AU2005279835A1 - Chemical compounds - Google Patents
Chemical compounds Download PDFInfo
- Publication number
- AU2005279835A1 AU2005279835A1 AU2005279835A AU2005279835A AU2005279835A1 AU 2005279835 A1 AU2005279835 A1 AU 2005279835A1 AU 2005279835 A AU2005279835 A AU 2005279835A AU 2005279835 A AU2005279835 A AU 2005279835A AU 2005279835 A1 AU2005279835 A1 AU 2005279835A1
- Authority
- AU
- Australia
- Prior art keywords
- methyl
- alkyl
- compound
- tetrahydro
- imidazo
- 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 description 352
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 221
- 125000000217 alkyl group Chemical group 0.000 claims description 179
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 122
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 114
- -1 Ethyloxy Chemical group 0.000 claims description 78
- 125000003342 alkenyl group Chemical group 0.000 claims description 75
- 125000000304 alkynyl group Chemical group 0.000 claims description 75
- 239000007787 solid Substances 0.000 claims description 62
- 125000001188 haloalkyl group Chemical group 0.000 claims description 60
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 53
- 239000000203 mixture Substances 0.000 claims description 48
- 238000006268 reductive amination reaction Methods 0.000 claims description 47
- 238000000034 method Methods 0.000 claims description 44
- 238000011282 treatment Methods 0.000 claims description 44
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 43
- 229910052736 halogen Inorganic materials 0.000 claims description 40
- 150000002367 halogens Chemical group 0.000 claims description 40
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 39
- 239000003795 chemical substances by application Substances 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 35
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 32
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 31
- UTCSSFWDNNEEBH-UHFFFAOYSA-N imidazo[1,2-a]pyridine Chemical compound C1=CC=CC2=NC=CN21 UTCSSFWDNNEEBH-UHFFFAOYSA-N 0.000 claims description 31
- 230000000694 effects Effects 0.000 claims description 29
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 29
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 28
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims description 26
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 25
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 claims description 24
- 201000010099 disease Diseases 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 23
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 21
- 238000005859 coupling reaction Methods 0.000 claims description 21
- 125000000623 heterocyclic group Chemical group 0.000 claims description 21
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 21
- 125000002947 alkylene group Chemical group 0.000 claims description 20
- 125000004043 oxo group Chemical group O=* 0.000 claims description 20
- 230000009467 reduction Effects 0.000 claims description 20
- 238000006722 reduction reaction Methods 0.000 claims description 20
- 208000031886 HIV Infections Diseases 0.000 claims description 19
- 208000037357 HIV infectious disease Diseases 0.000 claims description 19
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 230000008878 coupling Effects 0.000 claims description 17
- 238000010168 coupling process Methods 0.000 claims description 17
- 238000011321 prophylaxis Methods 0.000 claims description 17
- 102000009410 Chemokine receptor Human genes 0.000 claims description 16
- 108050000299 Chemokine receptor Proteins 0.000 claims description 16
- 208000029523 Interstitial Lung disease Diseases 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 230000002757 inflammatory effect Effects 0.000 claims description 15
- 230000008569 process Effects 0.000 claims description 15
- 201000004624 Dermatitis Diseases 0.000 claims description 14
- 201000004681 Psoriasis Diseases 0.000 claims description 14
- 208000026935 allergic disease Diseases 0.000 claims description 14
- 230000002708 enhancing effect Effects 0.000 claims description 14
- 230000009610 hypersensitivity Effects 0.000 claims description 14
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 14
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 claims description 13
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 claims description 13
- 206010061218 Inflammation Diseases 0.000 claims description 13
- 206010028980 Neoplasm Diseases 0.000 claims description 13
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 13
- 230000004054 inflammatory process Effects 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 13
- 210000001519 tissue Anatomy 0.000 claims description 13
- 125000005724 cycloalkenylene group Chemical group 0.000 claims description 12
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 12
- 125000004450 alkenylene group Chemical group 0.000 claims description 11
- 125000003282 alkyl amino group Chemical group 0.000 claims description 11
- 125000004419 alkynylene group Chemical group 0.000 claims description 11
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 10
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 10
- 239000003112 inhibitor Substances 0.000 claims description 10
- 125000003107 substituted aryl group Chemical group 0.000 claims description 10
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 9
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 9
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 9
- 208000006673 asthma Diseases 0.000 claims description 8
- 208000032839 leukemia Diseases 0.000 claims description 8
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 8
- 239000002773 nucleotide Substances 0.000 claims description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 8
- 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
- 206010039710 Scleroderma 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
- 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
- QUDMHFVRKBVGBY-FQEVSTJZSA-N [5-(4-methylpiperazin-1-yl)-2-[[methyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(=C(N12)CO)N=C1C=CC=C2N1CCN(C)CC1 QUDMHFVRKBVGBY-FQEVSTJZSA-N 0.000 claims description 6
- NJBRZHKNUUOYBN-QFIPXVFZSA-N [5-(4-methylpiperazin-1-yl)-2-[[propan-2-yl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound CC(C)N([C@@H]1C2=NC=CC=C2CCC1)CC(=C(N12)CO)N=C1C=CC=C2N1CCN(C)CC1 NJBRZHKNUUOYBN-QFIPXVFZSA-N 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
- 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
- OMQGJJGRSZIQQJ-QHCPKHFHSA-N [2-[[cyclopropylmethyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]-5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound C1CN(C)CCN1C1=CC=CC2=NC(CN(CC3CC3)[C@@H]3C4=NC=CC=C4CCC3)=C(CO)N12 OMQGJJGRSZIQQJ-QHCPKHFHSA-N 0.000 claims description 5
- VCFMOLJXJJHRDI-NRFANRHFSA-N [2-[[ethyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]-5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound CCN([C@@H]1C2=NC=CC=C2CCC1)CC(=C(N12)CO)N=C1C=CC=C2N1CCN(C)CC1 VCFMOLJXJJHRDI-NRFANRHFSA-N 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 229940124597 therapeutic agent Drugs 0.000 claims description 5
- BDERNNFJNOPAEC-UHFFFAOYSA-N 1-propanol Substances CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 229940044613 1-propanol Drugs 0.000 claims description 4
- MZRHSBOFBICIAU-FIPFOOKPSA-N [2-[[[(1s)-1-(4-methoxyphenyl)ethyl]-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]-5-(4-methylpiperazin-1-yl)imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound C1=CC(OC)=CC=C1[C@H](C)N([C@@H]1C2=NC=CC=C2CCC1)CC1=C(CO)N2C(N3CCN(C)CC3)=CC=CC2=N1 MZRHSBOFBICIAU-FIPFOOKPSA-N 0.000 claims description 4
- UAWUQXPDPOEYPP-VWNXMTODSA-N [2-[[cyclopropylmethyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]-5-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound C1[C@H](N(C)C)CCN1C1=CC=CC2=NC(CN(CC3CC3)[C@@H]3C4=NC=CC=C4CCC3)=C(CO)N12 UAWUQXPDPOEYPP-VWNXMTODSA-N 0.000 claims description 4
- ITOXKJBXAWDJBA-NRFANRHFSA-N [5-(4-ethylpiperazin-1-yl)-2-[[methyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound C1CN(CC)CCN1C1=CC=CC2=NC(CN(C)[C@@H]3C4=NC=CC=C4CCC3)=C(CO)N12 ITOXKJBXAWDJBA-NRFANRHFSA-N 0.000 claims description 4
- HGWYUSJZJFIGOG-QFIPXVFZSA-N [5-(4-methylpiperazin-1-yl)-2-[[propyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound CCCN([C@@H]1C2=NC=CC=C2CCC1)CC(=C(N12)CO)N=C1C=CC=C2N1CCN(C)CC1 HGWYUSJZJFIGOG-QFIPXVFZSA-N 0.000 claims description 4
- CZWUXDXQKLXFBS-CTNGQTDRSA-N [5-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]-2-[[methyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound C1[C@H](N(C)C)CCN1C1=CC=CC2=NC(CN(C)[C@@H]3C4=NC=CC=C4CCC3)=C(CO)N12 CZWUXDXQKLXFBS-CTNGQTDRSA-N 0.000 claims description 4
- FMKQGTBQHSFAOK-GGAORHGYSA-N [5-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]-2-[[propyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound CCCN([C@@H]1C2=NC=CC=C2CCC1)CC(=C(N12)CO)N=C1C=CC=C2N1CC[C@@H](N(C)C)C1 FMKQGTBQHSFAOK-GGAORHGYSA-N 0.000 claims description 4
- DBLIBYXKCXRXKI-QWAKEFERSA-N [5-[methyl-(1-methylpyrrolidin-3-yl)amino]-2-[[methyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(=C(N12)CO)N=C1C=CC=C2N(C)C1CCN(C)C1 DBLIBYXKCXRXKI-QWAKEFERSA-N 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 4
- 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
- QUDMHFVRKBVGBY-UHFFFAOYSA-N [5-(4-methylpiperazin-1-yl)-2-[[methyl(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound C1CCC2=CC=CN=C2C1N(C)CC(=C(N12)CO)N=C1C=CC=C2N1CCN(C)CC1 QUDMHFVRKBVGBY-UHFFFAOYSA-N 0.000 claims description 3
- QWHDVDASMCRJJZ-UHFFFAOYSA-N [5-(4-methylpiperazin-1-yl)-2-[[methyl(6,7,8,9-tetrahydro-5h-cyclohepta[b]pyridin-9-yl)amino]methyl]imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound C1CCCC2=CC=CN=C2C1N(C)CC(=C(N12)CO)N=C1C=CC=C2N1CCN(C)CC1 QWHDVDASMCRJJZ-UHFFFAOYSA-N 0.000 claims description 3
- CYYJZCMKOQFVEU-IRLDBZIGSA-N [5-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]-2-[[ethyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound CCN([C@@H]1C2=NC=CC=C2CCC1)CC(=C(N12)CO)N=C1C=CC=C2N1CC[C@@H](N(C)C)C1 CYYJZCMKOQFVEU-IRLDBZIGSA-N 0.000 claims description 3
- LJZYHHSTUCZUCV-QUCCMNQESA-N [5-[(3r)-3-(methylamino)pyrrolidin-1-yl]-2-[[methyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound C1[C@H](NC)CCN1C1=CC=CC2=NC(CN(C)[C@@H]3C4=NC=CC=C4CCC3)=C(CO)N12 LJZYHHSTUCZUCV-QUCCMNQESA-N 0.000 claims description 3
- BIABECXOMDEQRN-MJGOQNOKSA-N [5-[(3r)-3-aminopyrrolidin-1-yl]-2-[[methyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound CN([C@@H]1C2=NC=CC=C2CCC1)CC(=C(N12)CO)N=C1C=CC=C2N1CC[C@@H](N)C1 BIABECXOMDEQRN-MJGOQNOKSA-N 0.000 claims description 3
- TZXUJAFBNRHKQL-FQEVSTJZSA-N [5-[2-(dimethylamino)ethyl-methylamino]-2-[[methyl-[(8s)-5,6,7,8-tetrahydroquinolin-8-yl]amino]methyl]imidazo[1,2-a]pyridin-3-yl]methanol Chemical compound C1CCC2=CC=CN=C2[C@H]1N(C)CC1=C(CO)N2C(N(C)CCN(C)C)=CC=CC2=N1 TZXUJAFBNRHKQL-FQEVSTJZSA-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
- 150000001412 amines Chemical group 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
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Classifications
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Landscapes
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Applications Claiming Priority (5)
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| 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/US2005/031099 WO2006026703A2 (en) | 2004-09-02 | 2005-08-28 | Chemical compounds |
Publications (1)
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| AU2005279835A1 true AU2005279835A1 (en) | 2006-03-09 |
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| EP (2) | EP1799671A4 (https=) |
| JP (2) | JP2008511669A (https=) |
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| AR (2) | AR050302A1 (https=) |
| AU (2) | AU2005279835A1 (https=) |
| BR (1) | BRPI0514881A (https=) |
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| PE (2) | PE20060712A1 (https=) |
| RU (2) | RU2351592C2 (https=) |
| TW (2) | TW200621754A (https=) |
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| JP2008511669A (ja) * | 2004-09-02 | 2008-04-17 | スミスクライン ビーチャム コーポレーション | 化合物 |
| PE20070946A1 (es) * | 2006-01-25 | 2007-10-16 | Smithkline Beecham Corp | COMPUESTOS DERIVADOS DE IMIDAZO[1,2-a]PIRIDINA COMO MODULADORES DEL RECEPTOR DE QUIMIOQUINA (CXCR4) |
| EP2042503B1 (en) | 2006-05-16 | 2013-01-30 | 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 |
| EP2217069A4 (en) * | 2007-11-09 | 2012-03-14 | Salk Inst For Biological Studi | INHIBITORS OF NON-NUCLEOSIDE INHIBITORS OF THE REVERSE TRANSCRIPTASE |
| 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 |
| MX373103B (es) | 2014-02-13 | 2020-04-17 | Incyte Holdings Corp | Ciclopropilaminas como inhibidores de desmetilasa específica de lisina 1 (lsd1). |
| SI3105218T1 (sl) | 2014-02-13 | 2019-11-29 | Incyte Corp | Ciklopropilamini kot inhibitorji LSD1 |
| WO2016007722A1 (en) | 2014-07-10 | 2016-01-14 | Incyte Corporation | Triazolopyridines and triazolopyrazines as lsd1 inhibitors |
| EP3277689B1 (en) | 2015-04-03 | 2019-09-04 | Incyte Corporation | Heterocyclic compounds as lsd1 inhibitors |
| LT3334709T (lt) | 2015-08-12 | 2025-03-10 | Incyte Holdings Corporation | Lsd1 inhibitoriaus druskos |
| WO2017106332A1 (en) | 2015-12-14 | 2017-06-22 | X4 Pharmaceuticals, Inc. | Methods for treating cancer |
| CN109069426B (zh) | 2015-12-14 | 2021-10-29 | X4 制药有限公司 | 治疗癌症的方法 |
| KR102738306B1 (ko) * | 2015-12-15 | 2024-12-03 | 브리스톨-마이어스 스큅 컴퍼니 | Cxcr4 수용체 길항제 |
| PL3393468T3 (pl) | 2015-12-22 | 2023-01-23 | X4 Pharmaceuticals, Inc. | Metody leczenia niedoboru odporności |
| US11337969B2 (en) | 2016-04-08 | 2022-05-24 | X4 Pharmaceuticals, Inc. | Methods for treating cancer |
| WO2017223243A1 (en) | 2016-06-21 | 2017-12-28 | X4 Pharmaceuticals, Inc. | Cxcr4 inhibitors and uses thereof |
| CN109640988A (zh) | 2016-06-21 | 2019-04-16 | X4 制药有限公司 | Cxcr4抑制剂及其用途 |
| ES2870920T3 (es) | 2016-06-21 | 2021-10-28 | X4 Pharmaceuticals Inc | Inhibidores de CXCR4 y usos de los mismos |
| EP3585387A4 (en) | 2017-02-21 | 2020-08-12 | Emory University | CHEMIOKIN CXCR4 RECEIVER MODULATORS AND THEIR USES |
| JP7282786B2 (ja) * | 2017-09-25 | 2023-05-29 | シージーンテック （スーチョウ， チャイナ） カンパニー リミテッド | Ｃｘｃｒ４阻害剤としてのヘテロアリール化合物、それを用いた組成物及び方法 |
| KR102678977B1 (ko) * | 2017-09-25 | 2024-06-28 | 씨젠테크 (쑤저우, 차이나) 컴퍼니 리미티드 | Cxcr4 저해제로서 헤테로아릴 화합물, 그 조성물 및 이용 방법 |
| US11649235B2 (en) | 2018-03-19 | 2023-05-16 | Emory University | Pan-tropic entry inhibitors |
| US10548889B1 (en) | 2018-08-31 | 2020-02-04 | X4 Pharmaceuticals, Inc. | Compositions of CXCR4 inhibitors and methods of preparation and use |
| WO2020047198A1 (en) | 2018-08-31 | 2020-03-05 | Incyte Corporation | Salts of an lsd1 inhibitor and processes for preparing the same |
| CA3171250A1 (en) | 2020-03-10 | 2021-09-16 | E. Lynne KELLEY | Methods for treating neutropenia |
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 |
| 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 |
| PT1317451E (pt) * | 2000-09-15 | 2006-12-29 | Anormed Inc | Compostos heterocíclicos que se ligam a receptores de quimioquinas |
| US6835731B2 (en) * | 2000-09-15 | 2004-12-28 | Anormed, Inc. | Chemokine receptor binding heterocyclic compounds |
| CA2419224A1 (en) * | 2000-09-15 | 2002-03-21 | Anormed Inc. | Chemokine receptor binding heterocyclic compounds |
| CA2467718C (en) * | 2001-12-21 | 2011-04-26 | Anormed Inc. | Chemokine receptor binding heterocyclic compounds with enhanced efficacy |
| EP1613613B1 (en) * | 2003-04-11 | 2021-06-02 | Genzyme Corporation | Cxcr4 chemokine receptor binding compounds |
| JP2008511669A (ja) * | 2004-09-02 | 2008-04-17 | スミスクライン ビーチャム コーポレーション | 化合物 |
| WO2006036816A2 (en) * | 2004-09-24 | 2006-04-06 | Smithkline Beecham Corporation | Chemical compounds |
| EP1919872A4 (en) * | 2005-08-31 | 2009-08-05 | Smithkline Beecham Corp | CHEMICAL COMPOUNDS |
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