CA2579059A1 - Chemical compounds - Google Patents
Chemical compounds Download PDFInfo
- Publication number
- CA2579059A1 CA2579059A1 CA002579059A CA2579059A CA2579059A1 CA 2579059 A1 CA2579059 A1 CA 2579059A1 CA 002579059 A CA002579059 A CA 002579059A CA 2579059 A CA2579059 A CA 2579059A CA 2579059 A1 CA2579059 A1 CA 2579059A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- tetrahydro
- pyridin
- imidazo
- quinolinamine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 275
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims abstract description 27
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 claims abstract description 25
- 208000031886 HIV Infections Diseases 0.000 claims abstract description 20
- 208000037357 HIV infectious disease Diseases 0.000 claims abstract description 20
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims abstract description 20
- 102000009410 Chemokine receptor Human genes 0.000 claims abstract description 17
- 108050000299 Chemokine receptor Proteins 0.000 claims abstract description 17
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 claims abstract description 14
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 claims abstract description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 156
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 128
- 125000003342 alkenyl group Chemical group 0.000 claims description 75
- 125000000304 alkynyl group Chemical group 0.000 claims description 75
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 71
- 238000006268 reductive amination reaction Methods 0.000 claims description 71
- 125000001188 haloalkyl group Chemical group 0.000 claims description 67
- -1 stavidine Chemical compound 0.000 claims description 62
- 239000000203 mixture Substances 0.000 claims description 55
- 238000011282 treatment Methods 0.000 claims description 42
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 39
- 239000003795 chemical substances by application Substances 0.000 claims description 38
- 229910052736 halogen Inorganic materials 0.000 claims description 35
- 150000002367 halogens Chemical group 0.000 claims description 35
- 150000003839 salts Chemical class 0.000 claims description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- 230000000694 effects Effects 0.000 claims description 28
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 28
- 229910052757 nitrogen Inorganic materials 0.000 claims description 28
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 24
- 201000010099 disease Diseases 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 20
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 20
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 19
- 125000004043 oxo group Chemical group O=* 0.000 claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 238000011321 prophylaxis Methods 0.000 claims description 17
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 16
- 238000005859 coupling reaction Methods 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 208000029523 Interstitial Lung disease Diseases 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- 230000002757 inflammatory effect Effects 0.000 claims description 15
- 230000008569 process Effects 0.000 claims description 15
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 14
- 201000004624 Dermatitis Diseases 0.000 claims description 14
- 201000004681 Psoriasis Diseases 0.000 claims description 14
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 14
- 208000026935 allergic disease Diseases 0.000 claims description 14
- 230000002708 enhancing effect Effects 0.000 claims description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 230000009610 hypersensitivity Effects 0.000 claims description 14
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 14
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 14
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
- 206010061218 Inflammation Diseases 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- 230000004054 inflammatory process Effects 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 13
- 210000001519 tissue Anatomy 0.000 claims description 13
- 125000002947 alkylene group Chemical group 0.000 claims description 12
- 150000001412 amines Chemical group 0.000 claims description 12
- 230000008878 coupling Effects 0.000 claims description 12
- 238000010168 coupling process Methods 0.000 claims description 12
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 11
- 125000005724 cycloalkenylene group Chemical group 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- FRHRAPSVOIMXJY-FQEVSTJZSA-N (8s)-n-methyl-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CCN(C)CC1 FRHRAPSVOIMXJY-FQEVSTJZSA-N 0.000 claims description 10
- 125000004450 alkenylene group Chemical group 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000004419 alkynylene group Chemical group 0.000 claims description 10
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 10
- 150000002148 esters Chemical class 0.000 claims description 10
- 239000003112 inhibitor Substances 0.000 claims description 10
- RTYCIUZFGNBFDO-NRFANRHFSA-N (8s)-n-[[5-(4-ethylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(CC)CCN1C1=CC=CC2=NC(CN(C)[C@@H]3C4=NC=CC=C4CCC3)=CN12 RTYCIUZFGNBFDO-NRFANRHFSA-N 0.000 claims description 9
- PTROCZWZGUYFHN-QHCPKHFHSA-N (8s)-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-(2-methylpropyl)-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CC(C)CN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CCN(C)CC1 PTROCZWZGUYFHN-QHCPKHFHSA-N 0.000 claims description 9
- VLKZZNVOWQCIBI-QFIPXVFZSA-N (8s)-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-propyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CCCN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CCN(C)CC1 VLKZZNVOWQCIBI-QFIPXVFZSA-N 0.000 claims description 9
- SGMXLHJXSIULNM-QHCPKHFHSA-N (8s)-n-butyl-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CCCCN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CCN(C)CC1 SGMXLHJXSIULNM-QHCPKHFHSA-N 0.000 claims description 9
- QDYGAGPVZXUDBW-NRFANRHFSA-N (8s)-n-ethyl-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CCN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CCN(C)CC1 QDYGAGPVZXUDBW-NRFANRHFSA-N 0.000 claims description 9
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 9
- 150000003973 alkyl amines Chemical group 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- FRHRAPSVOIMXJY-UHFFFAOYSA-N n-methyl-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2N1CCN(C)CC1 FRHRAPSVOIMXJY-UHFFFAOYSA-N 0.000 claims description 9
- 125000003107 substituted aryl group Chemical group 0.000 claims description 9
- ZNYNQVPNMSPERK-QHCPKHFHSA-N (8s)-n-(cyclopropylmethyl)-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC3CC3)[C@@H]3C4=NC=CC=C4CCC3)=CN12 ZNYNQVPNMSPERK-QHCPKHFHSA-N 0.000 claims description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 8
- 208000006673 asthma Diseases 0.000 claims description 8
- 208000032839 leukemia Diseases 0.000 claims description 8
- RTYCIUZFGNBFDO-UHFFFAOYSA-N n-[[5-(4-ethylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(CC)CCN1C1=CC=CC2=NC(CN(C)C3C4=NC=CC=C4CCC3)=CN12 RTYCIUZFGNBFDO-UHFFFAOYSA-N 0.000 claims description 8
- 239000002773 nucleotide Substances 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- GRGVJGVHZOIZFP-FQEVSTJZSA-N (8s)-n-[[5-(4-aminopiperidin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CCC(N)CC1 GRGVJGVHZOIZFP-FQEVSTJZSA-N 0.000 claims description 7
- QJSUPMMHOXHUJT-QFIPXVFZSA-N (8s)-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-propan-2-yl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CC(C)N([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CCN(C)CC1 QJSUPMMHOXHUJT-QFIPXVFZSA-N 0.000 claims description 7
- LLTLSDYWBUFMNN-MJGOQNOKSA-N (8s)-n-[[5-[(3r)-3-aminopyrrolidin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CC[C@@H](N)C1 LLTLSDYWBUFMNN-MJGOQNOKSA-N 0.000 claims description 7
- RAGLHMFSABSZAL-ZYZRXSCRSA-N (8s)-n-methyl-n-[1-[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]ethyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)C(C)C(N=C1C=CC=2)=CN1C=2N1CCN(C)CC1 RAGLHMFSABSZAL-ZYZRXSCRSA-N 0.000 claims description 7
- KGGOEFQJWNRJEG-LBAQZLPGSA-N (8s)-n-methyl-n-[[5-[methyl-(1-methylpyrrolidin-3-yl)amino]imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N(C)C1CCN(C)C1 KGGOEFQJWNRJEG-LBAQZLPGSA-N 0.000 claims description 7
- VVCKQGVIFYLFLK-QFIPXVFZSA-N 3-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]propan-1-ol Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CCCO)[C@@H]3C4=NC=CC=C4CCC3)=CN12 VVCKQGVIFYLFLK-QFIPXVFZSA-N 0.000 claims description 7
- 206010058284 Allergy to arthropod sting Diseases 0.000 claims description 7
- 206010002198 Anaphylactic reaction Diseases 0.000 claims description 7
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 7
- 208000023275 Autoimmune disease Diseases 0.000 claims description 7
- 208000035143 Bacterial infection Diseases 0.000 claims description 7
- 208000011231 Crohn disease Diseases 0.000 claims description 7
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 7
- 206010012442 Dermatitis contact Diseases 0.000 claims description 7
- 206010013700 Drug hypersensitivity Diseases 0.000 claims description 7
- 206010014954 Eosinophilic fasciitis Diseases 0.000 claims description 7
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 7
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 7
- 206010020751 Hypersensitivity Diseases 0.000 claims description 7
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 claims description 7
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 7
- 208000034624 Leukocytoclastic Cutaneous Vasculitis Diseases 0.000 claims description 7
- 208000032514 Leukocytoclastic vasculitis Diseases 0.000 claims description 7
- 208000019693 Lung disease Diseases 0.000 claims description 7
- 241000288894 Myotis Species 0.000 claims description 7
- 206010035664 Pneumonia Diseases 0.000 claims description 7
- 206010035742 Pneumonitis Diseases 0.000 claims description 7
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 7
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 7
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 7
- 208000021386 Sjogren Syndrome Diseases 0.000 claims description 7
- 208000006045 Spondylarthropathies Diseases 0.000 claims description 7
- 201000009594 Systemic Scleroderma Diseases 0.000 claims description 7
- 206010042953 Systemic sclerosis Diseases 0.000 claims description 7
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 7
- 206010052779 Transplant rejections Diseases 0.000 claims description 7
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 7
- 206010053613 Type IV hypersensitivity reaction Diseases 0.000 claims description 7
- 208000025865 Ulcer Diseases 0.000 claims description 7
- 208000024780 Urticaria Diseases 0.000 claims description 7
- 206010047115 Vasculitis Diseases 0.000 claims description 7
- 208000002029 allergic contact dermatitis Diseases 0.000 claims description 7
- 201000010105 allergic rhinitis Diseases 0.000 claims description 7
- 208000003455 anaphylaxis Diseases 0.000 claims description 7
- 201000008937 atopic dermatitis Diseases 0.000 claims description 7
- 208000010668 atopic eczema Diseases 0.000 claims description 7
- 230000001363 autoimmune Effects 0.000 claims description 7
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 7
- 238000010322 bone marrow transplantation Methods 0.000 claims description 7
- 238000002512 chemotherapy Methods 0.000 claims description 7
- 201000001981 dermatomyositis Diseases 0.000 claims description 7
- 230000002327 eosinophilic effect Effects 0.000 claims description 7
- 201000001155 extrinsic allergic alveolitis Diseases 0.000 claims description 7
- 208000024908 graft versus host disease Diseases 0.000 claims description 7
- 230000011132 hemopoiesis Effects 0.000 claims description 7
- 208000022098 hypersensitivity pneumonitis Diseases 0.000 claims description 7
- 201000006362 hypersensitivity vasculitis Diseases 0.000 claims description 7
- 208000027866 inflammatory disease Diseases 0.000 claims description 7
- 208000036971 interstitial lung disease 2 Diseases 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 7
- AQOBWZRQYWFSAW-UHFFFAOYSA-N n-methyl-n-[(5-piperazin-1-ylimidazo[1,2-a]pyridin-2-yl)methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2N1CCNCC1 AQOBWZRQYWFSAW-UHFFFAOYSA-N 0.000 claims description 7
- MFPNAWHIPSNSRA-UHFFFAOYSA-N n-methyl-n-[[5-(4-propan-2-ylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C(C)C)CCN1C1=CC=CC2=NC(CN(C)C3C4=NC=CC=C4CCC3)=CN12 MFPNAWHIPSNSRA-UHFFFAOYSA-N 0.000 claims description 7
- JPTZJWVMCKRUDC-UHFFFAOYSA-N n-propan-2-yl-n-[[5-(4-propan-2-ylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C(C)C)CC(N=C1C=CC=2)=CN1C=2N1CCN(C(C)C)CC1 JPTZJWVMCKRUDC-UHFFFAOYSA-N 0.000 claims description 7
- 230000002956 necrotizing effect Effects 0.000 claims description 7
- 125000003729 nucleotide group Chemical group 0.000 claims description 7
- 208000005987 polymyositis Diseases 0.000 claims description 7
- 208000017520 skin disease Diseases 0.000 claims description 7
- 201000005671 spondyloarthropathy Diseases 0.000 claims description 7
- 230000005951 type IV hypersensitivity Effects 0.000 claims description 7
- 208000027930 type IV hypersensitivity disease Diseases 0.000 claims description 7
- 230000029663 wound healing Effects 0.000 claims description 7
- XCBGMXUKNZCYDY-RPWUZVMVSA-N (8s)-n-(cyclopropylmethyl)-n-[[5-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1[C@H](N(C)C)CCN1C1=CC=CC2=NC(CN(CC3CC3)[C@@H]3C4=NC=CC=C4CCC3)=CN12 XCBGMXUKNZCYDY-RPWUZVMVSA-N 0.000 claims description 6
- DUXQJVSQUNTORQ-PKTZIBPZSA-N (8s)-n-[[5-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-n-propan-2-yl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CC(C)N([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CC[C@@H](N(C)C)C1 DUXQJVSQUNTORQ-PKTZIBPZSA-N 0.000 claims description 6
- VMDADMFTSYKUBK-NRFANRHFSA-N (8s)-n-methyl-n-[[5-(4-methyl-1,4-diazepan-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CCCN(C)CC1 VMDADMFTSYKUBK-NRFANRHFSA-N 0.000 claims description 6
- OLNFUKUUTXMWRQ-NRFANRHFSA-N 2-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]ethanol Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CCO)[C@@H]3C4=NC=CC=C4CCC3)=CN12 OLNFUKUUTXMWRQ-NRFANRHFSA-N 0.000 claims description 6
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 6
- 206010039710 Scleroderma Diseases 0.000 claims description 6
- WOZSCQDILHKSGG-UHFFFAOYSA-N adefovir depivoxil Chemical compound N1=CN=C2N(CCOCP(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C)C=NC2=C1N WOZSCQDILHKSGG-UHFFFAOYSA-N 0.000 claims description 6
- 210000004556 brain Anatomy 0.000 claims description 6
- 210000000481 breast Anatomy 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine Chemical compound CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 WHBIGIKBNXZKFE-UHFFFAOYSA-N 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 210000004072 lung Anatomy 0.000 claims description 6
- GMZLORPERFPBOQ-UHFFFAOYSA-N n-[[5-(3,5-dimethylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1C(C)NC(C)CN1C1=CC=CC2=NC(CN(C)C3C4=NC=CC=C4CCC3)=CN12 GMZLORPERFPBOQ-UHFFFAOYSA-N 0.000 claims description 6
- XWVHXXMWDHKKAN-UHFFFAOYSA-N n-[[5-(3-aminoazetidin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2N1CC(N)C1 XWVHXXMWDHKKAN-UHFFFAOYSA-N 0.000 claims description 6
- QJSUPMMHOXHUJT-UHFFFAOYSA-N n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-propan-2-yl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C(C)C)CC(N=C1C=CC=2)=CN1C=2N1CCN(C)CC1 QJSUPMMHOXHUJT-UHFFFAOYSA-N 0.000 claims description 6
- NQDJXKOVJZTUJA-UHFFFAOYSA-N nevirapine Chemical compound C12=NC=CC=C2C(=O)NC=2C(C)=CC=NC=2N1C1CC1 NQDJXKOVJZTUJA-UHFFFAOYSA-N 0.000 claims description 6
- CKNAQFVBEHDJQV-UHFFFAOYSA-N oltipraz Chemical compound S1SC(=S)C(C)=C1C1=CN=CC=N1 CKNAQFVBEHDJQV-UHFFFAOYSA-N 0.000 claims description 6
- 229950008687 oltipraz Drugs 0.000 claims description 6
- 210000002307 prostate Anatomy 0.000 claims description 6
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 claims description 6
- 230000001225 therapeutic effect Effects 0.000 claims description 6
- UNJUOXFDBJBZSL-FQEVSTJZSA-N (8s)-n-[[5-(1,4-diazepan-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CCCNCC1 UNJUOXFDBJBZSL-FQEVSTJZSA-N 0.000 claims description 5
- GBXJUSLOSBALMG-YADHBBJMSA-N (8s)-n-[[5-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-n-ethyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CCN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CC[C@@H](N(C)C)C1 GBXJUSLOSBALMG-YADHBBJMSA-N 0.000 claims description 5
- MFPNAWHIPSNSRA-QFIPXVFZSA-N (8s)-n-methyl-n-[[5-(4-propan-2-ylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C(C)C)CCN1C1=CC=CC2=NC(CN(C)[C@@H]3C4=NC=CC=C4CCC3)=CN12 MFPNAWHIPSNSRA-QFIPXVFZSA-N 0.000 claims description 5
- IJRADFNTAYCYKO-QFIPXVFZSA-N (8s)-n-methyl-n-[[5-[methyl-(1-methylpiperidin-4-yl)amino]imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N(C)C1CCN(C)CC1 IJRADFNTAYCYKO-QFIPXVFZSA-N 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- ROQQDVQEYJVOLI-UHFFFAOYSA-N n-[(5-piperazin-1-ylimidazo[1,2-a]pyridin-2-yl)methyl]-n-propan-2-yl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C(C)C)CC(N=C1C=CC=2)=CN1C=2N1CCNCC1 ROQQDVQEYJVOLI-UHFFFAOYSA-N 0.000 claims description 5
- UNJUOXFDBJBZSL-UHFFFAOYSA-N n-[[5-(1,4-diazepan-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2N1CCCNCC1 UNJUOXFDBJBZSL-UHFFFAOYSA-N 0.000 claims description 5
- GRGVJGVHZOIZFP-UHFFFAOYSA-N n-[[5-(4-aminopiperidin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2N1CCC(N)CC1 GRGVJGVHZOIZFP-UHFFFAOYSA-N 0.000 claims description 5
- LLTLSDYWBUFMNN-DUSLRRAJSA-N n-[[5-[(3r)-3-aminopyrrolidin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2N1CC[C@@H](N)C1 LLTLSDYWBUFMNN-DUSLRRAJSA-N 0.000 claims description 5
- VMDADMFTSYKUBK-UHFFFAOYSA-N n-methyl-n-[[5-(4-methyl-1,4-diazepan-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2N1CCCN(C)CC1 VMDADMFTSYKUBK-UHFFFAOYSA-N 0.000 claims description 5
- NTZBKAPQFLBYKJ-UHFFFAOYSA-N n-methyl-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-6,7-dihydro-5h-cyclopenta[b]pyridin-7-amine Chemical compound C1CC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2N1CCN(C)CC1 NTZBKAPQFLBYKJ-UHFFFAOYSA-N 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- FRHRAPSVOIMXJY-HXUWFJFHSA-N (8r)-n-methyl-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CN([C@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CCN(C)CC1 FRHRAPSVOIMXJY-HXUWFJFHSA-N 0.000 claims description 4
- LXPJSHZFBKHPQH-PKTZIBPZSA-N (8s)-n-[[5-[(3r)-3-(diethylamino)pyrrolidin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1[C@H](N(CC)CC)CCN1C1=CC=CC2=NC(CN(C)[C@@H]3C4=NC=CC=C4CCC3)=CN12 LXPJSHZFBKHPQH-PKTZIBPZSA-N 0.000 claims description 4
- KCYJZDNOWILGPM-RTWAWAEBSA-N (8s)-n-[[5-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1[C@H](N(C)C)CCN1C1=CC=CC2=NC(CN(C)[C@@H]3C4=NC=CC=C4CCC3)=CN12 KCYJZDNOWILGPM-RTWAWAEBSA-N 0.000 claims description 4
- UOFZOCCQDPJRLD-PKTZIBPZSA-N (8s)-n-[[5-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-n-propyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CCCN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CC[C@@H](N(C)C)C1 UOFZOCCQDPJRLD-PKTZIBPZSA-N 0.000 claims description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- ITPSDEVJHDJOQI-UHFFFAOYSA-N n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CNC3C4=NC=CC=C4CCC3)=CN12 ITPSDEVJHDJOQI-UHFFFAOYSA-N 0.000 claims description 4
- VRZMFUIDEOPILH-UHFFFAOYSA-N n-[[5-[4-(2-methoxyethyl)piperazin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(CCOC)CCN1C1=CC=CC2=NC(CN(C)C3C4=NC=CC=C4CCC3)=CN12 VRZMFUIDEOPILH-UHFFFAOYSA-N 0.000 claims description 4
- BABAEMPTYIHDCU-UHFFFAOYSA-N n-[[5-[4-[(dimethylamino)methyl]phenyl]imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1=CC(CN(C)C)=CC=C1C1=CC=CC2=NC(CN(C)C3C4=NC=CC=C4CCC3)=CN12 BABAEMPTYIHDCU-UHFFFAOYSA-N 0.000 claims description 4
- IXNIIYLSQFRXKT-UHFFFAOYSA-N n-methyl-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-6,7,8,9-tetrahydro-5h-cyclohepta[b]pyridin-9-amine Chemical compound C1CCCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2N1CCN(C)CC1 IXNIIYLSQFRXKT-UHFFFAOYSA-N 0.000 claims description 4
- 239000012038 nucleophile Substances 0.000 claims description 4
- 125000003386 piperidinyl group Chemical group 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- TXIOIJSYWOLKNU-FLQODOFBSA-N (1r,3as,5ar,5br,7ar,9s,11ar,11br,13ar,13br)-9-(3-carboxy-3-methylbutanoyl)oxy-5a,5b,8,8,11a-pentamethyl-1-prop-1-en-2-yl-1,2,3,4,5,6,7,7a,9,10,11,11b,12,13,13a,13b-hexadecahydrocyclopenta[a]chrysene-3a-carboxylic acid;(2r,3r,4r,5s)-6-(methylamino)hexane-1 Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.C1C[C@H](OC(=O)CC(C)(C)C(O)=O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C(=C)C)[C@@H]5[C@H]4CC[C@@H]3[C@]21C TXIOIJSYWOLKNU-FLQODOFBSA-N 0.000 claims description 3
- KBFBYFZJSCVLLM-SANMLTNESA-N (8s)-n-[(2-fluorophenyl)methyl]-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC=3C(=CC=CC=3)F)[C@@H]3C4=NC=CC=C4CCC3)=CN12 KBFBYFZJSCVLLM-SANMLTNESA-N 0.000 claims description 3
- LEXHYGXGJQBYAI-SANMLTNESA-N (8s)-n-[(3-bromophenyl)methyl]-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC=3C=C(Br)C=CC=3)[C@@H]3C4=NC=CC=C4CCC3)=CN12 LEXHYGXGJQBYAI-SANMLTNESA-N 0.000 claims description 3
- SKODILUTZBONIX-SANMLTNESA-N (8s)-n-[(3-fluorophenyl)methyl]-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC=3C=C(F)C=CC=3)[C@@H]3C4=NC=CC=C4CCC3)=CN12 SKODILUTZBONIX-SANMLTNESA-N 0.000 claims description 3
- NRNCNGNZSXHFCR-MHZLTWQESA-N (8s)-n-[(3-methoxyphenyl)methyl]-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound COC1=CC=CC(CN(CC=2N=C3C=CC=C(N3C=2)N2CCN(C)CC2)[C@@H]2C3=NC=CC=C3CCC2)=C1 NRNCNGNZSXHFCR-MHZLTWQESA-N 0.000 claims description 3
- GCUYUUBRHMQCKE-SANMLTNESA-N (8s)-n-[(4-bromophenyl)methyl]-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC=3C=CC(Br)=CC=3)[C@@H]3C4=NC=CC=C4CCC3)=CN12 GCUYUUBRHMQCKE-SANMLTNESA-N 0.000 claims description 3
- KZJFXCOQWHOXAP-MHZLTWQESA-N (8s)-n-[(4-methoxyphenyl)methyl]-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1=CC(OC)=CC=C1CN([C@@H]1C2=NC=CC=C2CCC1)CC1=CN(C(=CC=C2)N3CCN(C)CC3)C2=N1 KZJFXCOQWHOXAP-MHZLTWQESA-N 0.000 claims description 3
- RJEKSBHPANGBOV-MHZLTWQESA-N (8s)-n-[(4-methylphenyl)methyl]-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC=3C=CC(C)=CC=3)[C@@H]3C4=NC=CC=C4CCC3)=CN12 RJEKSBHPANGBOV-MHZLTWQESA-N 0.000 claims description 3
- RZBMNHLGYITPKH-KEKNWZKVSA-N (8s)-n-[[5-(3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-2-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2[C@H]1N(C)CC1=CN(C(=CC=C2)N3CC4CCCN4CC3)C2=N1 RZBMNHLGYITPKH-KEKNWZKVSA-N 0.000 claims description 3
- JALJTKRUKDCSQJ-YTTGMZPUSA-N (8s)-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-[(4-phenylphenyl)methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC=3C=CC(=CC=3)C=3C=CC=CC=3)[C@@H]3C4=NC=CC=C4CCC3)=CN12 JALJTKRUKDCSQJ-YTTGMZPUSA-N 0.000 claims description 3
- JUGNNVPVNCGJGC-LJAQVGFWSA-N (8s)-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-[(4-propan-2-ylphenyl)methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1=CC(C(C)C)=CC=C1CN([C@@H]1C2=NC=CC=C2CCC1)CC1=CN(C(=CC=C2)N3CCN(C)CC3)C2=N1 JUGNNVPVNCGJGC-LJAQVGFWSA-N 0.000 claims description 3
- BSXVSUGBNPANRN-SANMLTNESA-N (8s)-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-[[3-(trifluoromethyl)phenyl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC=3C=C(C=CC=3)C(F)(F)F)[C@@H]3C4=NC=CC=C4CCC3)=CN12 BSXVSUGBNPANRN-SANMLTNESA-N 0.000 claims description 3
- YLKOIJWWHPLLSR-PMERELPUSA-N (8s)-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-[[4-(2-methylpropyl)phenyl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1=CC(CC(C)C)=CC=C1CN([C@@H]1C2=NC=CC=C2CCC1)CC1=CN(C(=CC=C2)N3CCN(C)CC3)C2=N1 YLKOIJWWHPLLSR-PMERELPUSA-N 0.000 claims description 3
- MJKGXNDWAPDFFX-SANMLTNESA-N (8s)-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-[[4-(trifluoromethyl)phenyl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC=3C=CC(=CC=3)C(F)(F)F)[C@@H]3C4=NC=CC=C4CCC3)=CN12 MJKGXNDWAPDFFX-SANMLTNESA-N 0.000 claims description 3
- KCYJZDNOWILGPM-SFTDATJTSA-N (8s)-n-[[5-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1[C@@H](N(C)C)CCN1C1=CC=CC2=NC(CN(C)[C@@H]3C4=NC=CC=C4CCC3)=CN12 KCYJZDNOWILGPM-SFTDATJTSA-N 0.000 claims description 3
- QGTROIYUDZXOLO-IBGZPJMESA-N (8s)-n-[[5-[2-(dimethylamino)ethoxy]imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2[C@H]1N(C)CC1=CN2C(OCCN(C)C)=CC=CC2=N1 QGTROIYUDZXOLO-IBGZPJMESA-N 0.000 claims description 3
- BNOPLAIRDVCQBH-SANMLTNESA-N (8s)-n-benzyl-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC=3C=CC=CC=3)[C@@H]3C4=NC=CC=C4CCC3)=CN12 BNOPLAIRDVCQBH-SANMLTNESA-N 0.000 claims description 3
- FIHSQKVAYHSCPE-QFIPXVFZSA-N (8s)-n-methyl-n-[[5-(2-piperidin-1-ylethylamino)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2NCCN1CCCCC1 FIHSQKVAYHSCPE-QFIPXVFZSA-N 0.000 claims description 3
- OKGPFTLYBPQBIX-CQSZACIVSA-N 1-[(2r)-4-benzoyl-2-methylpiperazin-1-yl]-2-(4-methoxy-1h-pyrrolo[2,3-b]pyridin-3-yl)ethane-1,2-dione Chemical compound C1=2C(OC)=CC=NC=2NC=C1C(=O)C(=O)N([C@@H](C1)C)CCN1C(=O)C1=CC=CC=C1 OKGPFTLYBPQBIX-CQSZACIVSA-N 0.000 claims description 3
- 108010036239 CD4-IgG(2) Proteins 0.000 claims description 3
- QAGYKUNXZHXKMR-UHFFFAOYSA-N CPD000469186 Natural products CC1=C(O)C=CC=C1C(=O)NC(C(O)CN1C(CC2CCCCC2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-UHFFFAOYSA-N 0.000 claims description 3
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 claims description 3
- XPOQHMRABVBWPR-UHFFFAOYSA-N Efavirenz Natural products O1C(=O)NC2=CC=C(Cl)C=C2C1(C(F)(F)F)C#CC1CC1 XPOQHMRABVBWPR-UHFFFAOYSA-N 0.000 claims description 3
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 claims description 3
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 claims description 3
- IBHARWXWOCPXCR-WELGVCPWSA-N [(2s,3s,5r)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl (2-decoxy-3-dodecylsulfanylpropyl) hydrogen phosphate Chemical compound C1[C@H](N=[N+]=[N-])[C@@H](COP(O)(=O)OCC(CSCCCCCCCCCCCC)OCCCCCCCCCC)O[C@H]1N1C(=O)NC(=O)C(C)=C1 IBHARWXWOCPXCR-WELGVCPWSA-N 0.000 claims description 3
- 229960004748 abacavir Drugs 0.000 claims description 3
- MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 claims description 3
- 229960001997 adefovir Drugs 0.000 claims description 3
- 229960003205 adefovir dipivoxil Drugs 0.000 claims description 3
- 230000003064 anti-oxidating effect Effects 0.000 claims description 3
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 3
- 230000034303 cell budding Effects 0.000 claims description 3
- 229960005319 delavirdine Drugs 0.000 claims description 3
- 229960002656 didanosine Drugs 0.000 claims description 3
- XNHZXMPLVSJQFK-UHFFFAOYSA-O dimethyl-[[4-[[3-(4-methylphenyl)-8,9-dihydro-7h-benzo[7]annulene-6-carbonyl]amino]phenyl]methyl]-(oxan-4-yl)azanium Chemical compound C1=CC(C)=CC=C1C1=CC=C(CCCC(=C2)C(=O)NC=3C=CC(C[N+](C)(C)C4CCOCC4)=CC=3)C2=C1 XNHZXMPLVSJQFK-UHFFFAOYSA-O 0.000 claims description 3
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 claims description 3
- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 claims description 3
- 229960003804 efavirenz Drugs 0.000 claims description 3
- 229950010245 ibalizumab Drugs 0.000 claims description 3
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 3
- CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 claims description 3
- 229960001936 indinavir Drugs 0.000 claims description 3
- 239000002850 integrase inhibitor Substances 0.000 claims description 3
- 229940124524 integrase inhibitor Drugs 0.000 claims description 3
- 229960001627 lamivudine Drugs 0.000 claims description 3
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 claims description 3
- 229950004697 lasinavir Drugs 0.000 claims description 3
- 229940121292 leronlimab Drugs 0.000 claims description 3
- CJPLEFFCVDQQFZ-UHFFFAOYSA-N loviride Chemical compound CC(=O)C1=CC=C(C)C=C1NC(C(N)=O)C1=C(Cl)C=CC=C1Cl CJPLEFFCVDQQFZ-UHFFFAOYSA-N 0.000 claims description 3
- 229950006243 loviride Drugs 0.000 claims description 3
- KCYJZDNOWILGPM-VQCQRNETSA-N n-[[5-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1[C@H](N(C)C)CCN1C1=CC=CC2=NC(CN(C)C3C4=NC=CC=C4CCC3)=CN12 KCYJZDNOWILGPM-VQCQRNETSA-N 0.000 claims description 3
- LAXBNABGPSQIHG-UHFFFAOYSA-N n-[[5-[4-(dimethylamino)piperidin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CC(N(C)C)CCN1C1=CC=CC2=NC(CN(C)C3C4=NC=CC=C4CCC3)=CN12 LAXBNABGPSQIHG-UHFFFAOYSA-N 0.000 claims description 3
- ZPGMMMUFUCRFPZ-UHFFFAOYSA-N n-cyclopropyl-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(C3CC3)C3C4=NC=CC=C4CCC3)=CN12 ZPGMMMUFUCRFPZ-UHFFFAOYSA-N 0.000 claims description 3
- NGWDLBUQTRJLNR-UHFFFAOYSA-N n-methyl-n-[[5-[4-(methylamino)piperidin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CC(NC)CCN1C1=CC=CC2=NC(CN(C)C3C4=NC=CC=C4CCC3)=CN12 NGWDLBUQTRJLNR-UHFFFAOYSA-N 0.000 claims description 3
- KGGOEFQJWNRJEG-UHFFFAOYSA-N n-methyl-n-[[5-[methyl-(1-methylpyrrolidin-3-yl)amino]imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2N(C)C1CCN(C)C1 KGGOEFQJWNRJEG-UHFFFAOYSA-N 0.000 claims description 3
- QAGYKUNXZHXKMR-HKWSIXNMSA-N nelfinavir Chemical compound CC1=C(O)C=CC=C1C(=O)N[C@H]([C@H](O)CN1[C@@H](C[C@@H]2CCCC[C@@H]2C1)C(=O)NC(C)(C)C)CSC1=CC=CC=C1 QAGYKUNXZHXKMR-HKWSIXNMSA-N 0.000 claims description 3
- 229960000884 nelfinavir Drugs 0.000 claims description 3
- 229960000689 nevirapine Drugs 0.000 claims description 3
- RXBWRFDZXRAEJT-SZNOJMITSA-N palinavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)C=1N=C2C=CC=CC2=CC=1)C(C)C)[C@H](O)CN1[C@@H](C[C@@H](CC1)OCC=1C=CN=CC=1)C(=O)NC(C)(C)C)C1=CC=CC=C1 RXBWRFDZXRAEJT-SZNOJMITSA-N 0.000 claims description 3
- 229950006460 palinavir Drugs 0.000 claims description 3
- 239000000137 peptide hydrolase inhibitor Substances 0.000 claims description 3
- 230000002265 prevention Effects 0.000 claims description 3
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 claims description 3
- 229960000311 ritonavir Drugs 0.000 claims description 3
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 claims description 3
- 229960001852 saquinavir Drugs 0.000 claims description 3
- BEUUJDAEPJZWHM-COROXYKFSA-N tert-butyl n-[(2s,3s,5r)-3-hydroxy-6-[[(2s)-1-(2-methoxyethylamino)-3-methyl-1-oxobutan-2-yl]amino]-6-oxo-1-phenyl-5-[(2,3,4-trimethoxyphenyl)methyl]hexan-2-yl]carbamate Chemical compound C([C@@H]([C@@H](O)C[C@H](C(=O)N[C@H](C(=O)NCCOC)C(C)C)CC=1C(=C(OC)C(OC)=CC=1)OC)NC(=O)OC(C)(C)C)C1=CC=CC=C1 BEUUJDAEPJZWHM-COROXYKFSA-N 0.000 claims description 3
- ZFEAMMNVDPDEGE-LGRGJMMZSA-N tifuvirtide Chemical compound C([C@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(C)=O)[C@@H](C)CC)[C@@H](C)O)[C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)C1=CC=C(O)C=C1 ZFEAMMNVDPDEGE-LGRGJMMZSA-N 0.000 claims description 3
- 229960000523 zalcitabine Drugs 0.000 claims description 3
- 229960002555 zidovudine Drugs 0.000 claims description 3
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 claims description 3
- FAFYHBSFPVJQDP-SANMLTNESA-N (8s)-n-[(2-methoxyphenyl)methyl]-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound COC1=CC=CC=C1CN([C@@H]1C2=NC=CC=C2CCC1)CC1=CN(C(=CC=C2)N3CCN(C)CC3)C2=N1 FAFYHBSFPVJQDP-SANMLTNESA-N 0.000 claims description 2
- SWYJJXCKLDOLPO-MHZLTWQESA-N (8s)-n-[(2-methylphenyl)methyl]-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC=3C(=CC=CC=3)C)[C@@H]3C4=NC=CC=C4CCC3)=CN12 SWYJJXCKLDOLPO-MHZLTWQESA-N 0.000 claims description 2
- QCBHCDXDDWGLKV-MHZLTWQESA-N (8s)-n-[(3-methylphenyl)methyl]-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC=3C=C(C)C=CC=3)[C@@H]3C4=NC=CC=C4CCC3)=CN12 QCBHCDXDDWGLKV-MHZLTWQESA-N 0.000 claims description 2
- QRNOOACBVHKSGK-SANMLTNESA-N (8s)-n-[(4-fluorophenyl)methyl]-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC=3C=CC(F)=CC=3)[C@@H]3C4=NC=CC=C4CCC3)=CN12 QRNOOACBVHKSGK-SANMLTNESA-N 0.000 claims description 2
- PLWPORJLNOVZAM-QFIPXVFZSA-N (8s)-n-methyl-n-[[5-(2-piperidin-1-ylethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2OCCN1CCCCC1 PLWPORJLNOVZAM-QFIPXVFZSA-N 0.000 claims description 2
- DSWUYFSZZHTGQQ-NRFANRHFSA-N (8s)-n-methyl-n-[[5-(2-pyrrolidin-1-ylethoxy)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2OCCN1CCCC1 DSWUYFSZZHTGQQ-NRFANRHFSA-N 0.000 claims description 2
- DNTSUXKFOYLEMP-UHFFFAOYSA-N n-methyl-n-[[5-(3,4,5-trimethylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1C(C)N(C)C(C)CN1C1=CC=CC2=NC(CN(C)C3C4=NC=CC=C4CCC3)=CN12 DNTSUXKFOYLEMP-UHFFFAOYSA-N 0.000 claims description 2
- SAUNXVLNCQIKEY-NRFANRHFSA-N (8s)-n-methyl-n-[[5-(2-pyrrolidin-1-ylethylamino)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2NCCN1CCCC1 SAUNXVLNCQIKEY-NRFANRHFSA-N 0.000 claims 1
- 208000036142 Viral infection Diseases 0.000 claims 1
- 125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims 1
- JPVKWRVSRZEMDF-UHFFFAOYSA-N n,n,n'-trimethyl-n'-[2-[[methyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]imidazo[1,2-a]pyridin-5-yl]ethane-1,2-diamine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC1=CN2C(N(C)CCN(C)C)=CC=CC2=N1 JPVKWRVSRZEMDF-UHFFFAOYSA-N 0.000 claims 1
- JPVKWRVSRZEMDF-FQEVSTJZSA-N n,n,n'-trimethyl-n'-[2-[[methyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-5-yl]ethane-1,2-diamine Chemical compound C1CCC2=CC=CN=C2[C@H]1N(C)CC1=CN2C(N(C)CCN(C)C)=CC=CC2=N1 JPVKWRVSRZEMDF-FQEVSTJZSA-N 0.000 claims 1
- KCYJZDNOWILGPM-BGERDNNASA-N n-[[5-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1[C@@H](N(C)C)CCN1C1=CC=CC2=NC(CN(C)C3C4=NC=CC=C4CCC3)=CN12 KCYJZDNOWILGPM-BGERDNNASA-N 0.000 claims 1
- 230000009385 viral infection Effects 0.000 claims 1
- 102000005962 receptors Human genes 0.000 abstract description 6
- 108020003175 receptors Proteins 0.000 abstract description 6
- 239000003446 ligand Substances 0.000 abstract description 5
- 230000001681 protective effect Effects 0.000 abstract description 4
- 102000019034 Chemokines Human genes 0.000 abstract description 3
- 108010012236 Chemokines Proteins 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 224
- 238000005481 NMR spectroscopy Methods 0.000 description 103
- 239000003921 oil Substances 0.000 description 82
- 235000019198 oils Nutrition 0.000 description 80
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 70
- 238000006243 chemical reaction Methods 0.000 description 70
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 69
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 64
- 239000000243 solution Substances 0.000 description 63
- 210000004027 cell Anatomy 0.000 description 51
- 239000007787 solid Substances 0.000 description 48
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 47
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 43
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 41
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 39
- 238000010511 deprotection reaction Methods 0.000 description 39
- 229920006395 saturated elastomer Polymers 0.000 description 38
- 239000012044 organic layer Substances 0.000 description 35
- 238000005160 1H NMR spectroscopy Methods 0.000 description 34
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 32
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 32
- 235000019341 magnesium sulphate Nutrition 0.000 description 32
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
- 235000002639 sodium chloride Nutrition 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- 239000002904 solvent Substances 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 26
- YFMYMVJGOKBODC-FIPFOOKPSA-N (8s)-n-[(1s)-1-(4-methoxyphenyl)ethyl]-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1=CC(OC)=CC=C1[C@H](C)N([C@@H]1C2=NC=CC=C2CCC1)CC1=CN(C(=CC=C2)N3CCN(C)CC3)C2=N1 YFMYMVJGOKBODC-FIPFOOKPSA-N 0.000 description 25
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 25
- 235000019502 Orange oil Nutrition 0.000 description 23
- 235000019439 ethyl acetate Nutrition 0.000 description 23
- 239000010502 orange oil Substances 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 21
- JFJRWADANRJCCO-HNNXBMFYSA-N (8s)-n-[(5-fluoroimidazo[1,2-a]pyridin-2-yl)methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2[C@H]1N(C)CC1=CN(C(F)=CC=C2)C2=N1 JFJRWADANRJCCO-HNNXBMFYSA-N 0.000 description 20
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- 241000725303 Human immunodeficiency virus Species 0.000 description 20
- 238000006073 displacement reaction Methods 0.000 description 20
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 229960000583 acetic acid Drugs 0.000 description 17
- JFJRWADANRJCCO-UHFFFAOYSA-N n-[(5-fluoroimidazo[1,2-a]pyridin-2-yl)methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC1=CN(C(F)=CC=C2)C2=N1 JFJRWADANRJCCO-UHFFFAOYSA-N 0.000 description 17
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 16
- 229910000029 sodium carbonate Inorganic materials 0.000 description 16
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 15
- 238000009472 formulation Methods 0.000 description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 14
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 13
- 235000011114 ammonium hydroxide Nutrition 0.000 description 13
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- 238000007792 addition Methods 0.000 description 12
- 239000000908 ammonium hydroxide Substances 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 239000000377 silicon dioxide Substances 0.000 description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 11
- 125000003118 aryl group Chemical group 0.000 description 11
- 238000003818 flash chromatography Methods 0.000 description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 11
- 239000012453 solvate Substances 0.000 description 11
- ICFHDYFCVQPVHM-UHFFFAOYSA-N 5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridine-2-carbaldehyde Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(C=O)=CN12 ICFHDYFCVQPVHM-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 235000019441 ethanol Nutrition 0.000 description 10
- 239000012362 glacial acetic acid Substances 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Inorganic materials O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 238000004237 preparative chromatography Methods 0.000 description 10
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 241000700605 Viruses Species 0.000 description 9
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 239000003638 chemical reducing agent Substances 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- ZWILTCXCTVMANU-UHFFFAOYSA-N 1,1,3-trichloropropan-2-one Chemical compound ClCC(=O)C(Cl)Cl ZWILTCXCTVMANU-UHFFFAOYSA-N 0.000 description 8
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 8
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 8
- 239000005089 Luciferase Substances 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 230000003647 oxidation Effects 0.000 description 8
- 238000007254 oxidation reaction Methods 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 239000012279 sodium borohydride Substances 0.000 description 8
- 229910000033 sodium borohydride Inorganic materials 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
- 239000000556 agonist Substances 0.000 description 7
- 150000001299 aldehydes Chemical class 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 239000012894 fetal calf serum Substances 0.000 description 7
- ZXTRMHOUGKPHHM-UHFFFAOYSA-N n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1=CN=C2C(NC)CCCC2=C1 ZXTRMHOUGKPHHM-UHFFFAOYSA-N 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 6
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- JXLPJCAIPGVFAA-UHFFFAOYSA-N azanium;acetonitrile;hydroxide Chemical compound [NH4+].[OH-].CC#N JXLPJCAIPGVFAA-UHFFFAOYSA-N 0.000 description 6
- 229910052799 carbon Inorganic materials 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 229930195733 hydrocarbon Natural products 0.000 description 6
- 239000012442 inert solvent Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 125000006239 protecting group Chemical group 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- HWIWZEQASCSYJM-GUYCJALGSA-N (8s)-n-[(1s)-1-(4-methoxyphenyl)ethyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1=CC(OC)=CC=C1[C@H](C)N[C@@H]1C2=NC=CC=C2CCC1 HWIWZEQASCSYJM-GUYCJALGSA-N 0.000 description 5
- ITPSDEVJHDJOQI-IBGZPJMESA-N (8s)-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN[C@@H]3C4=NC=CC=C4CCC3)=CN12 ITPSDEVJHDJOQI-IBGZPJMESA-N 0.000 description 5
- MKPYXJBRSQWUJN-UHFFFAOYSA-N 5-bromoimidazo[1,2-a]pyridine-2-carbaldehyde Chemical compound BrC1=CC=CC2=NC(C=O)=CN12 MKPYXJBRSQWUJN-UHFFFAOYSA-N 0.000 description 5
- JIAKIQWNYAZUJD-UHFFFAOYSA-N 6,7-dihydro-5h-quinolin-8-one Chemical compound C1=CN=C2C(=O)CCCC2=C1 JIAKIQWNYAZUJD-UHFFFAOYSA-N 0.000 description 5
- UZALKVXCOUSWSL-UHFFFAOYSA-N 6-fluoropyridin-2-amine Chemical compound NC1=CC=CC(F)=N1 UZALKVXCOUSWSL-UHFFFAOYSA-N 0.000 description 5
- 239000004215 Carbon black (E152) Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 238000006069 Suzuki reaction reaction Methods 0.000 description 5
- 101710090322 Truncated surface protein Proteins 0.000 description 5
- 230000036436 anti-hiv Effects 0.000 description 5
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 5
- 125000005842 heteroatom Chemical group 0.000 description 5
- GAADRYBSBDOGTN-UHFFFAOYSA-N n-[(5-bromoimidazo[1,2-a]pyridin-2-yl)methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC1=CN(C(Br)=CC=C2)C2=N1 GAADRYBSBDOGTN-UHFFFAOYSA-N 0.000 description 5
- 239000013612 plasmid Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- 238000004809 thin layer chromatography Methods 0.000 description 5
- 241000701447 unidentified baculovirus Species 0.000 description 5
- 238000001851 vibrational circular dichroism spectroscopy Methods 0.000 description 5
- ZXTRMHOUGKPHHM-VIFPVBQESA-N (8s)-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1=CN=C2[C@@H](NC)CCCC2=C1 ZXTRMHOUGKPHHM-VIFPVBQESA-N 0.000 description 4
- WHKWMTXTYKVFLK-UHFFFAOYSA-N 1-propan-2-ylpiperazine Chemical compound CC(C)N1CCNCC1 WHKWMTXTYKVFLK-UHFFFAOYSA-N 0.000 description 4
- ANTIOTRWBFOORM-UHFFFAOYSA-N 5-fluoroimidazo[1,2-a]pyridine-2-carbaldehyde Chemical compound FC1=CC=CC2=NC(C=O)=CN12 ANTIOTRWBFOORM-UHFFFAOYSA-N 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- 101150041968 CDC13 gene Proteins 0.000 description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- 102100021669 Stromal cell-derived factor 1 Human genes 0.000 description 4
- 101710088580 Stromal cell-derived factor 1 Proteins 0.000 description 4
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- 239000006071 cream Substances 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 4
- SXZIXHOMFPUIRK-UHFFFAOYSA-N diphenylmethanimine Chemical compound C=1C=CC=CC=1C(=N)C1=CC=CC=C1 SXZIXHOMFPUIRK-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000008187 granular material Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 150000004885 piperazines Chemical class 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- RXWNCPJZOCPEPQ-NVWDDTSBSA-N puromycin Chemical compound C1=CC(OC)=CC=C1C[C@H](N)C(=O)N[C@H]1[C@@H](O)[C@H](N2C3=NC=NC(=C3N=C2)N(C)C)O[C@@H]1CO RXWNCPJZOCPEPQ-NVWDDTSBSA-N 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
- 230000003612 virological effect Effects 0.000 description 4
- JTDGKQNNPKXKII-ZETCQYMHSA-N (1s)-1-(4-methoxyphenyl)ethanamine Chemical compound COC1=CC=C([C@H](C)N)C=C1 JTDGKQNNPKXKII-ZETCQYMHSA-N 0.000 description 3
- AVAWMINJNRAQFS-ZCFIWIBFSA-N (3r)-n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)[C@@H]1CCNC1 AVAWMINJNRAQFS-ZCFIWIBFSA-N 0.000 description 3
- RVWPTIDXLRPTRW-MBSDFSHPSA-N (8s)-n-[(5-fluoroimidazo[1,2-a]pyridin-2-yl)methyl]-n-[(1s)-1-(4-methoxyphenyl)ethyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1=CC(OC)=CC=C1[C@H](C)N([C@@H]1C2=NC=CC=C2CCC1)CC1=CN(C(F)=CC=C2)C2=N1 RVWPTIDXLRPTRW-MBSDFSHPSA-N 0.000 description 3
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 108060001084 Luciferase Proteins 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 229910000019 calcium carbonate Inorganic materials 0.000 description 3
- 230000007910 cell fusion Effects 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 230000004927 fusion Effects 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 3
- KYGSCWJENNYFHD-UHFFFAOYSA-N n-[(5-fluoroimidazo[1,2-a]pyridin-2-yl)methyl]-n-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(CC(F)(F)F)CC1=CN2C(F)=CC=CC2=N1 KYGSCWJENNYFHD-UHFFFAOYSA-N 0.000 description 3
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- NRQKORLEIODHSQ-UHFFFAOYSA-N tert-butyl 4-[2-[[methyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]imidazo[1,2-a]pyridin-5-yl]piperazine-1-carboxylate Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2N1CCN(C(=O)OC(C)(C)C)CC1 NRQKORLEIODHSQ-UHFFFAOYSA-N 0.000 description 3
- ULDDXODMVSSWNH-IRLDBZIGSA-N tert-butyl n-[(3r)-1-[2-[[methyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-5-yl]pyrrolidin-3-yl]carbamate Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CC[C@@H](NC(=O)OC(C)(C)C)C1 ULDDXODMVSSWNH-IRLDBZIGSA-N 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- 239000001993 wax Substances 0.000 description 3
- AVAWMINJNRAQFS-LURJTMIESA-N (3s)-n,n-dimethylpyrrolidin-3-amine Chemical compound CN(C)[C@H]1CCNC1 AVAWMINJNRAQFS-LURJTMIESA-N 0.000 description 2
- KRBUYVZVAOWCRU-UHFFFAOYSA-N (5-bromoimidazo[1,2-a]pyridin-2-yl)methanol Chemical compound BrC1=CC=CC2=NC(CO)=CN21 KRBUYVZVAOWCRU-UHFFFAOYSA-N 0.000 description 2
- JKFPKLUYRZNUGK-UHFFFAOYSA-N (5-fluoroimidazo[1,2-a]pyridin-2-yl)methanol Chemical compound FC1=CC=CC2=NC(CO)=CN21 JKFPKLUYRZNUGK-UHFFFAOYSA-N 0.000 description 2
- HWIWZEQASCSYJM-CXAGYDPISA-N (8r)-n-[(1r)-1-(4-methoxyphenyl)ethyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1=CC(OC)=CC=C1[C@@H](C)N[C@H]1C2=NC=CC=C2CCC1 HWIWZEQASCSYJM-CXAGYDPISA-N 0.000 description 2
- RVWPTIDXLRPTRW-WZONZLPQSA-N (8r)-n-[(5-fluoroimidazo[1,2-a]pyridin-2-yl)methyl]-n-[(1r)-1-(4-methoxyphenyl)ethyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1=CC(OC)=CC=C1[C@@H](C)N([C@H]1C2=NC=CC=C2CCC1)CC1=CN(C(F)=CC=C2)C2=N1 RVWPTIDXLRPTRW-WZONZLPQSA-N 0.000 description 2
- BSRSSMPEWJMVCH-LCRMXPIESA-N (8s)-n-[[5-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-n-[(1s)-1-(4-methoxyphenyl)ethyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1=CC(OC)=CC=C1[C@H](C)N([C@@H]1C2=NC=CC=C2CCC1)CC1=CN(C(=CC=C2)N3C[C@@H](CC3)N(C)C)C2=N1 BSRSSMPEWJMVCH-LCRMXPIESA-N 0.000 description 2
- SUNMBRGCANLOEG-UHFFFAOYSA-N 1,3-dichloroacetone Chemical compound ClCC(=O)CCl SUNMBRGCANLOEG-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 2
- JFIIICGKUFLQNF-UHFFFAOYSA-N 2-(chloromethyl)-5-fluoroimidazo[1,2-a]pyridine Chemical compound FC1=CC=CC2=NC(CCl)=CN12 JFIIICGKUFLQNF-UHFFFAOYSA-N 0.000 description 2
- YCOFITAQIPULIF-UHFFFAOYSA-N 2-(dichloromethyl)-5-fluoroimidazo[1,2-a]pyridine Chemical compound FC1=CC=CC2=NC(C(Cl)Cl)=CN12 YCOFITAQIPULIF-UHFFFAOYSA-N 0.000 description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
- YCYJZUODTCSPPB-UHFFFAOYSA-N 5,6,7,8-tetrahydrocyclohepta[b]pyridin-9-one Chemical compound O=C1CCCCC2=CC=CN=C12 YCYJZUODTCSPPB-UHFFFAOYSA-N 0.000 description 2
- JQGOUNFVDYUKMM-UHFFFAOYSA-N 5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1=CN=C2C(N)CCCC2=C1 JQGOUNFVDYUKMM-UHFFFAOYSA-N 0.000 description 2
- ZULJQRMXUOTWBU-UHFFFAOYSA-N 5,6-dihydrocyclopenta[b]pyridin-7-one Chemical compound C1=CN=C2C(=O)CCC2=C1 ZULJQRMXUOTWBU-UHFFFAOYSA-N 0.000 description 2
- ZGRUAADUYXMHJZ-UHFFFAOYSA-N 5-(benzhydrylideneamino)imidazo[1,2-a]pyridine-2-carbaldehyde Chemical compound C=1C=CC2=NC(C=O)=CN2C=1N=C(C=1C=CC=CC=1)C1=CC=CC=C1 ZGRUAADUYXMHJZ-UHFFFAOYSA-N 0.000 description 2
- CVNHXFZQLVNFRS-UHFFFAOYSA-N 6,7,8,9-tetrahydro-5h-cyclohepta[b]pyridin-9-ol Chemical compound OC1CCCCC2=CC=CN=C12 CVNHXFZQLVNFRS-UHFFFAOYSA-N 0.000 description 2
- XLPDFBUFTAWCIB-UHFFFAOYSA-N 6,7-dihydro-5h-cyclopenta[b]pyridin-7-ol Chemical compound C1=CN=C2C(O)CCC2=C1 XLPDFBUFTAWCIB-UHFFFAOYSA-N 0.000 description 2
- KRNSYSYRLQDHDK-UHFFFAOYSA-N 6,7-dihydro-5h-cyclopenta[b]pyridine Chemical compound C1=CN=C2CCCC2=C1 KRNSYSYRLQDHDK-UHFFFAOYSA-N 0.000 description 2
- BKLJUYPLUWUEOQ-UHFFFAOYSA-N 6-bromopyridin-2-amine Chemical compound NC1=CC=CC(Br)=N1 BKLJUYPLUWUEOQ-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- 229920001817 Agar Polymers 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 108010003533 Viral Envelope Proteins Proteins 0.000 description 2
- NDLWKLMYOAVWPJ-UHFFFAOYSA-N [5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methanol Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CO)=CN12 NDLWKLMYOAVWPJ-UHFFFAOYSA-N 0.000 description 2
- OSHJXHRANDINBU-UHFFFAOYSA-N [5-(benzhydrylideneamino)imidazo[1,2-a]pyridin-2-yl]methanol Chemical compound C=1C=CC2=NC(CO)=CN2C=1N=C(C=1C=CC=CC=1)C1=CC=CC=C1 OSHJXHRANDINBU-UHFFFAOYSA-N 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 235000010419 agar Nutrition 0.000 description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
- 238000005576 amination reaction Methods 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000002820 assay format Methods 0.000 description 2
- 238000003149 assay kit Methods 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- 235000012216 bentonite Nutrition 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- ILAHWRKJUDSMFH-UHFFFAOYSA-N boron tribromide Chemical compound BrB(Br)Br ILAHWRKJUDSMFH-UHFFFAOYSA-N 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 239000002576 chemokine receptor CXCR4 antagonist Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 229940121384 cxc chemokine receptor type 4 (cxcr4) antagonist Drugs 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- JMYVMOUINOAAPA-UHFFFAOYSA-N cyclopropanecarbaldehyde Chemical compound O=CC1CC1 JMYVMOUINOAAPA-UHFFFAOYSA-N 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 102000053523 human CXCR4 Human genes 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 238000004020 luminiscence type Methods 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- XRYGCVVVDCEPRL-UHFFFAOYSA-N n,1-dimethylpiperidin-4-amine Chemical compound CNC1CCN(C)CC1 XRYGCVVVDCEPRL-UHFFFAOYSA-N 0.000 description 2
- CZGIEJXGCLWRPY-UHFFFAOYSA-N n,1-dimethylpyrrolidin-3-amine Chemical compound CNC1CCN(C)C1 CZGIEJXGCLWRPY-UHFFFAOYSA-N 0.000 description 2
- JYQNUXRPJZFTLE-UHFFFAOYSA-N n-[(5-aminoimidazo[1,2-a]pyridin-2-yl)methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC1=CN(C(N)=CC=C2)C2=N1 JYQNUXRPJZFTLE-UHFFFAOYSA-N 0.000 description 2
- YFHHDEUDFFNCEW-UHFFFAOYSA-N n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC(F)(F)F)C3C4=NC=CC=C4CCC3)=CN12 YFHHDEUDFFNCEW-UHFFFAOYSA-N 0.000 description 2
- LZOHDEWKKCWXMM-UHFFFAOYSA-N n-[[5-(4-propan-2-ylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C(C)C)CCN1C1=CC=CC2=NC(CN(CC(F)(F)F)C3C4=NC=CC=C4CCC3)=CN12 LZOHDEWKKCWXMM-UHFFFAOYSA-N 0.000 description 2
- RGJJEIUSBCOPEL-UHFFFAOYSA-N n-[[5-(benzhydrylideneamino)imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2N=C(C=1C=CC=CC=1)C1=CC=CC=C1 RGJJEIUSBCOPEL-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- AAHZPISBDGIAHP-UHFFFAOYSA-N n-methyl-6,7-dihydro-5h-cyclopenta[b]pyridin-7-amine Chemical compound C1=CN=C2C(NC)CCC2=C1 AAHZPISBDGIAHP-UHFFFAOYSA-N 0.000 description 2
- ZUGLSIKNPULHFC-UHFFFAOYSA-N n-methyl-n-[(5-pyridin-4-ylimidazo[1,2-a]pyridin-2-yl)methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2C1=CC=NC=C1 ZUGLSIKNPULHFC-UHFFFAOYSA-N 0.000 description 2
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 235000006408 oxalic acid Nutrition 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N phenanthrene Chemical compound C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 description 2
- 230000000644 propagated effect Effects 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229950010131 puromycin Drugs 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 238000009491 slugging Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- XTQHKBHJIVJGKJ-UHFFFAOYSA-N sulfur monoxide Chemical class S=O XTQHKBHJIVJGKJ-UHFFFAOYSA-N 0.000 description 2
- 229910052815 sulfur oxide Inorganic materials 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 239000000454 talc Substances 0.000 description 2
- 229910052623 talc Inorganic materials 0.000 description 2
- 235000012222 talc Nutrition 0.000 description 2
- DQQJBEAXSOOCPG-SSDOTTSWSA-N tert-butyl n-[(3r)-pyrrolidin-3-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@@H]1CCNC1 DQQJBEAXSOOCPG-SSDOTTSWSA-N 0.000 description 2
- KNTRCIZNNJQPGS-UHFFFAOYSA-N tert-butyl n-[1-[2-[[methyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]imidazo[1,2-a]pyridin-5-yl]piperidin-4-yl]carbamate Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2N1CCC(NC(=O)OC(C)(C)C)CC1 KNTRCIZNNJQPGS-UHFFFAOYSA-N 0.000 description 2
- CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 2
- 239000002691 unilamellar liposome Substances 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- JTDGKQNNPKXKII-SSDOTTSWSA-N (1r)-1-(4-methoxyphenyl)ethanamine Chemical compound COC1=CC=C([C@@H](C)N)C=C1 JTDGKQNNPKXKII-SSDOTTSWSA-N 0.000 description 1
- FHHOYZGQRXQTSS-SANMLTNESA-N (8s)-n-[(2-bromophenyl)methyl]-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC=3C(=CC=CC=3)Br)[C@@H]3C4=NC=CC=C4CCC3)=CN12 FHHOYZGQRXQTSS-SANMLTNESA-N 0.000 description 1
- KHPJGNLWIGAFOU-SNYZSRNZSA-N (8s)-n-[(2-methoxyphenyl)methyl]-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine;quinolin-2-amine Chemical compound C1=CC=CC2=NC(N)=CC=C21.COC1=CC=CC=C1CN([C@@H]1C2=NC=CC=C2CCC1)CC1=CN(C(=CC=C2)N3CCN(C)CC3)C2=N1 KHPJGNLWIGAFOU-SNYZSRNZSA-N 0.000 description 1
- VCJNIOOQAFDOPH-SANMLTNESA-N (8s)-n-[[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]methyl]-n-[[2-(trifluoromethyl)phenyl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC=3C(=CC=CC=3)C(F)(F)F)[C@@H]3C4=NC=CC=C4CCC3)=CN12 VCJNIOOQAFDOPH-SANMLTNESA-N 0.000 description 1
- VAZJISFHBCFPSG-FVGYRXGTSA-N (8s)-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine;oxalic acid Chemical compound OC(=O)C(O)=O.C1=CN=C2[C@@H](NC)CCCC2=C1 VAZJISFHBCFPSG-FVGYRXGTSA-N 0.000 description 1
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
- FTTATHOUSOIFOQ-UHFFFAOYSA-N 1,2,3,4,6,7,8,8a-octahydropyrrolo[1,2-a]pyrazine Chemical compound C1NCCN2CCCC21 FTTATHOUSOIFOQ-UHFFFAOYSA-N 0.000 description 1
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
- BMEMBBFDTYHTLH-UHFFFAOYSA-N 1-(2-methoxyethyl)piperazine Chemical compound COCCN1CCNCC1 BMEMBBFDTYHTLH-UHFFFAOYSA-N 0.000 description 1
- VXNZUUAINFGPBY-UHFFFAOYSA-N 1-Butene Chemical group CCC=C VXNZUUAINFGPBY-UHFFFAOYSA-N 0.000 description 1
- XNGCUBPOCIXWRJ-UHFFFAOYSA-N 1-[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]ethanol Chemical compound C=1C=CC2=NC(C(O)C)=CN2C=1N1CCN(C)CC1 XNGCUBPOCIXWRJ-UHFFFAOYSA-N 0.000 description 1
- DTCWSXDBKSRIKY-UHFFFAOYSA-N 1-[5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-2-yl]ethanone Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(C(C)=O)=CN12 DTCWSXDBKSRIKY-UHFFFAOYSA-N 0.000 description 1
- FXHRAKUEZPSMLJ-UHFFFAOYSA-N 1-methyl-1,4-diazepane Chemical compound CN1CCCNCC1 FXHRAKUEZPSMLJ-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N 1-propanol Substances CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- MBTGBRYMJKYYOE-UHFFFAOYSA-N 2,6-difluoropyridine Chemical compound FC1=CC=CC(F)=N1 MBTGBRYMJKYYOE-UHFFFAOYSA-N 0.000 description 1
- IFNWESYYDINUHV-UHFFFAOYSA-N 2,6-dimethylpiperazine Chemical compound CC1CNCC(C)N1 IFNWESYYDINUHV-UHFFFAOYSA-N 0.000 description 1
- GSBDCKILABWJNG-UHFFFAOYSA-N 2-(4-phenylphenyl)benzaldehyde Chemical compound O=CC1=CC=CC=C1C1=CC=C(C=2C=CC=CC=2)C=C1 GSBDCKILABWJNG-UHFFFAOYSA-N 0.000 description 1
- KZTWONRVIPPDKH-UHFFFAOYSA-N 2-(piperidin-1-yl)ethanol Chemical compound OCCN1CCCCC1 KZTWONRVIPPDKH-UHFFFAOYSA-N 0.000 description 1
- ZDVRPKUWYQVVDX-UHFFFAOYSA-N 2-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC=C1C=O ZDVRPKUWYQVVDX-UHFFFAOYSA-N 0.000 description 1
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 1
- NDOPHXWIAZIXPR-UHFFFAOYSA-N 2-bromobenzaldehyde Chemical compound BrC1=CC=CC=C1C=O NDOPHXWIAZIXPR-UHFFFAOYSA-N 0.000 description 1
- JBKINHFZTVLNEM-UHFFFAOYSA-N 2-bromoethoxy-tert-butyl-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCBr JBKINHFZTVLNEM-UHFFFAOYSA-N 0.000 description 1
- ZWDVQMVZZYIAHO-UHFFFAOYSA-N 2-fluorobenzaldehyde Chemical compound FC1=CC=CC=C1C=O ZWDVQMVZZYIAHO-UHFFFAOYSA-N 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- CJNRGSHEMCMUOE-UHFFFAOYSA-N 2-piperidin-1-ylethanamine Chemical compound NCCN1CCCCC1 CJNRGSHEMCMUOE-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- WRXNJTBODVGDRY-UHFFFAOYSA-N 2-pyrrolidin-1-ylethanamine Chemical compound NCCN1CCCC1 WRXNJTBODVGDRY-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- UZGLOGCJCWBBIV-UHFFFAOYSA-N 3-(chloromethyl)pyridin-1-ium;chloride Chemical compound Cl.ClCC1=CC=CN=C1 UZGLOGCJCWBBIV-UHFFFAOYSA-N 0.000 description 1
- NMTUHPSKJJYGML-UHFFFAOYSA-N 3-(trifluoromethyl)benzaldehyde Chemical compound FC(F)(F)C1=CC=CC(C=O)=C1 NMTUHPSKJJYGML-UHFFFAOYSA-N 0.000 description 1
- SUISZCALMBHJQX-UHFFFAOYSA-N 3-bromobenzaldehyde Chemical compound BrC1=CC=CC(C=O)=C1 SUISZCALMBHJQX-UHFFFAOYSA-N 0.000 description 1
- QGMROEZDWJTIDW-UHFFFAOYSA-N 3-bromopropoxy-tert-butyl-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCCBr QGMROEZDWJTIDW-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
- PIKNVEVCWAAOMJ-UHFFFAOYSA-N 3-fluorobenzaldehyde Chemical compound FC1=CC=CC(C=O)=C1 PIKNVEVCWAAOMJ-UHFFFAOYSA-N 0.000 description 1
- WMPDAIZRQDCGFH-UHFFFAOYSA-N 3-methoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1 WMPDAIZRQDCGFH-UHFFFAOYSA-N 0.000 description 1
- LXPWGAZYJHUWPM-UHFFFAOYSA-N 4-(2-methylpropyl)benzaldehyde Chemical compound CC(C)CC1=CC=C(C=O)C=C1 LXPWGAZYJHUWPM-UHFFFAOYSA-N 0.000 description 1
- ZDHKVKPZQKYREU-UHFFFAOYSA-N 4-(chloromethyl)pyridine;hydron;chloride Chemical compound Cl.ClCC1=CC=NC=C1 ZDHKVKPZQKYREU-UHFFFAOYSA-N 0.000 description 1
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
- JKEQWPSFSZWILA-UHFFFAOYSA-N 5-morpholin-4-ylimidazo[1,2-a]pyridine-2-carbaldehyde Chemical compound C=1C=CC2=NC(C=O)=CN2C=1N1CCOCC1 JKEQWPSFSZWILA-UHFFFAOYSA-N 0.000 description 1
- CULUYAUTCSKQNM-UHFFFAOYSA-N 6,7,8,9-tetrahydro-5h-cyclohepta[b]pyridine Chemical compound C1CCCCC2=CC=CN=C21 CULUYAUTCSKQNM-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010065040 AIDS dementia complex Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- 229910015845 BBr3 Inorganic materials 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 1
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 1
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 description 1
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 description 1
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 1
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 1
- 101710149863 C-C chemokine receptor type 4 Proteins 0.000 description 1
- 102100037853 C-C chemokine receptor type 4 Human genes 0.000 description 1
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 1
- 102100036305 C-C chemokine receptor type 8 Human genes 0.000 description 1
- 102100025074 C-C chemokine receptor-like 2 Human genes 0.000 description 1
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 description 1
- 102100028989 C-X-C chemokine receptor type 2 Human genes 0.000 description 1
- 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 1
- 102100031658 C-X-C chemokine receptor type 5 Human genes 0.000 description 1
- 108700011778 CCR5 Proteins 0.000 description 1
- 108010041397 CD4 Antigens Proteins 0.000 description 1
- 108010061299 CXCR4 Receptors Proteins 0.000 description 1
- 102000012000 CXCR4 Receptors Human genes 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 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
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 206010011686 Cutaneous vasculitis Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- YWHLKYXPLRWGSE-UHFFFAOYSA-N Dimethyl trisulfide Chemical compound CSSSC YWHLKYXPLRWGSE-UHFFFAOYSA-N 0.000 description 1
- 241000792859 Enema Species 0.000 description 1
- YQYJSBFKSSDGFO-UHFFFAOYSA-N Epihygromycin Natural products OC1C(O)C(C(=O)C)OC1OC(C(=C1)O)=CC=C1C=C(C)C(=O)NC1C(O)C(O)C2OCOC2C1O YQYJSBFKSSDGFO-UHFFFAOYSA-N 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 208000036119 Frailty Diseases 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
- 241000237858 Gastropoda Species 0.000 description 1
- 241000206672 Gelidium Species 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000946926 Homo sapiens C-C chemokine receptor type 5 Proteins 0.000 description 1
- 101000716068 Homo sapiens C-C chemokine receptor type 6 Proteins 0.000 description 1
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 description 1
- 101000716063 Homo sapiens C-C chemokine receptor type 8 Proteins 0.000 description 1
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 description 1
- 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 1
- 101000922405 Homo sapiens C-X-C chemokine receptor type 5 Proteins 0.000 description 1
- 101100005713 Homo sapiens CD4 gene Proteins 0.000 description 1
- 108700020121 Human Immunodeficiency Virus-1 rev Proteins 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
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 108010018951 Interleukin-8B Receptors Proteins 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001077660 Molo Species 0.000 description 1
- 229920000715 Mucilage Polymers 0.000 description 1
- KWYHDKDOAIKMQN-UHFFFAOYSA-N N,N,N',N'-tetramethylethylenediamine Chemical compound CN(C)CCN(C)C KWYHDKDOAIKMQN-UHFFFAOYSA-N 0.000 description 1
- CDBBPOISMDNVNQ-UHFFFAOYSA-N N-(6,7-dihydro-5H-quinolin-8-ylidene)hydroxylamine Chemical compound C1=CN=C2C(=NO)CCCC2=C1 CDBBPOISMDNVNQ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010029113 Neovascularisation Diseases 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 108010039918 Polylysine Proteins 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 108700008625 Reporter Genes Proteins 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 241000256251 Spodoptera frugiperda Species 0.000 description 1
- 238000003120 Steady-Glo Luciferase Assay System Methods 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 230000033540 T cell apoptotic process Effects 0.000 description 1
- 229920002253 Tannate Polymers 0.000 description 1
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 206010047124 Vasculitis necrotising Diseases 0.000 description 1
- 108010067390 Viral Proteins Proteins 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- VUDCTLOJEPCNRS-UHFFFAOYSA-N [2-[(dimethylamino)methyl]phenyl]boronic acid Chemical compound CN(C)CC1=CC=CC=C1B(O)O VUDCTLOJEPCNRS-UHFFFAOYSA-N 0.000 description 1
- OFYQEYPITRRCBP-UHFFFAOYSA-N [3-[(dimethylamino)methyl]phenyl]boronic acid Chemical compound CN(C)CC1=CC=CC(B(O)O)=C1 OFYQEYPITRRCBP-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
- 208000037884 allergic airway inflammation Diseases 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 235000021311 artificial sweeteners Nutrition 0.000 description 1
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 description 1
- 206010003549 asthenia Diseases 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- RFRXIWQYSOIBDI-UHFFFAOYSA-N benzarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC=C(O)C=C1 RFRXIWQYSOIBDI-UHFFFAOYSA-N 0.000 description 1
- 150000001555 benzenes Chemical group 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N benzocyclopentane Natural products C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229920001400 block copolymer Polymers 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004271 bone marrow stromal cell Anatomy 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
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 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
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 229940105329 carboxymethylcellulose Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 229940090805 clavulanate Drugs 0.000 description 1
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000004891 communication Methods 0.000 description 1
- 229940125810 compound 20 Drugs 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000006184 cosolvent Substances 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004976 cyclobutylene group Chemical group 0.000 description 1
- 125000001162 cycloheptenyl group Chemical group C1(=CCCCCC1)* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004977 cycloheptylene group Chemical group 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000005725 cyclohexenylene 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
- 125000004956 cyclohexylene group Chemical group 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000004979 cyclopentylene group Chemical group 0.000 description 1
- 125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004980 cyclopropylene group Chemical group 0.000 description 1
- 210000001151 cytotoxic T lymphocyte Anatomy 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- ACYGYJFTZSAZKR-UHFFFAOYSA-J dicalcium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Ca+2].[Ca+2].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O ACYGYJFTZSAZKR-UHFFFAOYSA-J 0.000 description 1
- ZHXTWWCDMUWMDI-UHFFFAOYSA-N dihydroxyboron Chemical compound O[B]O ZHXTWWCDMUWMDI-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
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-M dodecanoate Chemical compound CCCCCCCCCCCC([O-])=O POULHZVOKOAJMA-UHFFFAOYSA-M 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000007876 drug discovery Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 229950005627 embonate Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 239000007920 enema Substances 0.000 description 1
- 229940079360 enema for constipation Drugs 0.000 description 1
- 230000026502 entry into host cell Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- XBRDBODLCHKXHI-UHFFFAOYSA-N epolamine Chemical compound OCCN1CCCC1 XBRDBODLCHKXHI-UHFFFAOYSA-N 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 229950000206 estolate Drugs 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229940050411 fumarate Drugs 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960001731 gluceptate Drugs 0.000 description 1
- KWMLJOLKUYYJFJ-VFUOTHLCSA-N glucoheptonic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)C(O)=O KWMLJOLKUYYJFJ-VFUOTHLCSA-N 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 229940049906 glutamate Drugs 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 1
- 235000015220 hamburgers Nutrition 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-M hexadecanoate Chemical compound CCCCCCCCCCCCCCCC([O-])=O IPCSVZSSVZVIGE-UHFFFAOYSA-M 0.000 description 1
- 102000048160 human CCR5 Human genes 0.000 description 1
- 210000005104 human peripheral blood lymphocyte Anatomy 0.000 description 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 description 1
- 239000000017 hydrogel 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
- 239000008309 hydrophilic cream Substances 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- QKKKBOZQZHBENG-UHFFFAOYSA-N imidazo[1,2-a]pyridine-2-carbaldehyde Chemical compound C1=CC=CC2=NC(C=O)=CN21 QKKKBOZQZHBENG-UHFFFAOYSA-N 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 239000012194 insect media Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229940125425 inverse agonist Drugs 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 229940099584 lactobionate Drugs 0.000 description 1
- JYTUSYBCFIZPBE-AMTLMPIISA-N lactobionic acid Chemical compound OC(=O)[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O JYTUSYBCFIZPBE-AMTLMPIISA-N 0.000 description 1
- 229940070765 laurate Drugs 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000001165 lymph node Anatomy 0.000 description 1
- OVWYEQOVUDKZNU-UHFFFAOYSA-N m-tolualdehyde Chemical compound CC1=CC=CC(C=O)=C1 OVWYEQOVUDKZNU-UHFFFAOYSA-N 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- HVOYZOQVDYHUPF-UHFFFAOYSA-N n,n',n'-trimethylethane-1,2-diamine Chemical compound CNCCN(C)C HVOYZOQVDYHUPF-UHFFFAOYSA-N 0.000 description 1
- KVKFRMCSXWQSNT-UHFFFAOYSA-N n,n'-dimethylethane-1,2-diamine Chemical compound CNCCNC KVKFRMCSXWQSNT-UHFFFAOYSA-N 0.000 description 1
- SATLWVSJANHADH-UHFFFAOYSA-N n,n-dimethyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methanamine Chemical compound C1=CC(CN(C)C)=CC=C1B1OC(C)(C)C(C)(C)O1 SATLWVSJANHADH-UHFFFAOYSA-N 0.000 description 1
- LGDNSGSJKBIVFG-UHFFFAOYSA-N n,n-dimethyl-2-piperazin-1-ylethanamine Chemical compound CN(C)CCN1CCNCC1 LGDNSGSJKBIVFG-UHFFFAOYSA-N 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- SLPGFSWNVAVZCW-CTNGQTDRSA-N n-[(3r)-1-[2-[[methyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-5-yl]pyrrolidin-3-yl]acetamide Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CC[C@@H](NC(C)=O)C1 SLPGFSWNVAVZCW-CTNGQTDRSA-N 0.000 description 1
- HDCCJUCOIKLZNM-ZCFIWIBFSA-N n-[(3r)-pyrrolidin-3-yl]acetamide Chemical compound CC(=O)N[C@@H]1CCNC1 HDCCJUCOIKLZNM-ZCFIWIBFSA-N 0.000 description 1
- RGWHMXOWYFTILB-UHFFFAOYSA-N n-[(5-fluoroimidazo[1,2-a]pyridin-2-yl)methyl]-n-propan-2-yl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C(C)C)CC1=CN(C(F)=CC=C2)C2=N1 RGWHMXOWYFTILB-UHFFFAOYSA-N 0.000 description 1
- VVMKGUQWAPDQMQ-UHFFFAOYSA-N n-[(5-piperazin-1-ylimidazo[1,2-a]pyridin-2-yl)methyl]-n-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(CC(F)(F)F)CC(N=C1C=CC=2)=CN1C=2N1CCNCC1 VVMKGUQWAPDQMQ-UHFFFAOYSA-N 0.000 description 1
- SNCOPFXTGDJHHW-UHFFFAOYSA-N n-[2-[[methyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]imidazo[1,2-a]pyridin-5-yl]pyridine-3-carboxamide Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2NC(=O)C1=CC=CN=C1 SNCOPFXTGDJHHW-UHFFFAOYSA-N 0.000 description 1
- KRQWHRIKEZAZME-UHFFFAOYSA-N n-[2-[[methyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]imidazo[1,2-a]pyridin-5-yl]pyridine-4-carboxamide Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2NC(=O)C1=CC=NC=C1 KRQWHRIKEZAZME-UHFFFAOYSA-N 0.000 description 1
- ITFMWLXOPJBBRK-UHFFFAOYSA-N n-[[5-[3-(dimethylamino)azetidin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1C(N(C)C)CN1C1=CC=CC2=NC(CN(C)C3C4=NC=CC=C4CCC3)=CN12 ITFMWLXOPJBBRK-UHFFFAOYSA-N 0.000 description 1
- GMAQSUGZLOMHPY-UHFFFAOYSA-N n-[[5-[4-[2-(dimethylamino)ethyl]piperazin-1-yl]imidazo[1,2-a]pyridin-2-yl]methyl]-n-methyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CN(CCN(C)C)CCN1C1=CC=CC2=NC(CN(C)C3C4=NC=CC=C4CCC3)=CN12 GMAQSUGZLOMHPY-UHFFFAOYSA-N 0.000 description 1
- DPCMPFLXANRCAX-UHFFFAOYSA-N n-cyclopropyl-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CC1NC1C2=NC=CC=C2CCC1 DPCMPFLXANRCAX-UHFFFAOYSA-N 0.000 description 1
- XLYHMIXFJBPMLF-UHFFFAOYSA-N n-methyl-n-[(5-morpholin-4-ylimidazo[1,2-a]pyridin-2-yl)methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2N1CCOCC1 XLYHMIXFJBPMLF-UHFFFAOYSA-N 0.000 description 1
- ACQYFIMAFDSFQF-UHFFFAOYSA-N n-methyl-n-[(5-pyridin-3-ylimidazo[1,2-a]pyridin-2-yl)methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2C1=CC=CN=C1 ACQYFIMAFDSFQF-UHFFFAOYSA-N 0.000 description 1
- IJRADFNTAYCYKO-UHFFFAOYSA-N n-methyl-n-[[5-[methyl-(1-methylpiperidin-4-yl)amino]imidazo[1,2-a]pyridin-2-yl]methyl]-5,6,7,8-tetrahydroquinolin-8-amine Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2N(C)C1CCN(C)CC1 IJRADFNTAYCYKO-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 235000021096 natural sweeteners Nutrition 0.000 description 1
- 230000019581 neuron apoptotic process Effects 0.000 description 1
- 229960003966 nicotinamide Drugs 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- BTFQKIATRPGRBS-UHFFFAOYSA-N o-tolualdehyde Chemical compound CC1=CC=CC=C1C=O BTFQKIATRPGRBS-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003883 ointment base Substances 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
- 125000001312 palmitoyl group Chemical group O=C([*])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])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940014662 pantothenate Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000002831 pharmacologic agent Substances 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
- 150000008105 phosphatidylcholines Chemical class 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 238000013492 plasmid preparation Methods 0.000 description 1
- 239000013600 plasmid vector Substances 0.000 description 1
- YIQPUIGJQJDJOS-UHFFFAOYSA-N plerixafor Chemical compound C=1C=C(CN2CCNCCCNCCNCCC2)C=CC=1CN1CCCNCCNCCCNCC1 YIQPUIGJQJDJOS-UHFFFAOYSA-N 0.000 description 1
- 229960002169 plerixafor Drugs 0.000 description 1
- 229920001983 poloxamer Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 229920002721 polycyanoacrylate Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 229920005990 polystyrene resin Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- QPMDWIOUHQWKHV-ODZAUARKSA-M potassium;(z)-4-hydroxy-4-oxobut-2-enoate Chemical compound [K+].OC(=O)\C=C/C([O-])=O QPMDWIOUHQWKHV-ODZAUARKSA-M 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000011253 protective coating Substances 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- ABMYEXAYWZJVOV-UHFFFAOYSA-N pyridin-3-ylboronic acid Chemical compound OB(O)C1=CC=CN=C1 ABMYEXAYWZJVOV-UHFFFAOYSA-N 0.000 description 1
- QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
- 150000003235 pyrrolidines Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 230000006884 regulation of angiogenesis Effects 0.000 description 1
- 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000002000 scavenging effect Effects 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000012163 sequencing technique Methods 0.000 description 1
- 239000011257 shell material Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000013605 shuttle vector Substances 0.000 description 1
- 229910052814 silicon oxide Inorganic materials 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-N sodium;2-hydroxybenzoic acid Chemical compound [Na+].OC(=O)C1=CC=CC=C1O ABBQHOQBGMUPJH-UHFFFAOYSA-N 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 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
- 150000008163 sugars Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229950002757 teoclate Drugs 0.000 description 1
- DHHKPEUQJIEKOA-UHFFFAOYSA-N tert-butyl 2-[6-(nitromethyl)-6-bicyclo[3.2.0]hept-3-enyl]acetate Chemical compound C1C=CC2C(CC(=O)OC(C)(C)C)(C[N+]([O-])=O)CC21 DHHKPEUQJIEKOA-UHFFFAOYSA-N 0.000 description 1
- NEMXVXVJGXZDRR-UHFFFAOYSA-N tert-butyl n-(azetidin-3-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CNC1 NEMXVXVJGXZDRR-UHFFFAOYSA-N 0.000 description 1
- KOYLVNMHGMZREZ-UHFFFAOYSA-N tert-butyl n-[1-[2-[[methyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]imidazo[1,2-a]pyridin-5-yl]azetidin-3-yl]carbamate Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(N=C1C=CC=2)=CN1C=2N1CC(NC(=O)OC(C)(C)C)C1 KOYLVNMHGMZREZ-UHFFFAOYSA-N 0.000 description 1
- KNTRCIZNNJQPGS-QHCPKHFHSA-N tert-butyl n-[1-[2-[[methyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-5-yl]piperidin-4-yl]carbamate Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CCC(NC(=O)OC(C)(C)C)CC1 KNTRCIZNNJQPGS-QHCPKHFHSA-N 0.000 description 1
- IABAWEOTUJTREN-PKTZIBPZSA-N tert-butyl n-methyl-n-[(3r)-1-[2-[[methyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-5-yl]pyrrolidin-3-yl]carbamate Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(N=C1C=CC=2)=CN1C=2N1CC[C@@H](N(C)C(=O)OC(C)(C)C)C1 IABAWEOTUJTREN-PKTZIBPZSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- NLJDBTZLVTWXRG-UHFFFAOYSA-N tert-butylazanium;iodide Chemical compound [I-].CC(C)(C)[NH3+] NLJDBTZLVTWXRG-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 229940100611 topical cream Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229940100615 topical ointment Drugs 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 239000012096 transfection reagent Substances 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical class CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000029812 viral genome replication Effects 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/08—Antiseborrheics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Dermatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Hematology (AREA)
- Neurology (AREA)
- Communicable Diseases (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Virology (AREA)
- Rheumatology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Molecular Biology (AREA)
- AIDS & HIV (AREA)
- Hospice & Palliative Care (AREA)
- Transplantation (AREA)
- Endocrinology (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Tropical Medicine & Parasitology (AREA)
- Heart & Thoracic Surgery (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US60674204P | 2004-09-02 | 2004-09-02 | |
| US60/606,742 | 2004-09-02 | ||
| US61076504P | 2004-09-17 | 2004-09-17 | |
| US60/610,765 | 2004-09-17 | ||
| PCT/US2005/031098 WO2006028896A2 (en) | 2004-09-02 | 2005-08-31 | Chemical compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2579059A1 true CA2579059A1 (en) | 2006-03-16 |
Family
ID=36000724
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002579059A Abandoned CA2579059A1 (en) | 2004-09-02 | 2005-08-31 | Chemical compounds |
| CA002578746A Abandoned CA2578746A1 (en) | 2004-09-02 | 2005-08-31 | Chemical compounds |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002578746A Abandoned CA2578746A1 (en) | 2004-09-02 | 2005-08-31 | Chemical compounds |
Country Status (16)
| Country | Link |
|---|---|
| US (2) | US20070232615A1 (enExample) |
| EP (2) | EP1799671A4 (enExample) |
| JP (2) | JP2008511669A (enExample) |
| KR (2) | KR20070049682A (enExample) |
| AR (2) | AR050302A1 (enExample) |
| AU (2) | AU2005279835A1 (enExample) |
| BR (1) | BRPI0514881A (enExample) |
| CA (2) | CA2579059A1 (enExample) |
| IL (1) | IL181419A0 (enExample) |
| MA (1) | MA28872B1 (enExample) |
| MX (2) | MX2007002679A (enExample) |
| NO (2) | NO20071366L (enExample) |
| PE (2) | PE20060712A1 (enExample) |
| RU (2) | RU2352567C2 (enExample) |
| TW (2) | TW200621754A (enExample) |
| WO (2) | WO2006026703A2 (enExample) |
Families Citing this family (29)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1799671A4 (en) * | 2004-09-02 | 2009-06-10 | Smithkline Beecham Corp | CHEMICAL COMPOUNDS |
| AR059197A1 (es) * | 2006-01-25 | 2008-03-19 | Smithkline Beecham Corp | Derivados de indazolo piridina para el tratamiento de hiv |
| US8618122B2 (en) | 2006-05-16 | 2013-12-31 | Ono Pharmaceutical Co., Ltd. | Compound having acidic group which may be protected, and use thereof |
| WO2008016006A1 (fr) | 2006-07-31 | 2008-02-07 | Ono Pharmaceutical Co., Ltd. | Composé auquel un groupe cyclique est lié par une liaison spiro et son utilisation |
| US7767826B2 (en) * | 2007-10-05 | 2010-08-03 | Pharmatech International, Inc. | Process for the synthesis of L-(+)-ergothioneine |
| CA2704645A1 (en) * | 2007-11-09 | 2009-05-14 | The Salk Institute For Biological Studies | Non-nucleoside reverse transcriptase inhibitors |
| CN102675305B (zh) * | 2011-03-08 | 2014-11-12 | 中国科学院上海药物研究所 | 一类咪唑并吡啶类化合物及其制备方法和用途 |
| CN103570683B (zh) * | 2012-07-30 | 2018-04-17 | 中国科学院上海药物研究所 | 多取代胺类化合物及其制备方法和用途 |
| WO2015123424A1 (en) | 2014-02-13 | 2015-08-20 | Incyte Corporation | Cyclopropylamines as lsd1 inhibitors |
| LT3105218T (lt) | 2014-02-13 | 2019-12-10 | Incyte Corp | Ciklopropilaminai kaip lsd1 inhibitoriai |
| WO2016007722A1 (en) | 2014-07-10 | 2016-01-14 | Incyte Corporation | Triazolopyridines and triazolopyrazines as lsd1 inhibitors |
| EA201792205A1 (ru) | 2015-04-03 | 2018-02-28 | Инсайт Корпорейшн | Гетероциклические соединения как ингибиторы lsd1 |
| DK3334709T3 (da) | 2015-08-12 | 2025-02-03 | Incyte Holdings Corp | Salte af en lsd1-hæmmer |
| CN109069426B (zh) | 2015-12-14 | 2021-10-29 | X4 制药有限公司 | 治疗癌症的方法 |
| CN109069486A (zh) | 2015-12-14 | 2018-12-21 | X4 制药有限公司 | 治疗癌症的方法 |
| US10450318B2 (en) * | 2015-12-15 | 2019-10-22 | Bristol-Myers Squibb Company | CXCR4 receptor antagonists |
| US10610527B2 (en) | 2015-12-22 | 2020-04-07 | X4 Pharmaceuticals, Inc. | Methods for treating immunodeficiency disease |
| US11337969B2 (en) | 2016-04-08 | 2022-05-24 | X4 Pharmaceuticals, Inc. | Methods for treating cancer |
| EP3808748B1 (en) | 2016-06-21 | 2026-05-20 | X4 Pharmaceuticals, Inc. | Substituted piperidines as cxcr4-inhibitors |
| JP6994767B2 (ja) * | 2016-06-21 | 2022-01-14 | エックス４ ファーマシューティカルズ， インコーポレイテッド | Ｃｘｃｒ４阻害剤およびその使用 |
| US10988465B2 (en) | 2016-06-21 | 2021-04-27 | X4 Pharmaceuticals, Inc. | CXCR4 inhibitors and uses thereof |
| US11497744B2 (en) | 2017-02-21 | 2022-11-15 | Emory University | Chemokine CXCR4 receptor modulators and uses related thereto |
| KR102678977B1 (ko) * | 2017-09-25 | 2024-06-28 | 씨젠테크 (쑤저우, 차이나) 컴퍼니 리미티드 | Cxcr4 저해제로서 헤테로아릴 화합물, 그 조성물 및 이용 방법 |
| US11396501B2 (en) * | 2017-09-25 | 2022-07-26 | Cgenetech (Suzhou, China) Co., Ltd. | Heteroaryl compounds as CXCR4 inhibitors, composition and method using the same |
| EP3768256A4 (en) | 2018-03-19 | 2021-11-24 | Emory University | PAN-TROPICAL ENTRANCE INHIBITORS |
| US10968200B2 (en) | 2018-08-31 | 2021-04-06 | Incyte Corporation | Salts of an LSD1 inhibitor and processes for preparing the same |
| US10548889B1 (en) | 2018-08-31 | 2020-02-04 | X4 Pharmaceuticals, Inc. | Compositions of CXCR4 inhibitors and methods of preparation and use |
| CN115515585A (zh) | 2020-03-10 | 2022-12-23 | X4 制药有限公司 | 用于治疗中性粒细胞减少症的方法 |
| WO2023003862A1 (en) | 2021-07-19 | 2023-01-26 | Emory University | Cxcr4 modulators and uses related thereto |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ225152A (en) * | 1987-07-17 | 1990-04-26 | Janssen Pharmaceutica Nv | Heterocyclically substituted piperidinyl benzamides as pharmaceuticals |
| NZ524421A (en) * | 2000-09-15 | 2005-02-25 | Anormed Inc | Chemokine receptor binding heterocyclic compounds |
| JP2004512336A (ja) * | 2000-09-15 | 2004-04-22 | アノーメッド インコーポレイティド | ケモカインレセプター結合複素環式化合物 |
| RU2289581C2 (ru) * | 2000-09-15 | 2006-12-20 | Анормед, Инк. | Гетероциклические соединения, содержащая их фармацевтическая композиция и их применение |
| KR20030034184A (ko) * | 2000-09-15 | 2003-05-01 | 아노르메드 인코포레이티드 | 케모킨 수용체 결합 헤테로사이클릭 화합물 |
| CA2467718C (en) * | 2001-12-21 | 2011-04-26 | Anormed Inc. | Chemokine receptor binding heterocyclic compounds with enhanced efficacy |
| CA2520259A1 (en) * | 2003-04-11 | 2004-10-28 | Anormed Inc. | Cxcr4 chemokine receptor binding compounds |
| EP1799671A4 (en) * | 2004-09-02 | 2009-06-10 | Smithkline Beecham Corp | CHEMICAL COMPOUNDS |
| WO2006036816A2 (en) * | 2004-09-24 | 2006-04-06 | Smithkline Beecham Corporation | Chemical compounds |
| US20080234318A1 (en) * | 2005-08-31 | 2008-09-25 | Kristjan Gudmundsson | Chemical Compounds |
-
2005
- 2005-08-28 EP EP05815072A patent/EP1799671A4/en not_active Withdrawn
- 2005-08-28 MX MX2007002679A patent/MX2007002679A/es not_active Application Discontinuation
- 2005-08-28 JP JP2007530353A patent/JP2008511669A/ja active Pending
- 2005-08-28 WO PCT/US2005/031099 patent/WO2006026703A2/en not_active Ceased
- 2005-08-31 CA CA002579059A patent/CA2579059A1/en not_active Abandoned
- 2005-08-31 KR KR1020077007349A patent/KR20070049682A/ko not_active Withdrawn
- 2005-08-31 AU AU2005279835A patent/AU2005279835A1/en not_active Abandoned
- 2005-08-31 RU RU2007106780/04A patent/RU2352567C2/ru not_active IP Right Cessation
- 2005-08-31 US US11/574,583 patent/US20070232615A1/en not_active Abandoned
- 2005-08-31 AU AU2005282753A patent/AU2005282753A1/en not_active Abandoned
- 2005-08-31 US US11/574,586 patent/US20070254910A1/en not_active Abandoned
- 2005-08-31 JP JP2007530352A patent/JP2008511668A/ja active Pending
- 2005-08-31 CA CA002578746A patent/CA2578746A1/en not_active Abandoned
- 2005-08-31 RU RU2007106779/04A patent/RU2351592C2/ru not_active IP Right Cessation
- 2005-08-31 EP EP05794929A patent/EP1784185A4/en not_active Withdrawn
- 2005-08-31 MX MX2007002615A patent/MX2007002615A/es not_active Application Discontinuation
- 2005-08-31 WO PCT/US2005/031098 patent/WO2006028896A2/en not_active Ceased
- 2005-08-31 BR BRPI0514881-2A patent/BRPI0514881A/pt not_active IP Right Cessation
- 2005-08-31 KR KR1020077007549A patent/KR20070053313A/ko not_active Withdrawn
- 2005-09-01 PE PE2005001007A patent/PE20060712A1/es not_active Application Discontinuation
- 2005-09-01 AR ARP050103665A patent/AR050302A1/es not_active Application Discontinuation
- 2005-09-01 AR ARP050103666A patent/AR051565A1/es not_active Application Discontinuation
- 2005-09-01 PE PE2005001008A patent/PE20060656A1/es not_active Application Discontinuation
- 2005-09-02 TW TW094130018A patent/TW200621754A/zh unknown
- 2005-09-02 TW TW094130013A patent/TW200612921A/zh unknown
-
2007
- 2007-02-19 IL IL181419A patent/IL181419A0/en unknown
- 2007-03-14 NO NO20071366A patent/NO20071366L/no not_active Application Discontinuation
- 2007-03-15 NO NO20071418A patent/NO20071418L/no not_active Application Discontinuation
- 2007-03-23 MA MA29772A patent/MA28872B1/fr unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20070232615A1 (en) | Chemical Compounds | |
| JP2009524690A (ja) | 化合物 | |
| US20100227880A1 (en) | Chemical compounds | |
| JP2008511669A6 (ja) | 化合物 | |
| JP2009507795A (ja) | 化合物 | |
| US20080045537A1 (en) | Chemical Compounds | |
| US20090093454A1 (en) | Chemical Compounds | |
| US20080171740A1 (en) | Chemical Compounds | |
| EP1904501A2 (en) | Chemical compounds | |
| US20240228489A1 (en) | Positive allosteric modulators of the muscarinic acetylcholine receptor m1 | |
| US20080207634A1 (en) | Chemical Compounds | |
| CN102675305B (zh) | 一类咪唑并吡啶类化合物及其制备方法和用途 | |
| WO2003077857A2 (en) | N-(substituted benzyl)-8-hydroxy-1,6-naphthyridine-7- carboxamides useful as hiv integrase inhibitors |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |