JP2019515947A - 可溶性C5aRアンタゴニスト - Google Patents
可溶性C5aRアンタゴニスト Download PDFInfo
- Publication number
- JP2019515947A JP2019515947A JP2019502541A JP2019502541A JP2019515947A JP 2019515947 A JP2019515947 A JP 2019515947A JP 2019502541 A JP2019502541 A JP 2019502541A JP 2019502541 A JP2019502541 A JP 2019502541A JP 2019515947 A JP2019515947 A JP 2019515947A
- Authority
- JP
- Japan
- Prior art keywords
- inhibitor
- antagonist
- acid
- group
- alkylene
- 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.)
- Granted
Links
- 229940126681 complement 5a receptor antagonist Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 143
- 150000003839 salts Chemical class 0.000 claims abstract description 71
- 238000000034 method Methods 0.000 claims abstract description 33
- 102000005590 Anaphylatoxin C5a Receptor Human genes 0.000 claims abstract description 23
- 108010059426 Anaphylatoxin C5a Receptor Proteins 0.000 claims abstract description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 23
- -1 hydrabamin Chemical compound 0.000 claims description 155
- 239000003112 inhibitor Substances 0.000 claims description 92
- 239000003814 drug Substances 0.000 claims description 58
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 54
- 239000005557 antagonist Substances 0.000 claims description 52
- 229940124597 therapeutic agent Drugs 0.000 claims description 47
- 125000000217 alkyl group Chemical group 0.000 claims description 41
- 239000003446 ligand Substances 0.000 claims description 40
- 201000010099 disease Diseases 0.000 claims description 36
- 125000003118 aryl group Chemical group 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 29
- 239000000556 agonist Substances 0.000 claims description 24
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims description 24
- 239000011734 sodium Substances 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 21
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 239000002253 acid Substances 0.000 claims description 19
- 206010028980 Neoplasm Diseases 0.000 claims description 18
- 206010047115 Vasculitis Diseases 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 208000035475 disorder Diseases 0.000 claims description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 16
- 229940044551 receptor antagonist Drugs 0.000 claims description 15
- 239000002464 receptor antagonist Substances 0.000 claims description 15
- 108060003951 Immunoglobulin Proteins 0.000 claims description 14
- 239000002559 chemokine receptor antagonist Substances 0.000 claims description 14
- 239000003246 corticosteroid Substances 0.000 claims description 14
- 150000002148 esters Chemical class 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 102000018358 immunoglobulin Human genes 0.000 claims description 14
- 150000003431 steroids Chemical class 0.000 claims description 14
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 claims description 13
- 229960000258 corticotropin Drugs 0.000 claims description 13
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 claims description 12
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 12
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 claims description 12
- 125000002947 alkylene group Chemical group 0.000 claims description 12
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 12
- 229960004397 cyclophosphamide Drugs 0.000 claims description 12
- 229960000890 hydrocortisone Drugs 0.000 claims description 12
- 229960003444 immunosuppressant agent Drugs 0.000 claims description 12
- 239000003018 immunosuppressive agent Substances 0.000 claims description 12
- 229960004641 rituximab Drugs 0.000 claims description 12
- 229910052708 sodium Inorganic materials 0.000 claims description 12
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims description 12
- 239000005483 tyrosine kinase inhibitor Substances 0.000 claims description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 206010061218 Inflammation Diseases 0.000 claims description 11
- 208000009956 adenocarcinoma Diseases 0.000 claims description 11
- 230000004054 inflammatory process Effects 0.000 claims description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 10
- 208000035913 Atypical hemolytic uremic syndrome Diseases 0.000 claims description 10
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 10
- 208000005777 Lupus Nephritis Diseases 0.000 claims description 10
- 206010025323 Lymphomas Diseases 0.000 claims description 10
- 229960002537 betamethasone Drugs 0.000 claims description 10
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-DVTGEIKXSA-N 0.000 claims description 10
- 210000004369 blood Anatomy 0.000 claims description 10
- 239000008280 blood Substances 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 201000008383 nephritis Diseases 0.000 claims description 10
- 229960004618 prednisone Drugs 0.000 claims description 10
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 claims description 10
- 229940083542 sodium Drugs 0.000 claims description 10
- 229960005294 triamcinolone Drugs 0.000 claims description 10
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 claims description 10
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 9
- 101800000414 Corticotropin Proteins 0.000 claims description 9
- MUQNGPZZQDCDFT-JNQJZLCISA-N Halcinonide Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CCl)[C@@]1(C)C[C@@H]2O MUQNGPZZQDCDFT-JNQJZLCISA-N 0.000 claims description 9
- 229960002383 halcinonide Drugs 0.000 claims description 9
- KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical compound CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 claims description 9
- 208000004235 neutropenia Diseases 0.000 claims description 9
- 210000000056 organ Anatomy 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 229950010765 pivalate Drugs 0.000 claims description 9
- 108010029697 CD40 Ligand Proteins 0.000 claims description 8
- 102100032937 CD40 ligand Human genes 0.000 claims description 8
- 102100025406 Complement C1s subcomponent Human genes 0.000 claims description 8
- 108050005572 Complement C1s subcomponent Proteins 0.000 claims description 8
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 229960001334 corticosteroids Drugs 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 229960004577 laquinimod Drugs 0.000 claims description 8
- GKWPCEFFIHSJOE-UHFFFAOYSA-N laquinimod Chemical compound OC=1C2=C(Cl)C=CC=C2N(C)C(=O)C=1C(=O)N(CC)C1=CC=CC=C1 GKWPCEFFIHSJOE-UHFFFAOYSA-N 0.000 claims description 8
- 201000006417 multiple sclerosis Diseases 0.000 claims description 8
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 8
- OAVGBZOFDPFGPJ-UHFFFAOYSA-N sotrastaurin Chemical compound C1CN(C)CCN1C1=NC(C=2C(NC(=O)C=2C=2C3=CC=CC=C3NC=2)=O)=C(C=CC=C2)C2=N1 OAVGBZOFDPFGPJ-UHFFFAOYSA-N 0.000 claims description 8
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 claims description 8
- 201000009030 Carcinoma Diseases 0.000 claims description 7
- 102100028892 Cardiotrophin-1 Human genes 0.000 claims description 7
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 7
- 102100026046 Mannan-binding lectin serine protease 2 Human genes 0.000 claims description 7
- 101710117460 Mannan-binding lectin serine protease 2 Proteins 0.000 claims description 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 7
- 206010039491 Sarcoma Diseases 0.000 claims description 7
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 7
- 108010041776 cardiotrophin 1 Proteins 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 208000010125 myocardial infarction Diseases 0.000 claims description 7
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 7
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 claims description 7
- 229960002930 sirolimus Drugs 0.000 claims description 7
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 claims description 7
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 6
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 6
- 125000006716 (C1-C6) heteroalkyl group Chemical group 0.000 claims description 6
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 6
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims description 6
- 102000008873 Angiotensin II receptor Human genes 0.000 claims description 6
- 108050000824 Angiotensin II receptor Proteins 0.000 claims description 6
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 claims description 6
- 102100031151 C-C chemokine receptor type 2 Human genes 0.000 claims description 6
- 101710149815 C-C chemokine receptor type 2 Proteins 0.000 claims description 6
- 102100036166 C-X-C chemokine receptor type 1 Human genes 0.000 claims description 6
- 102100031650 C-X-C chemokine receptor type 4 Human genes 0.000 claims description 6
- LUKZNWIVRBCLON-GXOBDPJESA-N Ciclesonide Chemical compound C1([C@H]2O[C@@]3([C@H](O2)C[C@@H]2[C@@]3(C[C@H](O)[C@@H]3[C@@]4(C)C=CC(=O)C=C4CC[C@H]32)C)C(=O)COC(=O)C(C)C)CCCCC1 LUKZNWIVRBCLON-GXOBDPJESA-N 0.000 claims description 6
- WJOHZNCJWYWUJD-IUGZLZTKSA-N Fluocinonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)C)[C@@]2(C)C[C@@H]1O WJOHZNCJWYWUJD-IUGZLZTKSA-N 0.000 claims description 6
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Chemical class O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 claims description 6
- 101000947174 Homo sapiens C-X-C chemokine receptor type 1 Proteins 0.000 claims description 6
- 101000922348 Homo sapiens C-X-C chemokine receptor type 4 Proteins 0.000 claims description 6
- 206010027406 Mesothelioma Diseases 0.000 claims description 6
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 claims description 6
- 241000721454 Pemphigus Species 0.000 claims description 6
- 206010040047 Sepsis Diseases 0.000 claims description 6
- 229940092705 beclomethasone Drugs 0.000 claims description 6
- NBMKJKDGKREAPL-DVTGEIKXSA-N beclomethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O NBMKJKDGKREAPL-DVTGEIKXSA-N 0.000 claims description 6
- 229960004436 budesonide Drugs 0.000 claims description 6
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims description 6
- 229960003728 ciclesonide Drugs 0.000 claims description 6
- 229960003290 cortisone acetate Drugs 0.000 claims description 6
- 229960003662 desonide Drugs 0.000 claims description 6
- WBGKWQHBNHJJPZ-LECWWXJVSA-N desonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O WBGKWQHBNHJJPZ-LECWWXJVSA-N 0.000 claims description 6
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 6
- 229960001347 fluocinolone acetonide Drugs 0.000 claims description 6
- FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 claims description 6
- 229960000785 fluocinonide Drugs 0.000 claims description 6
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims description 6
- GGXMRPUKBWXVHE-MIHLVHIWSA-N halometasone Chemical compound C1([C@@H](F)C2)=CC(=O)C(Cl)=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]2(C)C[C@@H]1O GGXMRPUKBWXVHE-MIHLVHIWSA-N 0.000 claims description 6
- 229960002475 halometasone Drugs 0.000 claims description 6
- 230000002949 hemolytic effect Effects 0.000 claims description 6
- 229960001067 hydrocortisone acetate Drugs 0.000 claims description 6
- 208000027866 inflammatory disease Diseases 0.000 claims description 6
- 206010025135 lupus erythematosus Diseases 0.000 claims description 6
- 201000001441 melanoma Diseases 0.000 claims description 6
- 229960004584 methylprednisolone Drugs 0.000 claims description 6
- 229960001664 mometasone Drugs 0.000 claims description 6
- QLIIKPVHVRXHRI-CXSFZGCWSA-N mometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CCl)(O)[C@@]1(C)C[C@@H]2O QLIIKPVHVRXHRI-CXSFZGCWSA-N 0.000 claims description 6
- 229940013982 octagam Drugs 0.000 claims description 6
- 201000010198 papillary carcinoma Diseases 0.000 claims description 6
- 208000003154 papilloma Diseases 0.000 claims description 6
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical class OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 claims description 6
- 229960005205 prednisolone Drugs 0.000 claims description 6
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- 102000005962 receptors Human genes 0.000 claims description 6
- 108020003175 receptors Proteins 0.000 claims description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 6
- TYFQFVWCELRYAO-UHFFFAOYSA-N suberic acid Chemical class OC(=O)CCCCCCC(O)=O TYFQFVWCELRYAO-UHFFFAOYSA-N 0.000 claims description 6
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 claims description 6
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 6
- 230000002792 vascular Effects 0.000 claims description 6
- 201000003076 Angiosarcoma Diseases 0.000 claims description 5
- 206010004146 Basal cell carcinoma Diseases 0.000 claims description 5
- 208000018084 Bone neoplasm Diseases 0.000 claims description 5
- 208000005243 Chondrosarcoma Diseases 0.000 claims description 5
- 102400000739 Corticotropin Human genes 0.000 claims description 5
- 201000008808 Fibrosarcoma Diseases 0.000 claims description 5
- 206010018370 Glomerulonephritis membranoproliferative Diseases 0.000 claims description 5
- 208000001258 Hemangiosarcoma Diseases 0.000 claims description 5
- 208000010159 IgA glomerulonephritis Diseases 0.000 claims description 5
- 206010021263 IgA nephropathy Diseases 0.000 claims description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 5
- 208000018142 Leiomyosarcoma Diseases 0.000 claims description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 5
- 208000004451 Membranoproliferative Glomerulonephritis Diseases 0.000 claims description 5
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 5
- 206010063837 Reperfusion injury Diseases 0.000 claims description 5
- 235000010443 alginic acid Nutrition 0.000 claims description 5
- 229920000615 alginic acid Chemical class 0.000 claims description 5
- 230000001363 autoimmune Effects 0.000 claims description 5
- 125000002393 azetidinyl group Chemical group 0.000 claims description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 5
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 5
- 208000002445 cystadenocarcinoma Diseases 0.000 claims description 5
- 229960003957 dexamethasone Drugs 0.000 claims description 5
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 5
- 229960004833 dexamethasone phosphate Drugs 0.000 claims description 5
- VQODGRNSFPNSQE-CXSFZGCWSA-N dexamethasone phosphate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)COP(O)(O)=O)(O)[C@@]1(C)C[C@@H]2O VQODGRNSFPNSQE-CXSFZGCWSA-N 0.000 claims description 5
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 5
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 5
- 229960000598 infliximab Drugs 0.000 claims description 5
- 208000017169 kidney disease Diseases 0.000 claims description 5
- 208000032839 leukemia Diseases 0.000 claims description 5
- 206010024627 liposarcoma Diseases 0.000 claims description 5
- 201000005202 lung cancer Diseases 0.000 claims description 5
- 208000020816 lung neoplasm Diseases 0.000 claims description 5
- 208000002780 macular degeneration Diseases 0.000 claims description 5
- 125000002757 morpholinyl group Chemical group 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 5
- 208000011580 syndromic disease Diseases 0.000 claims description 5
- 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 5
- 230000003582 thrombocytopenic effect Effects 0.000 claims description 5
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 claims description 4
- VQFKFAKEUMHBLV-BYSUZVQFSA-N 1-O-(alpha-D-galactosyl)-N-hexacosanoylphytosphingosine Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCC(=O)N[C@H]([C@H](O)[C@H](O)CCCCCCCCCCCCCC)CO[C@H]1O[C@H](CO)[C@H](O)[C@H](O)[C@H]1O VQFKFAKEUMHBLV-BYSUZVQFSA-N 0.000 claims description 4
- MUSGYEMSJUFFHT-UWABRSFTSA-N 2-[(4R,7S,10S,13S,19S,22S,25S,28S,31S,34R)-34-[[(2S,3S)-2-[[(2R)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-3-methylpentanoyl]amino]-4-[[(2S,3S)-1-amino-3-methyl-1-oxopentan-2-yl]-methylcarbamoyl]-25-(3-amino-3-oxopropyl)-7-(3-carbamimidamidopropyl)-10-(1H-imidazol-5-ylmethyl)-19-(1H-indol-3-ylmethyl)-13,17-dimethyl-28-[(1-methylindol-3-yl)methyl]-6,9,12,15,18,21,24,27,30,33-decaoxo-31-propan-2-yl-1,2-dithia-5,8,11,14,17,20,23,26,29,32-decazacyclopentatriacont-22-yl]acetic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@H](N)Cc1ccc(O)cc1)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc2cnc[nH]2)NC(=O)[C@H](C)NC(=O)CN(C)C(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](Cc2cn(C)c3ccccc23)NC(=O)[C@@H](NC1=O)C(C)C)C(=O)N(C)[C@@H]([C@@H](C)CC)C(N)=O MUSGYEMSJUFFHT-UWABRSFTSA-N 0.000 claims description 4
- MYIFLDFUXIHOCJ-UHFFFAOYSA-N 2-amino-2-[2-[2-chloro-4-(3-phenylmethoxyphenyl)sulfanylphenyl]ethyl]propane-1,3-diol;hydrochloride Chemical compound Cl.C1=C(Cl)C(CCC(CO)(CO)N)=CC=C1SC1=CC=CC(OCC=2C=CC=CC=2)=C1 MYIFLDFUXIHOCJ-UHFFFAOYSA-N 0.000 claims description 4
- 102100035277 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT6 Human genes 0.000 claims description 4
- 101710185185 4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT6 Proteins 0.000 claims description 4
- XGWFJBFNAQHLEF-UHFFFAOYSA-N 9-anthroic acid Chemical compound C1=CC=C2C(C(=O)O)=C(C=CC=C3)C3=CC2=C1 XGWFJBFNAQHLEF-UHFFFAOYSA-N 0.000 claims description 4
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
- 102100022712 Alpha-1-antitrypsin Human genes 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000023275 Autoimmune disease Diseases 0.000 claims description 4
- 108010028006 B-Cell Activating Factor Proteins 0.000 claims description 4
- 102100035875 C-C chemokine receptor type 5 Human genes 0.000 claims description 4
- 101710149870 C-C chemokine receptor type 5 Proteins 0.000 claims description 4
- 239000002947 C09CA04 - Irbesartan Substances 0.000 claims description 4
- 208000016323 C3 glomerulonephritis Diseases 0.000 claims description 4
- 208000029574 C3 glomerulopathy Diseases 0.000 claims description 4
- 102100031168 CCN family member 2 Human genes 0.000 claims description 4
- 229940123625 CD74 antagonist Drugs 0.000 claims description 4
- 229940122820 Cannabinoid receptor antagonist Drugs 0.000 claims description 4
- 229940123169 Caspase inhibitor Drugs 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 108010039419 Connective Tissue Growth Factor Proteins 0.000 claims description 4
- 229940121968 Cyclin-dependent kinase 2 inhibitor Drugs 0.000 claims description 4
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims description 4
- 229930105110 Cyclosporin A Natural products 0.000 claims description 4
- 108010036949 Cyclosporine Proteins 0.000 claims description 4
- 102000005927 Cysteine Proteases Human genes 0.000 claims description 4
- 108010005843 Cysteine Proteases Proteins 0.000 claims description 4
- 101710114790 Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims description 4
- 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 claims description 4
- 102100031334 Elongation factor 2 Human genes 0.000 claims description 4
- 241000283073 Equus caballus Species 0.000 claims description 4
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 4
- 108010071289 Factor XIII Proteins 0.000 claims description 4
- 102100028071 Fibroblast growth factor 7 Human genes 0.000 claims description 4
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 claims description 4
- 101710186840 Fucosyltransferase 6 Proteins 0.000 claims description 4
- 208000009329 Graft vs Host Disease Diseases 0.000 claims description 4
- 101150022655 HGF gene Proteins 0.000 claims description 4
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 claims description 4
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 claims description 4
- 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 claims description 4
- 101150030450 IRS1 gene Proteins 0.000 claims description 4
- 102000009490 IgG Receptors Human genes 0.000 claims description 4
- 108010073807 IgG Receptors Proteins 0.000 claims description 4
- PVHLMTREZMEJCG-GDTLVBQBSA-N Ile(5)-angiotensin II (1-7) Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 PVHLMTREZMEJCG-GDTLVBQBSA-N 0.000 claims description 4
- 102100022337 Integrin alpha-V Human genes 0.000 claims description 4
- 101710123022 Integrin alpha-V Proteins 0.000 claims description 4
- 102100033011 Integrin beta-6 Human genes 0.000 claims description 4
- 102000002227 Interferon Type I Human genes 0.000 claims description 4
- 108010014726 Interferon Type I Proteins 0.000 claims description 4
- 102000006992 Interferon-alpha Human genes 0.000 claims description 4
- 108010047761 Interferon-alpha Proteins 0.000 claims description 4
- 108010002350 Interleukin-2 Proteins 0.000 claims description 4
- 102000000588 Interleukin-2 Human genes 0.000 claims description 4
- 108010038453 Interleukin-2 Receptors Proteins 0.000 claims description 4
- 102000010789 Interleukin-2 Receptors Human genes 0.000 claims description 4
- 102100030703 Interleukin-22 Human genes 0.000 claims description 4
- 108010002616 Interleukin-5 Proteins 0.000 claims description 4
- 108090001005 Interleukin-6 Proteins 0.000 claims description 4
- 102000004889 Interleukin-6 Human genes 0.000 claims description 4
- 208000011200 Kawasaki disease Diseases 0.000 claims description 4
- 229940127171 LMB-2 Drugs 0.000 claims description 4
- 229940122696 MAP kinase inhibitor Drugs 0.000 claims description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 4
- HZQDCMWJEBCWBR-UUOKFMHZSA-N Mizoribine Chemical compound OC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 HZQDCMWJEBCWBR-UUOKFMHZSA-N 0.000 claims description 4
- 208000010718 Multiple Organ Failure Diseases 0.000 claims description 4
- 101100119865 Mus musculus Fcrla gene Proteins 0.000 claims description 4
- 102100033341 N-acetylmannosamine kinase Human genes 0.000 claims description 4
- 108010029147 N-acylmannosamine kinase Proteins 0.000 claims description 4
- 102100034925 P-selectin glycoprotein ligand 1 Human genes 0.000 claims description 4
- 108010054395 P-selectin ligand protein Proteins 0.000 claims description 4
- 108010077519 Peptide Elongation Factor 2 Proteins 0.000 claims description 4
- 229940079156 Proteasome inhibitor Drugs 0.000 claims description 4
- 229940120013 Protein kinase C alpha inhibitor Drugs 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 206010040070 Septic Shock Diseases 0.000 claims description 4
- 108010091769 Shiga Toxin 1 Proteins 0.000 claims description 4
- 102000011011 Sphingosine 1-phosphate receptors Human genes 0.000 claims description 4
- 108050001083 Sphingosine 1-phosphate receptors Proteins 0.000 claims description 4
- 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 claims description 4
- 206010051379 Systemic Inflammatory Response Syndrome Diseases 0.000 claims description 4
- 108091008874 T cell receptors Proteins 0.000 claims description 4
- 102000016266 T-Cell Antigen Receptors Human genes 0.000 claims description 4
- 102100027208 T-cell antigen CD7 Human genes 0.000 claims description 4
- 101710193588 T-cell antigen CD7 Proteins 0.000 claims description 4
- 101710179381 T-cell differentiation antigen CD6 Proteins 0.000 claims description 4
- 102100025131 T-cell differentiation antigen CD6 Human genes 0.000 claims description 4
- 108700002718 TACI receptor-IgG Fc fragment fusion Proteins 0.000 claims description 4
- 101150080074 TP53 gene Proteins 0.000 claims description 4
- 102000006601 Thymidine Kinase Human genes 0.000 claims description 4
- 108020004440 Thymidine kinase Proteins 0.000 claims description 4
- QHMBSVQNZZTUGM-UHFFFAOYSA-N Trans-Cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CCC(C)=C1 QHMBSVQNZZTUGM-UHFFFAOYSA-N 0.000 claims description 4
- 206010052779 Transplant rejections Diseases 0.000 claims description 4
- 102000004243 Tubulin Human genes 0.000 claims description 4
- 108090000704 Tubulin Proteins 0.000 claims description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 4
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 4
- 102100036922 Tumor necrosis factor ligand superfamily member 13B Human genes 0.000 claims description 4
- 102100040403 Tumor necrosis factor receptor superfamily member 6 Human genes 0.000 claims description 4
- JNWFIPVDEINBAI-UHFFFAOYSA-N [5-hydroxy-4-[4-(1-methylindol-5-yl)-5-oxo-1H-1,2,4-triazol-3-yl]-2-propan-2-ylphenyl] dihydrogen phosphate Chemical compound C1=C(OP(O)(O)=O)C(C(C)C)=CC(C=2N(C(=O)NN=2)C=2C=C3C=CN(C)C3=CC=2)=C1O JNWFIPVDEINBAI-UHFFFAOYSA-N 0.000 claims description 4
- 229960003697 abatacept Drugs 0.000 claims description 4
- 239000002487 adenosine deaminase inhibitor Substances 0.000 claims description 4
- 229960005310 aldesleukin Drugs 0.000 claims description 4
- 108700025316 aldesleukin Proteins 0.000 claims description 4
- 229960000548 alemtuzumab Drugs 0.000 claims description 4
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 claims description 4
- 229940024142 alpha 1-antitrypsin Drugs 0.000 claims description 4
- 108010021281 angiotensin I (1-7) Proteins 0.000 claims description 4
- 230000001494 anti-thymocyte effect Effects 0.000 claims description 4
- 229950004993 asunercept Drugs 0.000 claims description 4
- 229950009925 atacicept Drugs 0.000 claims description 4
- 229960004669 basiliximab Drugs 0.000 claims description 4
- 229960005347 belatacept Drugs 0.000 claims description 4
- 229960003270 belimumab Drugs 0.000 claims description 4
- 229960001102 betamethasone dipropionate Drugs 0.000 claims description 4
- CIWBQSYVNNPZIQ-XYWKZLDCSA-N betamethasone dipropionate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CIWBQSYVNNPZIQ-XYWKZLDCSA-N 0.000 claims description 4
- 229950006991 betamethasone phosphate Drugs 0.000 claims description 4
- VQODGRNSFPNSQE-DVTGEIKXSA-N betamethasone phosphate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COP(O)(O)=O)(O)[C@@]1(C)C[C@@H]2O VQODGRNSFPNSQE-DVTGEIKXSA-N 0.000 claims description 4
- SNHRLVCMMWUAJD-SUYDQAKGSA-N betamethasone valerate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(OC(=O)CCCC)[C@@]1(C)C[C@@H]2O SNHRLVCMMWUAJD-SUYDQAKGSA-N 0.000 claims description 4
- 229960004311 betamethasone valerate Drugs 0.000 claims description 4
- 229960001467 bortezomib Drugs 0.000 claims description 4
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims description 4
- 229960000455 brentuximab vedotin Drugs 0.000 claims description 4
- QHMBSVQNZZTUGM-ZWKOTPCHSA-N cannabidiol Chemical compound OC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)=C)CCC(C)=C1 QHMBSVQNZZTUGM-ZWKOTPCHSA-N 0.000 claims description 4
- 229950011318 cannabidiol Drugs 0.000 claims description 4
- ZTGXAWYVTLUPDT-UHFFFAOYSA-N cannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1C1C(C(C)=C)CC=C(C)C1 ZTGXAWYVTLUPDT-UHFFFAOYSA-N 0.000 claims description 4
- 239000003536 cannabinoid receptor antagonist Substances 0.000 claims description 4
- 229960001265 ciclosporin Drugs 0.000 claims description 4
- 108010084052 continuous erythropoietin receptor activator Proteins 0.000 claims description 4
- BMCQMVFGOVHVNG-TUFAYURCSA-N cortisol 17-butyrate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)CO)(OC(=O)CCC)[C@@]1(C)C[C@@H]2O BMCQMVFGOVHVNG-TUFAYURCSA-N 0.000 claims description 4
- 229930182912 cyclosporin Natural products 0.000 claims description 4
- 229960004120 defibrotide Drugs 0.000 claims description 4
- 230000008021 deposition Effects 0.000 claims description 4
- PCXRACLQFPRCBB-ZWKOTPCHSA-N dihydrocannabidiol Natural products OC1=CC(CCCCC)=CC(O)=C1[C@H]1[C@H](C(C)C)CCC(C)=C1 PCXRACLQFPRCBB-ZWKOTPCHSA-N 0.000 claims description 4
- UFIVEPVSAGBUSI-UHFFFAOYSA-N dihydroorotic acid Chemical compound OC(=O)C1CC(=O)NC(=O)N1 UFIVEPVSAGBUSI-UHFFFAOYSA-N 0.000 claims description 4
- 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 claims description 4
- 229960005167 everolimus Drugs 0.000 claims description 4
- 229940012444 factor xiii Drugs 0.000 claims description 4
- 208000024908 graft versus host disease Diseases 0.000 claims description 4
- 229960002706 gusperimus Drugs 0.000 claims description 4
- IDINUJSAMVOPCM-UHFFFAOYSA-N gusperimus Chemical compound NCCCNCCCCNC(=O)C(O)NC(=O)CCCCCCN=C(N)N IDINUJSAMVOPCM-UHFFFAOYSA-N 0.000 claims description 4
- 229940125926 hemoglobin modulator Drugs 0.000 claims description 4
- 229960001524 hydrocortisone butyrate Drugs 0.000 claims description 4
- 229940027941 immunoglobulin g Drugs 0.000 claims description 4
- 230000005764 inhibitory process Effects 0.000 claims description 4
- 229950007937 inolimomab Drugs 0.000 claims description 4
- 239000002348 inosinate dehydrogenase inhibitor Substances 0.000 claims description 4
- 108010021309 integrin beta6 Proteins 0.000 claims description 4
- 108010074109 interleukin-22 Proteins 0.000 claims description 4
- 229960002198 irbesartan Drugs 0.000 claims description 4
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 claims description 4
- 208000012947 ischemia reperfusion injury Diseases 0.000 claims description 4
- 229950003818 itolizumab Drugs 0.000 claims description 4
- 229960003648 ixazomib Drugs 0.000 claims description 4
- MXAYKZJJDUDWDS-LBPRGKRZSA-N ixazomib Chemical compound CC(C)C[C@@H](B(O)O)NC(=O)CNC(=O)C1=CC(Cl)=CC=C1Cl MXAYKZJJDUDWDS-LBPRGKRZSA-N 0.000 claims description 4
- 229960000681 leflunomide Drugs 0.000 claims description 4
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 claims description 4
- 229940121292 leronlimab Drugs 0.000 claims description 4
- 208000012804 lymphangiosarcoma Diseases 0.000 claims description 4
- 210000004698 lymphocyte Anatomy 0.000 claims description 4
- 229940124302 mTOR inhibitor Drugs 0.000 claims description 4
- 230000022275 macrophage chemotaxis Effects 0.000 claims description 4
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 claims description 4
- 229960001046 methoxy polyethylene glycol-epoetin beta Drugs 0.000 claims description 4
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 claims description 4
- 229950000844 mizoribine Drugs 0.000 claims description 4
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 claims description 4
- 208000029744 multiple organ dysfunction syndrome Diseases 0.000 claims description 4
- MOZRQQTUYAYCQT-FQEVSTJZSA-N n-[[(3s)-3-amino-1-(5-ethyl-7h-pyrrolo[2,3-d]pyrimidin-4-yl)pyrrolidin-3-yl]methyl]-2,4-difluorobenzamide Chemical compound C([C@]1(CCN(C1)C=1N=CN=C2NC=C(C=12)CC)N)NC(=O)C1=CC=C(F)C=C1F MOZRQQTUYAYCQT-FQEVSTJZSA-N 0.000 claims description 4
- 229960005027 natalizumab Drugs 0.000 claims description 4
- 208000027134 non-immunoglobulin-mediated membranoproliferative glomerulonephritis Diseases 0.000 claims description 4
- 201000008482 osteoarthritis Diseases 0.000 claims description 4
- 201000008968 osteosarcoma Diseases 0.000 claims description 4
- 229950002610 otelixizumab Drugs 0.000 claims description 4
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 4
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 claims description 4
- 108700025694 p53 Genes Proteins 0.000 claims description 4
- 229960005184 panobinostat Drugs 0.000 claims description 4
- 230000001717 pathogenic effect Effects 0.000 claims description 4
- 229960002340 pentostatin Drugs 0.000 claims description 4
- FPVKHBSQESCIEP-JQCXWYLXSA-N pentostatin Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(N=CNC[C@H]2O)=C2N=C1 FPVKHBSQESCIEP-JQCXWYLXSA-N 0.000 claims description 4
- 125000004193 piperazinyl group Chemical group 0.000 claims description 4
- 239000013612 plasmid Substances 0.000 claims description 4
- 239000003207 proteasome inhibitor Substances 0.000 claims description 4
- 210000003289 regulatory T cell Anatomy 0.000 claims description 4
- KQDRVXQXKZXMHP-LLVKDONJSA-N reparixin Chemical compound CC(C)CC1=CC=C([C@@H](C)C(=O)NS(C)(=O)=O)C=C1 KQDRVXQXKZXMHP-LLVKDONJSA-N 0.000 claims description 4
- 229950005650 reparixin Drugs 0.000 claims description 4
- 108010011655 saratin Proteins 0.000 claims description 4
- PLQRBFAACWRSKF-LJTMIZJLSA-M sodium;n-methyl-n-[(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl]carbamodithioate Chemical compound [Na+].[S-]C(=S)N(C)C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO PLQRBFAACWRSKF-LJTMIZJLSA-M 0.000 claims description 4
- 201000008753 synovium neoplasm Diseases 0.000 claims description 4
- 229940107955 thymoglobulin Drugs 0.000 claims description 4
- 229960003989 tocilizumab Drugs 0.000 claims description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Chemical class OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
- 229960005289 voclosporin Drugs 0.000 claims description 4
- 108010057559 voclosporin Proteins 0.000 claims description 4
- BICRTLVBTLFLRD-PTWUADNWSA-N voclosporin Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C=C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O BICRTLVBTLFLRD-PTWUADNWSA-N 0.000 claims description 4
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical class O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims description 3
- LKVFMOMQYXIFRK-KSVAIKAXSA-N (3S,6S,9S,12S,18S,21S,27S,30S,33S,36S,42R,47R,50S,53S,56S)-42-amino-3-(4-aminobutyl)-36-(3-amino-3-oxopropyl)-33-(3-carbamimidamidopropyl)-9,18,30-tris(2-carboxyethyl)-27-[(1R)-1-hydroxyethyl]-50-[(4-hydroxyphenyl)methyl]-53-(1H-indol-3-ylmethyl)-6,12-dimethyl-2,5,8,11,14,17,20,26,29,32,35,38,41,49,52,55-hexadecaoxo-44,45-dithia-1,4,7,10,13,16,19,25,28,31,34,37,40,48,51,54-hexadecazatricyclo[54.3.0.021,25]nonapentacontane-47-carboxylic acid Chemical compound C[C@@H](O)[C@@H]1NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@@H](N)CSSC[C@H](NC(=O)[C@H](Cc2ccc(O)cc2)NC(=O)[C@H](Cc2c[nH]c3ccccc23)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H]2CCCN2C1=O)C(O)=O LKVFMOMQYXIFRK-KSVAIKAXSA-N 0.000 claims description 3
- SCVHJVCATBPIHN-SJCJKPOMSA-N (3s)-3-[[(2s)-2-[[2-(2-tert-butylanilino)-2-oxoacetyl]amino]propanoyl]amino]-4-oxo-5-(2,3,5,6-tetrafluorophenoxy)pentanoic acid Chemical compound N([C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)COC=1C(=C(F)C=C(F)C=1F)F)C(=O)C(=O)NC1=CC=CC=C1C(C)(C)C SCVHJVCATBPIHN-SJCJKPOMSA-N 0.000 claims description 3
- WRFHGDPIDHPWIQ-UHFFFAOYSA-N 2-[4-[(2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-2-(ethoxymethyl)phenyl]-n-(4,5-dimethyl-1,2-oxazol-3-yl)benzenesulfonamide Chemical compound O=C1N(CC=2C=C(COCC)C(=CC=2)C=2C(=CC=CC=2)S(=O)(=O)NC=2C(=C(C)ON=2)C)C(CCCC)=NC21CCCC2 WRFHGDPIDHPWIQ-UHFFFAOYSA-N 0.000 claims description 3
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 claims description 3
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 claims description 3
- 229940013085 2-diethylaminoethanol Drugs 0.000 claims description 3
- HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 claims description 3
- 108010049501 AP301 peptide Proteins 0.000 claims description 3
- 239000004475 Arginine Substances 0.000 claims description 3
- 206010006417 Bronchial carcinoma Diseases 0.000 claims description 3
- 229940082465 CD30 antagonist Drugs 0.000 claims description 3
- 229940122739 Calcineurin inhibitor Drugs 0.000 claims description 3
- 101710192106 Calcineurin-binding protein cabin-1 Proteins 0.000 claims description 3
- 102100024123 Calcineurin-binding protein cabin-1 Human genes 0.000 claims description 3
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 3
- 108010067225 Cell Adhesion Molecules Proteins 0.000 claims description 3
- 102000016289 Cell Adhesion Molecules Human genes 0.000 claims description 3
- 229940105129 Chemotaxis inhibitor Drugs 0.000 claims description 3
- FBRAWBYQGRLCEK-AVVSTMBFSA-N Clobetasone butyrate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CCC)[C@@]1(C)CC2=O FBRAWBYQGRLCEK-AVVSTMBFSA-N 0.000 claims description 3
- 206010048832 Colon adenoma Diseases 0.000 claims description 3
- 206010011091 Coronary artery thrombosis Diseases 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 229940124186 Dehydrogenase inhibitor Drugs 0.000 claims description 3
- 206010012438 Dermatitis atopic Diseases 0.000 claims description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical class OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 3
- 229940087983 Erythropoietin receptor agonist Drugs 0.000 claims description 3
- 108010008165 Etanercept Proteins 0.000 claims description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 3
- 208000024869 Goodpasture syndrome Diseases 0.000 claims description 3
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 claims description 3
- 208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 3
- 208000032759 Hemolytic-Uremic Syndrome Diseases 0.000 claims description 3
- 101001081555 Homo sapiens Plasma protease C1 inhibitor Proteins 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- 229940121740 Inosine monophosphate dehydrogenase inhibitor Drugs 0.000 claims description 3
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 claims description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 3
- 239000005536 L01XE08 - Nilotinib Substances 0.000 claims description 3
- 102100030635 Leukocyte elastase inhibitor Human genes 0.000 claims description 3
- 101710091916 Leukocyte elastase inhibitor Proteins 0.000 claims description 3
- 206010025219 Lymphangioma Diseases 0.000 claims description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 3
- 239000004472 Lysine Substances 0.000 claims description 3
- 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 3
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 claims description 3
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 claims description 3
- 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 claims description 3
- 206010033645 Pancreatitis Diseases 0.000 claims description 3
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Chemical class OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims description 3
- 208000034541 Rare lymphatic malformation Diseases 0.000 claims description 3
- 206010038563 Reocclusion Diseases 0.000 claims description 3
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims description 3
- 206010039710 Scleroderma Diseases 0.000 claims description 3
- 201000010208 Seminoma Diseases 0.000 claims description 3
- 208000006011 Stroke Diseases 0.000 claims description 3
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 claims description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Chemical class [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 3
- 239000004012 Tofacitinib Substances 0.000 claims description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
- 206010052568 Urticaria chronic Diseases 0.000 claims description 3
- 206010053648 Vascular occlusion Diseases 0.000 claims description 3
- 208000008383 Wilms tumor Diseases 0.000 claims description 3
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical class O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 claims description 3
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical class O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 claims description 3
- 229960002459 alefacept Drugs 0.000 claims description 3
- 239000000783 alginic acid Chemical class 0.000 claims description 3
- 229960001126 alginic acid Drugs 0.000 claims description 3
- 150000004781 alginic acids Chemical class 0.000 claims description 3
- ILKJAFIWWBXGDU-MOGDOJJUSA-N amcinonide Chemical compound O([C@@]1([C@H](O2)C[C@@H]3[C@@]1(C[C@H](O)[C@]1(F)[C@@]4(C)C=CC(=O)C=C4CC[C@H]13)C)C(=O)COC(=O)C)C12CCCC1 ILKJAFIWWBXGDU-MOGDOJJUSA-N 0.000 claims description 3
- 229960003099 amcinonide Drugs 0.000 claims description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 3
- 208000006673 asthma Diseases 0.000 claims description 3
- 201000008937 atopic dermatitis Diseases 0.000 claims description 3
- 229960004965 begelomab Drugs 0.000 claims description 3
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 claims description 3
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 3
- 229940092714 benzenesulfonic acid Drugs 0.000 claims description 3
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 claims description 3
- 229960003237 betaine Drugs 0.000 claims description 3
- 208000003362 bronchogenic carcinoma Diseases 0.000 claims description 3
- 229960001948 caffeine Drugs 0.000 claims description 3
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims description 3
- 229960001838 canakinumab Drugs 0.000 claims description 3
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 3
- LPAUOXUZGSBGDU-STDDISTJSA-N chembl1096146 Chemical compound O=C1N(C=2C(=CC=CC=2)C)C(=N/CCC)/S\C1=C/C1=CC=C(OC[C@H](O)CO)C(Cl)=C1 LPAUOXUZGSBGDU-STDDISTJSA-N 0.000 claims description 3
- 239000002819 chemotaxis inhibitor Substances 0.000 claims description 3
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 3
- 229960001231 choline Drugs 0.000 claims description 3
- 208000024376 chronic urticaria Diseases 0.000 claims description 3
- 229940088949 cinryze Drugs 0.000 claims description 3
- CBGUOGMQLZIXBE-XGQKBEPLSA-N clobetasol propionate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CBGUOGMQLZIXBE-XGQKBEPLSA-N 0.000 claims description 3
- 229960004703 clobetasol propionate Drugs 0.000 claims description 3
- 229960005465 clobetasone butyrate Drugs 0.000 claims description 3
- 208000010247 contact dermatitis Diseases 0.000 claims description 3
- 208000002528 coronary thrombosis Diseases 0.000 claims description 3
- FZCHYNWYXKICIO-FZNHGJLXSA-N cortisol 17-valerate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)CO)(OC(=O)CCCC)[C@@]1(C)C[C@@H]2O FZCHYNWYXKICIO-FZNHGJLXSA-N 0.000 claims description 3
- PIBARDGJJAGJAJ-NQIIRXRSSA-N danicopan Chemical compound C(C)(=O)C1=NN(C2=CC=C(C=C12)C=1C=NC(=NC1)C)CC(=O)N1[C@@H](C[C@H](C1)F)C(=O)NC1=NC(=CC=C1)Br PIBARDGJJAGJAJ-NQIIRXRSSA-N 0.000 claims description 3
- 201000001981 dermatomyositis Diseases 0.000 claims description 3
- 206010012601 diabetes mellitus Diseases 0.000 claims description 3
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 claims description 3
- 206010013023 diphtheria Diseases 0.000 claims description 3
- 230000002526 effect on cardiovascular system Effects 0.000 claims description 3
- 229950000234 emricasan Drugs 0.000 claims description 3
- 229960000403 etanercept Drugs 0.000 claims description 3
- 229940125397 factor b inhibitor Drugs 0.000 claims description 3
- 206010016629 fibroma Diseases 0.000 claims description 3
- 229960000556 fingolimod Drugs 0.000 claims description 3
- KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 claims description 3
- 229960002650 fluprednidene acetate Drugs 0.000 claims description 3
- DEFOZIFYUBUHHU-IYQKUMFPSA-N fluprednidene acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1CC(=C)[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O DEFOZIFYUBUHHU-IYQKUMFPSA-N 0.000 claims description 3
- 229950004356 foralumab Drugs 0.000 claims description 3
- 239000001530 fumaric acid Chemical class 0.000 claims description 3
- 229960002442 glucosamine Drugs 0.000 claims description 3
- 229940097043 glucuronic acid Drugs 0.000 claims description 3
- 201000011066 hemangioma Diseases 0.000 claims description 3
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 claims description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 3
- 102000044507 human SERPING1 Human genes 0.000 claims description 3
- 239000002596 immunotoxin Substances 0.000 claims description 3
- 238000001990 intravenous administration Methods 0.000 claims description 3
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 3
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims description 3
- 201000010260 leiomyoma Diseases 0.000 claims description 3
- 239000003591 leukocyte elastase inhibitor Substances 0.000 claims description 3
- 239000011777 magnesium Substances 0.000 claims description 3
- 229960002510 mandelic acid Drugs 0.000 claims description 3
- 206010027191 meningioma Diseases 0.000 claims description 3
- 229960005108 mepolizumab Drugs 0.000 claims description 3
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 3
- 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 claims description 3
- 206010028417 myasthenia gravis Diseases 0.000 claims description 3
- 229940014456 mycophenolate Drugs 0.000 claims description 3
- 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 claims description 3
- 201000008026 nephroblastoma Diseases 0.000 claims description 3
- 229960001346 nilotinib Drugs 0.000 claims description 3
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 claims description 3
- 229950005751 ocrelizumab Drugs 0.000 claims description 3
- UVSMNLNDYGZFPF-UHFFFAOYSA-N pomalidomide Chemical compound O=C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O UVSMNLNDYGZFPF-UHFFFAOYSA-N 0.000 claims description 3
- 229960000688 pomalidomide Drugs 0.000 claims description 3
- 229950009275 ponesimod Drugs 0.000 claims description 3
- 230000002980 postoperative effect Effects 0.000 claims description 3
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 claims description 3
- 229960004919 procaine Drugs 0.000 claims description 3
- 235000019260 propionic acid Nutrition 0.000 claims description 3
- 150000003212 purines Chemical class 0.000 claims description 3
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 3
- 229940075993 receptor modulator Drugs 0.000 claims description 3
- 230000036303 septic shock Effects 0.000 claims description 3
- 229950008127 solnatide Drugs 0.000 claims description 3
- 229950002009 sparsentan Drugs 0.000 claims description 3
- 229960001967 tacrolimus Drugs 0.000 claims description 3
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 claims description 3
- 239000011975 tartaric acid Chemical class 0.000 claims description 3
- 235000002906 tartaric acid Nutrition 0.000 claims description 3
- 229950010127 teplizumab Drugs 0.000 claims description 3
- 229960004559 theobromine Drugs 0.000 claims description 3
- 229960001350 tofacitinib Drugs 0.000 claims description 3
- UJLAWZDWDVHWOW-YPMHNXCESA-N tofacitinib Chemical compound C[C@@H]1CCN(C(=O)CC#N)C[C@@H]1N(C)C1=NC=NC2=C1C=CN2 UJLAWZDWDVHWOW-YPMHNXCESA-N 0.000 claims description 3
- 206010044412 transitional cell carcinoma Diseases 0.000 claims description 3
- 230000000472 traumatic effect Effects 0.000 claims description 3
- 229950003873 triciribine Drugs 0.000 claims description 3
- HOGVTUZUJGHKPL-HTVVRFAVSA-N triciribine Chemical compound C=12C3=NC=NC=1N(C)N=C(N)C2=CN3[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O HOGVTUZUJGHKPL-HTVVRFAVSA-N 0.000 claims description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 3
- 229960000281 trometamol Drugs 0.000 claims description 3
- 208000022271 tubular adenoma Diseases 0.000 claims description 3
- 208000021331 vascular occlusion disease Diseases 0.000 claims description 3
- KTBSXLIQKWEBRB-UHFFFAOYSA-N 2-[1-[1-[3-fluoro-2-(trifluoromethyl)pyridine-4-carbonyl]piperidin-4-yl]-3-[4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]azetidin-3-yl]acetonitrile Chemical compound C1=CN=C(C(F)(F)F)C(F)=C1C(=O)N1CCC(N2CC(CC#N)(C2)N2N=CC(=C2)C=2C=3C=CNC=3N=CN=2)CC1 KTBSXLIQKWEBRB-UHFFFAOYSA-N 0.000 claims description 2
- 229940080778 Adenosine deaminase inhibitor Drugs 0.000 claims description 2
- 206010059245 Angiopathy Diseases 0.000 claims description 2
- 208000003343 Antiphospholipid Syndrome Diseases 0.000 claims description 2
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 2
- 239000002051 C09CA08 - Olmesartan medoxomil Substances 0.000 claims description 2
- 102100024217 CAMPATH-1 antigen Human genes 0.000 claims description 2
- 108010065524 CD52 Antigen Proteins 0.000 claims description 2
- 229940124111 CD52 antagonist Drugs 0.000 claims description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- 201000005262 Chondroma Diseases 0.000 claims description 2
- 239000005517 L01XE01 - Imatinib Substances 0.000 claims description 2
- 239000002177 L01XE27 - Ibrutinib Substances 0.000 claims description 2
- 208000004852 Lung Injury Diseases 0.000 claims description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 2
- 208000026072 Motor neurone disease Diseases 0.000 claims description 2
- 208000034486 Multi-organ failure Diseases 0.000 claims description 2
- 208000012902 Nervous system disease Diseases 0.000 claims description 2
- UQGKUQLKSCSZGY-UHFFFAOYSA-N Olmesartan medoxomil Chemical compound C=1C=C(C=2C(=CC=CC=2)C2=NNN=N2)C=CC=1CN1C(CCC)=NC(C(C)(C)O)=C1C(=O)OCC=1OC(=O)OC=1C UQGKUQLKSCSZGY-UHFFFAOYSA-N 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 108090000315 Protein Kinase C Proteins 0.000 claims description 2
- 102000003923 Protein Kinase C Human genes 0.000 claims description 2
- 206010069363 Traumatic lung injury Diseases 0.000 claims description 2
- 206010046851 Uveitis Diseases 0.000 claims description 2
- 208000000208 Wet Macular Degeneration Diseases 0.000 claims description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 230000004913 activation Effects 0.000 claims description 2
- 201000000028 adult respiratory distress syndrome Diseases 0.000 claims description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 2
- 235000010233 benzoic acid Nutrition 0.000 claims description 2
- 229960005354 betamethasone sodium phosphate Drugs 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
- 208000015114 central nervous system disease Diseases 0.000 claims description 2
- 229960004106 citric acid Drugs 0.000 claims description 2
- 229950005309 fostamatinib Drugs 0.000 claims description 2
- GKDRMWXFWHEQQT-UHFFFAOYSA-N fostamatinib Chemical compound COC1=C(OC)C(OC)=CC(NC=2N=C(NC=3N=C4N(COP(O)(O)=O)C(=O)C(C)(C)OC4=CC=3)C(F)=CN=2)=C1 GKDRMWXFWHEQQT-UHFFFAOYSA-N 0.000 claims description 2
- 210000003494 hepatocyte Anatomy 0.000 claims description 2
- 229960001507 ibrutinib Drugs 0.000 claims description 2
- XYFPWWZEPKGCCK-GOSISDBHSA-N ibrutinib Chemical compound C1=2C(N)=NC=NC=2N([C@H]2CN(CCC2)C(=O)C=C)N=C1C(C=C1)=CC=C1OC1=CC=CC=C1 XYFPWWZEPKGCCK-GOSISDBHSA-N 0.000 claims description 2
- 229960002411 imatinib Drugs 0.000 claims description 2
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims description 2
- 229950001890 itacitinib Drugs 0.000 claims description 2
- 231100000515 lung injury Toxicity 0.000 claims description 2
- 229910052749 magnesium Inorganic materials 0.000 claims description 2
- 208000005264 motor neuron disease Diseases 0.000 claims description 2
- 230000001613 neoplastic effect Effects 0.000 claims description 2
- 229960001199 olmesartan medoxomil Drugs 0.000 claims description 2
- 239000011591 potassium Substances 0.000 claims description 2
- 229910052700 potassium Inorganic materials 0.000 claims description 2
- 229940044601 receptor agonist Drugs 0.000 claims description 2
- 239000000018 receptor agonist Substances 0.000 claims description 2
- 229960001367 tartaric acid Drugs 0.000 claims description 2
- 229940116879 thymocyte immunoglobulin Drugs 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- 108010012236 Chemokines Proteins 0.000 claims 2
- 102000019034 Chemokines Human genes 0.000 claims 2
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 claims 2
- 102000015696 Interleukins Human genes 0.000 claims 2
- 108010063738 Interleukins Proteins 0.000 claims 2
- 150000001656 butanoic acid esters Chemical class 0.000 claims 2
- 229940121372 histone deacetylase inhibitor Drugs 0.000 claims 2
- 239000003276 histone deacetylase inhibitor Substances 0.000 claims 2
- 229940047122 interleukins Drugs 0.000 claims 2
- 229950008814 momelotinib Drugs 0.000 claims 2
- ZVHNDZWQTBEVRY-UHFFFAOYSA-N momelotinib Chemical compound C1=CC(C(NCC#N)=O)=CC=C1C1=CC=NC(NC=2C=CC(=CC=2)N2CCOCC2)=N1 ZVHNDZWQTBEVRY-UHFFFAOYSA-N 0.000 claims 2
- FWZRWHZDXBDTFK-ZHACJKMWSA-N panobinostat Chemical compound CC1=NC2=CC=C[CH]C2=C1CCNCC1=CC=C(\C=C\C(=O)NO)C=C1 FWZRWHZDXBDTFK-ZHACJKMWSA-N 0.000 claims 2
- 230000035755 proliferation Effects 0.000 claims 2
- 101710088194 Dehydrogenase Proteins 0.000 claims 1
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims 1
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 claims 1
- 108010028275 Leukocyte Elastase Proteins 0.000 claims 1
- 102100033174 Neutrophil elastase Human genes 0.000 claims 1
- 239000005480 Olmesartan Substances 0.000 claims 1
- 235000009037 Panicum miliaceum subsp. ruderale Nutrition 0.000 claims 1
- 208000000733 Paroxysmal Hemoglobinuria Diseases 0.000 claims 1
- 102100036050 Phosphatidylinositol N-acetylglucosaminyltransferase subunit A Human genes 0.000 claims 1
- 208000037062 Polyps Diseases 0.000 claims 1
- 102000001253 Protein Kinase Human genes 0.000 claims 1
- 208000021386 Sjogren Syndrome Diseases 0.000 claims 1
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 claims 1
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims 1
- 229940126317 angiotensin II receptor antagonist Drugs 0.000 claims 1
- 235000013527 bean curd Nutrition 0.000 claims 1
- PLCQGRYPOISRTQ-LWCNAHDDSA-L betamethasone sodium phosphate Chemical compound [Na+].[Na+].C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COP([O-])([O-])=O)(O)[C@@]1(C)C[C@@H]2O PLCQGRYPOISRTQ-LWCNAHDDSA-L 0.000 claims 1
- 244000022185 broomcorn panic Species 0.000 claims 1
- 229950001565 clazakizumab Drugs 0.000 claims 1
- 229960002923 denileukin diftitox Drugs 0.000 claims 1
- 208000011325 dry age related macular degeneration Diseases 0.000 claims 1
- 150000002168 ethanoic acid esters Chemical class 0.000 claims 1
- 208000019622 heart disease Diseases 0.000 claims 1
- 150000002400 hexanoic acid esters Chemical class 0.000 claims 1
- 230000002757 inflammatory effect Effects 0.000 claims 1
- 229940043355 kinase inhibitor Drugs 0.000 claims 1
- 229940015638 narsoplimab Drugs 0.000 claims 1
- 229960005117 olmesartan Drugs 0.000 claims 1
- VTRAEEWXHOVJFV-UHFFFAOYSA-N olmesartan Chemical compound CCCC1=NC(C(C)(C)O)=C(C(O)=O)N1CC1=CC=C(C=2C(=CC=CC=2)C=2NN=NN=2)C=C1 VTRAEEWXHOVJFV-UHFFFAOYSA-N 0.000 claims 1
- 201000003045 paroxysmal nocturnal hemoglobinuria Diseases 0.000 claims 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims 1
- 208000004333 pleomorphic adenoma Diseases 0.000 claims 1
- 108060006633 protein kinase Proteins 0.000 claims 1
- 238000007920 subcutaneous administration Methods 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 106
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 77
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 42
- 239000000243 solution Substances 0.000 description 39
- 125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 37
- 235000019439 ethyl acetate Nutrition 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 32
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 30
- 239000000203 mixture Substances 0.000 description 28
- 239000000460 chlorine Substances 0.000 description 27
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 26
- 230000015572 biosynthetic process Effects 0.000 description 23
- 238000003786 synthesis reaction Methods 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 238000010898 silica gel chromatography Methods 0.000 description 22
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 21
- 239000012043 crude product Substances 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 20
- BVOCPVIXARZNQN-UHFFFAOYSA-N nipecotamide Chemical compound NC(=O)C1CCCNC1 BVOCPVIXARZNQN-UHFFFAOYSA-N 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 238000011282 treatment Methods 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 125000005842 heteroatom Chemical group 0.000 description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 12
- 125000001072 heteroaryl group Chemical group 0.000 description 11
- 229940079593 drug Drugs 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 229910052760 oxygen Inorganic materials 0.000 description 9
- 229910052717 sulfur Inorganic materials 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 7
- GDZPTKXMNRKYMS-YZNIXAGQSA-N (2r,3s)-2-[4-(cyclopentylamino)phenyl]-1-(2-fluoro-6-methylbenzoyl)-n-[4-(hydroxymethyl)-3-(trifluoromethyl)phenyl]piperidine-3-carboxamide Chemical compound CC1=CC=CC(F)=C1C(=O)N1[C@@H](C=2C=CC(NC3CCCC3)=CC=2)[C@@H](C(=O)NC=2C=C(C(CO)=CC=2)C(F)(F)F)CCC1 GDZPTKXMNRKYMS-YZNIXAGQSA-N 0.000 description 6
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 6
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 6
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 208000007536 Thrombosis Diseases 0.000 description 6
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 239000000796 flavoring agent Substances 0.000 description 6
- 125000004404 heteroalkyl group Chemical group 0.000 description 6
- 150000002430 hydrocarbons Chemical group 0.000 description 6
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 description 6
- 229920000642 polymer Polymers 0.000 description 6
- 210000002966 serum Anatomy 0.000 description 6
- 239000003765 sweetening agent Substances 0.000 description 6
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 5
- 239000007821 HATU Substances 0.000 description 5
- 206010064930 age-related macular degeneration Diseases 0.000 description 5
- 125000003342 alkenyl group Chemical group 0.000 description 5
- 125000000304 alkynyl group Chemical group 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 210000003169 central nervous system Anatomy 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000000839 emulsion Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 235000013355 food flavoring agent Nutrition 0.000 description 5
- 235000003599 food sweetener Nutrition 0.000 description 5
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 5
- 230000000155 isotopic effect Effects 0.000 description 5
- 231100000252 nontoxic Toxicity 0.000 description 5
- 230000003000 nontoxic effect Effects 0.000 description 5
- 238000004806 packaging method and process Methods 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 230000002285 radioactive effect Effects 0.000 description 5
- 159000000000 sodium salts Chemical class 0.000 description 5
- 125000004434 sulfur atom Chemical group 0.000 description 5
- 239000000375 suspending agent Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 208000030507 AIDS Diseases 0.000 description 4
- 208000033116 Asbestos intoxication Diseases 0.000 description 4
- 102100022718 Atypical chemokine receptor 2 Human genes 0.000 description 4
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 4
- 102100025074 C-C chemokine receptor-like 2 Human genes 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 4
- 206010009944 Colon cancer Diseases 0.000 description 4
- ITRJWOMZKQRYTA-RFZYENFJSA-N Cortisone acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)CC2=O ITRJWOMZKQRYTA-RFZYENFJSA-N 0.000 description 4
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- 101000678892 Homo sapiens Atypical chemokine receptor 2 Proteins 0.000 description 4
- 101000851370 Homo sapiens Tumor necrosis factor receptor superfamily member 9 Proteins 0.000 description 4
- 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 description 4
- 102000017578 LAG3 Human genes 0.000 description 4
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 4
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 239000002202 Polyethylene glycol Substances 0.000 description 4
- 206010060862 Prostate cancer Diseases 0.000 description 4
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 206010041067 Small cell lung cancer Diseases 0.000 description 4
- 208000005718 Stomach Neoplasms Diseases 0.000 description 4
- 102100036856 Tumor necrosis factor receptor superfamily member 9 Human genes 0.000 description 4
- 102100038282 V-type immunoglobulin domain-containing suppressor of T-cell activation Human genes 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 239000007900 aqueous suspension Substances 0.000 description 4
- 206010003441 asbestosis Diseases 0.000 description 4
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
- 208000029742 colonic neoplasm Diseases 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- 239000007859 condensation product Substances 0.000 description 4
- ALEXXDVDDISNDU-JZYPGELDSA-N cortisol 21-acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O ALEXXDVDDISNDU-JZYPGELDSA-N 0.000 description 4
- 239000002270 dispersing agent Substances 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000000132 electrospray ionisation Methods 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 206010017758 gastric cancer Diseases 0.000 description 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 230000001861 immunosuppressant effect Effects 0.000 description 4
- 108020004201 indoleamine 2,3-dioxygenase Proteins 0.000 description 4
- 102000006639 indoleamine 2,3-dioxygenase Human genes 0.000 description 4
- 210000000265 leukocyte Anatomy 0.000 description 4
- 239000002207 metabolite Substances 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000002953 preparative HPLC Methods 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 208000000587 small cell lung carcinoma Diseases 0.000 description 4
- 201000011549 stomach cancer Diseases 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 239000000080 wetting agent Substances 0.000 description 4
- 244000215068 Acacia senegal Species 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 229920000084 Gum arabic Polymers 0.000 description 3
- 208000031886 HIV Infections Diseases 0.000 description 3
- 208000037357 HIV infectious disease Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 3
- 235000019483 Peanut oil Nutrition 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- 239000000205 acacia gum Substances 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- CGLRXKACBSXHIU-UHFFFAOYSA-N chloromethyl carbamate Chemical compound NC(=O)OCCl CGLRXKACBSXHIU-UHFFFAOYSA-N 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000010253 intravenous injection Methods 0.000 description 3
- ZCYVEMRRCGMTRW-YPZZEJLDSA-N iodine-125 Chemical compound [125I] ZCYVEMRRCGMTRW-YPZZEJLDSA-N 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 229940057995 liquid paraffin Drugs 0.000 description 3
- 244000144972 livestock Species 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 208000031225 myocardial ischemia Diseases 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 239000000312 peanut oil Substances 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000007901 soft capsule Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 2
- QUPFKBITVLIQNA-KPKJPENVSA-N (5e)-2-sulfanylidene-5-[[5-[3-(trifluoromethyl)phenyl]furan-2-yl]methylidene]-1,3-thiazolidin-4-one Chemical compound FC(F)(F)C1=CC=CC(C=2OC(\C=C\3C(NC(=S)S/3)=O)=CC=2)=C1 QUPFKBITVLIQNA-KPKJPENVSA-N 0.000 description 2
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 2
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
- ZIMLRKWQDLVPEK-UHFFFAOYSA-N 1-[4-(4-chloro-3-methoxyphenyl)piperazin-1-yl]-2-[3-(1H-imidazol-2-yl)pyrazolo[3,4-b]pyridin-1-yl]ethanone Chemical compound C1=C(Cl)C(OC)=CC(N2CCN(CC2)C(=O)CN2C3=NC=CC=C3C(C=3NC=CN=3)=N2)=C1 ZIMLRKWQDLVPEK-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- VRPJIFMKZZEXLR-UHFFFAOYSA-N 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(O)=O VRPJIFMKZZEXLR-UHFFFAOYSA-N 0.000 description 2
- IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 102100022464 5'-nucleotidase Human genes 0.000 description 2
- 206010000830 Acute leukaemia Diseases 0.000 description 2
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
- 208000003200 Adenoma Diseases 0.000 description 2
- 206010001233 Adenoma benign Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000416162 Astragalus gummifer Species 0.000 description 2
- 102100022716 Atypical chemokine receptor 3 Human genes 0.000 description 2
- 102100029822 B- and T-lymphocyte attenuator Human genes 0.000 description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 2
- 208000003950 B-cell lymphoma Diseases 0.000 description 2
- 206010005003 Bladder cancer Diseases 0.000 description 2
- 206010005949 Bone cancer Diseases 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 206010006143 Brain stem glioma Diseases 0.000 description 2
- 206010006187 Breast cancer Diseases 0.000 description 2
- 208000026310 Breast neoplasm Diseases 0.000 description 2
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 2
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 2
- 102100024167 C-C chemokine receptor type 3 Human genes 0.000 description 2
- 101710149862 C-C chemokine receptor type 3 Proteins 0.000 description 2
- 102100037853 C-C chemokine receptor type 4 Human genes 0.000 description 2
- 101710149863 C-C chemokine receptor type 4 Proteins 0.000 description 2
- 102100036301 C-C chemokine receptor type 7 Human genes 0.000 description 2
- 102100036305 C-C chemokine receptor type 8 Human genes 0.000 description 2
- 102100028989 C-X-C chemokine receptor type 2 Human genes 0.000 description 2
- 102100028990 C-X-C chemokine receptor type 3 Human genes 0.000 description 2
- 102100025618 C-X-C chemokine receptor type 6 Human genes 0.000 description 2
- 101150013553 CD40 gene Proteins 0.000 description 2
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 2
- 229940045513 CTLA4 antagonist Drugs 0.000 description 2
- 108090000835 CX3C Chemokine Receptor 1 Proteins 0.000 description 2
- 102100039196 CX3C chemokine receptor 1 Human genes 0.000 description 2
- HFOBENSCBRZVSP-LKXGYXEUSA-N C[C@@H](O)[C@H](NC(=O)N[C@@H](CC(N)=O)c1nc(no1)[C@@H](N)CO)C(O)=O Chemical compound C[C@@H](O)[C@H](NC(=O)N[C@@H](CC(N)=O)c1nc(no1)[C@@H](N)CO)C(O)=O HFOBENSCBRZVSP-LKXGYXEUSA-N 0.000 description 2
- 101100463133 Caenorhabditis elegans pdl-1 gene Proteins 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 2
- 206010007953 Central nervous system lymphoma Diseases 0.000 description 2
- 206010008342 Cervix carcinoma Diseases 0.000 description 2
- 101710093674 Cyclic nucleotide-gated cation channel beta-1 Proteins 0.000 description 2
- 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 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 description 2
- 206010014733 Endometrial cancer Diseases 0.000 description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 description 2
- 241000283086 Equidae Species 0.000 description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 2
- 201000001342 Fallopian tube cancer Diseases 0.000 description 2
- 208000013452 Fallopian tube neoplasm Diseases 0.000 description 2
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical class [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 2
- 208000007465 Giant cell arteritis Diseases 0.000 description 2
- 102100034458 Hepatitis A virus cellular receptor 2 Human genes 0.000 description 2
- 101710083479 Hepatitis A virus cellular receptor 2 homolog Proteins 0.000 description 2
- 108010033040 Histones Proteins 0.000 description 2
- 208000017604 Hodgkin disease Diseases 0.000 description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 2
- 101000678236 Homo sapiens 5'-nucleotidase Proteins 0.000 description 2
- 101000678890 Homo sapiens Atypical chemokine receptor 3 Proteins 0.000 description 2
- 101000798902 Homo sapiens Atypical chemokine receptor 4 Proteins 0.000 description 2
- 101000864344 Homo sapiens B- and T-lymphocyte attenuator Proteins 0.000 description 2
- 101000777558 Homo sapiens C-C chemokine receptor type 10 Proteins 0.000 description 2
- 101000716068 Homo sapiens C-C chemokine receptor type 6 Proteins 0.000 description 2
- 101000716065 Homo sapiens C-C chemokine receptor type 7 Proteins 0.000 description 2
- 101000716063 Homo sapiens C-C chemokine receptor type 8 Proteins 0.000 description 2
- 101000716070 Homo sapiens C-C chemokine receptor type 9 Proteins 0.000 description 2
- 101000916050 Homo sapiens C-X-C chemokine receptor type 3 Proteins 0.000 description 2
- 101000856683 Homo sapiens C-X-C chemokine receptor type 6 Proteins 0.000 description 2
- 101000868279 Homo sapiens Leukocyte surface antigen CD47 Proteins 0.000 description 2
- 101000831007 Homo sapiens T-cell immunoreceptor with Ig and ITIM domains Proteins 0.000 description 2
- 101000596234 Homo sapiens T-cell surface protein tactile Proteins 0.000 description 2
- 101000801234 Homo sapiens Tumor necrosis factor receptor superfamily member 18 Proteins 0.000 description 2
- 102100027268 Interferon-stimulated gene 20 kDa protein Human genes 0.000 description 2
- 102000003777 Interleukin-1 beta Human genes 0.000 description 2
- 108090000193 Interleukin-1 beta Proteins 0.000 description 2
- 108010018951 Interleukin-8B Receptors Proteins 0.000 description 2
- 102000002698 KIR Receptors Human genes 0.000 description 2
- 108010043610 KIR Receptors Proteins 0.000 description 2
- 101150069255 KLRC1 gene Proteins 0.000 description 2
- 208000007766 Kaposi sarcoma Diseases 0.000 description 2
- 208000008839 Kidney Neoplasms Diseases 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- 125000000635 L-ornithyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C([H])([H])C(N([H])[H])([H])[H] 0.000 description 2
- 101150030213 Lag3 gene Proteins 0.000 description 2
- 102100032913 Leukocyte surface antigen CD47 Human genes 0.000 description 2
- 206010024612 Lipoma Diseases 0.000 description 2
- 206010052178 Lymphocytic lymphoma Diseases 0.000 description 2
- 101100404845 Macaca mulatta NKG2A gene Proteins 0.000 description 2
- 102100028198 Macrophage colony-stimulating factor 1 receptor Human genes 0.000 description 2
- 101710150918 Macrophage colony-stimulating factor 1 receptor Proteins 0.000 description 2
- 208000032271 Malignant tumor of penis Diseases 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 208000034578 Multiple myelomas Diseases 0.000 description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 2
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
- 102100022682 NKG2-A/NKG2-B type II integral membrane protein Human genes 0.000 description 2
- BVMWIXWOIGJRGE-UHFFFAOYSA-N NP(O)=O Chemical compound NP(O)=O BVMWIXWOIGJRGE-UHFFFAOYSA-N 0.000 description 2
- 208000001894 Nasopharyngeal Neoplasms Diseases 0.000 description 2
- 206010061306 Nasopharyngeal cancer Diseases 0.000 description 2
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 2
- 206010033128 Ovarian cancer Diseases 0.000 description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- 208000000821 Parathyroid Neoplasms Diseases 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 208000002471 Penile Neoplasms Diseases 0.000 description 2
- 206010034299 Penile cancer Diseases 0.000 description 2
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 2
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 2
- 201000005746 Pituitary adenoma Diseases 0.000 description 2
- 206010061538 Pituitary tumour benign Diseases 0.000 description 2
- 206010035226 Plasma cell myeloma Diseases 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 229920000954 Polyglycolide Polymers 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 208000015634 Rectal Neoplasms Diseases 0.000 description 2
- 206010038389 Renal cancer Diseases 0.000 description 2
- 208000000453 Skin Neoplasms Diseases 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 208000021712 Soft tissue sarcoma Diseases 0.000 description 2
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 101100215487 Sus scrofa ADRA2A gene Proteins 0.000 description 2
- 229940126547 T-cell immunoglobulin mucin-3 Drugs 0.000 description 2
- 102100024834 T-cell immunoreceptor with Ig and ITIM domains Human genes 0.000 description 2
- 206010042971 T-cell lymphoma Diseases 0.000 description 2
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 2
- 102100035268 T-cell surface protein tactile Human genes 0.000 description 2
- 208000001106 Takayasu Arteritis Diseases 0.000 description 2
- 208000024313 Testicular Neoplasms Diseases 0.000 description 2
- 206010057644 Testis cancer Diseases 0.000 description 2
- 208000033781 Thyroid carcinoma Diseases 0.000 description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 description 2
- 229920001615 Tragacanth Polymers 0.000 description 2
- 102100025946 Transforming growth factor beta activator LRRC32 Human genes 0.000 description 2
- 101710169732 Transforming growth factor beta activator LRRC32 Proteins 0.000 description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
- 102100033728 Tumor necrosis factor receptor superfamily member 18 Human genes 0.000 description 2
- 102100022153 Tumor necrosis factor receptor superfamily member 4 Human genes 0.000 description 2
- 101710165473 Tumor necrosis factor receptor superfamily member 4 Proteins 0.000 description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
- 208000023915 Ureteral Neoplasms Diseases 0.000 description 2
- 206010046392 Ureteric cancer Diseases 0.000 description 2
- 206010046431 Urethral cancer Diseases 0.000 description 2
- 206010046458 Urethral neoplasms Diseases 0.000 description 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 2
- 201000005969 Uveal melanoma Diseases 0.000 description 2
- KRNYOVHEKOBTEF-YUMQZZPRSA-N Val-Val Chemical compound CC(C)[C@H](N)C(=O)N[C@@H](C(C)C)C(O)=O KRNYOVHEKOBTEF-YUMQZZPRSA-N 0.000 description 2
- 206010047741 Vulval cancer Diseases 0.000 description 2
- 208000004354 Vulvar Neoplasms Diseases 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 208000024447 adrenal gland neoplasm Diseases 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000003863 ammonium salts Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 229960003852 atezolizumab Drugs 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 230000027455 binding Effects 0.000 description 2
- 229920002988 biodegradable polymer Polymers 0.000 description 2
- 239000004621 biodegradable polymer Substances 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 2
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 159000000007 calcium salts Chemical class 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 201000010881 cervical cancer Diseases 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 230000035605 chemotaxis Effects 0.000 description 2
- 239000007910 chewable tablet Substances 0.000 description 2
- 229940112822 chewing gum Drugs 0.000 description 2
- 235000015218 chewing gum Nutrition 0.000 description 2
- JYWJULGYGOLCGW-UHFFFAOYSA-N chloromethyl chloroformate Chemical compound ClCOC(Cl)=O JYWJULGYGOLCGW-UHFFFAOYSA-N 0.000 description 2
- 208000006990 cholangiocarcinoma Diseases 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 208000024207 chronic leukemia Diseases 0.000 description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 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
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 208000024558 digestive system cancer Diseases 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 208000037765 diseases and disorders Diseases 0.000 description 2
- 239000007911 effervescent powder Substances 0.000 description 2
- 201000004101 esophageal cancer Diseases 0.000 description 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 208000021045 exocrine pancreatic carcinoma Diseases 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 229960003238 fluprednidene Drugs 0.000 description 2
- IJJVMEJXYNJXOJ-UHFFFAOYSA-N fluquinconazole Chemical compound C=1C=C(Cl)C=C(Cl)C=1N1C(=O)C2=CC(F)=CC=C2N=C1N1C=NC=N1 IJJVMEJXYNJXOJ-UHFFFAOYSA-N 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 230000003325 follicular Effects 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 201000010231 gastrointestinal system cancer Diseases 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 208000005017 glioblastoma Diseases 0.000 description 2
- 238000003881 globally optimized alternating phase rectangular pulse Methods 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 239000007902 hard capsule Substances 0.000 description 2
- 201000010536 head and neck cancer Diseases 0.000 description 2
- 208000014829 head and neck neoplasm Diseases 0.000 description 2
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 125000004474 heteroalkylene group Chemical group 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 229940044173 iodine-125 Drugs 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 201000010982 kidney cancer Diseases 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 239000007937 lozenge Substances 0.000 description 2
- 159000000003 magnesium salts Chemical class 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 208000029559 malignant endocrine neoplasm Diseases 0.000 description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
- 208000020984 malignant renal pelvis neoplasm Diseases 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- XXNZVJWJWMVONK-UHFFFAOYSA-N methyl 2-[(2-aminoacetyl)amino]acetate Chemical compound COC(=O)CNC(=O)CN XXNZVJWJWMVONK-UHFFFAOYSA-N 0.000 description 2
- XXFWNVBCLRIKNP-UHFFFAOYSA-N methyl 3-[(4-methylpiperazin-1-yl)methyl]benzoate Chemical compound COC(=O)C1=CC=CC(CN2CCN(C)CC2)=C1 XXFWNVBCLRIKNP-UHFFFAOYSA-N 0.000 description 2
- KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 208000025402 neoplasm of esophagus Diseases 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 229960003301 nivolumab Drugs 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 2
- 201000002528 pancreatic cancer Diseases 0.000 description 2
- 201000008129 pancreatic ductal adenocarcinoma Diseases 0.000 description 2
- FPOHNWQLNRZRFC-ZHACJKMWSA-N panobinostat Chemical compound CC=1NC2=CC=CC=C2C=1CCNCC1=CC=C(\C=C\C(=O)NO)C=C1 FPOHNWQLNRZRFC-ZHACJKMWSA-N 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 201000003913 parathyroid carcinoma Diseases 0.000 description 2
- 208000017954 parathyroid gland carcinoma Diseases 0.000 description 2
- 239000004031 partial agonist Substances 0.000 description 2
- 229960002621 pembrolizumab Drugs 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 208000021310 pituitary gland adenoma Diseases 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 125000003367 polycyclic group Chemical group 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 239000004633 polyglycolic acid Substances 0.000 description 2
- 239000004626 polylactic acid Substances 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 208000016800 primary central nervous system lymphoma Diseases 0.000 description 2
- UDEWPOVQBGFNGE-UHFFFAOYSA-N propyl benzoate Chemical compound CCCOC(=O)C1=CC=CC=C1 UDEWPOVQBGFNGE-UHFFFAOYSA-N 0.000 description 2
- 201000008158 rapidly progressive glomerulonephritis Diseases 0.000 description 2
- 206010038038 rectal cancer Diseases 0.000 description 2
- 201000001275 rectum cancer Diseases 0.000 description 2
- 201000007444 renal pelvis carcinoma Diseases 0.000 description 2
- 125000006413 ring segment Chemical group 0.000 description 2
- 239000012047 saturated solution Substances 0.000 description 2
- 229950010077 sifalimumab Drugs 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 229940121497 sintilimab Drugs 0.000 description 2
- 201000000849 skin cancer Diseases 0.000 description 2
- 201000002314 small intestine cancer Diseases 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 239000001593 sorbitan monooleate Substances 0.000 description 2
- 235000011069 sorbitan monooleate Nutrition 0.000 description 2
- 229940035049 sorbitan monooleate Drugs 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 206010043207 temporal arteritis Diseases 0.000 description 2
- CBPNZQVSJQDFBE-HGVVHKDOSA-N temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CCC2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-HGVVHKDOSA-N 0.000 description 2
- 201000003120 testicular cancer Diseases 0.000 description 2
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 2
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 125000005309 thioalkoxy group Chemical group 0.000 description 2
- 201000002510 thyroid cancer Diseases 0.000 description 2
- 208000013077 thyroid gland carcinoma Diseases 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 229910052722 tritium Inorganic materials 0.000 description 2
- 230000005747 tumor angiogenesis Effects 0.000 description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 2
- 201000005112 urinary bladder cancer Diseases 0.000 description 2
- 206010046766 uterine cancer Diseases 0.000 description 2
- 206010046885 vaginal cancer Diseases 0.000 description 2
- 208000013139 vaginal neoplasm Diseases 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 201000005102 vulva cancer Diseases 0.000 description 2
- OEQMYDDVKDTAKY-GVYVVWIYSA-N (2R,3S)-2-[4-[[2-[(2-aminoacetyl)amino]acetyl]-cyclopentylamino]phenyl]-1-(2-fluoro-6-methylbenzoyl)-N-[4-methyl-3-(trifluoromethyl)phenyl]piperidine-3-carboxamide Chemical compound NCC(=O)NCC(=O)N(C1=CC=C(C=C1)[C@@H]1N(CCC[C@@H]1C(=O)NC1=CC(=C(C=C1)C)C(F)(F)F)C(C1=C(C=CC=C1C)F)=O)C1CCCC1 OEQMYDDVKDTAKY-GVYVVWIYSA-N 0.000 description 1
- WXDXRZLPFQCDSS-YZNIXAGQSA-N (2R,3S)-2-[4-[cyclopentyl(dichlorophosphoryl)amino]phenyl]-1-(2-fluoro-6-methylbenzoyl)-N-[4-methyl-3-(trifluoromethyl)phenyl]piperidine-3-carboxamide Chemical compound C1(CCCC1)N(C1=CC=C(C=C1)[C@@H]1N(CCC[C@@H]1C(=O)NC1=CC(=C(C=C1)C)C(F)(F)F)C(C1=C(C=CC=C1C)F)=O)P(=O)(Cl)Cl WXDXRZLPFQCDSS-YZNIXAGQSA-N 0.000 description 1
- WUIPSIRILAJGAG-DODOAAEWSA-N (2R,3S)-2-[4-[cyclopentyl-[2-(dimethylamino)acetyl]amino]phenyl]-1-(2-fluoro-6-methylbenzoyl)-N-[4-methyl-3-(trifluoromethyl)phenyl]piperidine-3-carboxamide Chemical compound C1(CCCC1)N(C1=CC=C(C=C1)[C@@H]1N(CCC[C@@H]1C(=O)NC1=CC(=C(C=C1)C)C(F)(F)F)C(C1=C(C=CC=C1C)F)=O)C(CN(C)C)=O WUIPSIRILAJGAG-DODOAAEWSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- RJOJSMIZZYHNQG-JTQLQIEISA-N (2s)-2,5-bis[(2-methylpropan-2-yl)oxycarbonylamino]pentanoic acid Chemical compound CC(C)(C)OC(=O)NCCC[C@@H](C(O)=O)NC(=O)OC(C)(C)C RJOJSMIZZYHNQG-JTQLQIEISA-N 0.000 description 1
- QVHJQCGUWFKTSE-YFKPBYRVSA-N (2s)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid Chemical compound OC(=O)[C@H](C)NC(=O)OC(C)(C)C QVHJQCGUWFKTSE-YFKPBYRVSA-N 0.000 description 1
- CANZBRDGRHNSGZ-NSHDSACASA-N (2s)-3-methyl-2-(phenylmethoxycarbonylamino)butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)OCC1=CC=CC=C1 CANZBRDGRHNSGZ-NSHDSACASA-N 0.000 description 1
- SZXBQTSZISFIAO-ZETCQYMHSA-N (2s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)OC(C)(C)C SZXBQTSZISFIAO-ZETCQYMHSA-N 0.000 description 1
- IBABAURSJXMCQJ-QWRGUYRKSA-N (2s)-3-methyl-2-[[(2s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)[C@H](C(C)C)NC(=O)OC(C)(C)C IBABAURSJXMCQJ-QWRGUYRKSA-N 0.000 description 1
- YXXMEXYAHMBYIU-VIFPVBQESA-N (2s)-3-methyl-2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]amino]butanoic acid Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CNC(=O)OC(C)(C)C YXXMEXYAHMBYIU-VIFPVBQESA-N 0.000 description 1
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- IBQYJXBNELPBNT-WXXKFALUSA-L (e)-but-2-enedioate;tetrabutylazanium Chemical compound [O-]C(=O)\C=C\C([O-])=O.CCCC[N+](CCCC)(CCCC)CCCC.CCCC[N+](CCCC)(CCCC)CCCC IBQYJXBNELPBNT-WXXKFALUSA-L 0.000 description 1
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 description 1
- 125000000196 1,4-pentadienyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])=C([H])[H] 0.000 description 1
- YHIIJNLSGULWAA-UHFFFAOYSA-N 1,4-thiazinane 1-oxide Chemical compound O=S1CCNCC1 YHIIJNLSGULWAA-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
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- FKASAVXZZLJTNX-UHFFFAOYSA-N 2-(dimethylamino)acetic acid;hydrochloride Chemical compound [Cl-].C[NH+](C)CC(O)=O FKASAVXZZLJTNX-UHFFFAOYSA-N 0.000 description 1
- BWPKSNMGVTYXQQ-VIFPVBQESA-N 2-[[(2s)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]acetic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C(C)C)C(=O)NCC(O)=O BWPKSNMGVTYXQQ-VIFPVBQESA-N 0.000 description 1
- HWBAHOVOSOAFLE-UHFFFAOYSA-N 2-[[2-[(2-methylpropan-2-yl)oxycarbonylamino]acetyl]amino]acetic acid Chemical compound CC(C)(C)OC(=O)NCC(=O)NCC(O)=O HWBAHOVOSOAFLE-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- ACQYZSFXPXXIHL-UHFFFAOYSA-N 2-phenylmethoxycarbonyl-3,4-dihydro-1h-isoquinoline-1-carboxylic acid Chemical compound C1CC2=CC=CC=C2C(C(=O)O)N1C(=O)OCC1=CC=CC=C1 ACQYZSFXPXXIHL-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 1
- ZPSJGADGUYYRKE-UHFFFAOYSA-N 2H-pyran-2-one Chemical compound O=C1C=CC=CO1 ZPSJGADGUYYRKE-UHFFFAOYSA-N 0.000 description 1
- PHHPZLTVQUTGEY-UHFFFAOYSA-N 3,4,5-trifluoro-2H-pyran-2-amine Chemical compound FC=1C(=C(C(OC=1)N)F)F PHHPZLTVQUTGEY-UHFFFAOYSA-N 0.000 description 1
- SMSCFZLMSBEZQU-UHFFFAOYSA-N 3-[(4-methylpiperazin-4-ium-1-yl)methyl]benzoate Chemical compound C1CN(C)CCN1CC1=CC=CC(C(O)=O)=C1 SMSCFZLMSBEZQU-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- JVQIKJMSUIMUDI-UHFFFAOYSA-N 3-pyrroline Chemical compound C1NCC=C1 JVQIKJMSUIMUDI-UHFFFAOYSA-N 0.000 description 1
- 108010082808 4-1BB Ligand Proteins 0.000 description 1
- GAMYYCRTACQSBR-UHFFFAOYSA-N 4-azabenzimidazole Chemical compound C1=CC=C2NC=NC2=N1 GAMYYCRTACQSBR-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 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 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 description 1
- 241001514645 Agonis Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 206010061424 Anal cancer Diseases 0.000 description 1
- 208000007860 Anus Neoplasms Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000037157 Azotemia Diseases 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- 206010009895 Colitis ischaemic Diseases 0.000 description 1
- 108090000056 Complement factor B Proteins 0.000 description 1
- 102000003712 Complement factor B Human genes 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 201000005171 Cystadenoma Diseases 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
- KZSNJWFQEVHDMF-SCSAIBSYSA-N D-valine Chemical compound CC(C)[C@@H](N)C(O)=O KZSNJWFQEVHDMF-SCSAIBSYSA-N 0.000 description 1
- 102000016680 Dioxygenases Human genes 0.000 description 1
- 108010028143 Dioxygenases Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 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
- 229910004373 HOAc Inorganic materials 0.000 description 1
- 206010018910 Haemolysis Diseases 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 206010023230 Joint stiffness Diseases 0.000 description 1
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 101100456571 Mus musculus Med12 gene Proteins 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 208000001738 Nervous System Trauma Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229910003849 O-Si Inorganic materials 0.000 description 1
- BLZLODDEPXSDCY-UHFFFAOYSA-N OC(=O)CC(O)=O.OC(=O)C1=CC=CC=C1 Chemical compound OC(=O)CC(O)=O.OC(=O)C1=CC=CC=C1 BLZLODDEPXSDCY-UHFFFAOYSA-N 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 102000004020 Oxygenases Human genes 0.000 description 1
- 108090000417 Oxygenases Proteins 0.000 description 1
- 229910003872 O—Si Inorganic materials 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229930182556 Polyacetal Natural products 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 208000006994 Precancerous Conditions Diseases 0.000 description 1
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 description 1
- 206010036711 Primary mediastinal large B-cell lymphomas Diseases 0.000 description 1
- 206010037394 Pulmonary haemorrhage Diseases 0.000 description 1
- 206010037549 Purpura Diseases 0.000 description 1
- 241001672981 Purpura Species 0.000 description 1
- 206010038910 Retinitis Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 201000009365 Thymic carcinoma Diseases 0.000 description 1
- 208000000728 Thymus Neoplasms Diseases 0.000 description 1
- DRUIESSIVFYOMK-UHFFFAOYSA-N Trichloroacetonitrile Chemical compound ClC(Cl)(Cl)C#N DRUIESSIVFYOMK-UHFFFAOYSA-N 0.000 description 1
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 1
- 102100032101 Tumor necrosis factor ligand superfamily member 9 Human genes 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
- YUYKBKHKQJORHD-UHFFFAOYSA-N [4-(hydroxymethyl)phenyl] dihydrogen phosphate Chemical compound OCC1=CC=C(OP(O)(O)=O)C=C1 YUYKBKHKQJORHD-UHFFFAOYSA-N 0.000 description 1
- RTYRETBTIYMFPH-DODOAAEWSA-N [4-[[(2R,3S)-2-[4-(cyclopentylamino)phenyl]-1-(2-fluoro-6-methylbenzoyl)piperidine-3-carbonyl]amino]-2-(trifluoromethyl)phenyl]methyl 2-(dimethylamino)acetate Chemical compound CN(CC(=O)OCC1=C(C=C(C=C1)NC(=O)[C@@H]1[C@@H](N(CCC1)C(C1=C(C=CC=C1C)F)=O)C1=CC=C(C=C1)NC1CCCC1)C(F)(F)F)C RTYRETBTIYMFPH-DODOAAEWSA-N 0.000 description 1
- JKGLEMVRRMJZFV-IRJOAOCJSA-N [4-[[(2R,3S)-2-[4-(cyclopentylamino)phenyl]-1-(2-fluoro-6-methylbenzoyl)piperidine-3-carbonyl]amino]-2-(trifluoromethyl)phenyl]methyl 2-[[(2S)-2-amino-3-methylbutanoyl]amino]acetate Chemical compound N[C@H](C(=O)NCC(=O)OCC1=C(C=C(C=C1)NC(=O)[C@@H]1[C@@H](N(CCC1)C(C1=C(C=CC=C1C)F)=O)C1=CC=C(C=C1)NC1CCCC1)C(F)(F)F)C(C)C JKGLEMVRRMJZFV-IRJOAOCJSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- DICDGKBMLQSSLB-UHFFFAOYSA-N acetic acid;phosphoric acid Chemical compound CC(O)=O.OP(O)(O)=O.OP(O)(O)=O DICDGKBMLQSSLB-UHFFFAOYSA-N 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000005237 alkyleneamino group Chemical group 0.000 description 1
- 125000005238 alkylenediamino group Chemical group 0.000 description 1
- 125000005530 alkylenedioxy group Chemical group 0.000 description 1
- 125000005529 alkyleneoxy group Chemical group 0.000 description 1
- 125000004419 alkynylene group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 229920000469 amphiphilic block copolymer Polymers 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 230000002052 anaphylactic effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 201000011165 anus cancer Diseases 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960003121 arginine Drugs 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 239000002473 artificial blood Substances 0.000 description 1
- 125000005165 aryl thioxy group Chemical group 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000008901 benefit Effects 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
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 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
- GPRLTFBKWDERLU-UHFFFAOYSA-N bicyclo[2.2.2]octane Chemical group C1CC2CCC1CC2 GPRLTFBKWDERLU-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- MZDBWZZCIXRCBI-UHFFFAOYSA-N bis(phenylmethoxy)phosphoryloxymethyl carbonochloridate Chemical compound C=1C=CC=CC=1COP(=O)(OCOC(=O)Cl)OCC1=CC=CC=C1 MZDBWZZCIXRCBI-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 229950007227 buteprate Drugs 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-O butylazanium Chemical compound CCCC[NH3+] HQABUPZFAYXKJW-UHFFFAOYSA-O 0.000 description 1
- 229940046731 calcineurin inhibitors Drugs 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000011111 cardboard Substances 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 230000002612 cardiopulmonary effect Effects 0.000 description 1
- 210000000845 cartilage Anatomy 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 230000034196 cell chemotaxis Effects 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 230000006999 cognitive decline Effects 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 150000001879 copper Chemical class 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 201000003278 cryoglobulinemia Diseases 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 229960002806 daclizumab Drugs 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- LGTLXDJOAJDFLR-UHFFFAOYSA-N diethyl chlorophosphate Chemical compound CCOP(Cl)(=O)OCC LGTLXDJOAJDFLR-UHFFFAOYSA-N 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- CSVGEMRSDNSWRF-UHFFFAOYSA-L disodium;dihydrogen phosphate Chemical compound [Na+].[Na+].OP(O)([O-])=O.OP(O)([O-])=O CSVGEMRSDNSWRF-UHFFFAOYSA-L 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000007938 effervescent tablet Substances 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 229940083124 ganglion-blocking antiadrenergic secondary and tertiary amines Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940074045 glyceryl distearate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- STKYPAFSDFAEPH-LURJTMIESA-N glycylvaline Chemical compound CC(C)[C@@H](C(O)=O)NC(=O)CN STKYPAFSDFAEPH-LURJTMIESA-N 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 229920000591 gum Polymers 0.000 description 1
- 238000001631 haemodialysis Methods 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 210000002216 heart Anatomy 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 230000000322 hemodialysis Effects 0.000 description 1
- 230000008588 hemolysis Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
- 229940091173 hydantoin Drugs 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 231100000268 induced nephrotoxicity Toxicity 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 201000008222 ischemic colitis Diseases 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
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 210000004731 jugular vein Anatomy 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
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000001527 leucocytic effect Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 1
- 229910003002 lithium salt Inorganic materials 0.000 description 1
- 159000000002 lithium salts Chemical class 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 150000002696 manganese Chemical class 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 201000008350 membranous glomerulonephritis Diseases 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
- CKFGINPQOCXMAZ-UHFFFAOYSA-N methanediol Chemical compound OCO CKFGINPQOCXMAZ-UHFFFAOYSA-N 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- LRZFEBJUJIQVDQ-UHFFFAOYSA-N methyl 2-(dimethylamino)acetate Chemical compound COC(=O)CN(C)C LRZFEBJUJIQVDQ-UHFFFAOYSA-N 0.000 description 1
- DMZINWKNZOXHDH-ZETCQYMHSA-N methyl 2-[[(2s)-2-amino-3-methylbutanoyl]amino]acetate Chemical compound COC(=O)CNC(=O)[C@@H](N)C(C)C DMZINWKNZOXHDH-ZETCQYMHSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 201000010225 mixed cell type cancer Diseases 0.000 description 1
- 208000029638 mixed neoplasm Diseases 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 125000006682 monohaloalkyl group Chemical group 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 239000002324 mouth wash Substances 0.000 description 1
- 229940051866 mouthwash Drugs 0.000 description 1
- IFYDWYVPVAMGRO-UHFFFAOYSA-N n-[3-(dimethylamino)propyl]tetradecanamide Chemical compound CCCCCCCCCCCCCC(=O)NCCCN(C)C IFYDWYVPVAMGRO-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 208000028412 nervous system injury Diseases 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 210000000440 neutrophil Anatomy 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000000422 nocturnal effect Effects 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical group C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-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
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 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
- 239000000123 paper Substances 0.000 description 1
- 239000011087 paperboard Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 230000003285 pharmacodynamic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- QVLTXCYWHPZMCA-UHFFFAOYSA-N po4-po4 Chemical compound OP(O)(O)=O.OP(O)(O)=O QVLTXCYWHPZMCA-UHFFFAOYSA-N 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000002745 poly(ortho ester) Substances 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 229920002721 polycyanoacrylate Polymers 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 125000006684 polyhaloalkyl group Polymers 0.000 description 1
- 229920000656 polylysine Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920006324 polyoxymethylene Polymers 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 150000003151 propanoic acid esters Chemical class 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
- 231100000336 radiotoxic Toxicity 0.000 description 1
- 230000001690 radiotoxic effect Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007964 self emulsifier Substances 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 230000007781 signaling event Effects 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 230000000391 smoking effect Effects 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
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000008347 soybean phospholipid Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000008227 sterile water for injection Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- TYFQFVWCELRYAO-UHFFFAOYSA-L suberate(2-) Chemical compound [O-]C(=O)CCCCCCC([O-])=O TYFQFVWCELRYAO-UHFFFAOYSA-L 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 210000001258 synovial membrane Anatomy 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical class [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- IBBLKSWSCDAPIF-UHFFFAOYSA-N thiopyran Chemical compound S1C=CC=C=C1 IBBLKSWSCDAPIF-UHFFFAOYSA-N 0.000 description 1
- 208000008732 thymoma Diseases 0.000 description 1
- 230000024033 toxin binding Effects 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 229960002117 triamcinolone acetonide Drugs 0.000 description 1
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 208000012991 uterine carcinoma Diseases 0.000 description 1
- 238000007631 vascular surgery Methods 0.000 description 1
- 239000003981 vehicle Substances 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
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- 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
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/02—Drugs for disorders of the urinary system of urine or of the urinary tract, e.g. urine acidifiers
-
- 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
- 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
- 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
-
- 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
- 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
- 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
-
- 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
- A61P37/08—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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/59—Hydrogenated pyridine rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Pulmonology (AREA)
- Neurology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Dermatology (AREA)
- Cardiology (AREA)
- Physical Education & Sports Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Oncology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
Abstract
Description
本出願は、2016年4月4日に出願された米国特許法119条(e)のもと米国特許仮出願第62/317,721号の利益を主張するものであり、その出願の全内容が参考として本明細書に組み込まれているものとする。
連邦政府の支援による研究または開発のもとでなされた発明の権利に関する記載
コンパクト・ディスクで提出された「配列表」、表またはコンピュータ・プログラムリストへの言及
R1はH、-O-CH2-O-P(O)ORaORb、-O-C(O)-C1-6アルキレン-L2-X1、O-P(O)ORaORbおよび-O-C(O)-A1-(C1-3アルキレン)n-C4-7ヘテロシクリルから成る群より選択され、ここで前記C4-7ヘテロシクリルは任意に1〜6個のRc基により置換されてよく;
A1はC6-10アリール、C3-10シクロアルキル、C5-10ヘテロアリールおよびC5-10ヘテロシクリルから成る群より選択され、ここでその各々が任意に同一または異なる1〜5個のRxにより置換されてよく;
nは0または1であり;
L2は結合、-O-C(O)-C1-6アルキレン-および-NRd-C(O)-C1-6アルキレン-から成る群より選択され;
X1は独立に-NReRf、-P(O)ORaORb、-O-P(O)ORaORbおよび-CO2Hから成る選択され;
R2はH、-L3-C1-6アルキレン-L4-X2、-L3-(C1-6アルキレン)m-A2-X2、-P(O)ORaOC(O)-C1-6アルキル、-P(O)ORaNRgRhおよび-P(O)ORaORbから成る群より選択され;
L3 は独立に-C(O)-O-および-C(O)-から成る群より選択され;
L4 は独立に結合、-O-C(O)-C2-6 アルケニレン-、-O-C(O)-C1-6 アルキレン- および-NRd-C(O)-C1-6 アルキレン- から成る群より選択され、ここで前記-NRd-C(O)-C1-6 アルキレン-および-O-C(O)-C1-6 アルキレン-中の C1-6 アルキレンは任意にNReRfにより置換されてよく;
X2 は独立に-NRkRl、-P(O)ORaORb 、-O-P(O)ORaORbおよび-CO2Hから成る群より選択され;
m は0または1であり;
A2 はC6-10 アリール、C3-10 シクロアルキル、 C5-10 ヘテロアリールおよびC5-10 ヘテロシクリルから成る群より選択され、その各々が任意に同一または異なる1〜5個のRx により置換されてよく;
R3 は H または -L5-P(O)ORaORb であり、ここで L5 は独立に結合および-CH2-O-から成る群より選択され;
各Rx は独立にハロゲン、C1-6アルキル、C1-6ハロアルキル、C1-6ヘテロアルキル、CN、NRyRz、SRy およびORyから成る群より選択され;
各Rc は独立にハロゲン、C1-6アルキル、C1-6ハロアルキル、C1-6ヘテロアルキル、CN、NRyRz、SRy およびORyから成る群より選択され;
各Ra、Rb、Rd、Re、Rf、Rg、Rk、Rl、Ry およびRz は独立にHおよびC1-6 アルキルから成る群より選択され、
各Rhは独立にHおよびC1-6アルキルから成る群より選択され、ここで前記C1-6 アルキルは任意にCO2H、NRiRj、C6-10 アリール、C3-10 シクロアルキル、C5-10 ヘテロアリールおよび C5-10 ヘテロシクリルから独立に選択された1〜5個の置換基により置換されてよく、ここで各Ri と Rj は独立にH または C1-6 アルキルであり;そして
R1、R2 およびR3 のうちの2つがHであり、そしてR1、R2 およびR3 の1つはH以外である。
鎖または分枝鎖の炭化水素基を意味する。アルキル基の例として、メチル、エチル、n-プ
ロピル、イソプロピル、n-ブチル、t-ブチル、イソブチル、sec-ブチル、n-ペンチル、n-ヘキシル、n-ヘプチル、n-オクチルなどがある。最も広い意味での用語「アルキル」は、アルケニル基やアルキニル基といったそれらの不飽和基を含むものである。「アルケニル」という用語は、1つ以上の二重結合を有する不飽和アルキル基を指す。同様に、「アルキニル」という用語は、1つ以上の三重結合を有する不飽和アルキル基を指す。このような不飽和アルキル基の例として、ビニル、2-プロペニル、クロチル、2-イソペンテニル、2-(ブタジエニル)、2,4-ペンタジエニル、3-(1,4-ペンタジエニル)、エチニル、1-および3-プロピニル、3-ブチニルのほか、より高次の同族体と異性体が挙げられる。「シクロアルキル」という用語は、指定された数の環原子を有し(例えばC3-6シクロアルキル)かつ完全に飽和しているかまたは環の頂点間に多くて1個(0または1個)の二重結合を有する、炭化水素環を指す。「シクロアルキル」は、二環系および多環系炭化水素環も意味し、例えばビシクロ[2.2.1]ヘプタン、ビシクロ[2.2.2]オクタンなどがある。「ヘテロシクロアルキル」または「ヘテロシクリル」という用語は、N、O、Sの中から選択された1〜5個のヘテロ原子を環の頂点として含むシクロアルキル基であって、その窒素原子とイオウ原子が任意に酸化されていてよく、窒素原子が任意に四級化されていてよいシクロアルキル基を指す。ヘテロシクロアルキルは、単環系、二環系、多環系のいずれでもよい。ヘテロシクロアルキル基の例として、ピロリジン、イミダゾリジン、ピラゾリジン、ブチロラクタム、バレロラクタム、イミダゾリジノン、ヒダントイン、ジオキソラン、フタルイミド、ピペリジン、1,4-ジオキサン、モルホリン、チオモルホリン、チオモルホリン-S-オキシド、チオモルホリン-S,S-オキシド、ピペラジン、ピラン、ピリドン、3-ピロリン、チオピラン、ピロン、テトラヒドロフラン、テトラヒドロチオフェン、キヌクリジン等が挙げられるが、これに限定されない。ヘテロシクロアルキル基は、環炭素またはヘテロ原子経由で分子の残部に連結されてよい。
(またはアルキレン)基は、1〜24個の炭素原子を有するが、本発明では10個以下の炭素原子を有する基が好ましい。「低級アルキル」または「低級アルキレン」は、鎖がより短いアルキル基またはアルキレン基であり、一般に4個以下の炭素原子を有する。同様に、「アルケニレン」および「アルキニレン」は、それぞれ二重結合または三重結合を有する「アルキレン」の不飽和形態を指す。
わらない限り、指定された数の炭素原子と、O、N、SiおよびSからなる群より選択された1〜3個のヘテロ原子とからなる、直鎖、分枝鎖、環式の安定な炭化水素基、またはこ
れらの組み合わせを意味し、ここでその中の窒素原子と硫黄原子は任意に酸化されていてもよく、窒素ヘテロ原子は任意に四級化されていてよい。(1または複数の)ヘテロ原子O、N、Sはヘテロアルキル基内の任意の位置に位置することができる。ヘテロ原子Siは、ヘテロアルキル基の任意の位置(例えばアルキル基が分子の残部に連結する位置)に位置することができる。例として、-CH2-CH2-O-CH3、-CH2-CH2-NH-CH3、-CH2-CH2-N(CH3)-CH3、-CH2-S-CH2-CH3、-CH2-CH2、-S(O)-CH3、-CH2-CH2-S(O)2-CH3、-CH=CH-O-CH3、-Si(CH3)3、-CH2-CH=N-OCH3、および-CH=CH-N(CH3)-CH3が挙げられる。例えば-CH2-NH-OCH3や-CH2-O-Si(CH3)3のように、ヘテロ原子が2個まで連続していてもよい。同様に、それ自体でのまたは別の用語と組み合わせた「ヘテロアルケニル」および「ヘテロアルキニル」という用語は、特に断わらない限り、指定された数の炭素原子と、O、N、Si、Sからなる群より選択された1〜3個のヘテロ原子とからなるアルケニル基またはアルキニル基をそれぞれ意味し、ここでその中の窒素原子と硫黄原子は任意に酸化されていてよく、窒素ヘテロ原子は任意に四級化されていてよい。1または複数のヘテロ原子O、NおよびSは、ヘテロアルキル基の任意の分子内位置に存在することができる。
いう用語は通常の意味で用いられ、それぞれ、酸素原子、アミノ基、または硫黄原子経由で分子の残部に連結されたアルキル基を表わす。それに加え、ジアルキルアミノ基の場合、2つのアルキル部分は同じでも異なっていてもよく、また、各々が連結する窒素原子とともに3〜7員環を形成することもできる。したがって-NRaRbで表わされる基はピペリジニル、ピロリジニル、モルホリニル、アゼチジニルなどを含む意味である。
することによって再生できる。化合物の親形態は、ある種の物性、例えば極性溶媒中への溶解度に関してさまざまな塩の形態とは異なるが、それ以外の面では本発明の目的上、塩は化合物の親形態と同等である。
セミ体、ジアステレオマー、幾何異性体、位置異性体、個々の異性体(例えば個別の鏡像異性体)はすべて、本発明の範囲に含まれるものとする。立体化学的描写(破線またはくさび形結合)が示されている場合、それは異性体のうち1つが存在し他方の異性体は実質的に存在しない化合物を指すものである。他方の異性体が「実質的に存在しない」とは、2つの異性体が少なくとも80/20の比、より好ましくは90/10、95/10またはそれ以上であることを指す。ある態様では、異性体の一方が少なくとも99%の量で存在するであろう。
II.化合物
R1はH、-O-CH2-O-P(O)ORaORb、-O-C(O)-C1-6アルキレン-L2-X1、O-P(O)ORaORbおよび-O-C(O)-A1-(C1-3アルキレン)n-C4-7ヘテロシクリルから成る群より選択され、ここで前記C4-7ヘテロシクリルは任意に1〜6個のRc基により置換されてもよく;
A1はC6-10アリール、C3-10シクロアルキル、C5-10ヘテロアリールおよびC5-10ヘテロシクリルから成る群より選択され、ここでその各々が任意に同一または異なる1〜5個のRxにより置換されてよく;
nは0または1であり;
L2は結合、-O-C(O)-C1-6アルキレン-および-NRd-C(O)-C1-6アルキレン-から成る群より選択され;
X1は独立に-NReRf、-P(O)ORaORb、-O-P(O)ORaORbおよび-CO2Hから選択され;
R2はH、-L3-C1-6アルキレン-L4-X2、-L3-(C1-6アルキレン)m-A2-X2、-P(O)ORaOC(O)-C1-6アルキル、-P(O)ORaNRgRhおよび-P(O)ORaORbから成る群より選択され;
L3 は独立に-C(O)-O-および-C(O)-から成る群より選択され;
L4 は独立に結合、-O-C(O)-C2-6 アルケニレン-、-O-C(O)-C1-6 アルキレン- および-NRd-C(O)-C1-6 アルキレン- から成る群より選択され、ここで前記-NRd-C(O)-C1-6 アルキレン-および-O-C(O)-C1-6 アルキレン-中の C1-6 アルキレンは任意にNReRfにより置換されてよく;
X2 は独立に-NRkRl、-P(O)ORaORb 、-O-P(O)ORaORbおよび-CO2Hから成る群より選択され;
m は0または1であり;
A2 はC6-10 アリール、C3-10 シクロアルキル、 C5-10 ヘテロアリールおよびC5-10 ヘテロシクリルから成る群より選択され、その各々が任意に同一または異なる1〜5個のRx により置換されてよく;
R3 は H または -L5-P(O)ORaORb であり、ここで L5 は独立に結合および-CH2-O-から成る群より選択され;
各Rx は独立にハロゲン、C1-6アルキル、C1-6ハロアルキル、C1-6ヘテロアルキル、CN、NRyRz、SRy およびORyから成る群より選択され;
各Rc は独立にハロゲン、C1-6アルキル、C1-6ハロアルキル、C1-6ヘテロアルキル、CN、NRyRz、SRy およびORyから成る群より選択され;
各Ra、Rb、Rd、Re、Rf、Rg、Rk、Rl、Ry およびRz は独立にHおよびC1-6 アルキルから成る群より選択され、
各Rhは独立にHおよびC1-6アルキルから成る群より選択され、ここで前記C1-6 アルキルは任意にCO2H、NRiRj、C6-10 アリール、C3-10 シクロアルキル、C5-10 ヘテロアリールおよび C5-10 ヘテロシクリルから独立に選択された1〜5個の置換基により置換されてよく、ここで各Ri と Rj は独立にH または C1-6 アルキルであり;そして
R1、R2 およびR3 のうちの2つがHであり、そしてR1、R2 およびR3 の1つはH以外である。
III.医薬組成物
シウム、カオリン、様々な平均サイズのポリエチレングリコール(PEG)(例えばPEG400、PEG4000)およびある種の界面活性剤(例えばクレモフォルまたはソルトール)と混合されている硬質ゼラチンカプセルとして提供でき、または活性成分が水または油性媒体、例えば落花生油、液体パラフィン、オリーブ油と混合されている軟質カプセルとして提供することができる。加えて、油脂のような水不混和性成分を用いて乳剤を調製することができ、モノもしくはジグリセリドのような界面活性剤を使って安定化させることができる。
分散剤、湿潤剤、懸濁化剤の例はすでに上記に挙げてある。追加の賦形剤、例えば甘味剤、香味剤、着色剤も存在してよい。
トラガカントゴム、天然のホスファチド、例えば大豆レシチン、脂肪酸と無水ヘキシトールから誘導されるエステルまたは部分エステル、例えばモノオレイン酸ソルビタン、および前記部分エステルとエチレンオキシドとの縮合生成物、例えばモノオレイン酸ポリオキシエチレンソルビタンが可能である。このような乳剤は甘味剤と香味剤を含むこともできる。
IV.C5aによりモジュレートされる疾病と障害を治療する方法
C5aモジュレーションにより治療することができる状態:
変形性関節症、アトピー性皮膚炎、慢性蕁麻疹、虚血-再灌流障害、急性呼吸促拍症候群、全身性炎症反応症候群、多臓器不全症候群、ブドウ膜炎、臓器移植拒絶、移植臓器の超急性拒絶反応、心筋梗塞、冠動脈血栓症、血管閉塞、術後血管再閉塞、関節硬化症、ポリープ様脈略膜血管障害、外傷性中枢神経系障害、虚血性心臓病、関節リウマチ、全身性エリテマトーデス、ギラン・バレー(Guillain-Barre)症候群、膵炎、ループス腎炎、ループス糸球体腎炎、乾癬、クローン病、脈管炎、ANCA脈管炎、過敏性腸症候群、皮膚筋炎、多発性硬化症、気管支炎性喘息、天疱瘡、類天疱瘡、強皮症、重症筋無力症、自己免疫性の溶血状態と血小板減少状態、グッドパスチャー症候群、免疫性脈管炎、移植片対宿主病、発作性夜間血色素尿症、シェーグレン症候群、インスリン依存性糖尿病、糖尿病、ループス腎症、ハイマン腎炎、膜性腎炎、糸球体腎炎、IGA腎症、膜性増殖性糸球体腎炎、抗リン脂質症候群、加齢に伴う黄斑変性、乾燥性の加齢に伴う黄斑変性、湿潤性の加齢に伴う黄斑変性、運動ニューロン疾患、接触過敏症反応、血液と人工表面との接触に起因する炎症からなる群より選択される。
a活性に関与する疾患の治療または予防に有用である(ヒト患者一人当たり1日に約0.5 m
g〜約7 g)。単一の剤形を作るのに医薬担体材料と組み合わせることのできる本発明化合物の量は、治療する宿主と特定の投与形式によって異なるであろう。単位剤形は、一般に、約1 mg〜約500 mgの活性成分を含むだろう。経口、経皮、静脈内、筋肉内、または皮下投与される化合物に関しては、5 ng(ナノグラム)/mL〜10 μg(マイクログラム)/mL血清の血清濃度を達成するのに十分な量の化合物を投与することが好ましい。より好ましいのは、20ng〜1μg/mL血清という血清濃度を達成するのに十分な化合物を投与することであり、最も好ましいのは、50 ng/mL〜200 ng/mL血清という血清濃度を達成するのに十分な化合物を投与することである。(関節炎の治療のための)滑膜への直接注入に関しては、局所濃度が約1マイクロモル濃度となるのに十分な量の化合物を投与すべきである。
EtOH:エタノール
EtONa:ナトリウムエトキシド
THF:テトラヒドロフラン
TLC:薄層クロマトグラフィー
MeOH:メタノール
実施例1:(2R,3S)-2-[4-[シクロペンチル-[2-(ジメチルアミノ)アセチル]アミノ]フェニル]-1-(2-フルオロ-6-メチルベンゾイル)-N-[4-メチル-3-(トリフルオロメチル)フェニル]ピペリジン-3-カルボキサミドの合成
実施例2:(2R,3S)-2-[4-[(2-アミノアセチル)シクロペンチルアミノ]フェニル]-1-(2-フルオロ-6-メチルベンゾイル)-N-[4-メチル-3-(トリフルオロメチル)フェニル]ピペリジン-3-カルボキサミドの合成
実施例3:2-[[[N-シクロペンチル-4-[(2R,3S)-1-(2-フルオロ-6-メチルベンゾイル)-3-[[4-メチル-3-(トリフルオロメチル)フェニル]カルバモイル]-2-ピペリジル]アニリノ]ヒドロキシホスホリル] アミノ]-3-(1H-イミダゾール-4-イル)プロパン酸の合成
実施例4:N-シクロペンチル-N-[4-[(2R,3S)-1-(2-フルオロ-6-メチルベンゾイル)-3-[[4-メチル-3-(トリフルオロメチル)フェニル]カルバモイル]-2-[ピペリジル]フェニル]-(2-メチルプロパノイルオキシ)ホスホンアミド酸の合成
実施例5:(2R,3S)-2-[4-[[2-[(2-アミノアセチル)アミノ]アセチル]シクロペンチルアミノ]フェニル]-1-(2-フルオロ-6-メチルベンゾイル)-N-[4-メチル-3-(トリフルオロメチル)フェニル]ピペリジン-3-カルボキサミドの合成
実施例6:(2R,3S)-2-[4-[シクロペンチル-[2-[[(2S)-2,5-ジアミノペンタノイル]アミノ]アセチル]アミノ]フェニル]-1-(2-フルオロ-6-メチルベンゾイル)-N-[4-メチル-3-(トリフルオロメチル)フェニル]ピペリジン-3-カルボキサミド二塩酸塩の合成
実施例7:[シクロペンチル-[4-[(2R,3S)-1-(2-フルオロ-6-メチルベンゾイル)-3-[[4-メチル-3-(トリフルオロメチル)フェニル]カルバモイル]-2-ピペリジル]フェニル]カルバモイル]オキシメチル=(2S)-2-アミノ-3-メチルブタノエートの合成
実施例8:(4ーホスホノオキシフェニル)メチル=N-シクロペンチル-N-[4-[(2R,3S)-1-(2-フルオロ-6-メチルベンゾイル)-3-[[4-メチル-3-(トリフルオロメチル)フェニル]カルバモイル]-2-ピペリジル]フェニル]カルバメートの合成
実施例9:ホスホノオキシメチル=N-シクロペンチル-N-[4-[(2R,3S)-1-(2-フルオロ-6-メチルベンゾイル)-3-[[4-メチル-3-(トリフルオロメチル)フェニル]カルバモイル]-2-ピペリジル]フェニル]カルバメートの合成
実施例10:(E)-4-[[シクロペンチル-[4-[(2R,3S)-1-(2-フルオロ-6-メチルベンゾイル)-3-[[4-メチル-3-(トリフルオロメチル)フェニル]カルバモイル]-2-ピペリジル]フェニル]カルバモイル]オキシメトキシ]-4-オキソブタ-2-エン酸ナトリウム塩の合成
実施例11:N-[(2R,3S)-2-[4-(シクロペンチルアミノ)フェニル]-1-(2-フルオロ-6-メチルベンゾイル)ピペリジン-3-カルボニル]-4-メチル-3-(トリフルオロメチル)アニリノ]メチル=リン酸二水素エステル二ナトリウム塩の合成
実施例12:N-[(2R,3S)-2-[4-(シクロペンチルアミノ)フェニル]-1-(2-フルオロ-6-メチルベンゾイル)ピペリジン-3-カルボニル]-4-メチル-3-(トリフルオロメチル)アニリノ]ホスホン酸の合成
実施例13:([4-[[(2R,3S)-2-[4-(シクロペンチルアミノ)フェニル]-1-(2-フルオロ-6-メチルベンゾイル)ピペリジン-3-カルボニル]アミノ]-2-(トリフルオロメチル)フェニル]メチル=2-[(2-アミノアセチル)アミノ]アセテートの合成
実施例14:[4-[[(2R,3S)-2-[4-(シクロペンチルアミノ)フェニル]-1-(2-フルオロ-6-メチルベンゾイル)ピペリジン-3-カルボニル]アミノ]-2-(トリフルオロメチル)フェニル]メチル=2-[[(2S)-2-アミノ-3-メチルブタノイル]アミノ]アセテートの合成
実施例15:[4-[[(2R,3S)-2-[4-(シクロペンチルアミノ)フェニル]-1-(2-フルオロ-6-メチルベンゾイル)ピペリジン-3-カルボニル]アミノ]-2-(トリフルオロメチル)フェニル]メチル=(2S)-2-[(2-アミノアセチル)アミノ]-3-メチルブタノエートの合成
実施例16:[4-[[(2R,3S)-2-[4-(シクロペンチルアミノ)フェニル]-1-(2-フルオロ-6-メチルベンゾイル)ピペリジン-3-カルボニル]アミノ]-2-(トリフルオロメチル)フェニル]メチル=(2S)-2-[[(2S)-2-アミノ-3-メチルブタノイル]アミノ]-3-メチルブタノエートの合成
実施例17:[4-[[(2R,3S)-2-[4-(シクロペンチルアミノ)フェニル]-1-(2-フルオロ-6-メチルベンゾイル)ピペリジン-3-カルボニル]アミノ]-2-(トリフルオロメチル)フェニル]メチル=(2R)-2-アミノ-3-メチル-ブタノエートの合成
実施例18:[4-[[(2R,3S)-2-[4-(シクロペンチルアミノ)フェニル]-1-(2-フルオロ-6-メチルベンゾイル)ピペリジン-3-カルボニル]アミノ]-2-(トリフルオロメチル)フェニル]メチル=(2S)-2-アミノプロパノエートの合成
実施例19:[4-[[(2R,3S)-2-[4-(シクロペンチルアミノ)フェニル]-1-(2-フルオロ-6-メチルベンゾイル)ピペリジン-3-カルボニル]アミノ]-2-(トリフルオロメチル)フェニル]メチル=2-(ジメチルアミノ)アセテートの合成
実施例20:[4-[[(2R,3S)-2-[4-(シクロペンチルアミノ)フェニル]-1-(2-フルオロ-6-メチルベンゾイル)ピペリジン-3-カルボニル]アミノ]-2-(トリフルオロメチル)フェニル]メチル=2-アミノアセテートの合成
実施例21:[4-[[(2R,3S)-2-[4-(シクロペンチルアミノ)フェニル]-1-(2-フルオロ-6-メチルベンゾイル)ピペリジン-3-カルボニル]アミノ]-2-(トリフルオロメチル)フェニル]メチル=リン酸二水素エステルの合成
実施例22:[4-[[(2R,3S)-2-[4-(シクロペンチルアミノ)フェニル]-1-(2-フルオロ-6-メチルベンゾイル)ピペリジン-3-カルボニル]アミノ]-2-(トリフルオロメチル)フェニル]メトキシメチル=リン酸二水素エステルの二ナトリウム塩の合成
実施例23:[4-[[(2R,3S)-2-[4-(シクロペンチルアミノ)フェニル]-1-(2-フルオロ-6-メチルベンゾイル)ピペリジン-3-カルボニル]アミノ]-2-(トリフルオロメチル)フェニル]メチル=3-[(4-メチルピペラジン-1-イル)メチル]ベンゾエートの合成
実施例24:化合物の溶解度
Claims (30)
- 式(I)の化合物
〔前記式中
R1はH、-O-CH2-O-P(O)ORaORb、-O-C(O)-C1-6アルキレン-L2-X1、O-P(O)ORaORbおよび-O-C(O)-A1-(C1-3アルキレン)n-C4-7ヘテロシクリルから成る群より選択され、ここで前記C4-7ヘテロシクリルは任意に1〜6個のRc基により置換されてよく;
A1はC6-10アリール、C3-10シクロアルキル、C5-10ヘテロアリールおよびC5-10ヘテロシクリルから成る群より選択され、ここで前記基の各々が任意に同一または異なる1〜5個のRxにより置換されてよく;
nは0または1であり;
L2は結合、-O-C(O)-C1-6アルキレン-および-NRd-C(O)-C1-6アルキレン-から成る群より選択され;
X1は独立に-NReRf、-P(O)ORaORb、-O-P(O)ORaORbおよび-CO2Hから成る群より選択され;
R2はH、-L3-C1-6アルキレン-L4-X2、-L3-(C1-6アルキレン)m-A2-X2、-P(O)ORaOC(O)-C1-6アルキル、-P(O)ORaNRgRhおよび-P(O)ORaORbから成る群より選択され;
L3 は独立に-C(O)-O-および-C(O)-から成る群より選択され;
L4 は独立に結合、-O-C(O)-C2-6 アルケニレン-、-O-C(O)-C1-6 アルキレン- および-NRd-C(O)-C1-6 アルキレン- から成る群より選択され、ここで前記-NRd-C(O)-C1-6 アルキレン-および-O-C(O)-C1-6 アルキレン-中の C1-6 アルキレンは任意にNReRfにより置換されてよく;
X2 は独立に-NRkRl、-P(O)ORaORb 、-O-P(O)ORaORbおよび-CO2Hから成る群より選択され;
m は0または1であり;
A2 はC6-10 アリール、C3-10 シクロアルキル、C5-10 ヘテロアリールおよびC5-10 ヘテロシクリルから成る群より選択され、ここで前記基の各々が任意に同一または異なる1〜5個のRx により置換されてよく;
R3 は H または -L5-P(O)ORaORb であり、ここで L5 は独立に結合および-CH2-O-から成る群より選択され;
各Rx は独立にハロゲン、C1-6アルキル、C1-6ハロアルキル、C1-6ヘテロアルキル、CN、NRyRz、SRy およびORyから成る群より選択され;
各Rc は独立にハロゲン、C1-6アルキル、C1-6ハロアルキル、C1-6ヘテロアルキル、CN、NRyRz、SRy およびORyから成る群より選択され;
各Ra、Rb、Rd、Re、Rf、Rg、Rk、Rl、Ry およびRz は独立にHおよびC1-6 アルキルから成る群より選択され、
各Rhは独立にHおよびC1-6アルキルから成る群より選択され、ここで前記C1-6 アルキルは任意にCO2H、NRiRj、C6-10 アリール、C3-10 シクロアルキル、C5-10 ヘテロアリールおよび C5-10 ヘテロシクリルから独立に選択された1〜5個の置換基により置換されてよく、ここで各Ri と Rj は独立にH または C1-6 アルキルであり;そして
R1、R2 およびR3 のうちの2つがHであり、そしてR1、R2 およびR3 の1つはH以外である〕。 - R1がO-(CO)-C1-6アルキレン-NReRf、O-(CO)-C1-6アルキレン-NRd(CO)-C1-6アルキレン-NReRf、O-P(O)ORaORb、O-CH2-O-P(O)ORaORbおよびO-(CO)-C6-10アリーレン-C1-3アルキレン-C4-7ヘテロシクリルから成る群より選択され、ここで前記C4-7ヘテロシクリルはピペリジニル、ピペラジニル、ピロリジニル、モルホリニルおよびアゼチジニルから成る群より選択され、そして前記ピペリジニル、ピペラジニル、ピロリジニル、モルホリニルおよびアゼチジニルは任意に1〜6個のRc基により置換されている、請求項1記載の化合物または製薬上許容されるその塩。
- R1が
- R1が
- R1が
- R1が
- R3が -CH2-O-P(O)ORaORb および-P(O)ORaORbから成る群より選択される、請求項1記載の化合物または製薬上許容されるその塩。
- R3が
- R3が
- R3が
- R3が
- R2が -(CO)-C1-6アルキレン-NRkRl、-(CO)-O-C1-6アルキレン-O-P(O)ORaORb、-P(O)ORaO(CO)-C1-6アルキル、-P(O)ORaNRgRh、-(CO)-O-C1-6アルキレン-O-(CO)-C2-6アルケニレン-CO2H、-(CO)-C1-6アルキレン-NRd(CO)-C1-6アルキレン-NRkRl(ここで前記C1-6アルキレン-NRkRl は任意にNReRfにより置換されてよい)、-(CO)-O-C1-6アルキレン-O-(CO)-C1-6アルキレン-NRkRl および-(CO)-O-C1-6アルキレン-C6-10アリール-O-P(O)ORaORb(ここで前記C6-10アリールは任意に同一または異なる1〜5個のRxにより置換されてよい)から成る群より選択される、請求項1記載の化合物または製薬上許容されるその塩。
- R2が
- 次の群
- 製薬上許容される塩の形である、請求項1〜5、7〜10、12〜14のいずれか一項記載の化合物。
- 前記製薬上許容される塩が、アンモニウム、カルシウム、マグネシウム、カリウム、ナトリウム、亜鉛、アルギニン、ベタイン、カフェイン、コリン、N,N’-ジベンジルエチレンジアミン、ジエチルアミン、2-ジエチルアミノエタノール、2-ジメチルアミノエタノール、エタノールアミン、エチレンジアミン、N-エチルモルホリン、N-エチルピペリジン、グルカミン、グルコサミン、ヒスチジン、ヒドラバミン、イソプロピルアミン、リシン、メチルグルカミン、モルホリン、ピペラジン、ピペリジン、プロカイン、プリン類、テオブロミン、トリエチルアミン、トリメチルアミン、トリピロピルアミン、トロメタミン、塩酸、炭酸、炭酸一水素、リン酸、リン酸一水素、リン酸二水素、酢酸、プロピオン酸、イソ酪酸、マロン酸、安息香酸、コハク酸、スベリン酸、フマル酸、マンデル酸、フタル酸、ベンゼンスルホン酸、p-トシルスルホン酸、クエン酸、酒石酸、メタンスルホン酸、アルギン酸、グルクロン酸およびガラクツロン酸の各塩から選択される、請求項15記載の化合物。
- 請求項1〜16のいずれか一項記載の化合物または製薬上許容されるその塩と、製薬上許容される賦形剤とを含む、医薬組成物。
- 静脈内、経皮または皮下投与用に製剤化された、請求項17記載の医薬組成物。
- 1以上の追加の治療薬を更に含む、請求項17または18記載の医薬組成物。
- 前記1以上の追加の治療薬が、コルチコステロイド、ステロイド、免疫抑制剤、免疫グロブリンGアゴニスト、ジペプチジルペプチダーゼIV阻害剤、リンパ球機能抗原-3受容体アンタゴニスト、インターロイキン-2リガンド、インターロイキン-1βリガンド阻害剤、IL-2受容体αサブユニット阻害剤、HGF遺伝子刺激剤、IL-6アンタゴニスト、IL-5アンタゴニスト、α1アンチトリプシン刺激剤、カンナビノイド受容体アンタゴニスト、ヒストンデアセチラーゼ阻害剤、AKTプロテインキナーゼ阻害剤、CD20阻害剤、Ab1チロシンキナーゼ阻害剤、JAKチロシンキナーゼ阻害剤、TNFαリガンド阻害剤、ヘモグロビンモジュレーター、TNFアンタゴニスト、プロテアソーム阻害剤、CD3モジュレーター、Hsp 70ファミリー阻害剤、免疫グロブリンアゴニスト、CD30アンタゴニスト、チューブリンアンタゴニスト、スフィンゴシン-1-リン酸受容体-1アゴニスト、結合組織増殖因子リガンド阻害剤、カスパーゼ阻害剤、副腎皮質刺激ホルモンリガンド、Btkチロシンキナーゼ阻害剤、補体C1sサブコンポーネント阻害剤、エリスロポイエチン受容体アゴニスト、Bリンパ球刺激剤リガンド阻害剤、シクリン依存性キナーゼ-2阻害剤、P-セレクチン糖タンパクリガンド-1刺激剤、mTOR阻害剤、伸長因子2阻害剤、細胞接着分子阻害剤、第XIII因子アゴニスト、カルシニューリン阻害剤、免疫グロブリンG1アゴニスト、イノシン一リン酸デヒドロゲナーゼ阻害剤、補体C1sサブコンポーネント阻害剤、チミジンキナーゼモジュレーター、細胞傷害性Tリンパ球プロテイン-4モジュレーター、アンギオテンシンII受容体アンタゴニスト、アンギオテンシンII受容体モジュレーター、TNFスーパーファミリー受容体12Aアンタゴニスト、CD52アンタゴニスト、アデノシンデアミナーゼ阻害剤、T細胞分化抗原CD6阻害剤、FGF-7リガンド、ジヒドロオロチン酸デヒドロゲナーゼ阻害剤、CCR5ケモカインアンタゴニスト、CCR2ケモカインアンタゴニスト、Sykチロシンキナーゼ阻害剤、インターフェロンI型受容体アンタゴニスト、インターフェロンαリガンド阻害剤、マクロファージ走化性阻害因子阻害剤、インテグリンα-V/β-6アンタゴニスト、システインプロテアーゼ刺激剤、p38 MAPキナーゼ阻害剤、TP53遺伝子阻害剤、Shiga様毒素I阻害剤、フコシルトランスフェラーゼ6刺激剤、インターロイキン22リガンド、CXCR1ケモカインアンタゴニスト、CXCR4ケモカインアンタゴニスト、IRS1遺伝子阻害剤、プロテインキナーゼC刺激剤、プロテインキナーゼCα阻害剤、CD74アンタゴニスト、免疫グロブリンγFc受容体IIBアンタゴニスト、T細胞抗原CD7阻害剤、CD95アンタゴニスト、Nアセチルマンノサミンキナーゼ刺激剤、カルジオトロフィン-1リガンド、白血球エラスターゼ阻害剤、CD40リガンド受容体アンタゴニスト、CD40リガンドモジュレーター、IL-17アンタゴニスト、TLR-2アンタゴニスト、マンナン結合レクチンセリンプロテアーゼ-2(MASP-2)阻害剤、B因子阻害剤、D因子阻害剤、T細胞受容体アンタゴニスト、およびそれらの組み合わせから成る群より選択される、請求項19記載の医薬組成物。
- 前記1以上の追加の治療薬が、オビヌツズマブ、リツキシマブ、オクレリズマブ、シクロホスファミド、プレドニソン、ヒドロコルチゾン、ヒドロコルチゾン酢酸エステル、コルチゾン酢酸エステル、チキソコルトールピバル酸エステル、プレドニソロン、メチルプレドニソロン、トリアムシノロンアセトニド、トリアムシノロンアルコール、モメタゾン、アムシノニド、ブデソニド、デソニド、フルオシノニド、フルオシノロンアセトニド、ハルシノニド、ベタメタゾン、ベタメタゾンリン酸エステルナトリウム、デキサメタゾン、デキサメタゾンリン酸エステルナトリウム、フルオコルトロン、ヒドロコルチゾン-17吉草酸エステル、ハロメタゾン、アルクロメタゾンジプロピオン酸エステル、ベクロメタゾン、ベタメタゾン吉草酸エステル、ベタメタゾンジプロピオン酸エステル、プレドニカルベート、クロベタゾン-17酪酸エステル、クロベタゾール-17-プロピオン酸エステル、フルオコルトロンカプロン酸エステル、フルオコルトロンピバル酸エステル、フルプレドニデン酢酸エステル、ヒドロコルチゾン-17酪酸エステル、ヒドロコルチゾン-17アセポン酸エステル、ヒドロコルチゾン-17-酪酸エステルプロピオン酸エステル、シクレソニド、プレドニカルベート、GB-0998、イムグロ、ベゲロマブ、アレファセプト、アルデスロイキン、ゲボキズマブ、デクリズマブ、バシリキシマブ、イノリモマブ、ベペルミノゲンペルプラスミド、シルクマブ、トシリズマブ、クラザキズマブ、メポリズマブ、フィンゴリモド、パノビノスタット、トリシリビン、ニロチニブ、イマチニブ、トファシチニブ、モメロチニブ、ペフィシチニブ、イタシチニブ、インフリキシマブ、PEG-bHb-CO、エタネルセプト、イキサゾミブ、ボルテゾミブ、ムロモナブ、オテリキシズマブ、グスペリムス、ブレンツキシマブベドチン、ポネシモド、KRP-203、FG-3019、エムリカサン、コルチコトロピン、イブルチニブ、シンリゼ(cinryze)、コネスタット、メトキシポリエチレングリコール-エポエチンβ、ベリムマブ、ブリシビモド、アタシセプト、セリシクリブ、ネイフリズマブ、エベロリムス、シロリムス、デニロイキンジフチトクス、LMB-2、ナタリズマブ、カトリデカコグ、シクロスポリン、タクロリムス、ボクロスポリン、ボクロスポリン、カナキヌマブ、ミコフェノレート、ミゾリビン、CE-1145、TK-DLI、アバタセプト、ベラタセプト、オルメサルタン、メドキソミル、スパルセンタン、TXA-127、BIIB-023、アレムツズマブ、ペントスタチン、イトリズマブ、パリフェルミン、レフルノミド、PRO-140、セニクリビロク、フォスタマチニブ、アニフロルマブ、シファリムマブ、BAX-069、BG-00011、ロスマピモド、QPI-1002、ShigamAbs、TZ-101、F-652、レパリキシン、ラダリキシン、PTX-9908、アガニルセン、APH-703、ソトラスタウリン、ソトラスタウリン、ミラツズマブ、SM-101、T-Guard、APG-101、DEX-M74、カルジオトロフィン-1、チプレレスタット、ASKP-1240、BMS-986004、HPH-116、KD-025、OPN-305、TOL-101、デフィブロチド、ポマリドミド、チモグロブリン、ラキニモド、レメステムセル-L、ウマ抗胸腺細胞免疫グロブリン、ステムペウセル(Stempeucel)、LIV-γ、オクタガムOctagam 10%、t2c-001、99m Tc-セスタミビ、クライリグ(Clairyg)、プロソルバ、ポマリドミド、ラキニモド、テプリズマブ、FCRx、ソルナチド、フォラルマブ、ATIR-101、BPX-501、ACP-01、ALLO-ASC-DFU、イルベサルタン+プロパゲルマニウム、ApoCell、カンナビジオール、RGI-2001、サラチン、抗CD3二価抗体-ジフテリア毒素結合体、NOX-100、LT-1951、OMS721、ALN-CC5、ACH-4471、AMY-101、Actharゲル、およびCD4+CD25+調節T細胞、並びにそれらの組み合わせからなる群より選択される、請求項19または20のいずれか一項記載の医薬組成物。
- C5a受容体の病原性活性化を伴う疾患または障害を患っているかまたはそれにかかりやすいヒトを治療する方法であって、前記哺乳類に治療有効量の請求項1〜16のいずれか一項記載の化合物または請求項17〜21のいずれか一項記載の医薬組成物を投与することを含む方法。
- 前記疾患または障害が、炎症性疾患もしくは障害、自己免疫疾患、または腫瘍性疾病もしくは障害である、請求項22記載の方法。
- 前記疾患または障害が、心血管または脳血管障害である、請求項22記載の方法。
- 前記疾患または障害が、好中球減少症、好中球増加症、ウェゲナー肉芽腫症、顕微鏡的多発性血管炎、C3-糸球体症、C3-糸球体腎炎、高密度沈着病、膜性増殖性糸球体腎炎、カワサキ病、敗血症、敗血症性ショック、溶血性尿毒症症候群、非定型溶血性尿毒性症候群(aHUS)、アルツハイマー症候群、多発性硬化症、脳卒中、炎症性腸疾患、慢性閉塞性肺疾患、火傷に伴う炎症、肺障害、変形性関節症、アトピー性皮膚炎、慢性蕁麻疹、虚血-再灌流障害、急性呼吸促拍症候群、全身性炎症反応症候群、多臓器不全症候群、ブドウ膜炎、臓器移植拒絶、移植臓器の超急性拒絶反応、心筋梗塞、冠動脈血栓症、血管閉塞、術後血管再閉塞、関節硬化症、ポリープ様脈略膜血管障害、外傷性中枢神経系障害、虚血性心臓病、関節リウマチ、全身性エリテマトーデス、ギラン・バレー(Guillain-Barre)症候群、膵炎、ループス腎炎、ループス糸球体腎炎、乾癬、クローン病、脈管炎、ANCA脈管炎、過敏性腸症候群、皮膚筋炎、多発性硬化症、気管支炎性喘息、天疱瘡、類天疱瘡、強皮症、重症筋無力症、自己免疫性の溶血状態と血小板減少状態、グッドパスチャー症候群、免疫性脈管炎、移植片対宿主病、発作性夜間血色素尿症、シェーグレン症候群、インスリン依存性糖尿病、糖尿病、ループス腎症、ハイマン腎炎、膜性腎炎、糸球体腎炎、IGA腎症、膜性増殖性糸球体腎炎、抗リン脂質症候群、加齢に伴う黄斑変性、乾燥性の加齢に伴う黄斑変性、湿潤性の加齢に伴う黄斑変性、運動ニューロン疾患、接触過敏症反応、および血液と人工表面との接触に起因する炎症からなる群より選択される、請求項22記載の方法。
- 前記疾患または障害が、好中球減少症、好中球増加症、ウェゲナー肉芽腫症、顕微鏡的多発性血管炎、C3-糸球体症、C3-糸球体腎炎、高密度沈着病、膜性増殖性糸球体腎炎、カワサキ病、溶血性尿毒症症候群、非定型溶血性尿毒性症候群(aHUS)、臓器移植拒絶、移植臓器の超急性拒絶反応、慢性関節リウマチ、全身性エリテマトーデス、ループス腎炎、ループス糸球体腎炎、脈管炎、ANCA脈管炎、自己免疫性の溶血状態と血小板減少状態、免疫性脈管炎、移植片対宿主病、ループス腎症、ハイマン腎炎、膜性腎炎、糸球体腎炎、IGA腎症、膜性増殖性糸球体腎炎および糸球体腎炎からなる群より選択される、請求項22記載の方法。
- 前記疾患または障害が、黒色腫、肺癌、リンパ腫、肉腫、癌腫、線維肉腫、脂肪肉腫、軟骨肉腫、骨肉腫、血管肉腫、リンパ管肉腫、滑液腫瘍、中皮腫、髄膜腫、白血病、リンパ腫、平滑筋肉腫、横紋筋肉腫、扁平上皮癌、基底細胞癌、腺癌、乳頭癌、嚢胞腺癌、気管支癌、腎細胞癌、肝細胞癌、移行上皮癌、絨毛腫、セミノーマ、胎生期癌、ウィルムス腫瘍、多形腺腫、肝細胞乳頭腫、尿細管腺腫、嚢胞腺癌、乳頭腫、腺癌、平滑筋腫、横紋筋腫、血管腫、リンパ管腫、骨腫瘍、軟骨腫、脂肪腫および線維腫からなる群より選択される、請求項22記載の方法。
- ヒトに治療有効量の1以上の追加の治療薬を投与することをさらに含む、請求項22〜27のいずれか一項記載の方法。
- 前記1以上の追加の治療薬が、コルチコステロイド、ステロイド、免疫抑制剤、免疫グロブリンGアゴニスト、ジペプチジルペプチダーゼIV阻害剤、リンパ球機能抗原-3受容体アンタゴニスト、インターロイキン-2リガンド、インターロイキン-1βリガンド阻害剤、IL-2受容体αサブユニット阻害剤、HGF遺伝子刺激剤、IL-6アンタゴニスト、IL-5アンタゴニスト、α1抗トリプシン刺激剤、カンナビノイド受容体アンタゴニスト、ヒストンデアセチラーゼ阻害剤、AKTプロテインキナーゼ阻害剤、CD20阻害剤、Ab1チロシンキナーゼ阻害剤、JAKチロシンキナーゼ阻害剤、TNFαリガンド阻害剤、ヘモグロビンモジュレーター、TNFアンタゴニスト、プロテアソーム阻害剤、CD3モジュレーター、Hsp 70ファミリー阻害剤、免疫グロブリンアゴニスト、CD30アンタゴニスト、チューブリンアンタゴニスト、スフィンゴシン-1-リン酸受容体-1アゴニスト、結合組織増殖因子リガンド阻害剤、カスパーゼ阻害剤、副腎皮質刺激ホルモンリガンド、Btkチロシンキナーゼ阻害剤、補体C1sサブコンポーネント阻害剤、エリスロポイエチン受容体アゴニスト、Bリンパ球刺激剤リガンド阻害剤、シクリン依存性キナーゼ-2阻害剤、P-セレクチン糖タンパクリガンド-1刺激剤、mTOR阻害剤、伸長因子2阻害剤、細胞接着分子阻害剤、第XIII因子アゴニスト、カルシニューリン阻害剤、免疫グロブリンG1アゴニスト、イノシン一リン酸デヒドロゲナーゼ阻害剤、補体C1sサブコンポーネント阻害剤、チミジンキナーゼモジュレーター、細胞傷害性Tリンパ球プロテイン4モジュレーター、アンギオテンシンII受容体アンタゴニスト、アンギオテンシンII受容体モジュレーター、TNFスーパーファミリー受容体12Aアンタゴニスト、CD52アンタゴニスト、アデノシンデアミナーゼ阻害剤、T細胞分化抗原CD6阻害剤、FGF-7リガンド、ジヒドロオロチン酸デヒドロゲナーゼ阻害剤、CCR5ケモカインアンタゴニスト、CCR2ケモカインアンタゴニスト、Sykチロシンキナーゼ阻害剤、インターフェロンI型受容体アンタゴニスト、インターフェロンαリガンド阻害剤、マクロファージ走化性阻害因子阻害剤、インテグリンα-V/β-6アンタゴニスト、システインプロテアーゼ刺激剤、p38 MAPキナーゼ阻害剤、TP53遺伝子阻害剤、Shiga様毒素I阻害剤、フコシルトランスフェラーゼ6刺激剤、インターロイキン22リガンド、CXCR1ケモカインアンタゴニスト、CXCR4ケモカインアンタゴニスト、IRS1遺伝子阻害剤、プロテインキナーゼC阻害剤、プロテインキナーゼCα阻害剤、CD74アンタゴニスト、免疫グロブリンγFc受容体IIBアンタゴニスト、T細胞抗原CD7阻害剤、CD95アンタゴニスト、Nアセチルマンノサミンキナーゼ阻害剤、カルジオトロフィン-1リガンド、白血球エラスターゼ阻害剤、CD40リガンド受容体アンタゴニスト、CD40リガンドモジュレーター、IL-17アンタゴニスト、TLR-2アンタゴニスト、マンナン結合レクチンセリンプロテアーゼ-2(MASP-2)阻害剤、B因子阻害剤、D因子阻害剤、T細胞受容体アンタゴニスト、およびそれらの組み合わせから成る群より選択される、請求項28記載の方法。
- 前記1以上の追加の治療薬が、オビヌツズマブ、リツキシマブ、オクレリズマブ、シクロホスファミド、プレドニソン、ヒドロコルチゾン、ヒドロコルチゾン酢酸エステル、コルチゾン酢酸エステル、チキソコルトールピバル酸エステル、プレドニソロン、メチルプレドニソロン、トリアムシノロンアセトニド、トリアムシノロンアルコール、モメタゾン、アムシノニド、ブデソニド、デソニド、フルオシノニド、フルオシノロンアセトニド、ハルシノニド、ベタメタゾン、ベタメタゾンリン酸エステルナトリウム、フルオコルトロン、ヒドロコルチゾン-17吉草酸エステル、ハロメタゾン、アルクロメタゾンジプロピオン酸エステル、ベクロメタゾン、ベタメタゾン吉草酸エステル、ベタメタゾンジプロピオン酸エステル、プレドニカルベート、クロベタゾン-17酪酸エステル、フルオコルトロンカプロン酸エステル、フルオコルトロンピルビン酸エステル、フルプレドニデン酢酸エステル、ヒドロコルチゾン-17酪酸エステル、ヒドロコルチゾン-17アセポン酸エステル、ヒドロコルチゾン-17-酪酸エステルプロピオン酸エステル、シクレソニド、プレドニカルベート、GB-0998、イムグロ、ベゲロマブ、アレファセプト、アルデスロイキン、ゲボキズマブ、デクリズマブ、バシリキシマブ、イノリモマブ、ベペルミノゲンペルプラスミド、シルクマブ、トシリズマブ、クラザキズマブ、メポリズマブ、フィンゴリモド、パノビノスタット、トリシリビン、ニロチニブ、イマチニブ、トファシチニブ、モメロチニブ、ペフィシチニブ、イタシチニブ、インフリキシマブ、PEG-bHb-CO、エタネルセプト、イキサゾミブ、ボルテゾミブ、ムロモナブ、オテリキシズマブ、グスペリムス、ブレンツキシマブベドチン、ポネシモド、KRP-203、FG-3019、エムリカサン、コルチコトロピン、イブルチニブ、シンリゼ(cinryze)、コネスタット、メトキシポリエチレングリコール-エポエチンβ、ベリムマブ、ブリシビモド、アタシセプト、セリシクリブ、ネイフリズマブ、エベロリムス、シロリムス、デニロイキンジフチトクス、LMB-2、ナタリズマブ、カトリデカコグ、シクロスポリン、タクロリムス、ボクロスポリン、ボクロスポリン、カナキヌマブ、ミコフェノレート、ミゾリビン、CE-1145、TK-DLI、アバタセプト、ベラタセプト、オルメサルタンメドキソミル、スパルセンタン、TXA-127、BIIB-023、アレムツズマブ、ペントスタチン、イトリズマブ、パリフェルミン、レフルノミド、PRO-140、セニクリビロク、フォスタマチニブ、アニフロルマブ、シファリムマブ、BAX-069、BG-00011、ロスマピモド、QPI-1002、ShigamAbs、TZ-101、F-652、レパリキシン、ラダリキシン、PTX-9908、アガニルセン、APH-703、ソトラスタウリン、ソトラスタウリン、ミラツズマブ、SM-101、T-Guard、APG-101、DEX-M74、カルジオトロフィン-1、チプレレスタット、ASKP-1240、BMS-986004、HPH-116、KD-025、OPN-305、TOL-101、デフィブロチド、ポマリドミド、チモグロブリン、ラキニモド、レメステムセル-L、ウマ抗胸腺細胞免疫グロブリン、ステムペウセル(Stempeucel)、LIV-γ、オクタガム(Octagam) 10%、t2c-001、99mTc-セスタミビ、クライリグ(Clairyg)、プロソルバ、ポマリドミド、ラキニモド、テプリズマブ、FCRx、ソルナチド、フォラルマブ、ATIR-101、BPX-501、ACP-01、ALLO-ASC-DFU、イルベサルタン+プロパゲルマニウム、ApoCell、カンナビジオール、RGI-2001、サラチン、抗CD3二価抗体-ジフテリア毒素結合体、NOX-100、LT-1951、OMS721、ALN-CC5、ACH-4471、AMY-101、Actharゲル、およびCD4+CD25+調節T細胞、並びにそれらの組み合わせからなる群より選択される、請求項28または29記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201662317721P | 2016-04-04 | 2016-04-04 | |
US62/317,721 | 2016-04-04 | ||
PCT/US2017/025704 WO2017176620A2 (en) | 2016-04-04 | 2017-04-03 | SOLUBLE C5aR ANTAGONISTS |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2019515947A true JP2019515947A (ja) | 2019-06-13 |
JP2019515947A5 JP2019515947A5 (ja) | 2020-05-14 |
JP7121722B2 JP7121722B2 (ja) | 2022-08-18 |
Family
ID=59960805
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019502541A Active JP7121722B2 (ja) | 2016-04-04 | 2017-04-03 | 可溶性C5aRアンタゴニスト |
Country Status (18)
Country | Link |
---|---|
US (4) | US20170283446A1 (ja) |
EP (1) | EP3439658B1 (ja) |
JP (1) | JP7121722B2 (ja) |
KR (1) | KR102395093B1 (ja) |
CN (1) | CN109310686B (ja) |
AR (1) | AR108097A1 (ja) |
AU (1) | AU2017246228B2 (ja) |
CA (1) | CA3019137A1 (ja) |
CL (1) | CL2018002803A1 (ja) |
IL (1) | IL261997B (ja) |
MA (1) | MA44629A (ja) |
MX (1) | MX2018011831A (ja) |
NZ (1) | NZ747259A (ja) |
RU (1) | RU2748260C2 (ja) |
SG (1) | SG11201808625QA (ja) |
TW (1) | TWI760331B (ja) |
WO (1) | WO2017176620A2 (ja) |
ZA (1) | ZA201806632B (ja) |
Families Citing this family (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2015324111B2 (en) | 2014-09-29 | 2021-04-01 | Chemocentryx, Inc. | Processes and intermediates in the preparation of C5aR antagonists |
CN108601790A (zh) | 2016-01-14 | 2018-09-28 | 凯莫森特里克斯股份有限公司 | C3肾小球病的治疗方法 |
JP7121722B2 (ja) | 2016-04-04 | 2022-08-18 | ケモセントリックス,インコーポレイティド | 可溶性C5aRアンタゴニスト |
US10376595B2 (en) | 2017-04-03 | 2019-08-13 | Inflarx Gmbh | Treatment of inflammatory diseases with inhibitors of C5a activity |
MX2019011825A (es) | 2017-04-03 | 2020-12-11 | Inflarx Gmbh | Tratamiento de enfermedades inflamatorias con inhibidores de actividad de c5a. |
KR102586710B1 (ko) | 2017-05-31 | 2023-10-10 | 케모센트릭스, 인크. | C5a 억제제로서의 5-5 융합 고리 |
WO2018222598A1 (en) * | 2017-05-31 | 2018-12-06 | Chemocentryx, Inc. | 6-5 FUSED RINGS AS C5a INHIBITORS |
AU2018286754A1 (en) | 2017-06-23 | 2019-12-19 | Inflarx Gmbh | Treatment of inflammatory diseases with inhibitors of C5A activity |
US11542256B2 (en) | 2017-09-03 | 2023-01-03 | Angion Biomedica Corp. | Vinylheterocycles as Rho-associated coiled-coil kinase (ROCK) inhibitors |
KR20200109298A (ko) | 2017-10-30 | 2020-09-22 | 케모센트릭스, 인크. | 면역조절제로서의 중수소화된 화합물 |
AU2018359237A1 (en) * | 2017-10-31 | 2020-04-30 | Chemocentryx, Inc. | C5aR inhibitor reduction of urinary sCD163 |
US20200384069A1 (en) * | 2017-12-01 | 2020-12-10 | Soricimed Biopharma Inc. | Trpv6 inhibitors and combination therapies for treating cancers |
JP7253557B2 (ja) | 2017-12-22 | 2023-04-06 | ケモセントリックス,インコーポレイティド | C5aR阻害剤としてのジアリール置換5,5-縮合環化合物 |
EP3728203B1 (en) | 2017-12-22 | 2024-03-13 | ChemoCentryx, Inc. | DIARYL SUBSTITUTED 6,5-FUSED RING COMPOUNDS AS C5aR INHIBITORS |
CA3095184A1 (en) * | 2018-04-02 | 2019-10-10 | Chemocentryx, Inc. | Prodrugs of fused-bicyclic c5ar antagonists |
EP3775923A1 (en) * | 2018-04-13 | 2021-02-17 | Incyte Corporation | Biomarkers for graft-versus-host disease |
AU2019282327A1 (en) | 2018-06-07 | 2021-01-07 | Chemocentryx, Inc. | Dosing and effect of C5A antagonist with ANCA-associated vasculitis |
JP7342124B2 (ja) | 2018-11-30 | 2023-09-11 | ケモセントリックス,インコーポレイティド | カプセル製剤 |
BR112021016967A2 (pt) * | 2019-02-26 | 2021-11-23 | Equillium Inc | Composições de anticorpo anti-cd6 e métodos para tratar lúpus |
CN111658647A (zh) * | 2019-03-08 | 2020-09-15 | 首都医科大学宣武医院 | 沙利度胺及其衍生物的用途 |
JP7137696B2 (ja) | 2019-05-14 | 2022-09-14 | プロヴェンション・バイオ・インコーポレイテッド | 1型糖尿病を予防するための方法および組成物 |
BR112021025888A2 (pt) | 2019-07-10 | 2022-04-26 | Chemocentryx Inc | Indanos como inibidores de pd-l1 |
KR20220058605A (ko) * | 2019-09-04 | 2022-05-09 | 세다르스-신나이 메디칼 센터 | 고형 장기 이식 수여자의 장기 면역억제를 위한 칼시뉴린 억제제 불포함 ctla4-ig + 항-il6/il6r의 용도 |
EP3868368A1 (en) * | 2020-02-21 | 2021-08-25 | Dompe' Farmaceutici S.P.A. | Cxcl8 (interleukin-8) activity inhibitor and corticosteroid combination and pharmaceutical composition and use thereof |
JP2023518884A (ja) | 2020-03-27 | 2023-05-08 | インフラルクス・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | コロナウイルス感染の処置のためのC5aのインヒビター |
AU2021287998A1 (en) | 2020-06-11 | 2023-02-02 | Benaroya Research Institute At Virginia Mason | Methods and compositions for preventing type 1 diabetes |
WO2022057910A1 (en) * | 2020-09-17 | 2022-03-24 | I-Mab Biopharma Co., Ltd | Combination therapies targeting c5ar and pd-1/pd-l1 pathways |
KR20230097099A (ko) | 2020-10-28 | 2023-06-30 | 케모센트릭스, 인크. | 화농성 한선염의 치료 방법 |
AU2021410668A1 (en) * | 2020-12-21 | 2023-07-06 | Chemocentryx, Inc. | Treatment of c3 glomerulopathy using a c5a inhibitor |
IT202100019454A1 (it) * | 2021-07-22 | 2023-01-22 | Genetic S P A | Process for the preparation of budesonide 21-phosphate |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001527083A (ja) * | 1997-12-31 | 2001-12-25 | ザ・ユニバーシティ・オブ・カンザス | 第二級および第三級アミン含有薬剤の水溶性プロドラッグおよびその製造方法 |
JP2009535295A (ja) * | 2006-03-07 | 2009-10-01 | ブリストル−マイヤーズ スクイブ カンパニー | キナーゼ阻害剤として有用なピロロトリアジンアニリンプロドラッグ化合物 |
JP2010502656A (ja) * | 2006-09-07 | 2010-01-28 | ジョーアジアーン ダードーア ファーマスーティカル グループ カンパニー リミテッド | エトキシコンブレタスタチンとそのプロドラッグの製造方法及び用途 |
JP2011522838A (ja) * | 2008-06-06 | 2011-08-04 | アキリオン ファーマシューティカルズ,インコーポレーテッド | 抗hcv活性を有する化合物の置換アミノチアゾールプロドラッグ |
JP2012513402A (ja) * | 2008-12-22 | 2012-06-14 | ケモセントリックス,インコーポレイティド | C5aRアンタゴニスト |
WO2013032964A1 (en) * | 2011-08-26 | 2013-03-07 | Board Of Regents Of The University Of Nebraska | Compositions and methods for preventing and treating biofilms |
JP2013529647A (ja) * | 2010-06-24 | 2013-07-22 | ケモセントリックス,インコーポレイティド | C5aRアンタゴニスト |
JP2014510110A (ja) * | 2011-03-25 | 2014-04-24 | ブリストル−マイヤーズ スクイブ カンパニー | Lxr調節イミダゾール誘導体のプロドラッグ |
WO2014198647A2 (en) * | 2013-06-11 | 2014-12-18 | Bayer Pharma Aktiengesellschaft | Prodrug derivatives of substituted triazolopyridines |
JP2015529681A (ja) * | 2012-09-13 | 2015-10-08 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | アミノキナゾリンキナーゼ阻害剤のプロドラッグ |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4166452A (en) | 1976-05-03 | 1979-09-04 | Generales Constantine D J Jr | Apparatus for testing human responses to stimuli |
US4256108A (en) | 1977-04-07 | 1981-03-17 | Alza Corporation | Microporous-semipermeable laminated osmotic system |
US4265874A (en) | 1980-04-25 | 1981-05-05 | Alza Corporation | Method of delivering drug with aid of effervescent activity generated in environment of use |
IL154993A0 (en) | 2000-09-29 | 2003-10-31 | Neurogen Corp | High affinity small molecule c5a receptor modulators |
ITMI20012025A1 (it) | 2001-09-28 | 2003-03-28 | Dompe Spa | Sali di ammonio quaternari di omega-amminoalchilammidi di acidi r 2-aril-propionici e composizioni farmaceutiche che li contengono |
WO2003082828A1 (en) | 2002-03-28 | 2003-10-09 | Neurogen Corporation | Substituted tetrahydroisoquinolines as c5a receptor modulators |
CA2479928A1 (en) | 2002-03-28 | 2003-10-09 | Neurogen Corporation | Substituted biaryl amides as c5a receptor modulators |
CA2480082A1 (en) | 2002-03-29 | 2003-10-16 | Neurogen Corporation | Combination therapy for the treatment of conditions with pathogenic inflammatory components |
WO2004018460A1 (en) | 2002-08-21 | 2004-03-04 | Neurogen Corporation | Amino methyl imidazoles as c5a receptor modulators |
WO2004043925A2 (en) | 2002-11-08 | 2004-05-27 | Neurogen Corporation | 3-substituted-6-aryl pyridined as ligands of c5a receptors |
AU2003902354A0 (en) | 2003-05-15 | 2003-05-29 | Harkin, Denis W. | Treatment of haemorrhagic shock |
US20060154917A1 (en) | 2003-07-03 | 2006-07-13 | Neurogen Corporation | Substituted (heterocycloalkyl)methyl azole derivatives as c5a receptor modulators |
WO2005097803A1 (ja) * | 2004-04-09 | 2005-10-20 | Chugai Seiyaku Kabushiki Kaisha | 新規水溶性プロドラッグ |
SG176464A1 (en) * | 2008-05-09 | 2011-12-29 | Agency Science Tech & Res | Diagnosis and treatment of kawasaki disease |
US20110275639A1 (en) | 2008-12-22 | 2011-11-10 | Chemocentryx, Inc. | C5aR ANTAGONISTS |
JP7121722B2 (ja) | 2016-04-04 | 2022-08-18 | ケモセントリックス,インコーポレイティド | 可溶性C5aRアンタゴニスト |
-
2017
- 2017-04-03 JP JP2019502541A patent/JP7121722B2/ja active Active
- 2017-04-03 CA CA3019137A patent/CA3019137A1/en active Pending
- 2017-04-03 MX MX2018011831A patent/MX2018011831A/es unknown
- 2017-04-03 WO PCT/US2017/025704 patent/WO2017176620A2/en active Application Filing
- 2017-04-03 SG SG11201808625QA patent/SG11201808625QA/en unknown
- 2017-04-03 NZ NZ747259A patent/NZ747259A/en unknown
- 2017-04-03 MA MA044629A patent/MA44629A/fr unknown
- 2017-04-03 US US15/477,386 patent/US20170283446A1/en not_active Abandoned
- 2017-04-03 CN CN201780022458.9A patent/CN109310686B/zh active Active
- 2017-04-03 AU AU2017246228A patent/AU2017246228B2/en active Active
- 2017-04-03 EP EP17779588.7A patent/EP3439658B1/en active Active
- 2017-04-03 KR KR1020187031906A patent/KR102395093B1/ko active IP Right Grant
- 2017-04-03 RU RU2018138550A patent/RU2748260C2/ru active
- 2017-04-04 AR ARP170100857A patent/AR108097A1/es unknown
- 2017-04-05 TW TW106111387A patent/TWI760331B/zh active
-
2018
- 2018-02-28 US US15/908,508 patent/US10329314B2/en active Active
- 2018-09-27 IL IL261997A patent/IL261997B/en unknown
- 2018-10-02 CL CL2018002803A patent/CL2018002803A1/es unknown
- 2018-10-05 ZA ZA2018/06632A patent/ZA201806632B/en unknown
-
2019
- 2019-03-19 US US16/357,889 patent/US10487098B2/en active Active
- 2019-10-23 US US16/660,994 patent/US11254695B2/en active Active
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2001527083A (ja) * | 1997-12-31 | 2001-12-25 | ザ・ユニバーシティ・オブ・カンザス | 第二級および第三級アミン含有薬剤の水溶性プロドラッグおよびその製造方法 |
JP2009535295A (ja) * | 2006-03-07 | 2009-10-01 | ブリストル−マイヤーズ スクイブ カンパニー | キナーゼ阻害剤として有用なピロロトリアジンアニリンプロドラッグ化合物 |
JP2010502656A (ja) * | 2006-09-07 | 2010-01-28 | ジョーアジアーン ダードーア ファーマスーティカル グループ カンパニー リミテッド | エトキシコンブレタスタチンとそのプロドラッグの製造方法及び用途 |
JP2011522838A (ja) * | 2008-06-06 | 2011-08-04 | アキリオン ファーマシューティカルズ,インコーポレーテッド | 抗hcv活性を有する化合物の置換アミノチアゾールプロドラッグ |
JP2012513402A (ja) * | 2008-12-22 | 2012-06-14 | ケモセントリックス,インコーポレイティド | C5aRアンタゴニスト |
JP2013529647A (ja) * | 2010-06-24 | 2013-07-22 | ケモセントリックス,インコーポレイティド | C5aRアンタゴニスト |
JP2014510110A (ja) * | 2011-03-25 | 2014-04-24 | ブリストル−マイヤーズ スクイブ カンパニー | Lxr調節イミダゾール誘導体のプロドラッグ |
WO2013032964A1 (en) * | 2011-08-26 | 2013-03-07 | Board Of Regents Of The University Of Nebraska | Compositions and methods for preventing and treating biofilms |
JP2015529681A (ja) * | 2012-09-13 | 2015-10-08 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドGlaxosmithkline Intellectual Property Development Limited | アミノキナゾリンキナーゼ阻害剤のプロドラッグ |
WO2014198647A2 (en) * | 2013-06-11 | 2014-12-18 | Bayer Pharma Aktiengesellschaft | Prodrug derivatives of substituted triazolopyridines |
Non-Patent Citations (5)
Title |
---|
BUNDGAARD H: "NOVEL CHEMICAL APPROACHES IN PRODRUG DESIGN", DRUGS OF THE FUTURE, vol. 16, no. 5, JPN5011002072, 1 May 1991 (1991-05-01), ES, pages 443 - 58, XP000196088, ISSN: 0004705990 * |
LARSEN, C. S. ET AL., TEXTBOOK OF DRUG DESIGN AND DISCOVERY, vol. Charpter 14, JPN6014038866, 2002, pages 460 - 514, ISSN: 0004705989 * |
STELLA V.J., NTI-ADDAE K.W.: "Prodrug strategies to overcome poor water solubility", ADVANCED DRUG DELIVERY REVIEWS, vol. 59, JPN6021008430, 2007, pages 677 - 694, XP022211987, ISSN: 0004705988, DOI: 10.1016/j.addr.2007.05.013 * |
周東智, 有機医薬分子論, vol. 2刷, JPN6017042086, 25 August 2012 (2012-08-25), pages 169 - 171, ISSN: 0004705991 * |
製剤学・物理薬剤学, vol. 2版1刷, JPN6018001718, 2012, pages 259 - 66, ISSN: 0004705992 * |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7121722B2 (ja) | 可溶性C5aRアンタゴニスト | |
TWI791423B (zh) | C3腎絲球病變之治療方法 | |
AU2017289038B2 (en) | Immunomodulator compounds | |
TWI827590B (zh) | 稠和雙環C5aR拮抗劑之前藥 | |
TW201934552A (zh) | 作為C5aR抑制劑之經二芳基取代之5,5-稠合環化合物 | |
TW201927782A (zh) | 作為C5aR抑制劑之經二芳基取代之6,5-稠合環化合物 | |
JP2022554019A (ja) | 補体成分C5a受容体の遊離塩基結晶形態 | |
CN114206338A (zh) | 作为pd-l1抑制剂的二氢化茚类 | |
JP2023501789A (ja) | 補体成分C5a受容体の非晶質形態 | |
JP2022553835A (ja) | 塩形態の補体成分c5a受容体 | |
BR112018070214B1 (pt) | ANTAGONISTAS C5Ar SOLÚVEIS, COMPOSIÇÕES FARMACEUTICAS E SEUS USOS |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200402 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200402 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20210303 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210316 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20210615 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210914 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20220215 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220614 |
|
C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20220614 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20220621 |
|
C21 | Notice of transfer of a case for reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C21 Effective date: 20220628 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20220712 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20220805 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7121722 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |