ethyl n-[2-[(6-chloroquinolin-4-yl)methyl]-3-(4-cyano-1-methylpyrrol-2-yl)-5-methyl-4-oxopyrazolo[3,4-d]pyrimidin-6-yl]carbamate Chemical compound C=12C(=O)N(C)C(NC(=O)OCC)=NC2=NN(CC=2C3=CC(Cl)=CC=C3N=CC=2)C=1C1=CC(C#N)=CN1C WYNIUVFTTPVXHN-UHFFFAOYSA-N 0.000 claims description 2
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 2
• CKOXCYCDFQGAFS-UHFFFAOYSA-N n-[2-[(6-chloroquinolin-4-yl)methyl]-3-(4-cyano-1-methylpyrrol-2-yl)-5-methyl-4-oxopyrazolo[3,4-d]pyrimidin-6-yl]propane-1-sulfonamide Chemical compound C=12C(=O)N(C)C(NS(=O)(=O)CCC)=NC2=NN(CC=2C3=CC(Cl)=CC=C3N=CC=2)C=1C1=CC(C#N)=CN1C CKOXCYCDFQGAFS-UHFFFAOYSA-N 0.000 claims description 2
• BOOAUMLQBYWQTH-UHFFFAOYSA-N n-[2-[(6-chloroquinolin-4-yl)methyl]-3-(4-cyano-1-methylpyrrol-2-yl)-7-(2-methylpropyl)-6-oxopyrazolo[3,4-d]pyrimidin-4-yl]acetamide Chemical compound C=12C(NC(C)=O)=NC(=O)N(CC(C)C)C2=NN(CC=2C3=CC(Cl)=CC=C3N=CC=2)C=1C1=CC(C#N)=CN1C BOOAUMLQBYWQTH-UHFFFAOYSA-N 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• BSAXWMSAVVOOHO-UHFFFAOYSA-N 2,2-dioxo-1,5-dihydroimidazo[4,5-c][1,2,6]thiadiazin-4-one Chemical class O=C1NS(=O)(=O)NC2=C1NC=N2 BSAXWMSAVVOOHO-UHFFFAOYSA-N 0.000 claims 1
• QMLYVUZBIAAJEP-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-4-(2,2-dimethylhydrazinyl)-7-(2-methylpropyl)-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound C=12C(NN(C)C)=NC(=O)N(CC(C)C)C2=NN(CC=2C3=CC(Cl)=CC=C3N=CC=2)C=1C1=CC(C#N)=CN1C QMLYVUZBIAAJEP-UHFFFAOYSA-N 0.000 claims 1
• ARLUIPDCRWAUTC-UHFFFAOYSA-N 5-[4-amino-2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound CN1C=C(C#N)C=C1C1=C2C(N)=NC(=O)N(CC3CC3)C2=NN1CC1=CC=NC2=CC=C(Cl)C=C12 ARLUIPDCRWAUTC-UHFFFAOYSA-N 0.000 claims 1
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 19
• 238000010586 diagram Methods 0.000 abstract 1
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
• 238000006243 chemical reaction Methods 0.000 description 35
• 238000005160 1H NMR spectroscopy Methods 0.000 description 31
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
• 239000000243 solution Substances 0.000 description 30
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 27
• 150000001412 amines Chemical class 0.000 description 26
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
• 239000000203 mixture Substances 0.000 description 20
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 19
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
• 239000007787 solid Substances 0.000 description 16
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
• 125000004432 carbon atom Chemical group C* 0.000 description 14
• 235000019439 ethyl acetate Nutrition 0.000 description 13
• 239000002904 solvent Substances 0.000 description 13
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
• 125000004429 atom Chemical group 0.000 description 12
• 239000000725 suspension Substances 0.000 description 12
• 0 C*C(N1*)=Nc2n[n](C*)c(*)c2C1=* Chemical compound C*C(N1*)=Nc2n[n](C*)c(*)c2C1=* 0.000 description 10
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
• 230000015572 biosynthetic process Effects 0.000 description 8
• 239000012267 brine Substances 0.000 description 8
• 230000000694 effects Effects 0.000 description 8
• 239000011541 reaction mixture Substances 0.000 description 8
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
• 238000003756 stirring Methods 0.000 description 8
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 7
• 210000002421 cell wall Anatomy 0.000 description 7
• 239000000047 product Substances 0.000 description 7
• 239000011734 sodium Substances 0.000 description 7
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
• 238000003556 assay Methods 0.000 description 6
• 238000004587 chromatography analysis Methods 0.000 description 6
• 238000002360 preparation method Methods 0.000 description 6
• 239000000651 prodrug Substances 0.000 description 6
• 229940002612 prodrug Drugs 0.000 description 6
• 238000010992 reflux Methods 0.000 description 6
• 108700016167 Glutamate racemases Proteins 0.000 description 5
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
• 239000002253 acid Substances 0.000 description 5
• 201000010099 disease Diseases 0.000 description 5
• 238000003818 flash chromatography Methods 0.000 description 5
• 125000001183 hydrocarbyl group Chemical group 0.000 description 5
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
• 239000003826 tablet Substances 0.000 description 5
• 238000002560 therapeutic procedure Methods 0.000 description 5
• 238000004809 thin layer chromatography Methods 0.000 description 5
• HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
• 241000894006 Bacteria Species 0.000 description 4
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 4
• 108090000790 Enzymes Proteins 0.000 description 4
• 102000004190 Enzymes Human genes 0.000 description 4
• 241000590002 Helicobacter pylori Species 0.000 description 4
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
• 125000003118 aryl group Chemical group 0.000 description 4
• 239000002775 capsule Substances 0.000 description 4
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 4
• 239000002552 dosage form Substances 0.000 description 4
• 238000009472 formulation Methods 0.000 description 4
• 229940037467 helicobacter pylori Drugs 0.000 description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• 239000007788 liquid Substances 0.000 description 4
• 238000001819 mass spectrum Methods 0.000 description 4
• 239000000463 material Substances 0.000 description 4
• 231100000252 nontoxic Toxicity 0.000 description 4
• 230000003000 nontoxic effect Effects 0.000 description 4
• 239000000843 powder Substances 0.000 description 4
• 230000002265 prevention Effects 0.000 description 4
• 229910052938 sodium sulfate Inorganic materials 0.000 description 4
• 235000011152 sodium sulphate Nutrition 0.000 description 4
• 238000003786 synthesis reaction Methods 0.000 description 4
• JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 4
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
• KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
• WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 3
• 230000000845 anti-microbial effect Effects 0.000 description 3
• 239000003153 chemical reaction reagent 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
• 239000000839 emulsion Substances 0.000 description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
• 238000001914 filtration Methods 0.000 description 3
• 229940093915 gynecological organic acid Drugs 0.000 description 3
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
• 238000002844 melting Methods 0.000 description 3
• 230000008018 melting Effects 0.000 description 3
• LWJROJCJINYWOX-UHFFFAOYSA-L mercury dichloride Chemical compound Cl[Hg]Cl LWJROJCJINYWOX-UHFFFAOYSA-L 0.000 description 3
• 150000007522 mineralic acids Chemical class 0.000 description 3
• 150000007524 organic acids Chemical class 0.000 description 3
• 235000005985 organic acids Nutrition 0.000 description 3
• 239000012044 organic layer Substances 0.000 description 3
• 239000002244 precipitate Substances 0.000 description 3
• 239000000741 silica gel Substances 0.000 description 3
• 229910002027 silica gel Inorganic materials 0.000 description 3
• 239000000377 silicon dioxide Substances 0.000 description 3
• 229960001866 silicon dioxide Drugs 0.000 description 3
• 238000001228 spectrum Methods 0.000 description 3
• 239000000829 suppository Substances 0.000 description 3
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
• DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
• 239000003039 volatile agent Substances 0.000 description 3
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
• ARGCQEVBJHPOGB-UHFFFAOYSA-N 2,5-dihydrofuran Chemical compound C1OCC=C1 ARGCQEVBJHPOGB-UHFFFAOYSA-N 0.000 description 2
• HWIWKIXXLQZBBD-UHFFFAOYSA-N 2-amino-6-[2-[(6-chloroquinolin-4-yl)methylidene]hydrazinyl]-3-methylpyrimidin-4-one Chemical compound O=C1N(C)C(N)=NC(NN=CC=2C3=CC(Cl)=CC=C3N=CC=2)=C1 HWIWKIXXLQZBBD-UHFFFAOYSA-N 0.000 description 2
• VBWACOJLJYUFKJ-UHFFFAOYSA-N 2-amino-6-chloro-1h-pyrimidin-4-one Chemical compound NC1=NC(O)=CC(Cl)=N1 VBWACOJLJYUFKJ-UHFFFAOYSA-N 0.000 description 2
• QMMJHXCWJBYQNP-UHFFFAOYSA-N 2-amino-6-chloro-3-methylpyrimidin-4-one Chemical compound CN1C(N)=NC(Cl)=CC1=O QMMJHXCWJBYQNP-UHFFFAOYSA-N 0.000 description 2
• ISULZYQDGYXDFW-UHFFFAOYSA-N 3-methylbutanoyl chloride Chemical compound CC(C)CC(Cl)=O ISULZYQDGYXDFW-UHFFFAOYSA-N 0.000 description 2
• 125000005986 4-piperidonyl group Chemical group 0.000 description 2
• 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 2
• VVLNIBBMYWUBRU-UHFFFAOYSA-N 5-formyl-1-methylpyrrole-3-carbonitrile Chemical compound CN1C=C(C#N)C=C1C=O VVLNIBBMYWUBRU-UHFFFAOYSA-N 0.000 description 2
• VITYFCYLOLBEPP-UHFFFAOYSA-N 6-[2-[(6-chloroquinolin-4-yl)methylidene]hydrazinyl]-1-(cyclopropylmethyl)pyrimidine-2,4-dione Chemical compound C12=CC(Cl)=CC=C2N=CC=C1C=NNC1=CC(=O)NC(=O)N1CC1CC1 VITYFCYLOLBEPP-UHFFFAOYSA-N 0.000 description 2
• ULSIXYQFCNCUBL-UHFFFAOYSA-N 6-chloro-1-(cyclopropylmethyl)pyrimidine-2,4-dione Chemical compound ClC1=CC(=O)NC(=O)N1CC1CC1 ULSIXYQFCNCUBL-UHFFFAOYSA-N 0.000 description 2
• CBKMCVSSHQYURY-UHFFFAOYSA-N 6-chloroquinoline-4-carbaldehyde Chemical compound N1=CC=C(C=O)C2=CC(Cl)=CC=C21 CBKMCVSSHQYURY-UHFFFAOYSA-N 0.000 description 2
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
• 239000004215 Carbon black (E152) Substances 0.000 description 2
• OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 2
• FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
• 208000007882 Gastritis Diseases 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 2
• BAWFJGJZGIEFAR-NNYOXOHSSA-N NAD zwitterion Chemical compound NC(=O)C1=CC=C[N+]([C@H]2[C@@H]([C@H](O)[C@@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 BAWFJGJZGIEFAR-NNYOXOHSSA-N 0.000 description 2
• PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
• 208000007107 Stomach Ulcer Diseases 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• 125000002252 acyl group Chemical group 0.000 description 2
• 125000001931 aliphatic group Chemical group 0.000 description 2
• 125000002947 alkylene group Chemical group 0.000 description 2
• 239000000908 ammonium hydroxide Substances 0.000 description 2
• 150000001450 anions Chemical class 0.000 description 2
• 235000010323 ascorbic acid Nutrition 0.000 description 2
• 239000011668 ascorbic acid Substances 0.000 description 2
• 230000001580 bacterial effect Effects 0.000 description 2
• TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
• 229940077388 benzenesulfonate Drugs 0.000 description 2
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
• AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 2
• 239000001768 carboxy methyl cellulose Substances 0.000 description 2
• 239000000460 chlorine Substances 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• 229940110456 cocoa butter Drugs 0.000 description 2
• 235000019868 cocoa butter Nutrition 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
• 208000035475 disorder Diseases 0.000 description 2
• 230000008029 eradication Effects 0.000 description 2
• 238000001704 evaporation Methods 0.000 description 2
• 230000008020 evaporation Effects 0.000 description 2
• 239000006260 foam Substances 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• 201000006585 gastric adenocarcinoma Diseases 0.000 description 2
• 201000005917 gastric ulcer Diseases 0.000 description 2
• 229930195712 glutamate Natural products 0.000 description 2
• 238000010438 heat treatment Methods 0.000 description 2
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
• 229930195733 hydrocarbon Natural products 0.000 description 2
• UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• QTBFPMKWQKYFLR-UHFFFAOYSA-N isobutyl chloride Chemical compound CC(C)CCl QTBFPMKWQKYFLR-UHFFFAOYSA-N 0.000 description 2
• JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
• 239000007937 lozenge Substances 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
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 229920000609 methyl cellulose Polymers 0.000 description 2
• 239000001923 methylcellulose Substances 0.000 description 2
• 235000010981 methylcellulose Nutrition 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
• XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
• 229920001223 polyethylene glycol Polymers 0.000 description 2
• 230000008569 process Effects 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
• 125000004076 pyridyl group Chemical group 0.000 description 2
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
• 239000000126 substance Substances 0.000 description 2
• 239000011593 sulfur Substances 0.000 description 2
• 239000000375 suspending agent Substances 0.000 description 2
• 208000024891 symptom Diseases 0.000 description 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
• CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 2
• 125000001544 thienyl group Chemical group 0.000 description 2
• 125000003396 thiol group Chemical group [H]S* 0.000 description 2
• LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
• HXKKHQJGJAFBHI-VKHMYHEASA-N (2s)-1-aminopropan-2-ol Chemical compound C[C@H](O)CN HXKKHQJGJAFBHI-VKHMYHEASA-N 0.000 description 1
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 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
• 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 1
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 1
• 125000004514 1,2,4-thiadiazolyl 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
• DIIIISSCIXVANO-UHFFFAOYSA-N 1,2-Dimethylhydrazine Chemical compound CNNC DIIIISSCIXVANO-UHFFFAOYSA-N 0.000 description 1
• NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
• AVGHIQUXSVAJBC-UHFFFAOYSA-N 1,2-diazabicyclo[2.2.1]heptane Chemical compound C1C2CCN1NC2 AVGHIQUXSVAJBC-UHFFFAOYSA-N 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
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
• OUKQTRFCDKSEPL-UHFFFAOYSA-N 1-Methyl-2-pyrrolecarboxaldehyde Chemical compound CN1C=CC=C1C=O OUKQTRFCDKSEPL-UHFFFAOYSA-N 0.000 description 1
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
• HXKKHQJGJAFBHI-UHFFFAOYSA-N 1-aminopropan-2-ol Chemical compound CC(O)CN HXKKHQJGJAFBHI-UHFFFAOYSA-N 0.000 description 1
• 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
• 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
• CCZMQYGSXWZFKI-UHFFFAOYSA-N 1-chloro-4-dichlorophosphoryloxybenzene Chemical compound ClC1=CC=C(OP(Cl)(Cl)=O)C=C1 CCZMQYGSXWZFKI-UHFFFAOYSA-N 0.000 description 1
• JWACULPGAGVTLA-UHFFFAOYSA-N 1-ethylpyrrole-3-carbonitrile Chemical compound CCN1C=CC(C#N)=C1 JWACULPGAGVTLA-UHFFFAOYSA-N 0.000 description 1
• SQAINHDHICKHLX-UHFFFAOYSA-N 1-naphthaldehyde Chemical compound C1=CC=C2C(C=O)=CC=CC2=C1 SQAINHDHICKHLX-UHFFFAOYSA-N 0.000 description 1
• 125000006017 1-propenyl group Chemical group 0.000 description 1
• 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 1
• BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
• 125000005955 1H-indazolyl group Chemical group 0.000 description 1
• DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-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
• 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 1
• SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 description 1
• JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 description 1
• WMRIKRYIKCYRKF-UHFFFAOYSA-N 2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-5-methyl-3-(3-methylimidazol-4-yl)pyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound CN1C=NC=C1C1=C2C(=O)N(C)C(=O)N(CC3CC3)C2=NN1CC1=CC=NC2=CC=C(Cl)C=C12 WMRIKRYIKCYRKF-UHFFFAOYSA-N 0.000 description 1
• 125000005273 2-acetoxybenzoic acid group Chemical group 0.000 description 1
• QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
• ZXXATOBUKOTTFW-UHFFFAOYSA-N 2-amino-6-hydrazinyl-3-methylpyrimidin-4-one Chemical compound CN1C(N)=NC(NN)=CC1=O ZXXATOBUKOTTFW-UHFFFAOYSA-N 0.000 description 1
• BKMMTJMQCTUHRP-UHFFFAOYSA-N 2-aminopropan-1-ol Chemical compound CC(N)CO BKMMTJMQCTUHRP-UHFFFAOYSA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
• IVHKZCSZELZKSJ-UHFFFAOYSA-N 2-hydroxyethyl sulfonate Chemical compound OCCOS(=O)=O IVHKZCSZELZKSJ-UHFFFAOYSA-N 0.000 description 1
• 229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
• 125000006024 2-pentenyl group Chemical group 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
• RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
• 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
• 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
• JPZOAVGMSDSWSW-UHFFFAOYSA-N 4,6-dichloropyrimidin-2-amine Chemical compound NC1=NC(Cl)=CC(Cl)=N1 JPZOAVGMSDSWSW-UHFFFAOYSA-N 0.000 description 1
• HVBSAKJJOYLTQU-UHFFFAOYSA-M 4-aminobenzenesulfonate Chemical compound NC1=CC=C(S([O-])(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-M 0.000 description 1
• GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
• CYBHWCLUGRHMCK-UHFFFAOYSA-N 4aH-carbazole Chemical compound C1=CC=C2C3C=CC=CC3=NC2=C1 CYBHWCLUGRHMCK-UHFFFAOYSA-N 0.000 description 1
• XEBINKVGOWURTH-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-4-(1-hydroxypropan-2-ylamino)-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound C12=NN(CC=3C4=CC(Cl)=CC=C4N=CC=3)C(C=3N(C=C(C=3)C#N)C)=C2C(NC(CO)C)=NC(=O)N1CC1CC1 XEBINKVGOWURTH-UHFFFAOYSA-N 0.000 description 1
• UZALJGJBYXBJQM-INIZCTEOSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-4-[[(2s)-2-hydroxypropyl]amino]-6-oxopyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound C12=NN(CC=3C4=CC(Cl)=CC=C4N=CC=3)C(C=3N(C=C(C=3)C#N)C)=C2C(NC[C@@H](O)C)=NC(=O)N1CC1CC1 UZALJGJBYXBJQM-INIZCTEOSA-N 0.000 description 1
• CDCXXPTXUBWPHS-UHFFFAOYSA-N 5-[2-[(6-chloroquinolin-4-yl)methyl]-7-(cyclopropylmethyl)-6-oxo-4-sulfanylidenepyrazolo[3,4-d]pyrimidin-3-yl]-1-methylpyrrole-3-carbonitrile Chemical compound CN1C=C(C#N)C=C1C1=C2C(=S)NC(=O)N(CC3CC3)C2=NN1CC1=CC=NC2=CC=C(Cl)C=C12 CDCXXPTXUBWPHS-UHFFFAOYSA-N 0.000 description 1
• KUEFXPHXHHANKS-UHFFFAOYSA-N 5-nitro-1h-1,2,4-triazole Chemical compound [O-][N+](=O)C1=NC=NN1 KUEFXPHXHHANKS-UHFFFAOYSA-N 0.000 description 1
• CHGLLOVPDGLPBY-UHFFFAOYSA-N 6-chloro-1-(2-methylpropyl)pyrimidine-2,4-dione Chemical compound CC(C)CN1C(Cl)=CC(=O)NC1=O CHGLLOVPDGLPBY-UHFFFAOYSA-N 0.000 description 1
• USXTVHGYMXMJDI-UHFFFAOYSA-N 7-(2-methylpropyl)-2-(naphthalen-1-ylmethyl)-3-pyridin-4-ylpyrazolo[3,4-d]pyrimidine-4,6-dione Chemical compound C=12C(=O)NC(=O)N(CC(C)C)C2=NN(CC=2C3=CC=CC=C3C=CC=2)C=1C1=CC=NC=C1 USXTVHGYMXMJDI-UHFFFAOYSA-N 0.000 description 1
• YPWFNLSXQIGJCK-UHFFFAOYSA-N 7-oxabicyclo[2.2.1]heptane Chemical compound C1CC2CCC1O2 YPWFNLSXQIGJCK-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
• 208000036170 B-Cell Marginal Zone Lymphoma Diseases 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 241000283690 Bos taurus Species 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
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 1
• 229930195713 D-glutamate Natural products 0.000 description 1
• WHUUTDBJXJRKMK-GSVOUGTGSA-N D-glutamic acid Chemical compound OC(=O)[C@H](N)CCC(O)=O WHUUTDBJXJRKMK-GSVOUGTGSA-N 0.000 description 1
• 101710088194 Dehydrogenase Proteins 0.000 description 1
• 239000004375 Dextrin Substances 0.000 description 1
• 229920001353 Dextrin Polymers 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• 241000588724 Escherichia coli Species 0.000 description 1
• 108700039887 Essential Genes Proteins 0.000 description 1
• 206010061850 Extranodal marginal zone B-cell lymphoma (MALT type) Diseases 0.000 description 1
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 208000018522 Gastrointestinal disease Diseases 0.000 description 1
• AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
• 108010015899 Glycopeptides Proteins 0.000 description 1
• 102000002068 Glycopeptides Human genes 0.000 description 1
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
• AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• 101150017040 I gene Proteins 0.000 description 1
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
• WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
• 229930194542 Keto Natural products 0.000 description 1
• AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• 229930195714 L-glutamate Natural products 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
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 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
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 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
• 201000003791 MALT lymphoma Diseases 0.000 description 1
• 241000124008 Mammalia Species 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• MSFSPUZXLOGKHJ-UHFFFAOYSA-N Muraminsaeure Natural products OC(=O)C(C)OC1C(N)C(O)OC(CO)C1O MSFSPUZXLOGKHJ-UHFFFAOYSA-N 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
• AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
• UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 229910019213 POCl3 Inorganic materials 0.000 description 1
• 229930182555 Penicillin Natural products 0.000 description 1
• 108010013639 Peptidoglycan Proteins 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
• WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-UHFFFAOYSA-N 0.000 description 1
• XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
• 235000021355 Stearic acid Nutrition 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-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
• 229920001615 Tragacanth Polymers 0.000 description 1
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
• 239000007983 Tris buffer Substances 0.000 description 1
• 208000025865 Ulcer Diseases 0.000 description 1
• BBAWTPDTGRXPDG-UHFFFAOYSA-N [1,3]thiazolo[4,5-b]pyridine Chemical compound C1=CC=C2SC=NC2=N1 BBAWTPDTGRXPDG-UHFFFAOYSA-N 0.000 description 1
• IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 239000004480 active ingredient Substances 0.000 description 1
• 150000001263 acyl chlorides Chemical class 0.000 description 1
• WNLRTRBMVRJNCN-UHFFFAOYSA-L adipate(2-) Chemical compound [O-]C(=O)CCCCC([O-])=O WNLRTRBMVRJNCN-UHFFFAOYSA-L 0.000 description 1
• 230000002411 adverse Effects 0.000 description 1
• 239000000443 aerosol Substances 0.000 description 1
• 239000003513 alkali Substances 0.000 description 1
• 229910052783 alkali metal Inorganic materials 0.000 description 1
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 125000004450 alkenylene group Chemical group 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• 125000004414 alkyl thio group Chemical group 0.000 description 1
• 125000004419 alkynylene group Chemical group 0.000 description 1
• 208000030961 allergic reaction Diseases 0.000 description 1
• 125000005336 allyloxy group Chemical group 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-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
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 150000001413 amino acids Chemical class 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 230000000844 anti-bacterial effect Effects 0.000 description 1
• 239000004599 antimicrobial Substances 0.000 description 1
• 238000011203 antimicrobial therapy Methods 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 239000007864 aqueous solution Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
• 125000004931 azocinyl group Chemical group N1=C(C=CC=CC=C1)* 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 229940050390 benzoate Drugs 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
• 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
• AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
• 238000003339 best practice Methods 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000003115 biocidal effect Effects 0.000 description 1
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 239000000872 buffer Substances 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
• VOAKFMDUSHTMLP-OKVQFNOJSA-N c1cnc2ccc(Cl)cc2c1Cn(c(c1c(=N/C)/n(C)/c2=N/C)-c3n(cc(C#N)c3)C)nc1n2CC1CC1 Chemical compound c1cnc2ccc(Cl)cc2c1Cn(c(c1c(=N/C)/n(C)/c2=N/C)-c3n(cc(C#N)c3)C)nc1n2CC1CC1 VOAKFMDUSHTMLP-OKVQFNOJSA-N 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
• 125000004623 carbolinyl group Chemical group 0.000 description 1
• 150000001735 carboxylic acids Chemical class 0.000 description 1
• 230000003197 catalytic effect Effects 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 239000003795 chemical substances by application Substances 0.000 description 1
• RZWZDIVNLQZHGB-UHFFFAOYSA-N chloroform;methylsulfinylmethane Chemical compound CS(C)=O.ClC(Cl)Cl RZWZDIVNLQZHGB-UHFFFAOYSA-N 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
• 125000004230 chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 235000015165 citric acid Nutrition 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 238000002648 combination therapy Methods 0.000 description 1
• 230000001010 compromised effect Effects 0.000 description 1
• 239000000470 constituent Substances 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 230000008878 coupling Effects 0.000 description 1
• 238000010168 coupling process Methods 0.000 description 1
• 238000005859 coupling reaction Methods 0.000 description 1
• 239000006071 cream Substances 0.000 description 1
• 239000012043 crude product Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000006622 cycloheptylmethyl group Chemical group 0.000 description 1
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
• 125000006317 cyclopropyl amino group Chemical group 0.000 description 1
• 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 description 1
• 238000000354 decomposition reaction Methods 0.000 description 1
• 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 1
• 238000013461 design Methods 0.000 description 1
• 235000019425 dextrin Nutrition 0.000 description 1
• 150000008050 dialkyl sulfates Chemical class 0.000 description 1
• 235000014113 dietary fatty acids Nutrition 0.000 description 1
• 229960004132 diethyl ether Drugs 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 208000010643 digestive system disease Diseases 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
• GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical class CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
• 239000001177 diphosphate Substances 0.000 description 1
• XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
• 235000011180 diphosphates Nutrition 0.000 description 1
• VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 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
• 229940079593 drug Drugs 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 238000000132 electrospray ionisation Methods 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 229940071106 ethylenediaminetetraacetate Drugs 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 230000005284 excitation Effects 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
• 239000000796 flavoring agent Substances 0.000 description 1
• 235000019634 flavors Nutrition 0.000 description 1
• 229910052731 fluorine Inorganic materials 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 238000005187 foaming Methods 0.000 description 1
• 239000012458 free base Substances 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 125000000524 functional group Chemical group 0.000 description 1
• 125000003838 furazanyl group Chemical group 0.000 description 1
• 230000004927 fusion Effects 0.000 description 1
• 208000017215 gastric mucosa-associated lymphoid tissue lymphoma Diseases 0.000 description 1
• 208000018685 gastrointestinal system disease Diseases 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 239000000499 gel Substances 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 125000004438 haloalkoxy group Chemical group 0.000 description 1
• 125000004995 haloalkylthio group Chemical group 0.000 description 1
• 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
• MNWFXJYAOYHMED-UHFFFAOYSA-N heptanoic acid Chemical compound CCCCCCC(O)=O MNWFXJYAOYHMED-UHFFFAOYSA-N 0.000 description 1
• FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
• 125000006038 hexenyl group Chemical group 0.000 description 1
• 239000008240 homogeneous mixture Substances 0.000 description 1
• XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 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
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 125000002883 imidazolyl group Chemical group 0.000 description 1
• 125000004926 indolenyl group Chemical group 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 125000001041 indolyl group Chemical group 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 229910052500 inorganic mineral Inorganic materials 0.000 description 1
• 238000009413 insulation Methods 0.000 description 1
• 238000000185 intracerebroventricular administration Methods 0.000 description 1
• 238000007912 intraperitoneal administration Methods 0.000 description 1
• 238000007913 intrathecal administration Methods 0.000 description 1
• 239000011630 iodine Substances 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 239000003456 ion exchange resin Substances 0.000 description 1
• 229920003303 ion-exchange polymer Polymers 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 230000007794 irritation Effects 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
• 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
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 125000000468 ketone group Chemical group 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
• 239000010410 layer Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 210000003563 lymphoid tissue Anatomy 0.000 description 1
• 239000008176 lyophilized powder Substances 0.000 description 1
• ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
• 239000001095 magnesium carbonate Substances 0.000 description 1
• 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
• 159000000003 magnesium salts Chemical class 0.000 description 1
• 235000019359 magnesium stearate Nutrition 0.000 description 1
• 229940049920 malate Drugs 0.000 description 1
• 239000011976 maleic acid Substances 0.000 description 1
• BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 229960003194 meglumine Drugs 0.000 description 1
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
• 239000011707 mineral Substances 0.000 description 1
• 235000010755 mineral Nutrition 0.000 description 1
• 238000012986 modification Methods 0.000 description 1
• 230000004048 modification Effects 0.000 description 1
• 230000009456 molecular mechanism Effects 0.000 description 1
• 238000012544 monitoring process Methods 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 210000004877 mucosa Anatomy 0.000 description 1
• 125000001421 myristyl 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])C([H])([H])C([H])([H])C([H])([H])[H] 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
• KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 239000007922 nasal spray Substances 0.000 description 1
• 230000007935 neutral effect Effects 0.000 description 1
• 229910052759 nickel Inorganic materials 0.000 description 1
• 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
• BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
• 229910017604 nitric acid Inorganic materials 0.000 description 1
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
• 239000012457 nonaqueous media Substances 0.000 description 1
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
• 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 description 1
• 239000002674 ointment Substances 0.000 description 1
• 150000007530 organic bases Chemical class 0.000 description 1
• 239000003960 organic solvent Substances 0.000 description 1
• 229960003104 ornithine Drugs 0.000 description 1
• 230000003204 osmotic effect Effects 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• QNNHQVPFZIFNFK-UHFFFAOYSA-N oxazolo[4,5-b]pyridine Chemical compound C1=CC=C2OC=NC2=N1 QNNHQVPFZIFNFK-UHFFFAOYSA-N 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 125000004430 oxygen atom Chemical group O* 0.000 description 1
• IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 239000001814 pectin Substances 0.000 description 1
• 235000010987 pectin Nutrition 0.000 description 1
• 229920001277 pectin Polymers 0.000 description 1
• 150000002960 penicillins Chemical class 0.000 description 1
• 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
• 230000000144 pharmacologic effect Effects 0.000 description 1
• 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
• 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
• 125000004624 phenarsazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3[As]=C12)* 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
• 125000005954 phenoxathiinyl group Chemical group 0.000 description 1
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
• 229940049953 phenylacetate Drugs 0.000 description 1
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
• 239000010452 phosphate Substances 0.000 description 1
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 229940075930 picrate Drugs 0.000 description 1
• OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 125000004928 piperidonyl group Chemical group 0.000 description 1
• 229950010765 pivalate Drugs 0.000 description 1
• IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
• 125000003367 polycyclic group Chemical group 0.000 description 1
• 125000004585 polycyclic heterocycle group Chemical group 0.000 description 1
• 159000000001 potassium salts Chemical class 0.000 description 1
• 238000001556 precipitation Methods 0.000 description 1
• 125000001844 prenyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
• KPBSJEBFALFJTO-UHFFFAOYSA-N propane-1-sulfonyl chloride Chemical compound CCCS(Cl)(=O)=O KPBSJEBFALFJTO-UHFFFAOYSA-N 0.000 description 1
• 235000019260 propionic acid Nutrition 0.000 description 1
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
• DNIAPMSPPWPWGF-UHFFFAOYSA-N propylene glycol Substances CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 1
• 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
• 125000003373 pyrazinyl group Chemical group 0.000 description 1
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
• 125000002755 pyrazolinyl group Chemical group 0.000 description 1
• 125000002098 pyridazinyl group Chemical group 0.000 description 1
• BGUWFUQJCDRPTL-UHFFFAOYSA-N pyridine-4-carbaldehyde Chemical compound O=CC1=CC=NC=C1 BGUWFUQJCDRPTL-UHFFFAOYSA-N 0.000 description 1
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
• 125000000714 pyrimidinyl group Chemical group 0.000 description 1
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 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 description 1
• ZHNFLHYOFXQIOW-LPYZJUEESA-N quinine sulfate dihydrate Chemical compound [H+].[H+].O.O.[O-]S([O-])(=O)=O.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21.C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 ZHNFLHYOFXQIOW-LPYZJUEESA-N 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
• SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
• 150000003254 radicals Chemical class 0.000 description 1
• 230000035484 reaction time Effects 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 239000011347 resin Substances 0.000 description 1
• 229920005989 resin Polymers 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
• 229960001860 salicylate Drugs 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 238000000926 separation method Methods 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• 238000009097 single-agent therapy Methods 0.000 description 1
• 239000002002 slurry Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 230000003595 spectral effect Effects 0.000 description 1
• 239000003381 stabilizer Substances 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 239000008117 stearic acid Substances 0.000 description 1
• 239000008223 sterile water Substances 0.000 description 1
• 239000011550 stock solution Substances 0.000 description 1
• 210000002784 stomach Anatomy 0.000 description 1
• 239000002731 stomach secretion inhibitor Substances 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 235000000346 sugar Nutrition 0.000 description 1
• IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 239000007885 tablet disintegrant Substances 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 239000011975 tartaric acid Substances 0.000 description 1
• 235000002906 tartaric acid Nutrition 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
• 229940124597 therapeutic agent Drugs 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 150000003553 thiiranes Chemical class 0.000 description 1
• 125000005309 thioalkoxy group Chemical group 0.000 description 1
• 210000001519 tissue Anatomy 0.000 description 1
• 238000004448 titration Methods 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 231100000419 toxicity Toxicity 0.000 description 1
• 230000001988 toxicity Effects 0.000 description 1
• 239000000196 tragacanth Substances 0.000 description 1
• 235000010487 tragacanth Nutrition 0.000 description 1
• 229940116362 tragacanth Drugs 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
• LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
• ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
• 239000003981 vehicle Substances 0.000 description 1
• 230000035899 viability Effects 0.000 description 1
• 239000011345 viscous material Substances 0.000 description 1
• 238000010626 work up procedure Methods 0.000 description 1
• 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1