CN105473586B - 晶体溴结构域抑制剂 - Google Patents
晶体溴结构域抑制剂 Download PDFInfo
- Publication number
- CN105473586B CN105473586B CN201480042976.3A CN201480042976A CN105473586B CN 105473586 B CN105473586 B CN 105473586B CN 201480042976 A CN201480042976 A CN 201480042976A CN 105473586 B CN105473586 B CN 105473586B
- Authority
- CN
- China
- Prior art keywords
- cancer
- disease
- crystal form
- methyl
- phenyl
- 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.)
- Active
Links
- 239000013078 crystal Substances 0.000 title claims abstract description 46
- 239000003112 inhibitor Substances 0.000 title description 41
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 title description 14
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 title description 14
- 229910052794 bromium Inorganic materials 0.000 title description 14
- -1 2,4- difluoro phenoxy Chemical group 0.000 claims abstract description 158
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 108
- ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical group CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 claims abstract description 105
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 52
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 37
- 201000010099 disease Diseases 0.000 claims abstract description 33
- 201000011510 cancer Diseases 0.000 claims abstract description 32
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 30
- 239000003814 drug Substances 0.000 claims description 96
- 239000000843 powder Substances 0.000 claims description 33
- 206010029164 Nephrotic syndrome Diseases 0.000 claims description 32
- 210000004027 cell Anatomy 0.000 claims description 32
- 239000000203 mixture Substances 0.000 claims description 32
- 208000009928 nephrosis Diseases 0.000 claims description 32
- 231100001027 nephrosis Toxicity 0.000 claims description 32
- 238000011282 treatment Methods 0.000 claims description 31
- 229940079593 drug Drugs 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 26
- 238000002360 preparation method Methods 0.000 claims description 26
- 230000006698 induction Effects 0.000 claims description 21
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 16
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 12
- 238000000113 differential scanning calorimetry Methods 0.000 claims description 12
- 208000032839 leukemia Diseases 0.000 claims description 12
- 230000001154 acute effect Effects 0.000 claims description 11
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 10
- 210000003719 b-lymphocyte Anatomy 0.000 claims description 9
- 201000009030 Carcinoma Diseases 0.000 claims description 8
- 206010039491 Sarcoma Diseases 0.000 claims description 7
- 206010040047 Sepsis Diseases 0.000 claims description 7
- 208000013223 septicemia Diseases 0.000 claims description 7
- 206010009944 Colon cancer Diseases 0.000 claims description 6
- 208000032612 Glial tumor Diseases 0.000 claims description 6
- 206010018338 Glioma Diseases 0.000 claims description 6
- 206010018364 Glomerulonephritis Diseases 0.000 claims description 6
- 206010022489 Insulin Resistance Diseases 0.000 claims description 6
- 206010035664 Pneumonia Diseases 0.000 claims description 6
- 206010060862 Prostate cancer Diseases 0.000 claims description 6
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 6
- 230000035755 proliferation Effects 0.000 claims description 6
- 210000003491 skin Anatomy 0.000 claims description 6
- 208000030507 AIDS Diseases 0.000 claims description 5
- 201000004624 Dermatitis Diseases 0.000 claims description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 5
- 201000005202 lung cancer Diseases 0.000 claims description 5
- 208000020816 lung neoplasm Diseases 0.000 claims description 5
- 208000012804 lymphangiosarcoma Diseases 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 206010002556 Ankylosing Spondylitis Diseases 0.000 claims description 4
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims description 4
- 208000011231 Crohn disease Diseases 0.000 claims description 4
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 4
- 206010019280 Heart failures Diseases 0.000 claims description 4
- 206010019708 Hepatic steatosis Diseases 0.000 claims description 4
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 4
- 208000005777 Lupus Nephritis Diseases 0.000 claims description 4
- 208000001145 Metabolic Syndrome Diseases 0.000 claims description 4
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims description 4
- 201000002481 Myositis Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 201000001263 Psoriatic Arthritis Diseases 0.000 claims description 4
- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 4
- 206010040070 Septic Shock Diseases 0.000 claims description 4
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 4
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 210000000481 breast Anatomy 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 210000003734 kidney Anatomy 0.000 claims description 4
- 210000004072 lung Anatomy 0.000 claims description 4
- 206010025135 lupus erythematosus Diseases 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 210000000496 pancreas Anatomy 0.000 claims description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 4
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 4
- 206010000830 Acute leukaemia Diseases 0.000 claims description 3
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 3
- 206010003571 Astrocytoma Diseases 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- 206010004146 Basal cell carcinoma Diseases 0.000 claims description 3
- 206010005003 Bladder cancer Diseases 0.000 claims description 3
- 208000019838 Blood disease Diseases 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
- 208000003170 Bronchiolo-Alveolar Adenocarcinoma Diseases 0.000 claims description 3
- 208000017897 Carcinoma of esophagus Diseases 0.000 claims description 3
- 208000006029 Cardiomegaly Diseases 0.000 claims description 3
- 208000005243 Chondrosarcoma Diseases 0.000 claims description 3
- 201000009047 Chordoma Diseases 0.000 claims description 3
- 208000006332 Choriocarcinoma Diseases 0.000 claims description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 3
- 206010058314 Dysplasia Diseases 0.000 claims description 3
- 201000009051 Embryonal Carcinoma Diseases 0.000 claims description 3
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 3
- 208000031637 Erythroblastic Acute Leukemia Diseases 0.000 claims description 3
- 208000036566 Erythroleukaemia Diseases 0.000 claims description 3
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 3
- 208000032027 Essential Thrombocythemia Diseases 0.000 claims description 3
- 208000006168 Ewing Sarcoma Diseases 0.000 claims description 3
- 206010018374 Glomerulonephritis minimal lesion Diseases 0.000 claims description 3
- 201000005569 Gout Diseases 0.000 claims description 3
- 206010072579 Granulomatosis with polyangiitis Diseases 0.000 claims description 3
- 208000017604 Hodgkin disease Diseases 0.000 claims description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 3
- 206010055171 Hypertensive nephropathy Diseases 0.000 claims description 3
- 206010062767 Hypophysitis Diseases 0.000 claims description 3
- 208000011200 Kawasaki disease Diseases 0.000 claims description 3
- 208000018142 Leiomyosarcoma Diseases 0.000 claims description 3
- 206010061523 Lip and/or oral cavity cancer Diseases 0.000 claims description 3
- 208000004883 Lipoid Nephrosis Diseases 0.000 claims description 3
- 208000000172 Medulloblastoma Diseases 0.000 claims description 3
- 208000021642 Muscular disease Diseases 0.000 claims description 3
- 201000009623 Myopathy Diseases 0.000 claims description 3
- 206010029260 Neuroblastoma Diseases 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 201000010133 Oligodendroglioma Diseases 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 206010033645 Pancreatitis Diseases 0.000 claims description 3
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 3
- 201000000582 Retinoblastoma Diseases 0.000 claims description 3
- 201000010208 Seminoma Diseases 0.000 claims description 3
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 3
- 208000029052 T-cell acute lymphoblastic leukemia Diseases 0.000 claims description 3
- 208000001106 Takayasu Arteritis Diseases 0.000 claims description 3
- 206010044248 Toxic shock syndrome Diseases 0.000 claims description 3
- 231100000650 Toxic shock syndrome Toxicity 0.000 claims description 3
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 3
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 3
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 3
- 206010046851 Uveitis Diseases 0.000 claims description 3
- 206010047115 Vasculitis Diseases 0.000 claims description 3
- 208000014070 Vestibular schwannoma Diseases 0.000 claims description 3
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 claims description 3
- 208000004064 acoustic neuroma Diseases 0.000 claims description 3
- 208000017733 acquired polycythemia vera Diseases 0.000 claims description 3
- 208000021841 acute erythroid leukemia Diseases 0.000 claims description 3
- 208000009956 adenocarcinoma Diseases 0.000 claims description 3
- 230000008901 benefit Effects 0.000 claims description 3
- 201000010881 cervical cancer Diseases 0.000 claims description 3
- 208000006990 cholangiocarcinoma Diseases 0.000 claims description 3
- 208000020832 chronic kidney disease Diseases 0.000 claims description 3
- 208000024207 chronic leukemia Diseases 0.000 claims description 3
- 208000009060 clear cell adenocarcinoma Diseases 0.000 claims description 3
- 210000001072 colon Anatomy 0.000 claims description 3
- 208000029742 colonic neoplasm Diseases 0.000 claims description 3
- 239000002872 contrast media Substances 0.000 claims description 3
- 208000002445 cystadenocarcinoma Diseases 0.000 claims description 3
- 201000003914 endometrial carcinoma Diseases 0.000 claims description 3
- 208000010932 epithelial neoplasm Diseases 0.000 claims description 3
- 201000003444 follicular lymphoma Diseases 0.000 claims description 3
- 206010017758 gastric cancer Diseases 0.000 claims description 3
- 210000004907 gland Anatomy 0.000 claims description 3
- 208000005017 glioblastoma Diseases 0.000 claims description 3
- 208000014951 hematologic disease Diseases 0.000 claims description 3
- 208000018706 hematopoietic system disease Diseases 0.000 claims description 3
- 208000006454 hepatitis Diseases 0.000 claims description 3
- 231100000283 hepatitis Toxicity 0.000 claims description 3
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 3
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 3
- 229940088597 hormone Drugs 0.000 claims description 3
- 239000005556 hormone Substances 0.000 claims description 3
- 208000028867 ischemia Diseases 0.000 claims description 3
- 201000007270 liver cancer Diseases 0.000 claims description 3
- 208000014018 liver neoplasm Diseases 0.000 claims description 3
- 208000019420 lymphoid neoplasm Diseases 0.000 claims description 3
- 201000000564 macroglobulinemia Diseases 0.000 claims description 3
- 230000036210 malignancy Effects 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 201000008350 membranous glomerulonephritis Diseases 0.000 claims description 3
- 208000001725 mucocutaneous lymph node syndrome Diseases 0.000 claims description 3
- 208000025113 myeloid leukemia Diseases 0.000 claims description 3
- 201000000050 myeloid neoplasm Diseases 0.000 claims description 3
- 201000008383 nephritis Diseases 0.000 claims description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- 208000020717 oral cavity carcinoma Diseases 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- 210000001672 ovary Anatomy 0.000 claims description 3
- 208000004019 papillary adenocarcinoma Diseases 0.000 claims description 3
- 208000008494 pericarditis Diseases 0.000 claims description 3
- 208000024724 pineal body neoplasm Diseases 0.000 claims description 3
- 231100000614 poison Toxicity 0.000 claims description 3
- 239000002574 poison Substances 0.000 claims description 3
- 208000030761 polycystic kidney disease Diseases 0.000 claims description 3
- 208000037244 polycythemia vera Diseases 0.000 claims description 3
- 210000002307 prostate Anatomy 0.000 claims description 3
- 201000008407 sebaceous adenocarcinoma Diseases 0.000 claims description 3
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 3
- 201000011549 stomach cancer Diseases 0.000 claims description 3
- 238000001356 surgical procedure Methods 0.000 claims description 3
- 201000002510 thyroid cancer Diseases 0.000 claims description 3
- 206010043778 thyroiditis Diseases 0.000 claims description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 3
- 210000003932 urinary bladder Anatomy 0.000 claims description 3
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 3
- 206010046766 uterine cancer Diseases 0.000 claims description 3
- 208000026872 Addison Disease Diseases 0.000 claims description 2
- 201000003076 Angiosarcoma Diseases 0.000 claims description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 2
- 208000009137 Behcet syndrome Diseases 0.000 claims description 2
- 206010008609 Cholangitis sclerosing Diseases 0.000 claims description 2
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
- 206010066786 Diabetic keratopathy Diseases 0.000 claims description 2
- 208000001258 Hemangiosarcoma Diseases 0.000 claims description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 2
- 206010054949 Metaplasia Diseases 0.000 claims description 2
- 208000035327 Oestrogen receptor positive breast cancer Diseases 0.000 claims description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
- 210000001367 artery Anatomy 0.000 claims description 2
- 208000010668 atopic eczema Diseases 0.000 claims description 2
- 210000004369 blood Anatomy 0.000 claims description 2
- 239000008280 blood Substances 0.000 claims description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 2
- 208000025302 chronic primary adrenal insufficiency Diseases 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 201000007281 estrogen-receptor positive breast cancer Diseases 0.000 claims description 2
- 201000005206 focal segmental glomerulosclerosis Diseases 0.000 claims description 2
- 231100000854 focal segmental glomerulosclerosis Toxicity 0.000 claims description 2
- 208000025750 heavy chain disease Diseases 0.000 claims description 2
- 235000013372 meat Nutrition 0.000 claims description 2
- 230000015689 metaplastic ossification Effects 0.000 claims description 2
- 208000001611 myxosarcoma Diseases 0.000 claims description 2
- 201000008968 osteosarcoma Diseases 0.000 claims description 2
- 201000010198 papillary carcinoma Diseases 0.000 claims description 2
- 201000006292 polyarteritis nodosa Diseases 0.000 claims description 2
- 230000002062 proliferating effect Effects 0.000 claims description 2
- 201000001275 rectum cancer Diseases 0.000 claims description 2
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 2
- 208000010157 sclerosing cholangitis Diseases 0.000 claims description 2
- 210000001550 testis Anatomy 0.000 claims description 2
- 210000004291 uterus Anatomy 0.000 claims description 2
- 210000003462 vein Anatomy 0.000 claims description 2
- ZLKWLYKVKAVOMD-UHFFFAOYSA-N 6-methyl-1h-pyrrolo[2,3-c]pyridin-7-one Chemical compound O=C1N(C)C=CC2=C1NC=C2 ZLKWLYKVKAVOMD-UHFFFAOYSA-N 0.000 claims 3
- 210000002751 lymph Anatomy 0.000 claims 2
- 206010000871 Acute monocytic leukaemia Diseases 0.000 claims 1
- 206010000890 Acute myelomonocytic leukaemia Diseases 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims 1
- 206010053177 Epidermolysis Diseases 0.000 claims 1
- 206010016654 Fibrosis Diseases 0.000 claims 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims 1
- 208000035489 Monocytic Acute Leukemia Diseases 0.000 claims 1
- 208000006735 Periostitis Diseases 0.000 claims 1
- 208000009052 Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims 1
- 201000011186 acute T cell leukemia Diseases 0.000 claims 1
- 210000000648 angioblast Anatomy 0.000 claims 1
- 206010003230 arteritis Diseases 0.000 claims 1
- 210000004556 brain Anatomy 0.000 claims 1
- 230000007882 cirrhosis Effects 0.000 claims 1
- 208000019425 cirrhosis of liver Diseases 0.000 claims 1
- 239000000835 fiber Substances 0.000 claims 1
- 208000017169 kidney disease Diseases 0.000 claims 1
- 210000001365 lymphatic vessel Anatomy 0.000 claims 1
- 210000003460 periosteum Anatomy 0.000 claims 1
- 230000000505 pernicious effect Effects 0.000 claims 1
- 208000017520 skin disease Diseases 0.000 claims 1
- 239000004615 ingredient Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- 239000003795 chemical substances by application Substances 0.000 description 22
- 239000000243 solution Substances 0.000 description 22
- 229940124597 therapeutic agent Drugs 0.000 description 22
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 17
- 239000003937 drug carrier Substances 0.000 description 17
- 239000007787 solid Substances 0.000 description 15
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 150000001875 compounds Chemical class 0.000 description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 11
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 11
- 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 description 11
- 229940043355 kinase inhibitor Drugs 0.000 description 11
- 229960000485 methotrexate Drugs 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 11
- 238000000634 powder X-ray diffraction Methods 0.000 description 11
- OQANPHBRHBJGNZ-FYJGNVAPSA-N (3e)-6-oxo-3-[[4-(pyridin-2-ylsulfamoyl)phenyl]hydrazinylidene]cyclohexa-1,4-diene-1-carboxylic acid Chemical compound C1=CC(=O)C(C(=O)O)=C\C1=N\NC1=CC=C(S(=O)(=O)NC=2N=CC=CC=2)C=C1 OQANPHBRHBJGNZ-FYJGNVAPSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 102000000589 Interleukin-1 Human genes 0.000 description 10
- 108010002352 Interleukin-1 Proteins 0.000 description 10
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 10
- 229940073062 imuran Drugs 0.000 description 10
- 229960001940 sulfasalazine Drugs 0.000 description 10
- 229960002117 triamcinolone acetonide Drugs 0.000 description 10
- 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 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 102000014914 Carrier Proteins Human genes 0.000 description 9
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 9
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 9
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 9
- 102100040247 Tumor necrosis factor Human genes 0.000 description 9
- 108091008324 binding proteins Proteins 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- 229940083542 sodium Drugs 0.000 description 9
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 9
- 229960005486 vaccine Drugs 0.000 description 9
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
- 102100026662 Delta and Notch-like epidermal growth factor-related receptor Human genes 0.000 description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000000427 antigen Substances 0.000 description 8
- 108091007433 antigens Proteins 0.000 description 8
- 102000036639 antigens Human genes 0.000 description 8
- 229960004584 methylprednisolone Drugs 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 241000894006 Bacteria Species 0.000 description 7
- 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 description 7
- 108010036949 Cyclosporine Proteins 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 7
- 108090000695 Cytokines Proteins 0.000 description 7
- 108010008165 Etanercept Proteins 0.000 description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
- XNRVGTHNYCNCFF-UHFFFAOYSA-N Lapatinib ditosylate monohydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 XNRVGTHNYCNCFF-UHFFFAOYSA-N 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 239000005557 antagonist Substances 0.000 description 7
- 229940047495 celebrex Drugs 0.000 description 7
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 7
- 229960001265 ciclosporin Drugs 0.000 description 7
- 229930182912 cyclosporin Natural products 0.000 description 7
- 229960000304 folic acid Drugs 0.000 description 7
- 235000019152 folic acid Nutrition 0.000 description 7
- 239000011724 folic acid Substances 0.000 description 7
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 7
- 229960004963 mesalazine Drugs 0.000 description 7
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 7
- 229960005205 prednisolone Drugs 0.000 description 7
- 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 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 229960004641 rituximab Drugs 0.000 description 7
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 6
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 6
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 6
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 6
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 235000019483 Peanut oil Nutrition 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- NAVMQTYZDKMPEU-UHFFFAOYSA-N Targretin Chemical compound CC1=CC(C(CCC2(C)C)(C)C)=C2C=C1C(=C)C1=CC=C(C(O)=O)C=C1 NAVMQTYZDKMPEU-UHFFFAOYSA-N 0.000 description 6
- 239000000556 agonist Substances 0.000 description 6
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 6
- 239000003246 corticosteroid Substances 0.000 description 6
- 150000002012 dioxanes Chemical class 0.000 description 6
- 229960000403 etanercept Drugs 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol group Chemical group OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 229940089536 indocin Drugs 0.000 description 6
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 239000000312 peanut oil Substances 0.000 description 6
- 229960004618 prednisone Drugs 0.000 description 6
- 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 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 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 description 6
- 229940116176 remicade Drugs 0.000 description 6
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 6
- 229960002930 sirolimus Drugs 0.000 description 6
- 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 description 6
- 229940124530 sulfonamide Drugs 0.000 description 6
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 6
- 108091005625 BRD4 Proteins 0.000 description 5
- 102100029895 Bromodomain-containing protein 4 Human genes 0.000 description 5
- 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 description 5
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 5
- 102000001301 EGF receptor Human genes 0.000 description 5
- 108060006698 EGF receptor Proteins 0.000 description 5
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 5
- 102000014150 Interferons Human genes 0.000 description 5
- 108010050904 Interferons Proteins 0.000 description 5
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 5
- BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 description 5
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 5
- 240000007594 Oryza sativa Species 0.000 description 5
- 235000007164 Oryza sativa Nutrition 0.000 description 5
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 5
- 239000005864 Sulphur Substances 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 230000003110 anti-inflammatory effect Effects 0.000 description 5
- 150000003851 azoles Chemical class 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 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 description 5
- 229960004436 budesonide Drugs 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 229960004397 cyclophosphamide Drugs 0.000 description 5
- 229960000684 cytarabine Drugs 0.000 description 5
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 5
- HKXBNHCUPKIYDM-CGMHZMFXSA-N doxercalciferol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C HKXBNHCUPKIYDM-CGMHZMFXSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- ZVYVPGLRVWUPMP-FYSMJZIKSA-N exatecan Chemical compound C1C[C@H](N)C2=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC3=CC(F)=C(C)C1=C32 ZVYVPGLRVWUPMP-FYSMJZIKSA-N 0.000 description 5
- 229950009429 exatecan Drugs 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 229960004171 hydroxychloroquine Drugs 0.000 description 5
- XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 description 5
- 229940079322 interferon Drugs 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 229950003063 mitumomab Drugs 0.000 description 5
- 229960002009 naproxen Drugs 0.000 description 5
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 5
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 5
- 229960000435 oblimersen Drugs 0.000 description 5
- MIMNFCVQODTQDP-NDLVEFNKSA-N oblimersen Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](COP(S)(=O)O[C@@H]2[C@H](O[C@H](C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(N=C(N)C=C2)=O)COP(O)(=S)O[C@@H]2[C@H](O[C@H](C2)N2C(NC(=O)C(C)=C2)=O)CO)[C@@H](O)C1 MIMNFCVQODTQDP-NDLVEFNKSA-N 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 description 5
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 230000000770 proinflammatory effect Effects 0.000 description 5
- 235000009566 rice Nutrition 0.000 description 5
- 229960000371 rofecoxib Drugs 0.000 description 5
- 229950009213 rubitecan Drugs 0.000 description 5
- VHXNKPBCCMUMSW-FQEVSTJZSA-N rubitecan Chemical compound C1=CC([N+]([O-])=O)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VHXNKPBCCMUMSW-FQEVSTJZSA-N 0.000 description 5
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 5
- KVJXBPDAXMEYOA-CXANFOAXSA-N trilostane Chemical compound OC1=C(C#N)C[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CC[C@@]32O[C@@H]31 KVJXBPDAXMEYOA-CXANFOAXSA-N 0.000 description 5
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 description 5
- XUBOMFCQGDBHNK-JTQLQIEISA-N (S)-gatifloxacin Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCN[C@@H](C)C1 XUBOMFCQGDBHNK-JTQLQIEISA-N 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 4
- 206010011224 Cough Diseases 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 108090000177 Interleukin-11 Proteins 0.000 description 4
- 102000003815 Interleukin-11 Human genes 0.000 description 4
- 108090000978 Interleukin-4 Proteins 0.000 description 4
- 102000004388 Interleukin-4 Human genes 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- 108020004459 Small interfering RNA Proteins 0.000 description 4
- 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 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 229960002964 adalimumab Drugs 0.000 description 4
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 description 4
- 229960000548 alemtuzumab Drugs 0.000 description 4
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 4
- 229960000397 bevacizumab Drugs 0.000 description 4
- 229960002938 bexarotene Drugs 0.000 description 4
- 229960001467 bortezomib Drugs 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- LWQQLNNNIPYSNX-UROSTWAQSA-N calcipotriol Chemical compound C1([C@H](O)/C=C/[C@@H](C)[C@@H]2[C@]3(CCCC(/[C@@H]3CC2)=C\C=C\2C([C@@H](O)C[C@H](O)C/2)=C)C)CC1 LWQQLNNNIPYSNX-UROSTWAQSA-N 0.000 description 4
- 229960002882 calcipotriol Drugs 0.000 description 4
- 239000004359 castor oil Substances 0.000 description 4
- 235000019438 castor oil Nutrition 0.000 description 4
- 229960005395 cetuximab Drugs 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 4
- 229960003957 dexamethasone Drugs 0.000 description 4
- 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 description 4
- 229960001259 diclofenac Drugs 0.000 description 4
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 4
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 4
- 229960000413 doxercalciferol Drugs 0.000 description 4
- 239000002532 enzyme inhibitor Substances 0.000 description 4
- 229940125532 enzyme inhibitor Drugs 0.000 description 4
- MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical compound C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 description 4
- 229910052731 fluorine Inorganic materials 0.000 description 4
- 239000011737 fluorine Substances 0.000 description 4
- 229960003923 gatifloxacin Drugs 0.000 description 4
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 4
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 4
- HHXHVIJIIXKSOE-QILQGKCVSA-N histrelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC(N=C1)=CN1CC1=CC=CC=C1 HHXHVIJIIXKSOE-QILQGKCVSA-N 0.000 description 4
- 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 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- 229960004891 lapatinib Drugs 0.000 description 4
- 229960000681 leflunomide Drugs 0.000 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 description 4
- 239000000463 material Substances 0.000 description 4
- OJLOPKGSLYJEMD-URPKTTJQSA-N methyl 7-[(1r,2r,3r)-3-hydroxy-2-[(1e)-4-hydroxy-4-methyloct-1-en-1-yl]-5-oxocyclopentyl]heptanoate Chemical compound CCCCC(C)(O)C\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(=O)OC OJLOPKGSLYJEMD-URPKTTJQSA-N 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 229960005249 misoprostol Drugs 0.000 description 4
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 229960004270 nabumetone Drugs 0.000 description 4
- 229960005027 natalizumab Drugs 0.000 description 4
- 239000002773 nucleotide Substances 0.000 description 4
- 125000003729 nucleotide group Chemical group 0.000 description 4
- 229960001592 paclitaxel Drugs 0.000 description 4
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 4
- 229960002702 piroxicam Drugs 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 229940117820 purinethol Drugs 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 229930002330 retinoic acid Natural products 0.000 description 4
- 229960002052 salbutamol Drugs 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- WVYADZUPLLSGPU-UHFFFAOYSA-N salsalate Chemical compound OC(=O)C1=CC=CC=C1OC(=O)C1=CC=CC=C1O WVYADZUPLLSGPU-UHFFFAOYSA-N 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 229960000894 sulindac Drugs 0.000 description 4
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 4
- 230000001629 suppression Effects 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 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 description 4
- AYUNIORJHRXIBJ-TXHRRWQRSA-N tanespimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC2=C(NCC=C)C(=O)C=C1C2=O AYUNIORJHRXIBJ-TXHRRWQRSA-N 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 4
- 238000001931 thermography Methods 0.000 description 4
- 238000002411 thermogravimetry Methods 0.000 description 4
- 238000001757 thermogravimetry curve Methods 0.000 description 4
- 229960000575 trastuzumab Drugs 0.000 description 4
- 229960001670 trilostane Drugs 0.000 description 4
- 229960002004 valdecoxib Drugs 0.000 description 4
- BMKDZUISNHGIBY-ZETCQYMHSA-N (+)-dexrazoxane Chemical compound C([C@H](C)N1CC(=O)NC(=O)C1)N1CC(=O)NC(=O)C1 BMKDZUISNHGIBY-ZETCQYMHSA-N 0.000 description 3
- LVLLALCJVJNGQQ-SEODYNFXSA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-1-[(2r,3e,5e)-7-ethyl-7-hydroxynona-3,5-dien-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/C=C/C(O)(CC)CC)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C LVLLALCJVJNGQQ-SEODYNFXSA-N 0.000 description 3
- IUAXSWPNEQYKDR-GXTZACRKSA-N (4R,4aR,7aR,12bS)-9-methoxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one 2,3-dihydroxybutanedioic acid dihydrate Chemical compound O.O.OC(C(O)C(O)=O)C(O)=O.COc1ccc2C[C@@H]3[C@@H]4CCC(=O)[C@@H]5Oc1c2[C@]45CCN3C IUAXSWPNEQYKDR-GXTZACRKSA-N 0.000 description 3
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- PVCULFYROUOVGJ-UHFFFAOYSA-N 1-[2-chloroethyl(methylsulfonyl)amino]-3-methyl-1-methylsulfonylurea Chemical compound CNC(=O)N(S(C)(=O)=O)N(S(C)(=O)=O)CCCl PVCULFYROUOVGJ-UHFFFAOYSA-N 0.000 description 3
- AXPZIVKEZRHGAS-UHFFFAOYSA-N 3-benzyl-5-[(2-nitrophenoxy)methyl]oxolan-2-one Chemical compound [O-][N+](=O)C1=CC=CC=C1OCC1OC(=O)C(CC=2C=CC=CC=2)C1 AXPZIVKEZRHGAS-UHFFFAOYSA-N 0.000 description 3
- 239000005541 ACE inhibitor Substances 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 102100033641 Bromodomain-containing protein 2 Human genes 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 description 3
- 229940124073 Complement inhibitor Drugs 0.000 description 3
- 102000009058 Death Domain Receptors Human genes 0.000 description 3
- 108010049207 Death Domain Receptors Proteins 0.000 description 3
- 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 description 3
- 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 3
- 206010018473 Glycosuria Diseases 0.000 description 3
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 3
- 101000871850 Homo sapiens Bromodomain-containing protein 2 Proteins 0.000 description 3
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 239000003458 I kappa b kinase inhibitor Substances 0.000 description 3
- 108010074328 Interferon-gamma Proteins 0.000 description 3
- 102000008070 Interferon-gamma Human genes 0.000 description 3
- 101800001003 Interleukin-1 receptor type 2, soluble form Proteins 0.000 description 3
- 102400000027 Interleukin-1 receptor type 2, soluble form Human genes 0.000 description 3
- 102000003814 Interleukin-10 Human genes 0.000 description 3
- 108090000174 Interleukin-10 Proteins 0.000 description 3
- 108090000176 Interleukin-13 Proteins 0.000 description 3
- 102000003816 Interleukin-13 Human genes 0.000 description 3
- 108010002350 Interleukin-2 Proteins 0.000 description 3
- 102000000588 Interleukin-2 Human genes 0.000 description 3
- 102000004889 Interleukin-6 Human genes 0.000 description 3
- 108090001005 Interleukin-6 Proteins 0.000 description 3
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 3
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 3
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 3
- 229940122696 MAP kinase inhibitor Drugs 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000012826 P38 inhibitor Substances 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 3
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 3
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- BPEGJWRSRHCHSN-UHFFFAOYSA-N Temozolomide Chemical compound O=C1N(C)N=NC2=C(C(N)=O)N=CN21 BPEGJWRSRHCHSN-UHFFFAOYSA-N 0.000 description 3
- 108010078233 Thymalfasin Proteins 0.000 description 3
- IVTVGDXNLFLDRM-HNNXBMFYSA-N Tomudex Chemical compound C=1C=C2NC(C)=NC(=O)C2=CC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)S1 IVTVGDXNLFLDRM-HNNXBMFYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000002441 X-ray diffraction Methods 0.000 description 3
- OGQICQVSFDPSEI-UHFFFAOYSA-N Zorac Chemical compound N1=CC(C(=O)OCC)=CC=C1C#CC1=CC=C(SCCC2(C)C)C2=C1 OGQICQVSFDPSEI-UHFFFAOYSA-N 0.000 description 3
- 230000021736 acetylation Effects 0.000 description 3
- 238000006640 acetylation reaction Methods 0.000 description 3
- 230000001800 adrenalinergic effect Effects 0.000 description 3
- 229930013930 alkaloid Natural products 0.000 description 3
- 150000003797 alkaloid derivatives Chemical class 0.000 description 3
- IHUNBGSDBOWDMA-AQFIFDHZSA-N all-trans-acitretin Chemical compound COC1=CC(C)=C(\C=C\C(\C)=C\C=C\C(\C)=C\C(O)=O)C(C)=C1C IHUNBGSDBOWDMA-AQFIFDHZSA-N 0.000 description 3
- 229940049595 antibody-drug conjugate Drugs 0.000 description 3
- MOTJMGVDPWRKOC-QPVYNBJUSA-N atrasentan Chemical compound C1([C@H]2[C@@H]([C@H](CN2CC(=O)N(CCCC)CCCC)C=2C=C3OCOC3=CC=2)C(O)=O)=CC=C(OC)C=C1 MOTJMGVDPWRKOC-QPVYNBJUSA-N 0.000 description 3
- 239000003719 aurora kinase inhibitor Substances 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 239000004074 complement inhibitor Substances 0.000 description 3
- 235000005687 corn oil Nutrition 0.000 description 3
- 239000002285 corn oil Substances 0.000 description 3
- 239000002385 cottonseed oil Substances 0.000 description 3
- 235000012343 cottonseed oil Nutrition 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 3
- 238000006356 dehydrogenation reaction Methods 0.000 description 3
- WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine mesylate Natural products CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 WHBIGIKBNXZKFE-UHFFFAOYSA-N 0.000 description 3
- 229960001193 diclofenac sodium Drugs 0.000 description 3
- LFQCJSBXBZRMTN-OAQYLSRUSA-N diflomotecan Chemical compound CC[C@@]1(O)CC(=O)OCC(C2=O)=C1C=C1N2CC2=CC3=CC(F)=C(F)C=C3N=C21 LFQCJSBXBZRMTN-OAQYLSRUSA-N 0.000 description 3
- 229960004679 doxorubicin Drugs 0.000 description 3
- BNFRJXLZYUTIII-UHFFFAOYSA-N efaproxiral Chemical compound CC1=CC(C)=CC(NC(=O)CC=2C=CC(OC(C)(C)C(O)=O)=CC=2)=C1 BNFRJXLZYUTIII-UHFFFAOYSA-N 0.000 description 3
- 229960002179 ephedrine Drugs 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- NNYBQONXHNTVIJ-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=C1C(C=CC=C1CC)=C1N2 NNYBQONXHNTVIJ-UHFFFAOYSA-N 0.000 description 3
- 229960004945 etoricoxib Drugs 0.000 description 3
- 229950000484 exisulind Drugs 0.000 description 3
- 229960000676 flunisolide Drugs 0.000 description 3
- 229960000785 fluocinonide Drugs 0.000 description 3
- 229960002949 fluorouracil Drugs 0.000 description 3
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 229940022353 herceptin Drugs 0.000 description 3
- 108700020746 histrelin Proteins 0.000 description 3
- 229960002193 histrelin Drugs 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 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 description 3
- 238000002513 implantation Methods 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 229960001888 ipratropium Drugs 0.000 description 3
- OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 description 3
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 3
- GOTYRUGSSMKFNF-UHFFFAOYSA-N lenalidomide Chemical compound C1C=2C(N)=CC=CC=2C(=O)N1C1CCC(=O)NC1=O GOTYRUGSSMKFNF-UHFFFAOYSA-N 0.000 description 3
- 229950007278 lenercept Drugs 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 3
- KHPKQFYUPIUARC-UHFFFAOYSA-N lumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1Cl KHPKQFYUPIUARC-UHFFFAOYSA-N 0.000 description 3
- 210000001161 mammalian embryo Anatomy 0.000 description 3
- 229960001929 meloxicam Drugs 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 229960000334 methylprednisolone sodium succinate Drugs 0.000 description 3
- 229960005225 mifamurtide Drugs 0.000 description 3
- JMUHBNWAORSSBD-WKYWBUFDSA-N mifamurtide Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCC)COP(O)(=O)OCCNC(=O)[C@H](C)NC(=O)CC[C@H](C(N)=O)NC(=O)[C@H](C)NC(=O)[C@@H](C)O[C@H]1[C@H](O)[C@@H](CO)OC(O)[C@@H]1NC(C)=O JMUHBNWAORSSBD-WKYWBUFDSA-N 0.000 description 3
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 description 3
- 229960001156 mitoxantrone Drugs 0.000 description 3
- VOWOEBADKMXUBU-UHFFFAOYSA-J molecular oxygen;tetrachlorite;hydrate Chemical compound O.O=O.[O-]Cl=O.[O-]Cl=O.[O-]Cl=O.[O-]Cl=O VOWOEBADKMXUBU-UHFFFAOYSA-J 0.000 description 3
- 229960002744 mometasone furoate Drugs 0.000 description 3
- WOFMFGQZHJDGCX-ZULDAHANSA-N mometasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(Cl)[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@H]1C)C(=O)CCl)C(=O)C1=CC=CO1 WOFMFGQZHJDGCX-ZULDAHANSA-N 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 3
- 229960004866 mycophenolate mofetil Drugs 0.000 description 3
- LBWFXVZLPYTWQI-IPOVEDGCSA-N n-[2-(diethylamino)ethyl]-5-[(z)-(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C LBWFXVZLPYTWQI-IPOVEDGCSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 229960001699 ofloxacin Drugs 0.000 description 3
- FDLYAMZZIXQODN-UHFFFAOYSA-N olaparib Chemical compound FC1=CC=C(CC=2C3=CC=CC=C3C(=O)NN=2)C=C1C(=O)N(CC1)CCN1C(=O)C1CC1 FDLYAMZZIXQODN-UHFFFAOYSA-N 0.000 description 3
- 239000004006 olive oil Substances 0.000 description 3
- 235000008390 olive oil Nutrition 0.000 description 3
- 229960004110 olsalazine Drugs 0.000 description 3
- QQBDLJCYGRGAKP-FOCLMDBBSA-N olsalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=C(C(O)=CC=2)C(O)=O)=C1 QQBDLJCYGRGAKP-FOCLMDBBSA-N 0.000 description 3
- 239000005416 organic matter Substances 0.000 description 3
- MUZQPDBAOYKNLO-RKXJKUSZSA-N oxycodone hydrochloride Chemical compound [H+].[Cl-].O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C MUZQPDBAOYKNLO-RKXJKUSZSA-N 0.000 description 3
- 108700027936 paclitaxel poliglumex Proteins 0.000 description 3
- 229960005489 paracetamol Drugs 0.000 description 3
- WBXPDJSOTKVWSJ-ZDUSSCGKSA-N pemetrexed Chemical compound C=1NC=2NC(N)=NC(=O)C=2C=1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 WBXPDJSOTKVWSJ-ZDUSSCGKSA-N 0.000 description 3
- 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 description 3
- IIMIOEBMYPRQGU-UHFFFAOYSA-L picoplatin Chemical compound N.[Cl-].[Cl-].[Pt+2].CC1=CC=CC=N1 IIMIOEBMYPRQGU-UHFFFAOYSA-L 0.000 description 3
- 229910052697 platinum Inorganic materials 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229920001184 polypeptide Polymers 0.000 description 3
- 229910000160 potassium phosphate Inorganic materials 0.000 description 3
- 235000011009 potassium phosphates Nutrition 0.000 description 3
- 230000001376 precipitating effect Effects 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 3
- 230000005855 radiation Effects 0.000 description 3
- 238000001959 radiotherapy Methods 0.000 description 3
- 229960004432 raltitrexed Drugs 0.000 description 3
- 210000000664 rectum Anatomy 0.000 description 3
- 230000001177 retroviral effect Effects 0.000 description 3
- 239000002336 ribonucleotide Substances 0.000 description 3
- 229960004017 salmeterol Drugs 0.000 description 3
- BTIHMVBBUGXLCJ-OAHLLOKOSA-N seliciclib Chemical compound C=12N=CN(C(C)C)C2=NC(N[C@@H](CO)CC)=NC=1NCC1=CC=CC=C1 BTIHMVBBUGXLCJ-OAHLLOKOSA-N 0.000 description 3
- 239000008159 sesame oil Substances 0.000 description 3
- 235000011803 sesame oil Nutrition 0.000 description 3
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 description 3
- 229960003787 sorafenib Drugs 0.000 description 3
- 150000003456 sulfonamides Chemical class 0.000 description 3
- MVGSNCBCUWPVDA-MFOYZWKCSA-N sulindac sulfone Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)(=O)=O)C=C1 MVGSNCBCUWPVDA-MFOYZWKCSA-N 0.000 description 3
- NZVYCXVTEHPMHE-ZSUJOUNUSA-N thymalfasin Chemical compound CC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O NZVYCXVTEHPMHE-ZSUJOUNUSA-N 0.000 description 3
- 229960004231 thymalfasin Drugs 0.000 description 3
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 3
- 229960005267 tositumomab Drugs 0.000 description 3
- 229950010147 troxacitabine Drugs 0.000 description 3
- RXRGZNYSEHTMHC-BQBZGAKWSA-N troxacitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)OC1 RXRGZNYSEHTMHC-BQBZGAKWSA-N 0.000 description 3
- ZOCKGBMQLCSHFP-KQRAQHLDSA-N valrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC(OC)=C4C(=O)C=3C(O)=C21)(O)C(=O)COC(=O)CCCC)[C@H]1C[C@H](NC(=O)C(F)(F)F)[C@H](O)[C@H](C)O1 ZOCKGBMQLCSHFP-KQRAQHLDSA-N 0.000 description 3
- YCOYDOIWSSHVCK-UHFFFAOYSA-N vatalanib Chemical compound C1=CC(Cl)=CC=C1NC(C1=CC=CC=C11)=NN=C1CC1=CC=NC=C1 YCOYDOIWSSHVCK-UHFFFAOYSA-N 0.000 description 3
- 229960004528 vincristine Drugs 0.000 description 3
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 3
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 3
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 2
- WVTKBKWTSCPRNU-KYJUHHDHSA-N (+)-Tetrandrine Chemical compound C([C@H]1C=2C=C(C(=CC=2CCN1C)OC)O1)C(C=C2)=CC=C2OC(=C2)C(OC)=CC=C2C[C@@H]2N(C)CCC3=CC(OC)=C(OC)C1=C23 WVTKBKWTSCPRNU-KYJUHHDHSA-N 0.000 description 2
- KLZOTDOJMRMLDX-YBBVPDDNSA-N (1r,3s,5z)-5-[(2e)-2-[(1s,3as,7as)-1-[(1r)-1-(4-ethyl-4-hydroxyhexoxy)ethyl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](C)OCCCC(O)(CC)CC)=C\C=C1\C[C@@H](O)C[C@H](O)C1=C KLZOTDOJMRMLDX-YBBVPDDNSA-N 0.000 description 2
- NITUEMISTORFON-PPFXTMJRSA-N (2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S)-1-[(2S,3R)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-4-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2R)-2-aminopropanoyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-methylbutanoyl]amino]-3-methylbutanoyl]amino]-3-(1H-imidazol-5-yl)propanoyl]amino]-4-methylpentanoyl]amino]-3-phenylpropanoyl]amino]propanoyl]amino]-4-oxobutanoyl]amino]-3-methylpentanoyl]amino]-3-methylbutanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carbonyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-3-hydroxybutanoyl]pyrrolidine-2-carboxylic acid Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@@H](C)N)C(C)C)C(C)C)C1=CC=CC=C1 NITUEMISTORFON-PPFXTMJRSA-N 0.000 description 2
- CVCQAQVBOPNTFI-AAONGDSNSA-N (3r,4r,5s,6r)-3-amino-6-(hydroxymethyl)oxane-2,4,5-triol;sulfuric acid Chemical compound OS(O)(=O)=O.N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O.N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O CVCQAQVBOPNTFI-AAONGDSNSA-N 0.000 description 2
- UUEZOEBHFHYMGR-RNWHKREASA-N (4r,4ar,7ar,12bs)-9-methoxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinoline-7-one;3-(4-chlorophenyl)-n,n-dimethyl-3-pyridin-2-ylpropan-1-amine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1.C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC UUEZOEBHFHYMGR-RNWHKREASA-N 0.000 description 2
- PQMFVUNERGGBPG-UHFFFAOYSA-N (6-bromopyridin-2-yl)hydrazine Chemical compound NNC1=CC=CC(Br)=N1 PQMFVUNERGGBPG-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- NDAUXUAQIAJITI-LBPRGKRZSA-N (R)-salbutamol Chemical compound CC(C)(C)NC[C@H](O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-LBPRGKRZSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- TZJUVVIWVWFLCD-UHFFFAOYSA-N 1,1-dioxo-2-[4-[4-(2-pyrimidinyl)-1-piperazinyl]butyl]-1,2-benzothiazol-3-one Chemical compound O=S1(=O)C2=CC=CC=C2C(=O)N1CCCCN(CC1)CCN1C1=NC=CC=N1 TZJUVVIWVWFLCD-UHFFFAOYSA-N 0.000 description 2
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 2
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 2
- VTAKZNRDSPNOAU-UHFFFAOYSA-M 2-(chloromethyl)oxirane;hydron;prop-2-en-1-amine;n-prop-2-enyldecan-1-amine;trimethyl-[6-(prop-2-enylamino)hexyl]azanium;dichloride Chemical compound Cl.[Cl-].NCC=C.ClCC1CO1.CCCCCCCCCCNCC=C.C[N+](C)(C)CCCCCCNCC=C VTAKZNRDSPNOAU-UHFFFAOYSA-M 0.000 description 2
- OXBBIHZWNDPBMQ-UHFFFAOYSA-N 2-[2-(4-benzhydrylpiperazin-1-yl)ethoxy]ethanol Chemical compound C1CN(CCOCCO)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 OXBBIHZWNDPBMQ-UHFFFAOYSA-N 0.000 description 2
- PBUUPFTVAPUWDE-UGZDLDLSSA-N 2-[[(2S,4S)-2-[bis(2-chloroethyl)amino]-2-oxo-1,3,2lambda5-oxazaphosphinan-4-yl]sulfanyl]ethanesulfonic acid Chemical compound OS(=O)(=O)CCS[C@H]1CCO[P@](=O)(N(CCCl)CCCl)N1 PBUUPFTVAPUWDE-UGZDLDLSSA-N 0.000 description 2
- RTQWWZBSTRGEAV-PKHIMPSTSA-N 2-[[(2s)-2-[bis(carboxymethyl)amino]-3-[4-(methylcarbamoylamino)phenyl]propyl]-[2-[bis(carboxymethyl)amino]propyl]amino]acetic acid Chemical compound CNC(=O)NC1=CC=C(C[C@@H](CN(CC(C)N(CC(O)=O)CC(O)=O)CC(O)=O)N(CC(O)=O)CC(O)=O)C=C1 RTQWWZBSTRGEAV-PKHIMPSTSA-N 0.000 description 2
- PJKVJJYMWOCLIJ-UHFFFAOYSA-N 2-amino-6-methyl-5-pyridin-4-ylsulfanyl-1h-quinazolin-4-one;hydron;dichloride Chemical compound Cl.Cl.CC1=CC=C2NC(N)=NC(=O)C2=C1SC1=CC=NC=C1 PJKVJJYMWOCLIJ-UHFFFAOYSA-N 0.000 description 2
- ZZUBHVMHNVYXRR-UHFFFAOYSA-N 3-(4-hydroxyphenyl)-2h-chromen-7-ol Chemical compound C1=CC(O)=CC=C1C1=CC2=CC=C(O)C=C2OC1 ZZUBHVMHNVYXRR-UHFFFAOYSA-N 0.000 description 2
- WEVYNIUIFUYDGI-UHFFFAOYSA-N 3-[6-[4-(trifluoromethoxy)anilino]-4-pyrimidinyl]benzamide Chemical compound NC(=O)C1=CC=CC(C=2N=CN=C(NC=3C=CC(OC(F)(F)F)=CC=3)C=2)=C1 WEVYNIUIFUYDGI-UHFFFAOYSA-N 0.000 description 2
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 2
- DMPBYEVIGRTAAL-UHFFFAOYSA-N 4-(4-methylphenyl)sulfonyl-1,6-dihydropyrrolo[2,3-c]pyridin-7-one Chemical compound Cc1ccc(cc1)S(=O)(=O)c1c[nH]c(=O)c2[nH]ccc12 DMPBYEVIGRTAAL-UHFFFAOYSA-N 0.000 description 2
- NUKYPUAOHBNCPY-UHFFFAOYSA-N 4-aminopyridine Chemical compound NC1=CC=NC=C1 NUKYPUAOHBNCPY-UHFFFAOYSA-N 0.000 description 2
- XTWYTFMLZFPYCI-KQYNXXCUSA-N 5'-adenylphosphoric acid Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O XTWYTFMLZFPYCI-KQYNXXCUSA-N 0.000 description 2
- LGZKGOGODCLQHG-CYBMUJFWSA-N 5-[(2r)-2-hydroxy-2-(3,4,5-trimethoxyphenyl)ethyl]-2-methoxyphenol Chemical compound C1=C(O)C(OC)=CC=C1C[C@@H](O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-CYBMUJFWSA-N 0.000 description 2
- SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 description 2
- DQOGWKZQQBYYMW-LQGIGNHCSA-N 5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline-2,4-diamine;(2s,3s,4s,5r,6s)-3,4,5,6-tetrahydroxyoxane-2-carboxylic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O.COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 DQOGWKZQQBYYMW-LQGIGNHCSA-N 0.000 description 2
- 102100026802 72 kDa type IV collagenase Human genes 0.000 description 2
- 101710151806 72 kDa type IV collagenase Proteins 0.000 description 2
- AVVSJWUWBATQBX-UHFFFAOYSA-N 97739-46-3 Chemical compound O1C(C)(O2)CC3(C)OC2(C)CC1(C)P3C1=CC=CC=C1 AVVSJWUWBATQBX-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- 208000030090 Acute Disease Diseases 0.000 description 2
- 208000009304 Acute Kidney Injury Diseases 0.000 description 2
- XTWYTFMLZFPYCI-UHFFFAOYSA-N Adenosine diphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(O)=O)C(O)C1O XTWYTFMLZFPYCI-UHFFFAOYSA-N 0.000 description 2
- 108010012934 Albumin-Bound Paclitaxel Proteins 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 2
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 description 2
- GOLCXWYRSKYTSP-UHFFFAOYSA-N Arsenious Acid Chemical compound O1[As]2O[As]1O2 GOLCXWYRSKYTSP-UHFFFAOYSA-N 0.000 description 2
- AXRYRYVKAWYZBR-UHFFFAOYSA-N Atazanavir Natural products C=1C=C(C=2N=CC=CC=2)C=CC=1CN(NC(=O)C(NC(=O)OC)C(C)(C)C)CC(O)C(NC(=O)C(NC(=O)OC)C(C)(C)C)CC1=CC=CC=C1 AXRYRYVKAWYZBR-UHFFFAOYSA-N 0.000 description 2
- 108010019625 Atazanavir Sulfate Proteins 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 102100022005 B-lymphocyte antigen CD20 Human genes 0.000 description 2
- 101150034980 BRDT gene Proteins 0.000 description 2
- KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone 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)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 description 2
- VGGGPCQERPFHOB-MCIONIFRSA-N Bestatin Chemical compound CC(C)C[C@H](C(O)=O)NC(=O)[C@@H](O)[C@H](N)CC1=CC=CC=C1 VGGGPCQERPFHOB-MCIONIFRSA-N 0.000 description 2
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 2
- 108010006654 Bleomycin Proteins 0.000 description 2
- 102100033642 Bromodomain-containing protein 3 Human genes 0.000 description 2
- 108010037003 Buserelin Proteins 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- 102000017420 CD3 protein, epsilon/gamma/delta subunit Human genes 0.000 description 2
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Proteins 0.000 description 2
- 101150013553 CD40 gene Proteins 0.000 description 2
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 2
- 108090000994 Catalytic RNA Proteins 0.000 description 2
- 102000053642 Catalytic RNA Human genes 0.000 description 2
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 description 2
- 241001227713 Chiron Species 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 229920002905 Colesevelam Polymers 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 2
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 2
- 229930105110 Cyclosporin A Natural products 0.000 description 2
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
- 108020004414 DNA Proteins 0.000 description 2
- 108010092160 Dactinomycin Proteins 0.000 description 2
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 2
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 2
- 102100033553 Delta-like protein 4 Human genes 0.000 description 2
- 101100296720 Dictyostelium discoideum Pde4 gene Proteins 0.000 description 2
- 102100025137 Early activation antigen CD69 Human genes 0.000 description 2
- XXPXYPLPSDPERN-UHFFFAOYSA-N Ecteinascidin 743 Natural products COc1cc2C(NCCc2cc1O)C(=O)OCC3N4C(O)C5Cc6cc(C)c(OC)c(O)c6C(C4C(S)c7c(OC(=O)C)c(C)c8OCOc8c37)N5C XXPXYPLPSDPERN-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- XQSPYNMVSIKCOC-NTSWFWBYSA-N Emtricitabine Chemical compound C1=C(F)C(N)=NC(=O)N1[C@H]1O[C@@H](CO)SC1 XQSPYNMVSIKCOC-NTSWFWBYSA-N 0.000 description 2
- 102400000792 Endothelial monocyte-activating polypeptide 2 Human genes 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 206010014967 Ependymoma Diseases 0.000 description 2
- 241000283073 Equus caballus Species 0.000 description 2
- 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 description 2
- 101150021185 FGF gene Proteins 0.000 description 2
- 201000008808 Fibrosarcoma Diseases 0.000 description 2
- 108010029961 Filgrastim Proteins 0.000 description 2
- VWUXBMIQPBEWFH-WCCTWKNTSA-N Fulvestrant Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3[C@H](CCCCCCCCCS(=O)CCCC(F)(F)C(F)(F)F)CC2=C1 VWUXBMIQPBEWFH-WCCTWKNTSA-N 0.000 description 2
- 208000007465 Giant cell arteritis Diseases 0.000 description 2
- 108010072051 Glatiramer Acetate Proteins 0.000 description 2
- 108010069236 Goserelin Proteins 0.000 description 2
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 2
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102000001398 Granzyme Human genes 0.000 description 2
- 108060005986 Granzyme Proteins 0.000 description 2
- 102000009465 Growth Factor Receptors Human genes 0.000 description 2
- 108010009202 Growth Factor Receptors Proteins 0.000 description 2
- 108010004889 Heat-Shock Proteins Proteins 0.000 description 2
- 102000002812 Heat-Shock Proteins Human genes 0.000 description 2
- 108090000353 Histone deacetylase Proteins 0.000 description 2
- 102000003964 Histone deacetylase Human genes 0.000 description 2
- 108010033040 Histones Proteins 0.000 description 2
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 2
- 101000897405 Homo sapiens B-lymphocyte antigen CD20 Proteins 0.000 description 2
- 101000871851 Homo sapiens Bromodomain-containing protein 3 Proteins 0.000 description 2
- 101000872077 Homo sapiens Delta-like protein 4 Proteins 0.000 description 2
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 description 2
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 2
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 2
- 101000692455 Homo sapiens Platelet-derived growth factor receptor beta Proteins 0.000 description 2
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 2
- 101000934346 Homo sapiens T-cell surface antigen CD2 Proteins 0.000 description 2
- 101000716102 Homo sapiens T-cell surface glycoprotein CD4 Proteins 0.000 description 2
- 101000946843 Homo sapiens T-cell surface glycoprotein CD8 alpha chain Proteins 0.000 description 2
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 2
- 101000800116 Homo sapiens Thy-1 membrane glycoprotein Proteins 0.000 description 2
- 101000851376 Homo sapiens Tumor necrosis factor receptor superfamily member 8 Proteins 0.000 description 2
- VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 2
- 108010023610 IL13-PE38 Proteins 0.000 description 2
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 108010005716 Interferon beta-1a Proteins 0.000 description 2
- 108010005714 Interferon beta-1b Proteins 0.000 description 2
- 108010047761 Interferon-alpha Proteins 0.000 description 2
- 102000006992 Interferon-alpha Human genes 0.000 description 2
- 102000003996 Interferon-beta Human genes 0.000 description 2
- 108090000467 Interferon-beta Proteins 0.000 description 2
- 102000013462 Interleukin-12 Human genes 0.000 description 2
- 108010065805 Interleukin-12 Proteins 0.000 description 2
- 102000049772 Interleukin-16 Human genes 0.000 description 2
- 101800003050 Interleukin-16 Proteins 0.000 description 2
- 102000013264 Interleukin-23 Human genes 0.000 description 2
- 108010065637 Interleukin-23 Proteins 0.000 description 2
- 108010002586 Interleukin-7 Proteins 0.000 description 2
- 102000000704 Interleukin-7 Human genes 0.000 description 2
- 108090001007 Interleukin-8 Proteins 0.000 description 2
- 102000004890 Interleukin-8 Human genes 0.000 description 2
- 229940121730 Janus kinase 2 inhibitor Drugs 0.000 description 2
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 2
- UIARLYUEJFELEN-LROUJFHJSA-N LSM-1231 Chemical compound C12=C3N4C5=CC=CC=C5C3=C3C(=O)NCC3=C2C2=CC=CC=C2N1[C@]1(C)[C@](CO)(O)C[C@H]4O1 UIARLYUEJFELEN-LROUJFHJSA-N 0.000 description 2
- 108010062867 Lenograstim Proteins 0.000 description 2
- LTXREWYXXSTFRX-QGZVFWFLSA-N Linagliptin Chemical compound N=1C=2N(C)C(=O)N(CC=3N=C4C=CC=CC4=C(C)N=3)C(=O)C=2N(CC#CC)C=1N1CCC[C@@H](N)C1 LTXREWYXXSTFRX-QGZVFWFLSA-N 0.000 description 2
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 2
- 108010019598 Liraglutide Proteins 0.000 description 2
- GQYIWUVLTXOXAJ-UHFFFAOYSA-N Lomustine Chemical compound ClCCN(N=O)C(=O)NC1CCCCC1 GQYIWUVLTXOXAJ-UHFFFAOYSA-N 0.000 description 2
- 102000001776 Matrix metalloproteinase-9 Human genes 0.000 description 2
- 108010015302 Matrix metalloproteinase-9 Proteins 0.000 description 2
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 2
- 208000009525 Myocarditis Diseases 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 2
- 239000007832 Na2SO4 Substances 0.000 description 2
- SHGAZHPCJJPHSC-UHFFFAOYSA-N Panrexin Chemical compound OC(=O)C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-UHFFFAOYSA-N 0.000 description 2
- KHGNFPUMBJSZSM-UHFFFAOYSA-N Perforine Natural products COC1=C2CCC(O)C(CCC(C)(C)O)(OC)C2=NC2=C1C=CO2 KHGNFPUMBJSZSM-UHFFFAOYSA-N 0.000 description 2
- 208000007641 Pinealoma Diseases 0.000 description 2
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 2
- 235000011613 Pinus brutia Nutrition 0.000 description 2
- 241000018646 Pinus brutia Species 0.000 description 2
- KMSKQZKKOZQFFG-HSUXVGOQSA-N Pirarubicin Chemical compound O([C@H]1[C@@H](N)C[C@@H](O[C@H]1C)O[C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1CCCCO1 KMSKQZKKOZQFFG-HSUXVGOQSA-N 0.000 description 2
- 101100082610 Plasmodium falciparum (isolate 3D7) PDEdelta gene Proteins 0.000 description 2
- 102100026547 Platelet-derived growth factor receptor beta Human genes 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 102100033237 Pro-epidermal growth factor Human genes 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- 229940079156 Proteasome inhibitor Drugs 0.000 description 2
- AHHFEZNOXOZZQA-ZEBDFXRSSA-N Ranimustine Chemical compound CO[C@H]1O[C@H](CNC(=O)N(CCCl)N=O)[C@@H](O)[C@H](O)[C@H]1O AHHFEZNOXOZZQA-ZEBDFXRSSA-N 0.000 description 2
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 2
- 208000033626 Renal failure acute Diseases 0.000 description 2
- 108091028664 Ribonucleotide Proteins 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- 235000019485 Safflower oil Nutrition 0.000 description 2
- 241000124033 Salix Species 0.000 description 2
- 190014017285 Satraplatin Chemical compound 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000004902 Softening Agent Substances 0.000 description 2
- 102100025750 Sphingosine 1-phosphate receptor 1 Human genes 0.000 description 2
- 101710155454 Sphingosine 1-phosphate receptor 1 Proteins 0.000 description 2
- UIRKNQLZZXALBI-MSVGPLKSSA-N Squalamine Chemical compound C([C@@H]1C[C@H]2O)[C@@H](NCCCNCCCCN)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CC[C@H](C(C)C)OS(O)(=O)=O)[C@@]2(C)CC1 UIRKNQLZZXALBI-MSVGPLKSSA-N 0.000 description 2
- UIRKNQLZZXALBI-UHFFFAOYSA-N Squalamine Natural products OC1CC2CC(NCCCNCCCCN)CCC2(C)C2C1C1CCC(C(C)CCC(C(C)C)OS(O)(=O)=O)C1(C)CC2 UIRKNQLZZXALBI-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
- 102100025237 T-cell surface antigen CD2 Human genes 0.000 description 2
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 2
- 102100034922 T-cell surface glycoprotein CD8 alpha chain Human genes 0.000 description 2
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 2
- 108700011582 TER 286 Proteins 0.000 description 2
- CYQFCXCEBYINGO-UHFFFAOYSA-N THC Natural products C1=C(C)CCC2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3C21 CYQFCXCEBYINGO-UHFFFAOYSA-N 0.000 description 2
- JACAAXNEHGBPOQ-LLVKDONJSA-N Talampanel Chemical compound C([C@H](N(N=1)C(C)=O)C)C2=CC=3OCOC=3C=C2C=1C1=CC=C(N)C=C1 JACAAXNEHGBPOQ-LLVKDONJSA-N 0.000 description 2
- CBPNZQVSJQDFBE-FUXHJELOSA-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)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 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 102100033523 Thy-1 membrane glycoprotein Human genes 0.000 description 2
- SUJUHGSWHZTSEU-UHFFFAOYSA-N Tipranavir Natural products C1C(O)=C(C(CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)C(=O)OC1(CCC)CCC1=CC=CC=C1 SUJUHGSWHZTSEU-UHFFFAOYSA-N 0.000 description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 2
- 101710183280 Topoisomerase Proteins 0.000 description 2
- IWEQQRMGNVVKQW-OQKDUQJOSA-N Toremifene citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1=CC(OCCN(C)C)=CC=C1C(\C=1C=CC=CC=1)=C(\CCCl)C1=CC=CC=C1 IWEQQRMGNVVKQW-OQKDUQJOSA-N 0.000 description 2
- YCPOZVAOBBQLRI-WDSKDSINSA-N Treosulfan Chemical compound CS(=O)(=O)OC[C@H](O)[C@@H](O)COS(C)(=O)=O YCPOZVAOBBQLRI-WDSKDSINSA-N 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102100040245 Tumor necrosis factor receptor superfamily member 5 Human genes 0.000 description 2
- 102100036857 Tumor necrosis factor receptor superfamily member 8 Human genes 0.000 description 2
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 2
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 2
- 206010052428 Wound Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- YEEZWCHGZNKEEK-UHFFFAOYSA-N Zafirlukast Chemical compound COC1=CC(C(=O)NS(=O)(=O)C=2C(=CC=CC=2)C)=CC=C1CC(C1=C2)=CN(C)C1=CC=C2NC(=O)OC1CCCC1 YEEZWCHGZNKEEK-UHFFFAOYSA-N 0.000 description 2
- 108010023617 abarelix Proteins 0.000 description 2
- AIWRTTMUVOZGPW-HSPKUQOVSA-N abarelix Chemical compound C([C@@H](C(=O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)N(C)C(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 AIWRTTMUVOZGPW-HSPKUQOVSA-N 0.000 description 2
- 229960002184 abarelix Drugs 0.000 description 2
- 229960001683 abetimus Drugs 0.000 description 2
- 229960005339 acitretin Drugs 0.000 description 2
- USZYSDMBJDPRIF-SVEJIMAYSA-N aclacinomycin A Chemical compound O([C@H]1[C@@H](O)C[C@@H](O[C@H]1C)O[C@H]1[C@H](C[C@@H](O[C@H]1C)O[C@H]1C[C@]([C@@H](C2=CC=3C(=O)C4=CC=CC(O)=C4C(=O)C=3C(O)=C21)C(=O)OC)(O)CC)N(C)C)[C@H]1CCC(=O)[C@H](C)O1 USZYSDMBJDPRIF-SVEJIMAYSA-N 0.000 description 2
- 229960004176 aclarubicin Drugs 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 201000011040 acute kidney failure Diseases 0.000 description 2
- 229950009084 adecatumumab Drugs 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- BNPSSFBOAGDEEL-UHFFFAOYSA-N albuterol sulfate Chemical compound OS(O)(=O)=O.CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1.CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 BNPSSFBOAGDEEL-UHFFFAOYSA-N 0.000 description 2
- 108700025316 aldesleukin Proteins 0.000 description 2
- 229960002459 alefacept Drugs 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 239000004411 aluminium Substances 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229960003022 amoxicillin Drugs 0.000 description 2
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 description 2
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 2
- 239000004037 angiogenesis inhibitor Substances 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000002155 anti-virotic effect Effects 0.000 description 2
- 239000000611 antibody drug conjugate Substances 0.000 description 2
- 239000003146 anticoagulant agent Substances 0.000 description 2
- 239000003080 antimitotic agent Substances 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- MCGDSOGUHLTADD-UHFFFAOYSA-N arzoxifene Chemical compound C1=CC(OC)=CC=C1C1=C(OC=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 MCGDSOGUHLTADD-UHFFFAOYSA-N 0.000 description 2
- 229950005529 arzoxifene Drugs 0.000 description 2
- 229960003277 atazanavir Drugs 0.000 description 2
- AXRYRYVKAWYZBR-GASGPIRDSA-N atazanavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)[C@@H](O)CN(CC=1C=CC(=CC=1)C=1N=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C1=CC=CC=C1 AXRYRYVKAWYZBR-GASGPIRDSA-N 0.000 description 2
- 229950010993 atrasentan Drugs 0.000 description 2
- 239000005441 aurora Substances 0.000 description 2
- 229940120638 avastin Drugs 0.000 description 2
- 229960003005 axitinib Drugs 0.000 description 2
- RITAVMQDGBJQJZ-FMIVXFBMSA-N axitinib Chemical compound CNC(=O)C1=CC=CC=C1SC1=CC=C(C(\C=C\C=2N=CC=CC=2)=NN2)C2=C1 RITAVMQDGBJQJZ-FMIVXFBMSA-N 0.000 description 2
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 description 2
- 230000003796 beauty Effects 0.000 description 2
- 229950000210 beclometasone dipropionate Drugs 0.000 description 2
- 229950011276 belotecan Drugs 0.000 description 2
- LNHWXBUNXOXMRL-VWLOTQADSA-N belotecan Chemical compound C1=CC=C2C(CCNC(C)C)=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 LNHWXBUNXOXMRL-VWLOTQADSA-N 0.000 description 2
- YTKUWDBFDASYHO-UHFFFAOYSA-N bendamustine Chemical compound ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(O)=O)=NC2=C1 YTKUWDBFDASYHO-UHFFFAOYSA-N 0.000 description 2
- 229960002707 bendamustine Drugs 0.000 description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 2
- 229960002537 betamethasone Drugs 0.000 description 2
- 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 description 2
- 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 description 2
- 229960003008 blinatumomab Drugs 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- GJPICJJJRGTNOD-UHFFFAOYSA-N bosentan Chemical compound COC1=CC=CC=C1OC(C(=NC(=N1)C=2N=CC=CN=2)OCCO)=C1NS(=O)(=O)C1=CC=C(C(C)(C)C)C=C1 GJPICJJJRGTNOD-UHFFFAOYSA-N 0.000 description 2
- 208000019748 bullous skin disease Diseases 0.000 description 2
- CUWODFFVMXJOKD-UVLQAERKSA-N buserelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 CUWODFFVMXJOKD-UVLQAERKSA-N 0.000 description 2
- 229940022399 cancer vaccine Drugs 0.000 description 2
- 238000009566 cancer vaccine Methods 0.000 description 2
- 229950002826 canertinib Drugs 0.000 description 2
- OMZCMEYTWSXEPZ-UHFFFAOYSA-N canertinib Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCCN3CCOCC3)=C(NC(=O)C=C)C=C12 OMZCMEYTWSXEPZ-UHFFFAOYSA-N 0.000 description 2
- OJLHWPALWODJPQ-QNWVGRARSA-N canfosfamide Chemical compound ClCCN(CCCl)P(=O)(N(CCCl)CCCl)OCCS(=O)(=O)C[C@H](NC(=O)CC[C@H](N)C(O)=O)C(=O)N[C@@H](C(O)=O)C1=CC=CC=C1 OJLHWPALWODJPQ-QNWVGRARSA-N 0.000 description 2
- 229950000772 canfosfamide Drugs 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 2
- 229960000419 catumaxomab Drugs 0.000 description 2
- 108700008462 cetrorelix Proteins 0.000 description 2
- SBNPWPIBESPSIF-MHWMIDJBSA-N cetrorelix Chemical compound C([C@@H](C(=O)N[C@H](CCCNC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 SBNPWPIBESPSIF-MHWMIDJBSA-N 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- CFBUZOUXXHZCFB-OYOVHJISSA-N chembl511115 Chemical compound COC1=CC=C([C@@]2(CC[C@H](CC2)C(O)=O)C#N)C=C1OC1CCCC1 CFBUZOUXXHZCFB-OYOVHJISSA-N 0.000 description 2
- 238000007385 chemical modification Methods 0.000 description 2
- 229960005091 chloramphenicol Drugs 0.000 description 2
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 2
- 229940041586 chlorpheniramine / hydrocodone Drugs 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 229950001653 cilomilast Drugs 0.000 description 2
- 229960003315 cinacalcet Drugs 0.000 description 2
- VDHAWDNDOKGFTD-MRXNPFEDSA-N cinacalcet Chemical compound N([C@H](C)C=1C2=CC=CC=C2C=CC=1)CCCC1=CC=CC(C(F)(F)F)=C1 VDHAWDNDOKGFTD-MRXNPFEDSA-N 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 229960002436 cladribine Drugs 0.000 description 2
- WDDPHFBMKLOVOX-AYQXTPAHSA-N clofarabine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1F WDDPHFBMKLOVOX-AYQXTPAHSA-N 0.000 description 2
- 229960000928 clofarabine Drugs 0.000 description 2
- 229940053219 coal tar / salicylic acid Drugs 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 229960001152 colesevelam Drugs 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- LGZKGOGODCLQHG-UHFFFAOYSA-N combretastatin Natural products C1=C(O)C(OC)=CC=C1CC(O)C1=CC(OC)=C(OC)C(OC)=C1 LGZKGOGODCLQHG-UHFFFAOYSA-N 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- 229960004544 cortisone Drugs 0.000 description 2
- 229940111134 coxibs Drugs 0.000 description 2
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 2
- 229960002104 cyanocobalamin Drugs 0.000 description 2
- 235000000639 cyanocobalamin Nutrition 0.000 description 2
- 239000011666 cyanocobalamin Substances 0.000 description 2
- UHDGCWIWMRVCDJ-ZAKLUEHWSA-N cytidine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-ZAKLUEHWSA-N 0.000 description 2
- 231100000433 cytotoxic Toxicity 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 229960000640 dactinomycin Drugs 0.000 description 2
- CJBJHOAVZSMMDJ-HEXNFIEUSA-N darunavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1[C@@H]2CCO[C@@H]2OC1)C1=CC=CC=C1 CJBJHOAVZSMMDJ-HEXNFIEUSA-N 0.000 description 2
- 229960002448 dasatinib Drugs 0.000 description 2
- PCCPERGCFKIYIS-AWEZNQCLSA-N daxalipram Chemical compound C1=C(OC)C(OCCC)=CC([C@@]2(C)OC(=O)NC2)=C1 PCCPERGCFKIYIS-AWEZNQCLSA-N 0.000 description 2
- 229950002790 decloxizine Drugs 0.000 description 2
- 229960005319 delavirdine Drugs 0.000 description 2
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 2
- WAZQAZKAZLXFMK-UHFFFAOYSA-N deracoxib Chemical compound C1=C(F)C(OC)=CC=C1C1=CC(C(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 WAZQAZKAZLXFMK-UHFFFAOYSA-N 0.000 description 2
- 229960000605 dexrazoxane Drugs 0.000 description 2
- XLMALTXPSGQGBX-GCJKJVERSA-N dextropropoxyphene Chemical compound C([C@](OC(=O)CC)([C@H](C)CN(C)C)C=1C=CC=CC=1)C1=CC=CC=C1 XLMALTXPSGQGBX-GCJKJVERSA-N 0.000 description 2
- 229960004193 dextropropoxyphene Drugs 0.000 description 2
- HUPFGZXOMWLGNK-UHFFFAOYSA-N diflunisal Chemical compound C1=C(O)C(C(=O)O)=CC(C=2C(=CC(F)=CC=2)F)=C1 HUPFGZXOMWLGNK-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- VXIHRIQNJCRFQX-UHFFFAOYSA-K disodium aurothiomalate Chemical compound [Na+].[Na+].[O-]C(=O)CC(S[Au])C([O-])=O VXIHRIQNJCRFQX-UHFFFAOYSA-K 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- HALQELOKLVRWRI-VDBOFHIQSA-N doxycycline hyclate Chemical compound O.[Cl-].[Cl-].CCO.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H]([NH+](C)C)[C@@H]1[C@H]2O.O=C1C2=C(O)C=CC=C2[C@H](C)[C@@H]2C1=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@@H]([NH+](C)C)[C@@H]1[C@H]2O HALQELOKLVRWRI-VDBOFHIQSA-N 0.000 description 2
- 229960001172 doxycycline hyclate Drugs 0.000 description 2
- 229960004242 dronabinol Drugs 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 229960000284 efalizumab Drugs 0.000 description 2
- 229960000925 efaproxiral Drugs 0.000 description 2
- 229960000366 emtricitabine Drugs 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 229930013356 epothilone Natural products 0.000 description 2
- HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 description 2
- QXRSDHAAWVKZLJ-PVYNADRNSA-N epothilone B Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 QXRSDHAAWVKZLJ-PVYNADRNSA-N 0.000 description 2
- XOZIUKBZLSUILX-GIQCAXHBSA-N epothilone D Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](C)[C@@H](O)[C@@H](C)CCC\C(C)=C/C[C@H]1C(\C)=C\C1=CSC(C)=N1 XOZIUKBZLSUILX-GIQCAXHBSA-N 0.000 description 2
- 229950009760 epratuzumab Drugs 0.000 description 2
- 229940082789 erbitux Drugs 0.000 description 2
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 2
- FRYHCSODNHYDPU-UHFFFAOYSA-N ethanesulfonyl chloride Chemical compound CCS(Cl)(=O)=O FRYHCSODNHYDPU-UHFFFAOYSA-N 0.000 description 2
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 2
- MMXKVMNBHPAILY-UHFFFAOYSA-N ethyl laurate Chemical compound CCCCCCCCCCCC(=O)OCC MMXKVMNBHPAILY-UHFFFAOYSA-N 0.000 description 2
- 229960005293 etodolac Drugs 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 229960004979 fampridine Drugs 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- DBEPLOCGEIEOCV-WSBQPABSSA-N finasteride Chemical compound N([C@@H]1CC2)C(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H](C(=O)NC(C)(C)C)[C@@]2(C)CC1 DBEPLOCGEIEOCV-WSBQPABSSA-N 0.000 description 2
- 229940063190 flagyl Drugs 0.000 description 2
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 description 2
- 229960001347 fluocinolone acetonide Drugs 0.000 description 2
- 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 description 2
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 description 2
- 229960002714 fluticasone Drugs 0.000 description 2
- MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone 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](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 description 2
- 229960000289 fluticasone propionate Drugs 0.000 description 2
- WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate 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](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 229960002584 gefitinib Drugs 0.000 description 2
- 229960005277 gemcitabine Drugs 0.000 description 2
- 229960003297 gemtuzumab ozogamicin Drugs 0.000 description 2
- 229940020967 gemzar Drugs 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 229930182470 glycoside Natural products 0.000 description 2
- 150000002338 glycosides Chemical class 0.000 description 2
- 210000003714 granulocyte Anatomy 0.000 description 2
- LVASCWIMLIKXLA-LSDHHAIUSA-N halofuginone Chemical compound O[C@@H]1CCCN[C@H]1CC(=O)CN1C(=O)C2=CC(Cl)=C(Br)C=C2N=C1 LVASCWIMLIKXLA-LSDHHAIUSA-N 0.000 description 2
- 229950010152 halofuginone Drugs 0.000 description 2
- 201000002222 hemangioblastoma Diseases 0.000 description 2
- 238000001794 hormone therapy Methods 0.000 description 2
- 210000005260 human cell Anatomy 0.000 description 2
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 2
- 229960000890 hydrocortisone Drugs 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 229960001330 hydroxycarbamide Drugs 0.000 description 2
- 229960001001 ibritumomab tiuxetan Drugs 0.000 description 2
- 229960002411 imatinib Drugs 0.000 description 2
- 239000000367 immunologic factor Substances 0.000 description 2
- 229910052738 indium Inorganic materials 0.000 description 2
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 229960003130 interferon gamma Drugs 0.000 description 2
- 229960001388 interferon-beta Drugs 0.000 description 2
- 102000009634 interleukin-1 receptor antagonist activity proteins Human genes 0.000 description 2
- 108040001669 interleukin-1 receptor antagonist activity proteins Proteins 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 229960001361 ipratropium bromide Drugs 0.000 description 2
- KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 description 2
- 229950003599 ipsapirone Drugs 0.000 description 2
- GURKHSYORGJETM-WAQYZQTGSA-N irinotecan hydrochloride (anhydrous) Chemical compound Cl.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 GURKHSYORGJETM-WAQYZQTGSA-N 0.000 description 2
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 2
- FABUFPQFXZVHFB-CFWQTKTJSA-N ixabepilone Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@H](C)C(=O)C(C)(C)[C@H](O)CC(=O)N1)O)C)=C\C1=CSC(C)=N1 FABUFPQFXZVHFB-CFWQTKTJSA-N 0.000 description 2
- 229960002014 ixabepilone Drugs 0.000 description 2
- 229960000991 ketoprofen Drugs 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 108010021336 lanreotide Proteins 0.000 description 2
- DXOJIXGRFSHVKA-BZVZGCBYSA-N larotaxel Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@@]23[C@H]1[C@@]1(CO[C@@H]1C[C@@H]2C3)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 DXOJIXGRFSHVKA-BZVZGCBYSA-N 0.000 description 2
- 229960004942 lenalidomide Drugs 0.000 description 2
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 description 2
- 229950002884 lexatumumab Drugs 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 229960002397 linagliptin Drugs 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 229960002701 liraglutide Drugs 0.000 description 2
- 229960000994 lumiracoxib Drugs 0.000 description 2
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
- 229950000547 mafosfamide Drugs 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
- 238000004519 manufacturing process Methods 0.000 description 2
- GSNHKUDZZFZSJB-QYOOZWMWSA-N maraviroc Chemical compound CC(C)C1=NN=C(C)N1[C@@H]1C[C@H](N2CC[C@H](NC(=O)C3CCC(F)(F)CC3)C=3C=CC=CC=3)CC[C@H]2C1 GSNHKUDZZFZSJB-QYOOZWMWSA-N 0.000 description 2
- 229960004710 maraviroc Drugs 0.000 description 2
- HAWPXGHAZFHHAD-UHFFFAOYSA-N mechlorethamine Chemical compound ClCCN(C)CCCl HAWPXGHAZFHHAD-UHFFFAOYSA-N 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 2
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 description 2
- 108010000525 member 1 small inducible cytokine subfamily E Proteins 0.000 description 2
- 206010027191 meningioma Diseases 0.000 description 2
- 229940041616 menthol Drugs 0.000 description 2
- 230000002503 metabolic effect Effects 0.000 description 2
- FPTPAIQTXYFGJC-UHFFFAOYSA-N metronidazole hydrochloride Chemical group Cl.CC1=NC=C([N+]([O-])=O)N1CCO FPTPAIQTXYFGJC-UHFFFAOYSA-N 0.000 description 2
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 description 2
- 108700007621 mifamurtide Proteins 0.000 description 2
- VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 description 2
- 229960003248 mifepristone Drugs 0.000 description 2
- PQLXHQMOHUQAKB-UHFFFAOYSA-N miltefosine Chemical compound CCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+](C)(C)C PQLXHQMOHUQAKB-UHFFFAOYSA-N 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- JFOHFDSMPQIOES-UHFFFAOYSA-N motexafin Chemical compound C1=NC2=CC(OCCOCCOCCOC)=C(OCCOCCOCCOC)C=C2N=CC(C(=C2CCCO)C)=NC2=CC(C(CC)=C2CC)=NC2=CC2=C(CCCO)C(C)=C1N2 JFOHFDSMPQIOES-UHFFFAOYSA-N 0.000 description 2
- 229950011637 motexafin Drugs 0.000 description 2
- 229960003702 moxifloxacin Drugs 0.000 description 2
- FABPRXSRWADJSP-MEDUHNTESA-N moxifloxacin Chemical compound COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 FABPRXSRWADJSP-MEDUHNTESA-N 0.000 description 2
- 229940087004 mustargen Drugs 0.000 description 2
- 210000001167 myeloblast Anatomy 0.000 description 2
- IXOXBSCIXZEQEQ-UHTZMRCNSA-N nelarabine Chemical compound C1=NC=2C(OC)=NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O IXOXBSCIXZEQEQ-UHTZMRCNSA-N 0.000 description 2
- 229960000801 nelarabine Drugs 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- XWXYUMMDTVBTOU-UHFFFAOYSA-N nilutamide Chemical compound O=C1C(C)(C)NC(=O)N1C1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 XWXYUMMDTVBTOU-UHFFFAOYSA-N 0.000 description 2
- 229960000572 olaparib Drugs 0.000 description 2
- 229960004114 olopatadine Drugs 0.000 description 2
- JBIMVDZLSHOPLA-LSCVHKIXSA-N olopatadine Chemical compound C1OC2=CC=C(CC(O)=O)C=C2C(=C/CCN(C)C)\C2=CC=CC=C21 JBIMVDZLSHOPLA-LSCVHKIXSA-N 0.000 description 2
- 229960000381 omeprazole Drugs 0.000 description 2
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 2
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 2
- 229960001972 panitumumab Drugs 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 229960000987 paricalcitol Drugs 0.000 description 2
- BPKAHTKRCLCHEA-UBFJEZKGSA-N paricalcitol Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@@H](\C=C\[C@H](C)C(C)(C)O)C)=C\C=C1C[C@@H](O)C[C@H](O)C1 BPKAHTKRCLCHEA-UBFJEZKGSA-N 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 229960000639 pazopanib Drugs 0.000 description 2
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 description 2
- 229960002340 pentostatin Drugs 0.000 description 2
- 229930192851 perforin Natural products 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 2
- 229950005566 picoplatin Drugs 0.000 description 2
- 201000004123 pineal gland cancer Diseases 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 229960001221 pirarubicin Drugs 0.000 description 2
- 229960003073 pirfenidone Drugs 0.000 description 2
- ISWRGOKTTBVCFA-UHFFFAOYSA-N pirfenidone Chemical compound C1=C(C)C=CC(=O)N1C1=CC=CC=C1 ISWRGOKTTBVCFA-UHFFFAOYSA-N 0.000 description 2
- PEZPMAYDXJQYRV-UHFFFAOYSA-N pixantrone Chemical compound O=C1C2=CN=CC=C2C(=O)C2=C1C(NCCN)=CC=C2NCCN PEZPMAYDXJQYRV-UHFFFAOYSA-N 0.000 description 2
- 229960004403 pixantrone Drugs 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000003207 proteasome inhibitor Substances 0.000 description 2
- 229940121649 protein inhibitor Drugs 0.000 description 2
- 239000012268 protein inhibitor Substances 0.000 description 2
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 description 2
- 229960003908 pseudoephedrine Drugs 0.000 description 2
- ZCCUUQDIBDJBTK-UHFFFAOYSA-N psoralen Chemical compound C1=C2OC(=O)C=CC2=CC2=C1OC=C2 ZCCUUQDIBDJBTK-UHFFFAOYSA-N 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 150000003230 pyrimidines Chemical class 0.000 description 2
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 2
- 229960002185 ranimustine Drugs 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 108091092562 ribozyme Proteins 0.000 description 2
- 229960002814 rilpivirine Drugs 0.000 description 2
- YIBOMRUWOWDFLG-ONEGZZNKSA-N rilpivirine Chemical compound CC1=CC(\C=C\C#N)=CC(C)=C1NC1=CC=NC(NC=2C=CC(=CC=2)C#N)=N1 YIBOMRUWOWDFLG-ONEGZZNKSA-N 0.000 description 2
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 2
- MNDBXUUTURYVHR-UHFFFAOYSA-N roflumilast Chemical compound FC(F)OC1=CC=C(C(=O)NC=2C(=CN=CC=2Cl)Cl)C=C1OCC1CC1 MNDBXUUTURYVHR-UHFFFAOYSA-N 0.000 description 2
- 229960002586 roflumilast Drugs 0.000 description 2
- 239000003813 safflower oil Substances 0.000 description 2
- 235000005713 safflower oil Nutrition 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 229960005018 salmeterol xinafoate Drugs 0.000 description 2
- 229960000953 salsalate Drugs 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229960005399 satraplatin Drugs 0.000 description 2
- 229960004937 saxagliptin Drugs 0.000 description 2
- 108010033693 saxagliptin Proteins 0.000 description 2
- QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 description 2
- 229950009921 seocalcitol Drugs 0.000 description 2
- ZNSIZMQNQCNRBW-UHFFFAOYSA-N sevelamer Chemical compound NCC=C.ClCC1CO1 ZNSIZMQNQCNRBW-UHFFFAOYSA-N 0.000 description 2
- 235000015170 shellfish Nutrition 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 238000011125 single therapy Methods 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 239000007909 solid dosage form Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000003549 soybean oil Substances 0.000 description 2
- 235000012424 soybean oil Nutrition 0.000 description 2
- 229950001248 squalamine Drugs 0.000 description 2
- 230000003637 steroidlike Effects 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 150000005846 sugar alcohols Chemical class 0.000 description 2
- SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 2
- 229960004306 sulfadiazine Drugs 0.000 description 2
- 229940032330 sulfuric acid Drugs 0.000 description 2
- 229940034785 sutent Drugs 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 229950004608 talampanel Drugs 0.000 description 2
- FQZYTYWMLGAPFJ-OQKDUQJOSA-N tamoxifen citrate Chemical compound [H+].[H+].[H+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 FQZYTYWMLGAPFJ-OQKDUQJOSA-N 0.000 description 2
- 229940099419 targretin Drugs 0.000 description 2
- 229960000565 tazarotene Drugs 0.000 description 2
- 229950001699 teceleukin Drugs 0.000 description 2
- 229960004964 temozolomide Drugs 0.000 description 2
- 206010043207 temporal arteritis Diseases 0.000 description 2
- 229960000235 temsirolimus Drugs 0.000 description 2
- KFVSLSTULZVNPG-UHFFFAOYSA-N terbutaline sulfate Chemical compound [O-]S([O-])(=O)=O.CC(C)(C)[NH2+]CC(O)C1=CC(O)=CC(O)=C1.CC(C)(C)[NH2+]CC(O)C1=CC(O)=CC(O)=C1 KFVSLSTULZVNPG-UHFFFAOYSA-N 0.000 description 2
- 229960005105 terbutaline sulfate Drugs 0.000 description 2
- 229960000331 teriflunomide Drugs 0.000 description 2
- UTNUDOFZCWSZMS-YFHOEESVSA-N teriflunomide Chemical compound C\C(O)=C(/C#N)C(=O)NC1=CC=C(C(F)(F)F)C=C1 UTNUDOFZCWSZMS-YFHOEESVSA-N 0.000 description 2
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)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)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
- 229960004674 theophylline anhydrous Drugs 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 2
- 229940033663 thimerosal Drugs 0.000 description 2
- 229950010980 tiplimotide Drugs 0.000 description 2
- 229960000838 tipranavir Drugs 0.000 description 2
- NZPXPXAGXYTROM-FYBSXPHGSA-N tipranavir Chemical compound C([C@@]1(CCC)OC(O)=C([C@H](CC)C=2C=C(NS(=O)(=O)C=3N=CC(=CC=3)C(F)(F)F)C=CC=2)C(=O)C1)CC1=CC=CC=C1 NZPXPXAGXYTROM-FYBSXPHGSA-N 0.000 description 2
- PKVRCIRHQMSYJX-AIFWHQITSA-N trabectedin Chemical compound C([C@@]1(C(OC2)=O)NCCC3=C1C=C(C(=C3)O)OC)S[C@@H]1C3=C(OC(C)=O)C(C)=C4OCOC4=C3[C@H]2N2[C@@H](O)[C@H](CC=3C4=C(O)C(OC)=C(C)C=3)N(C)[C@H]4[C@@H]21 PKVRCIRHQMSYJX-AIFWHQITSA-N 0.000 description 2
- 229960003181 treosulfan Drugs 0.000 description 2
- 239000002447 tumor necrosis factor alpha converting enzyme inhibitor Substances 0.000 description 2
- 229940094060 tykerb Drugs 0.000 description 2
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 2
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 2
- 229950009811 ubenimex Drugs 0.000 description 2
- BDSYKGHYMJNPAB-LICBFIPMSA-N ulobetasol propionate 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](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]2(C)C[C@@H]1O BDSYKGHYMJNPAB-LICBFIPMSA-N 0.000 description 2
- 210000001215 vagina Anatomy 0.000 description 2
- 229960000653 valrubicin Drugs 0.000 description 2
- 229960000241 vandetanib Drugs 0.000 description 2
- UHTHHESEBZOYNR-UHFFFAOYSA-N vandetanib Chemical compound COC1=CC(C(/N=CN2)=N/C=3C(=CC(Br)=CC=3)F)=C2C=C1OCC1CCN(C)CC1 UHTHHESEBZOYNR-UHFFFAOYSA-N 0.000 description 2
- 229950000578 vatalanib Drugs 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- WJJYZXPHLSLMGE-UHFFFAOYSA-N xaliproden Chemical compound FC(F)(F)C1=CC=CC(C=2CCN(CCC=3C=C4C=CC=CC4=CC=3)CC=2)=C1 WJJYZXPHLSLMGE-UHFFFAOYSA-N 0.000 description 2
- 229960004664 xaliproden Drugs 0.000 description 2
- ZPUHVPYXSITYDI-HEUWMMRCSA-N xyotax Chemical compound OC(=O)[C@@H](N)CCC(O)=O.O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 ZPUHVPYXSITYDI-HEUWMMRCSA-N 0.000 description 2
- 229960004764 zafirlukast Drugs 0.000 description 2
- XRASPMIURGNCCH-UHFFFAOYSA-N zoledronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CN1C=CN=C1 XRASPMIURGNCCH-UHFFFAOYSA-N 0.000 description 2
- AADVCYNFEREWOS-UHFFFAOYSA-N (+)-DDM Natural products C=CC=CC(C)C(OC(N)=O)C(C)C(O)C(C)CC(C)=CC(C)C(O)C(C)C=CC(O)CC1OC(=O)C(C)C(O)C1C AADVCYNFEREWOS-UHFFFAOYSA-N 0.000 description 1
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 description 1
- LXWLJGMQHZWSGD-UHFFFAOYSA-N (2-methylphenyl)-(1h-pyrrol-2-yl)methanone Chemical compound CC1=CC=CC=C1C(=O)C1=CC=CN1 LXWLJGMQHZWSGD-UHFFFAOYSA-N 0.000 description 1
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 description 1
- JMPZTWDLOGTBPM-OUQSKUGOSA-N (2e,4e,6e)-7-(3,5-ditert-butylphenyl)-3-methylocta-2,4,6-trienoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)C1=CC(C(C)(C)C)=CC(C(C)(C)C)=C1 JMPZTWDLOGTBPM-OUQSKUGOSA-N 0.000 description 1
- SFGFYNXPJMOUHK-PKAFTLKUSA-N (2r)-2-[[(2r)-2-amino-5-(diaminomethylideneamino)pentanoyl]amino]-n-[(2r)-1-[[(2r)-1-[[(2r)-1-[[(2r)-1-[[(2r)-1-[[(2r)-1-[[2-[[(2r)-1-amino-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohe Chemical compound NC(N)=NCCC[C@@H](N)C(=O)N[C@H](CCCC)C(=O)N[C@H](CCCC)C(=O)N[C@H](CCCC)C(=O)N[C@H](CCCN=C(N)N)C(=O)N[C@H](CCCC)C(=O)N[C@H](CCCC)C(=O)N[C@H](CCCC)C(=O)NCC(=O)N[C@@H](C(N)=O)CC1=CC=C(O)C=C1 SFGFYNXPJMOUHK-PKAFTLKUSA-N 0.000 description 1
- WDQLRUYAYXDIFW-RWKIJVEZSA-N (2r,3r,4s,5r,6r)-4-[(2s,3r,4s,5r,6r)-3,5-dihydroxy-4-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-[[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxy-6-(hydroxymethyl)oxane-2,3,5-triol Chemical compound O[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@@H](CO[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)O1 WDQLRUYAYXDIFW-RWKIJVEZSA-N 0.000 description 1
- SPFMQWBKVUQXJV-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;hydrate Chemical compound O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O SPFMQWBKVUQXJV-BTVCFUMJSA-N 0.000 description 1
- RIWLPSIAFBLILR-WVNGMBSFSA-N (2s)-1-[(2s)-2-[[(2s,3s)-2-[[(2s)-2-[[(2s,3r)-2-[[(2r,3s)-2-[[(2s)-2-[[2-[[2-[acetyl(methyl)amino]acetyl]amino]acetyl]amino]-3-methylbutanoyl]amino]-3-methylpentanoyl]amino]-3-hydroxybutanoyl]amino]pentanoyl]amino]-3-methylpentanoyl]amino]-5-(diaminomethy Chemical compound CC(=O)N(C)CC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1CCC[C@H]1C(=O)NCC RIWLPSIAFBLILR-WVNGMBSFSA-N 0.000 description 1
- WZRFLSDVFPIXOV-LRQRDZAKSA-N (2s)-1-[(2s)-2-cyclohexyl-2-[[(2s)-2-(methylamino)propanoyl]amino]acetyl]-n-(4-phenylthiadiazol-5-yl)pyrrolidine-2-carboxamide Chemical compound C1([C@H](NC(=O)[C@H](C)NC)C(=O)N2[C@@H](CCC2)C(=O)NC2=C(N=NS2)C=2C=CC=CC=2)CCCCC1 WZRFLSDVFPIXOV-LRQRDZAKSA-N 0.000 description 1
- IJWCGVPEDDQUDE-YGJAXBLXSA-N (2s)-2-[[(1s)-2-[[(2s)-5-amino-1,5-dioxo-1-[[(2s)-1-oxopropan-2-yl]amino]pentan-2-yl]amino]-1-[(6s)-2-amino-1,4,5,6-tetrahydropyrimidin-6-yl]-2-oxoethyl]carbamoylamino]-4-methylpentanoic acid Chemical compound O=C[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)N[C@@H](CC(C)C)C(O)=O)[C@@H]1CCN=C(N)N1 IJWCGVPEDDQUDE-YGJAXBLXSA-N 0.000 description 1
- BXTJCSYMGFJEID-XMTADJHZSA-N (2s)-2-[[(2r,3r)-3-[(2s)-1-[(3r,4s,5s)-4-[[(2s)-2-[[(2s)-2-[6-[3-[(2r)-2-amino-2-carboxyethyl]sulfanyl-2,5-dioxopyrrolidin-1-yl]hexanoyl-methylamino]-3-methylbutanoyl]amino]-3-methylbutanoyl]-methylamino]-3-methoxy-5-methylheptanoyl]pyrrolidin-2-yl]-3-met Chemical compound C([C@H](NC(=O)[C@H](C)[C@@H](OC)[C@@H]1CCCN1C(=O)C[C@H]([C@H]([C@@H](C)CC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C(=O)CCCCCN1C(C(SC[C@H](N)C(O)=O)CC1=O)=O)C(C)C)OC)C(O)=O)C1=CC=CC=C1 BXTJCSYMGFJEID-XMTADJHZSA-N 0.000 description 1
- QXOPTIPQEVJERB-JQWIXIFHSA-N (2s)-2-[[5-[2-[(6s)-2-amino-4-oxo-5,6,7,8-tetrahydro-1h-pyrido[2,3-d]pyrimidin-6-yl]ethyl]-4-methylthiophene-2-carbonyl]amino]pentanedioic acid Chemical compound C1=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)SC(CC[C@H]2CC=3C(=O)N=C(N)NC=3NC2)=C1C QXOPTIPQEVJERB-JQWIXIFHSA-N 0.000 description 1
- YLOCGHYTXIINAI-XKUOMLDTSA-N (2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 YLOCGHYTXIINAI-XKUOMLDTSA-N 0.000 description 1
- NECZZOFFLFZNHL-XVGZVFJZSA-N (2s)-2-amino-5-[[(2r)-3-[2-[bis[bis(2-chloroethyl)amino]-oxidophosphaniumyl]oxyethylsulfonyl]-1-[[(r)-carboxy(phenyl)methyl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoic acid;hydron;chloride Chemical compound Cl.ClCCN(CCCl)P(=O)(N(CCCl)CCCl)OCCS(=O)(=O)C[C@H](NC(=O)CC[C@H](N)C(O)=O)C(=O)N[C@@H](C(O)=O)C1=CC=CC=C1 NECZZOFFLFZNHL-XVGZVFJZSA-N 0.000 description 1
- MHFUWOIXNMZFIW-WNQIDUERSA-N (2s)-2-hydroxypropanoic acid;n-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide Chemical compound C[C@H](O)C(O)=O.C1CN(C)CCN1C1=CC(NC2=NNC(C)=C2)=NC(SC=2C=CC(NC(=O)C3CC3)=CC=2)=N1 MHFUWOIXNMZFIW-WNQIDUERSA-N 0.000 description 1
- UFPFGVNKHCLJJO-SSKFGXFMSA-N (2s)-n-[(1s)-1-cyclohexyl-2-[(2s)-2-[4-(4-fluorobenzoyl)-1,3-thiazol-2-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide Chemical compound C1([C@H](NC(=O)[C@H](C)NC)C(=O)N2[C@@H](CCC2)C=2SC=C(N=2)C(=O)C=2C=CC(F)=CC=2)CCCCC1 UFPFGVNKHCLJJO-SSKFGXFMSA-N 0.000 description 1
- GTXSRFUZSLTDFX-HRCADAONSA-N (2s)-n-[(2s)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl]-4-methyl-2-[[(2s)-2-sulfanyl-4-(3,4,4-trimethyl-2,5-dioxoimidazolidin-1-yl)butanoyl]amino]pentanamide Chemical compound CNC(=O)[C@H](C(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](S)CCN1C(=O)N(C)C(C)(C)C1=O GTXSRFUZSLTDFX-HRCADAONSA-N 0.000 description 1
- LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 description 1
- CVCLJVVBHYOXDC-IAZSKANUSA-N (2z)-2-[(5z)-5-[(3,5-dimethyl-1h-pyrrol-2-yl)methylidene]-4-methoxypyrrol-2-ylidene]indole Chemical compound COC1=C\C(=C/2N=C3C=CC=CC3=C\2)N\C1=C/C=1NC(C)=CC=1C CVCLJVVBHYOXDC-IAZSKANUSA-N 0.000 description 1
- DKSZLDSPXIWGFO-BLOJGBSASA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O.OP(O)(O)=O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC DKSZLDSPXIWGFO-BLOJGBSASA-N 0.000 description 1
- PUDHBTGHUJUUFI-SCTWWAJVSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-n-[(2s,3r)-1-amino-3-hydroxy-1-oxobutan-2-yl]-19-[[(2r)-2-amino-3-naphthalen-2-ylpropanoyl]amino]-16-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-7-propan-2-yl-1,2-dithia-5,8,11,14,17-p Chemical compound C([C@H]1C(=O)N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](N)CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(N)=O)=O)C(C)C)C1=CC=C(O)C=C1 PUDHBTGHUJUUFI-SCTWWAJVSA-N 0.000 description 1
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 description 1
- YCIHPQHVWDULOY-FMZCEJRJSA-N (4s,4as,5as,6s,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide;hydrochloride Chemical compound Cl.C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O YCIHPQHVWDULOY-FMZCEJRJSA-N 0.000 description 1
- CXAGHAZMQSCAKJ-WAHHBDPQSA-N (4s,7s)-n-[(2r,3s)-2-ethoxy-5-oxooxolan-3-yl]-7-(isoquinoline-1-carbonylamino)-6,10-dioxo-2,3,4,7,8,9-hexahydro-1h-pyridazino[1,2-a]diazepine-4-carboxamide Chemical compound CCO[C@@H]1OC(=O)C[C@@H]1NC(=O)[C@H]1N(C(=O)[C@H](CCC2=O)NC(=O)C=3C4=CC=CC=C4C=CN=3)N2CCC1 CXAGHAZMQSCAKJ-WAHHBDPQSA-N 0.000 description 1
- QYNUQALWYRSVHF-OLZOCXBDSA-N (6R)-5,10-methylenetetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1C1)N)N1C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QYNUQALWYRSVHF-OLZOCXBDSA-N 0.000 description 1
- WDLWHQDACQUCJR-ZAMMOSSLSA-N (6r,7r)-7-[[(2r)-2-azaniumyl-2-(4-hydroxyphenyl)acetyl]amino]-8-oxo-3-[(e)-prop-1-enyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)/C=C/C)C(O)=O)=CC=C(O)C=C1 WDLWHQDACQUCJR-ZAMMOSSLSA-N 0.000 description 1
- HMLGSIZOMSVISS-ONJSNURVSA-N (7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2,2-dimethylpropanoyloxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(C=C)CSC21)C(O)=O)=O)C(=O)\C(=N/OCOC(=O)C(C)(C)C)C1=CSC(N)=N1 HMLGSIZOMSVISS-ONJSNURVSA-N 0.000 description 1
- MWWSFMDVAYGXBV-FGBSZODSSA-N (7s,9s)-7-[(2r,4s,5r,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydron;chloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-FGBSZODSSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical compound CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 description 1
- LKJPYSCBVHEWIU-KRWDZBQOSA-N (R)-bicalutamide Chemical compound C([C@@](O)(C)C(=O)NC=1C=C(C(C#N)=CC=1)C(F)(F)F)S(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-KRWDZBQOSA-N 0.000 description 1
- PPKXEPBICJTCRU-XMZRARIVSA-N (R,R)-tramadol hydrochloride Chemical compound Cl.COC1=CC=CC([C@]2(O)[C@H](CCCC2)CN(C)C)=C1 PPKXEPBICJTCRU-XMZRARIVSA-N 0.000 description 1
- RKUNBYITZUJHSG-FXUDXRNXSA-N (S)-atropine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@H]3CC[C@@H](C2)N3C)=CC=CC=C1 RKUNBYITZUJHSG-FXUDXRNXSA-N 0.000 description 1
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 1
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 1
- OBRNDARFFFHCGE-PERKLWIXSA-N (S,S)-formoterol fumarate Chemical compound OC(=O)\C=C\C(O)=O.C1=CC(OC)=CC=C1C[C@H](C)NC[C@@H](O)C1=CC=C(O)C(NC=O)=C1.C1=CC(OC)=CC=C1C[C@H](C)NC[C@@H](O)C1=CC=C(O)C(NC=O)=C1 OBRNDARFFFHCGE-PERKLWIXSA-N 0.000 description 1
- BSFDDBUSIZRAPB-VHEBQXMUSA-N (e)-2-octadecanoylbut-2-enedioic acid Chemical class CCCCCCCCCCCCCCCCCC(=O)C(\C(O)=O)=C/C(O)=O BSFDDBUSIZRAPB-VHEBQXMUSA-N 0.000 description 1
- BWDQBBCUWLSASG-MDZDMXLPSA-N (e)-n-hydroxy-3-[4-[[2-hydroxyethyl-[2-(1h-indol-3-yl)ethyl]amino]methyl]phenyl]prop-2-enamide Chemical compound C=1NC2=CC=CC=C2C=1CCN(CCO)CC1=CC=C(\C=C\C(=O)NO)C=C1 BWDQBBCUWLSASG-MDZDMXLPSA-N 0.000 description 1
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 1
- IRELROQHIPLASX-SEYXRHQNSA-N (z)-2-cyano-3-hydroxy-n-[4-(trifluoromethyl)phenyl]hept-2-en-6-ynamide Chemical compound C#CCCC(/O)=C(\C#N)C(=O)NC1=CC=C(C(F)(F)F)C=C1 IRELROQHIPLASX-SEYXRHQNSA-N 0.000 description 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- HJTAZXHBEBIQQX-UHFFFAOYSA-N 1,5-bis(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1CCl HJTAZXHBEBIQQX-UHFFFAOYSA-N 0.000 description 1
- SWQQELWGJDXCFT-PNHWDRBUSA-N 1-[(2r,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-ethynylimidazole-4-carboxamide Chemical compound C#CC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 SWQQELWGJDXCFT-PNHWDRBUSA-N 0.000 description 1
- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 1
- WPHKIQPVPYJNAX-UHFFFAOYSA-N 1-[4-[4-amino-7-[1-(2-hydroxyethyl)pyrazol-4-yl]thieno[3,2-c]pyridin-3-yl]phenyl]-3-(3-fluorophenyl)urea Chemical compound C1=2SC=C(C=3C=CC(NC(=O)NC=4C=C(F)C=CC=4)=CC=3)C=2C(N)=NC=C1C=1C=NN(CCO)C=1 WPHKIQPVPYJNAX-UHFFFAOYSA-N 0.000 description 1
- 102100025573 1-alkyl-2-acetylglycerophosphocholine esterase Human genes 0.000 description 1
- LLJFMFZYVVLQKT-UHFFFAOYSA-N 1-cyclohexyl-3-[4-[2-(7-methoxy-4,4-dimethyl-1,3-dioxo-2-isoquinolinyl)ethyl]phenyl]sulfonylurea Chemical compound C=1C(OC)=CC=C(C(C2=O)(C)C)C=1C(=O)N2CCC(C=C1)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 LLJFMFZYVVLQKT-UHFFFAOYSA-N 0.000 description 1
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 1
- CZDWSKBKCZWXFI-UHFFFAOYSA-N 1-morpholin-4-yl-3-[4-oxo-3-[4-[2-oxo-2-(4-propan-2-ylpiperazin-1-yl)ethoxy]phenyl]-1h-indeno[1,2-c]pyrazol-5-yl]urea Chemical compound C1CN(C(C)C)CCN1C(=O)COC1=CC=C(C=2C=3C(=O)C4=C(NC(=O)NN5CCOCC5)C=CC=C4C=3NN=2)C=C1 CZDWSKBKCZWXFI-UHFFFAOYSA-N 0.000 description 1
- HAWSQZCWOQZXHI-FQEVSTJZSA-N 10-Hydroxycamptothecin Chemical compound C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-FQEVSTJZSA-N 0.000 description 1
- KUFRQPKVAWMTJO-QSTRRNJOSA-N 17-dmag Chemical compound N1C(=O)\C(C)=C/C=C\[C@@H](OC)[C@H](OC(N)=O)\C(C)=C/[C@@H](C)[C@@H](O)[C@H](OC)C[C@@H](C)CC2=C(NCCN(C)C)C(=O)C=C1C2=O KUFRQPKVAWMTJO-QSTRRNJOSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- QMVPQBFHUJZJCS-NTKFZFFISA-N 1v8x590xdp Chemical compound O=C1N(NC(CO)CO)C(=O)C(C2=C3[CH]C=C(O)C=C3NC2=C23)=C1C2=C1C=CC(O)=C[C]1N3[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O QMVPQBFHUJZJCS-NTKFZFFISA-N 0.000 description 1
- ROZCIVXTLACYNY-UHFFFAOYSA-N 2,3,4,5,6-pentafluoro-n-(3-fluoro-4-methoxyphenyl)benzenesulfonamide Chemical compound C1=C(F)C(OC)=CC=C1NS(=O)(=O)C1=C(F)C(F)=C(F)C(F)=C1F ROZCIVXTLACYNY-UHFFFAOYSA-N 0.000 description 1
- NVWVWEWVLBKPSM-UHFFFAOYSA-N 2,4-difluorophenol Chemical compound OC1=CC=C(F)C=C1F NVWVWEWVLBKPSM-UHFFFAOYSA-N 0.000 description 1
- JNAHVYVRKWKWKQ-UHFFFAOYSA-N 2-(2-methyl-2-pyrrolidinyl)-1H-benzimidazole-4-carboxamide Chemical compound N=1C2=C(C(N)=O)C=CC=C2NC=1C1(C)CCCN1 JNAHVYVRKWKWKQ-UHFFFAOYSA-N 0.000 description 1
- XNTLXAUHLBBEKP-UHFFFAOYSA-N 2-(3,4-difluorophenyl)-4-(3-hydroxy-3-methylbutoxy)-5-(4-methylsulfonylphenyl)pyridazin-3-one Chemical compound O=C1C(OCCC(C)(O)C)=C(C=2C=CC(=CC=2)S(C)(=O)=O)C=NN1C1=CC=C(F)C(F)=C1 XNTLXAUHLBBEKP-UHFFFAOYSA-N 0.000 description 1
- QXLQZLBNPTZMRK-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-(2,4-dimethylphenyl)prop-2-en-1-one Chemical compound CN(C)CC(=C)C(=O)C1=CC=C(C)C=C1C QXLQZLBNPTZMRK-UHFFFAOYSA-N 0.000 description 1
- RQVKVJIRFKVPBF-VWLOTQADSA-N 2-[[(2s)-2-amino-3-phenylpropyl]amino]-3-methyl-5-naphthalen-2-yl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C([C@H](N)CNC=1N(C(C(C=2C=C3C=CC=CC3=CC=2)=C(C=2C=CN=CC=2)N=1)=O)C)C1=CC=CC=C1 RQVKVJIRFKVPBF-VWLOTQADSA-N 0.000 description 1
- RGHYDLZMTYDBDT-UHFFFAOYSA-N 2-amino-8-ethyl-4-methyl-6-(1H-pyrazol-5-yl)-7-pyrido[2,3-d]pyrimidinone Chemical compound O=C1N(CC)C2=NC(N)=NC(C)=C2C=C1C=1C=CNN=1 RGHYDLZMTYDBDT-UHFFFAOYSA-N 0.000 description 1
- QINPEPAQOBZPOF-UHFFFAOYSA-N 2-amino-n-[3-[[3-(2-chloro-5-methoxyanilino)quinoxalin-2-yl]sulfamoyl]phenyl]-2-methylpropanamide Chemical compound COC1=CC=C(Cl)C(NC=2C(=NC3=CC=CC=C3N=2)NS(=O)(=O)C=2C=C(NC(=O)C(C)(C)N)C=CC=2)=C1 QINPEPAQOBZPOF-UHFFFAOYSA-N 0.000 description 1
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- RTRRWXSWYRXKTG-UHFFFAOYSA-N 2-sulfonyl-3,6-dihydro-1H-pyrrolo[2,3-c]pyridin-7-one Chemical compound S(=O)(=O)=C1CC2=C(C(NC=C2)=O)N1 RTRRWXSWYRXKTG-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- AXRCEOKUDYDWLF-UHFFFAOYSA-N 3-(1-methyl-3-indolyl)-4-[1-[1-(2-pyridinylmethyl)-4-piperidinyl]-3-indolyl]pyrrole-2,5-dione Chemical compound C12=CC=CC=C2N(C)C=C1C(C(NC1=O)=O)=C1C(C1=CC=CC=C11)=CN1C(CC1)CCN1CC1=CC=CC=N1 AXRCEOKUDYDWLF-UHFFFAOYSA-N 0.000 description 1
- BJVRNXSHJLDZJR-UHFFFAOYSA-N 3-(1-methyl-4-morpholin-4-ylpyrazolo[3,4-d]pyrimidin-6-yl)phenol Chemical compound N1=C2N(C)N=CC2=C(N2CCOCC2)N=C1C1=CC=CC(O)=C1 BJVRNXSHJLDZJR-UHFFFAOYSA-N 0.000 description 1
- DDYUBCCTNHWSQM-UHFFFAOYSA-N 3-(3-cyclopentyloxy-4-methoxyphenyl)-3-(1,3-dioxoisoindol-2-yl)propanamide Chemical compound COC1=CC=C(C(CC(N)=O)N2C(C3=CC=CC=C3C2=O)=O)C=C1OC1CCCC1 DDYUBCCTNHWSQM-UHFFFAOYSA-N 0.000 description 1
- WUIABRMSWOKTOF-OYALTWQYSA-N 3-[[2-[2-[2-[[(2s,3r)-2-[[(2s,3s,4r)-4-[[(2s,3r)-2-[[6-amino-2-[(1s)-3-amino-1-[[(2s)-2,3-diamino-3-oxopropyl]amino]-3-oxopropyl]-5-methylpyrimidine-4-carbonyl]amino]-3-[(2r,3s,4s,5s,6s)-3-[(2r,3s,4s,5r,6r)-4-carbamoyloxy-3,5-dihydroxy-6-(hydroxymethyl)ox Chemical compound OS([O-])(=O)=O.N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C WUIABRMSWOKTOF-OYALTWQYSA-N 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-M 3-carboxynaphthalen-2-olate Chemical compound C1=CC=C2C=C(C([O-])=O)C(O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-M 0.000 description 1
- VXGRJERITKFWPL-UHFFFAOYSA-N 4',5'-Dihydropsoralen Natural products C1=C2OC(=O)C=CC2=CC2=C1OCC2 VXGRJERITKFWPL-UHFFFAOYSA-N 0.000 description 1
- WJRRGYBTGDJBFX-UHFFFAOYSA-N 4-(2-methyl-3-propan-2-yl-4-imidazolyl)-N-(4-methylsulfonylphenyl)-2-pyrimidinamine Chemical compound CC(C)N1C(C)=NC=C1C1=CC=NC(NC=2C=CC(=CC=2)S(C)(=O)=O)=N1 WJRRGYBTGDJBFX-UHFFFAOYSA-N 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- AKJHMTWEGVYYSE-AIRMAKDCSA-N 4-HPR Chemical compound C=1C=C(O)C=CC=1NC(=O)/C=C(\C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C AKJHMTWEGVYYSE-AIRMAKDCSA-N 0.000 description 1
- HEUVRFNVTLGKMZ-SANMLTNESA-N 4-[(2s)-2-(4-cyanophenyl)-2-hydroxy-2-(3-methylimidazol-4-yl)ethoxy]-3-[4-(trifluoromethoxy)phenyl]benzonitrile Chemical compound CN1C=NC=C1[C@@](O)(C=1C=CC(=CC=1)C#N)COC1=CC=C(C#N)C=C1C1=CC=C(OC(F)(F)F)C=C1 HEUVRFNVTLGKMZ-SANMLTNESA-N 0.000 description 1
- XXJWYDDUDKYVKI-UHFFFAOYSA-N 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(1-pyrrolidinyl)propoxy]quinazoline Chemical compound COC1=CC2=C(OC=3C(=C4C=C(C)NC4=CC=3)F)N=CN=C2C=C1OCCCN1CCCC1 XXJWYDDUDKYVKI-UHFFFAOYSA-N 0.000 description 1
- ZHSKUOZOLHMKEA-UHFFFAOYSA-N 4-[5-[bis(2-chloroethyl)amino]-1-methylbenzimidazol-2-yl]butanoic acid;hydron;chloride Chemical compound Cl.ClCCN(CCCl)C1=CC=C2N(C)C(CCCC(O)=O)=NC2=C1 ZHSKUOZOLHMKEA-UHFFFAOYSA-N 0.000 description 1
- HHFBDROWDBDFBR-UHFFFAOYSA-N 4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1NC1=NC=C(CN=C(C=2C3=CC=C(Cl)C=2)C=2C(=CC=CC=2F)F)C3=N1 HHFBDROWDBDFBR-UHFFFAOYSA-N 0.000 description 1
- DJKNRCWSXSZACF-UHFFFAOYSA-N 4-acetamido-n-tert-butylbenzamide Chemical compound CC(=O)NC1=CC=C(C(=O)NC(C)(C)C)C=C1 DJKNRCWSXSZACF-UHFFFAOYSA-N 0.000 description 1
- WUBBRNOQWQTFEX-UHFFFAOYSA-N 4-aminosalicylic acid Chemical compound NC1=CC=C(C(O)=O)C(O)=C1 WUBBRNOQWQTFEX-UHFFFAOYSA-N 0.000 description 1
- MDOJTZQKHMAPBK-UHFFFAOYSA-N 4-iodo-3-nitrobenzamide Chemical compound NC(=O)C1=CC=C(I)C([N+]([O-])=O)=C1 MDOJTZQKHMAPBK-UHFFFAOYSA-N 0.000 description 1
- HEROWGICZZJWKP-UHFFFAOYSA-N 4-pyrrol-1-ylbenzenesulfonamide Chemical compound C1=CC(S(=O)(=O)N)=CC=C1N1C=CC=C1 HEROWGICZZJWKP-UHFFFAOYSA-N 0.000 description 1
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
- WUUGFSXJNOTRMR-IOSLPCCCSA-N 5'-S-methyl-5'-thioadenosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CSC)O[C@H]1N1C2=NC=NC(N)=C2N=C1 WUUGFSXJNOTRMR-IOSLPCCCSA-N 0.000 description 1
- HUNAOTXNHVALTN-UHFFFAOYSA-N 5-(5-chloro-2,4-dihydroxyphenyl)-N-ethyl-4-(4-methoxyphenyl)pyrazole-3-carboxamide Chemical compound CCNC(=O)C1=NNC(C=2C(=CC(O)=C(Cl)C=2)O)=C1C1=CC=C(OC)C=C1 HUNAOTXNHVALTN-UHFFFAOYSA-N 0.000 description 1
- UPALIKSFLSVKIS-UHFFFAOYSA-N 5-amino-2-[2-(dimethylamino)ethyl]benzo[de]isoquinoline-1,3-dione Chemical compound NC1=CC(C(N(CCN(C)C)C2=O)=O)=C3C2=CC=CC3=C1 UPALIKSFLSVKIS-UHFFFAOYSA-N 0.000 description 1
- XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 description 1
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 description 1
- QYYMDNHUJFIDDQ-UHFFFAOYSA-N 5-chloro-2-methyl-1,2-thiazol-3-one;2-methyl-1,2-thiazol-3-one Chemical compound CN1SC=CC1=O.CN1SC(Cl)=CC1=O QYYMDNHUJFIDDQ-UHFFFAOYSA-N 0.000 description 1
- SVAGFBGXEWPNJC-SPIKMXEPSA-N 6,9-bis(2-aminoethylamino)benzo[g]isoquinoline-5,10-dione;(z)-but-2-enedioic acid Chemical compound OC(=O)\C=C/C(O)=O.OC(=O)\C=C/C(O)=O.O=C1C2=CN=CC=C2C(=O)C2=C1C(NCCN)=CC=C2NCCN SVAGFBGXEWPNJC-SPIKMXEPSA-N 0.000 description 1
- FYSRKRZDBHOFAY-UHFFFAOYSA-N 6-(N-carbamoyl-2,6-difluoroanilino)-2-(2,4-difluorophenyl)-3-pyridinecarboxamide Chemical compound FC=1C=CC=C(F)C=1N(C(=O)N)C(N=1)=CC=C(C(N)=O)C=1C1=CC=C(F)C=C1F FYSRKRZDBHOFAY-UHFFFAOYSA-N 0.000 description 1
- WYXSYVWAUAUWLD-SHUUEZRQSA-N 6-azauridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=N1 WYXSYVWAUAUWLD-SHUUEZRQSA-N 0.000 description 1
- DOCINCLJNAXZQF-LBPRGKRZSA-N 6-fluoro-3-phenyl-2-[(1s)-1-(7h-purin-6-ylamino)ethyl]quinazolin-4-one Chemical compound C1([C@@H](NC=2C=3N=CNC=3N=CN=2)C)=NC2=CC=C(F)C=C2C(=O)N1C1=CC=CC=C1 DOCINCLJNAXZQF-LBPRGKRZSA-N 0.000 description 1
- VVIAGPKUTFNRDU-UHFFFAOYSA-N 6S-folinic acid Natural products C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-UHFFFAOYSA-N 0.000 description 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- FJHBVJOVLFPMQE-QFIPXVFZSA-N 7-Ethyl-10-Hydroxy-Camptothecin Chemical compound C1=C(O)C=C2C(CC)=C(CN3C(C4=C([C@@](C(=O)OC4)(O)CC)C=C33)=O)C3=NC2=C1 FJHBVJOVLFPMQE-QFIPXVFZSA-N 0.000 description 1
- WLCZTRVUXYALDD-IBGZPJMESA-N 7-[[(2s)-2,6-bis(2-methoxyethoxycarbonylamino)hexanoyl]amino]heptoxy-methylphosphinic acid Chemical compound COCCOC(=O)NCCCC[C@H](NC(=O)OCCOC)C(=O)NCCCCCCCOP(C)(O)=O WLCZTRVUXYALDD-IBGZPJMESA-N 0.000 description 1
- KCIOVTSUEXGUFJ-UHFFFAOYSA-N 8-(2-chloro-3,4,5-trimethoxybenzyl)-2-fluoro-9-pent-4-yn-1-yl-9H-purin-6-amine Chemical compound COC1=C(OC)C(OC)=CC(CC=2N(C3=NC(F)=NC(N)=C3N=2)CCCC#C)=C1Cl KCIOVTSUEXGUFJ-UHFFFAOYSA-N 0.000 description 1
- FUXVKZWTXQUGMW-FQEVSTJZSA-N 9-Aminocamptothecin Chemical compound C1=CC(N)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 FUXVKZWTXQUGMW-FQEVSTJZSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- TUOSCZDRWRYPRS-UHFFFAOYSA-N 9-butyl-8-(3,4,5-trimethoxybenzyl)-9h-purin-6-amine Chemical compound N=1C2=C(N)N=CN=C2N(CCCC)C=1CC1=CC(OC)=C(OC)C(OC)=C1 TUOSCZDRWRYPRS-UHFFFAOYSA-N 0.000 description 1
- 229940127124 90Y-ibritumomab tiuxetan Drugs 0.000 description 1
- HPLNQCPCUACXLM-PGUFJCEWSA-N ABT-737 Chemical compound C([C@@H](CCN(C)C)NC=1C(=CC(=CC=1)S(=O)(=O)NC(=O)C=1C=CC(=CC=1)N1CCN(CC=2C(=CC=CC=2)C=2C=CC(Cl)=CC=2)CC1)[N+]([O-])=O)SC1=CC=CC=C1 HPLNQCPCUACXLM-PGUFJCEWSA-N 0.000 description 1
- OONFNUWBHFSNBT-HXUWFJFHSA-N AEE788 Chemical compound C1CN(CC)CCN1CC1=CC=C(C=2NC3=NC=NC(N[C@H](C)C=4C=CC=CC=4)=C3C=2)C=C1 OONFNUWBHFSNBT-HXUWFJFHSA-N 0.000 description 1
- BUROJSBIWGDYCN-GAUTUEMISA-N AP 23573 Chemical compound C1C[C@@H](OP(C)(C)=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 BUROJSBIWGDYCN-GAUTUEMISA-N 0.000 description 1
- GBJVVSCPOBPEIT-UHFFFAOYSA-N AZT-1152 Chemical compound N=1C=NC2=CC(OCCCN(CC)CCOP(O)(O)=O)=CC=C2C=1NC(=NN1)C=C1CC(=O)NC1=CC=CC(F)=C1 GBJVVSCPOBPEIT-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 1
- ZGCSNRKSJLVANE-UHFFFAOYSA-N Aglycone-Rebeccamycin Natural products N1C2=C3NC4=C(Cl)C=CC=C4C3=C(C(=O)NC3=O)C3=C2C2=C1C(Cl)=CC=C2 ZGCSNRKSJLVANE-UHFFFAOYSA-N 0.000 description 1
- 206010001580 Albuminuria Diseases 0.000 description 1
- OGSPWJRAVKPPFI-UHFFFAOYSA-N Alendronic Acid Chemical compound NCCCC(O)(P(O)(O)=O)P(O)(O)=O OGSPWJRAVKPPFI-UHFFFAOYSA-N 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
- 101710099478 Aminopeptidase Q Proteins 0.000 description 1
- 108090000644 Angiozyme Proteins 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- MXPOCMVWFLDDLZ-NSCUHMNNSA-N Apaziquone Chemical compound CN1C(\C=C\CO)=C(CO)C(C2=O)=C1C(=O)C=C2N1CC1 MXPOCMVWFLDDLZ-NSCUHMNNSA-N 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 1
- 102100024222 B-lymphocyte antigen CD19 Human genes 0.000 description 1
- YUXMAKUNSXIEKN-BTJKTKAUSA-N BGT226 Chemical compound OC(=O)\C=C/C(O)=O.C1=NC(OC)=CC=C1C1=CC=C(N=CC2=C3N(C=4C=C(C(N5CCNCC5)=CC=4)C(F)(F)F)C(=O)N2C)C3=C1 YUXMAKUNSXIEKN-BTJKTKAUSA-N 0.000 description 1
- 108091007065 BIRCs Proteins 0.000 description 1
- 102100026596 Bcl-2-like protein 1 Human genes 0.000 description 1
- FRUALZRDEJNPTB-UHFFFAOYSA-N BrC1=CC2=C(C(NC=C2)=O)N1S(=O)(=O)C1=CC=C(C)C=C1 Chemical compound BrC1=CC2=C(C(NC=C2)=O)N1S(=O)(=O)C1=CC=C(C)C=C1 FRUALZRDEJNPTB-UHFFFAOYSA-N 0.000 description 1
- FRPHFZCDPYBUAU-UHFFFAOYSA-N Bromocresolgreen Chemical compound CC1=C(Br)C(O)=C(Br)C=C1C1(C=2C(=C(Br)C(O)=C(Br)C=2)C)C2=CC=CC=C2S(=O)(=O)O1 FRPHFZCDPYBUAU-UHFFFAOYSA-N 0.000 description 1
- 102000001805 Bromodomains Human genes 0.000 description 1
- 108050009021 Bromodomains Proteins 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 229940045513 CTLA4 antagonist Drugs 0.000 description 1
- 241000036318 Callitris preissii Species 0.000 description 1
- 239000005461 Canertinib Substances 0.000 description 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- SHHKQEUPHAENFK-UHFFFAOYSA-N Carboquone Chemical compound O=C1C(C)=C(N2CC2)C(=O)C(C(COC(N)=O)OC)=C1N1CC1 SHHKQEUPHAENFK-UHFFFAOYSA-N 0.000 description 1
- AOCCBINRVIKJHY-UHFFFAOYSA-N Carmofur Chemical compound CCCCCCNC(=O)N1C=C(F)C(=O)NC1=O AOCCBINRVIKJHY-UHFFFAOYSA-N 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 229940123587 Cell cycle inhibitor Drugs 0.000 description 1
- 102100025832 Centromere-associated protein E Human genes 0.000 description 1
- 229940124957 Cervarix Drugs 0.000 description 1
- 241001233914 Chelidonium majus Species 0.000 description 1
- 102000009410 Chemokine receptor Human genes 0.000 description 1
- 108050000299 Chemokine receptor Proteins 0.000 description 1
- RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 1
- 229920001268 Cholestyramine Polymers 0.000 description 1
- 229920002567 Chondroitin Polymers 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 108010060123 Conjugate Vaccines Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 208000009798 Craniopharyngioma Diseases 0.000 description 1
- 102000016736 Cyclin Human genes 0.000 description 1
- 108050006400 Cyclin Proteins 0.000 description 1
- 102100021906 Cyclin-O Human genes 0.000 description 1
- 229940093444 Cyclooxygenase 2 inhibitor Drugs 0.000 description 1
- 101710112752 Cytotoxin Proteins 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
- 229960005500 DHA-paclitaxel Drugs 0.000 description 1
- 108010002156 Depsipeptides Proteins 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 1
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 1
- 102000016607 Diphtheria Toxin Human genes 0.000 description 1
- 108010053187 Diphtheria Toxin Proteins 0.000 description 1
- AADVCYNFEREWOS-OBRABYBLSA-N Discodermolide Chemical compound C=C\C=C/[C@H](C)[C@H](OC(N)=O)[C@@H](C)[C@H](O)[C@@H](C)C\C(C)=C/[C@H](C)[C@@H](O)[C@@H](C)\C=C/[C@@H](O)C[C@@H]1OC(=O)[C@H](C)[C@@H](O)[C@H]1C AADVCYNFEREWOS-OBRABYBLSA-N 0.000 description 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- CYQFCXCEBYINGO-DLBZAZTESA-N Dronabinol Natural products C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@H]21 CYQFCXCEBYINGO-DLBZAZTESA-N 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- IJWCGVPEDDQUDE-UHFFFAOYSA-N Elastatinal Natural products O=CC(C)NC(=O)C(CCC(N)=O)NC(=O)C(NC(=O)NC(CC(C)C)C(O)=O)C1CCN=C(N)N1 IJWCGVPEDDQUDE-UHFFFAOYSA-N 0.000 description 1
- 206010014824 Endotoxic shock Diseases 0.000 description 1
- SAMRUMKYXPVKPA-VFKOLLTISA-N Enocitabine Chemical compound O=C1N=C(NC(=O)CCCCCCCCCCCCCCCCCCCCC)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 SAMRUMKYXPVKPA-VFKOLLTISA-N 0.000 description 1
- 101000877447 Enterobacteria phage T4 Endonuclease V Proteins 0.000 description 1
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- 102000056372 ErbB-3 Receptor Human genes 0.000 description 1
- 102100038595 Estrogen receptor Human genes 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 108010011459 Exenatide Proteins 0.000 description 1
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 1
- UKCVAQGKEOJTSR-UHFFFAOYSA-N Fadrozole hydrochloride Chemical compound Cl.C1=CC(C#N)=CC=C1C1N2C=NC=C2CCC1 UKCVAQGKEOJTSR-UHFFFAOYSA-N 0.000 description 1
- 229940124226 Farnesyltransferase inhibitor Drugs 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- POPFMWWJOGLOIF-XWCQMRHXSA-N Flurandrenolide Chemical compound C1([C@@H](F)C2)=CC(=O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O POPFMWWJOGLOIF-XWCQMRHXSA-N 0.000 description 1
- MPJKWIXIYCLVCU-UHFFFAOYSA-N Folinic acid Natural products NC1=NC2=C(N(C=O)C(CNc3ccc(cc3)C(=O)NC(CCC(=O)O)CC(=O)O)CN2)C(=O)N1 MPJKWIXIYCLVCU-UHFFFAOYSA-N 0.000 description 1
- 108700012941 GNRH1 Proteins 0.000 description 1
- 108700000266 GSK923295 Proteins 0.000 description 1
- 229940032072 GVAX vaccine Drugs 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- RVAQIUULWULRNW-UHFFFAOYSA-N Ganetespib Chemical compound C1=C(O)C(C(C)C)=CC(C=2N(C(O)=NN=2)C=2C=C3C=CN(C)C3=CC=2)=C1O RVAQIUULWULRNW-UHFFFAOYSA-N 0.000 description 1
- 229940124897 Gardasil Drugs 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- JRZJKWGQFNTSRN-UHFFFAOYSA-N Geldanamycin Natural products C1C(C)CC(OC)C(O)C(C)C=C(C)C(OC(N)=O)C(OC)CCC=C(C)C(=O)NC2=CC(=O)C(OC)=C1C2=O JRZJKWGQFNTSRN-UHFFFAOYSA-N 0.000 description 1
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 1
- 108010088406 Glucagon-Like Peptides Proteins 0.000 description 1
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
- 108010024636 Glutathione Proteins 0.000 description 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 description 1
- 108010078851 HIV Reverse Transcriptase Proteins 0.000 description 1
- 229940122440 HIV protease inhibitor Drugs 0.000 description 1
- 102100031547 HLA class II histocompatibility antigen, DO alpha chain Human genes 0.000 description 1
- 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 description 1
- 102100032510 Heat shock protein HSP 90-beta Human genes 0.000 description 1
- 101000980825 Homo sapiens B-lymphocyte antigen CD19 Proteins 0.000 description 1
- 101000914247 Homo sapiens Centromere-associated protein E Proteins 0.000 description 1
- 101000897441 Homo sapiens Cyclin-O Proteins 0.000 description 1
- 101500025419 Homo sapiens Epidermal growth factor Proteins 0.000 description 1
- 101000866278 Homo sapiens HLA class II histocompatibility antigen, DO alpha chain Proteins 0.000 description 1
- 101001016856 Homo sapiens Heat shock protein HSP 90-beta Proteins 0.000 description 1
- 101000904173 Homo sapiens Progonadoliberin-1 Proteins 0.000 description 1
- 101000914484 Homo sapiens T-lymphocyte activation antigen CD80 Proteins 0.000 description 1
- 241000701806 Human papillomavirus Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
- 229940124873 Influenza virus vaccine Drugs 0.000 description 1
- 102000055031 Inhibitor of Apoptosis Proteins Human genes 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 description 1
- 102000014429 Insulin-like growth factor Human genes 0.000 description 1
- 108010008212 Integrin alpha4beta1 Proteins 0.000 description 1
- 102100040018 Interferon alpha-2 Human genes 0.000 description 1
- 229940124137 Interferon gamma antagonist Drugs 0.000 description 1
- 108010079944 Interferon-alpha2b Proteins 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 1
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 1
- 102100026018 Interleukin-1 receptor antagonist protein Human genes 0.000 description 1
- 101710144554 Interleukin-1 receptor antagonist protein Proteins 0.000 description 1
- 101800000542 Interleukin-1 receptor type 1, soluble form Proteins 0.000 description 1
- 102400000025 Interleukin-1 receptor type 1, soluble form Human genes 0.000 description 1
- 102000003812 Interleukin-15 Human genes 0.000 description 1
- 108090000172 Interleukin-15 Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 208000005016 Intestinal Neoplasms Diseases 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 description 1
- AXISYYRBXTVTFY-UHFFFAOYSA-N Isopropyl tetradecanoate Chemical compound CCCCCCCCCCCCCC(=O)OC(C)C AXISYYRBXTVTFY-UHFFFAOYSA-N 0.000 description 1
- KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 description 1
- ZCVMWBYGMWKGHF-UHFFFAOYSA-N Ketotifene Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 ZCVMWBYGMWKGHF-UHFFFAOYSA-N 0.000 description 1
- 102100027629 Kinesin-like protein KIF11 Human genes 0.000 description 1
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
- 239000003798 L01XE11 - Pazopanib Substances 0.000 description 1
- 239000002118 L01XE12 - Vandetanib Substances 0.000 description 1
- 239000002144 L01XE18 - Ruxolitinib Substances 0.000 description 1
- CZQHHVNHHHRRDU-UHFFFAOYSA-N LY294002 Chemical compound C1=CC=C2C(=O)C=C(N3CCOCC3)OC2=C1C1=CC=CC=C1 CZQHHVNHHHRRDU-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000008415 Lactuca sativa Species 0.000 description 1
- 101000988090 Leishmania donovani Heat shock protein 83 Proteins 0.000 description 1
- 229920001491 Lentinan Polymers 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 102000003820 Lipoxygenases Human genes 0.000 description 1
- 108090000128 Lipoxygenases Proteins 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 229910052765 Lutetium Inorganic materials 0.000 description 1
- 208000028018 Lymphocytic leukaemia Diseases 0.000 description 1
- 108010016230 MBP-8298 Proteins 0.000 description 1
- 229940083338 MDM2 inhibitor Drugs 0.000 description 1
- 239000012819 MDM2-Inhibitor Substances 0.000 description 1
- 229940124647 MEK inhibitor Drugs 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000008135 Mechanistic Target of Rapamycin Complex 1 Human genes 0.000 description 1
- 108010035196 Mechanistic Target of Rapamycin Complex 1 Proteins 0.000 description 1
- 102000009308 Mechanistic Target of Rapamycin Complex 2 Human genes 0.000 description 1
- 108010034057 Mechanistic Target of Rapamycin Complex 2 Proteins 0.000 description 1
- XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000560222 Mibora minima Species 0.000 description 1
- 108700011259 MicroRNAs Proteins 0.000 description 1
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
- VFKZTMPDYBFSTM-KVTDHHQDSA-N Mitobronitol Chemical compound BrC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CBr VFKZTMPDYBFSTM-KVTDHHQDSA-N 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241001467552 Mycobacterium bovis BCG Species 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 1
- NFIXBCVWIPOYCD-UHFFFAOYSA-N N,N-diethyl-2-[4-(phenylmethyl)phenoxy]ethanamine Chemical compound C1=CC(OCCN(CC)CC)=CC=C1CC1=CC=CC=C1 NFIXBCVWIPOYCD-UHFFFAOYSA-N 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 description 1
- UBQYURCVBFRUQT-UHFFFAOYSA-N N-benzoyl-Ferrioxamine B Chemical compound CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN UBQYURCVBFRUQT-UHFFFAOYSA-N 0.000 description 1
- VQRUZCYRWYUQEL-UHFFFAOYSA-N N1=CC=CC2=CC=CC=C12.O1C=CC=C1.S1C=NC=C1 Chemical compound N1=CC=CC2=CC=CC=C12.O1C=CC=C1.S1C=NC=C1 VQRUZCYRWYUQEL-UHFFFAOYSA-N 0.000 description 1
- DGLDGDXUSXPUSI-UHFFFAOYSA-N N1=CC=CC=C1.[S].[N] Chemical compound N1=CC=CC=C1.[S].[N] DGLDGDXUSXPUSI-UHFFFAOYSA-N 0.000 description 1
- 108010072915 NAc-Sar-Gly-Val-(d-allo-Ile)-Thr-Nva-Ile-Arg-ProNEt Proteins 0.000 description 1
- PVQLIDFBJHGSQD-JJKGCWMISA-N NC(=O)[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.[S] Chemical compound NC(=O)[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.[S] PVQLIDFBJHGSQD-JJKGCWMISA-N 0.000 description 1
- 102100031911 NEDD8 Human genes 0.000 description 1
- 108700004934 NEDD8 Proteins 0.000 description 1
- 101150107958 NEDD8 gene Proteins 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 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
- 108700020796 Oncogene Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101100532088 Oryza sativa subsp. japonica RUB2 gene Proteins 0.000 description 1
- 101100532090 Oryza sativa subsp. japonica RUB3 gene Proteins 0.000 description 1
- ZPTHLDCJRIPWDB-BTVCFUMJSA-N P(N)(O)=O.O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO Chemical compound P(N)(O)=O.O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO ZPTHLDCJRIPWDB-BTVCFUMJSA-N 0.000 description 1
- 229940029536 PANVAC Drugs 0.000 description 1
- 239000012661 PARP inhibitor Substances 0.000 description 1
- 102000042846 PKC family Human genes 0.000 description 1
- 108091082203 PKC family Proteins 0.000 description 1
- QIUASFSNWYMDFS-NILGECQDSA-N PX-866 Chemical compound CC(=O)O[C@@H]1C[C@]2(C)C(=O)CC[C@H]2C2=C1[C@@]1(C)[C@@H](COC)OC(=O)\C(=C\N(CC=C)CC=C)C1=C(O)C2=O QIUASFSNWYMDFS-NILGECQDSA-N 0.000 description 1
- 244000131316 Panax pseudoginseng Species 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 108010057150 Peplomycin Proteins 0.000 description 1
- 229940122985 Peptide agonist Drugs 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 1
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 1
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 1
- 108091000080 Phosphotransferase Proteins 0.000 description 1
- VQDBNKDJNJQRDG-UHFFFAOYSA-N Pirbuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=N1 VQDBNKDJNJQRDG-UHFFFAOYSA-N 0.000 description 1
- QSXMZJGGEWYVCN-UHFFFAOYSA-N Pirbuterol acetate Chemical compound CC(O)=O.CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=N1 QSXMZJGGEWYVCN-UHFFFAOYSA-N 0.000 description 1
- 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 description 1
- 229920000148 Polycarbophil calcium Polymers 0.000 description 1
- 102000019014 Positive Transcriptional Elongation Factor B Human genes 0.000 description 1
- 108010012271 Positive Transcriptional Elongation Factor B Proteins 0.000 description 1
- 102100025067 Potassium voltage-gated channel subfamily H member 4 Human genes 0.000 description 1
- 101710163352 Potassium voltage-gated channel subfamily H member 4 Proteins 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 101100528525 Prochlorococcus marinus (strain SARG / CCMP1375 / SS120) rnc gene Proteins 0.000 description 1
- 102100024028 Progonadoliberin-1 Human genes 0.000 description 1
- 108010090931 Proto-Oncogene Proteins c-bcl-2 Proteins 0.000 description 1
- 102000013535 Proto-Oncogene Proteins c-bcl-2 Human genes 0.000 description 1
- 101000762949 Pseudomonas aeruginosa (strain ATCC 15692 / DSM 22644 / CIP 104116 / JCM 14847 / LMG 12228 / 1C / PRS 101 / PAO1) Exotoxin A Proteins 0.000 description 1
- 241000274582 Pycnanthus angolensis Species 0.000 description 1
- BPZSYCZIITTYBL-YJYMSZOUSA-N R-Formoterol Chemical compound C1=CC(OC)=CC=C1C[C@@H](C)NC[C@H](O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-YJYMSZOUSA-N 0.000 description 1
- 229910000564 Raney nickel Inorganic materials 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- QEHOIJJIZXRMAN-UHFFFAOYSA-N Rebeccamycin Natural products OC1C(O)C(OC)C(CO)OC1N1C2=C3NC4=C(Cl)C=CC=C4C3=C3C(=O)NC(=O)C3=C2C2=CC=CC(Cl)=C21 QEHOIJJIZXRMAN-UHFFFAOYSA-N 0.000 description 1
- 229940127361 Receptor Tyrosine Kinase Inhibitors Drugs 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- IWUCXVSUMQZMFG-AFCXAGJDSA-N Ribavirin Chemical compound N1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 IWUCXVSUMQZMFG-AFCXAGJDSA-N 0.000 description 1
- IIDJRNMFWXDHID-UHFFFAOYSA-N Risedronic acid Chemical compound OP(=O)(O)C(P(O)(O)=O)(O)CC1=CC=CN=C1 IIDJRNMFWXDHID-UHFFFAOYSA-N 0.000 description 1
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
- BFZKMNSQCNVFGM-UCEYFQQTSA-N Sagopilone Chemical compound O1C(=O)C[C@H](O)C(C)(C)C(=O)[C@H](CC=C)[C@@H](O)[C@@H](C)CCC[C@@]2(C)O[C@H]2C[C@H]1C1=CC=C(SC(C)=N2)C2=C1 BFZKMNSQCNVFGM-UCEYFQQTSA-N 0.000 description 1
- 240000003946 Saponaria officinalis Species 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 229920000519 Sizofiran Polymers 0.000 description 1
- OCOKWVBYZHBHLU-UHFFFAOYSA-N Sobuzoxane Chemical compound C1C(=O)N(COC(=O)OCC(C)C)C(=O)CN1CCN1CC(=O)N(COC(=O)OCC(C)C)C(=O)C1 OCOKWVBYZHBHLU-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- XNKLLVCARDGLGL-JGVFFNPUSA-N Stavudine Chemical compound O=C1NC(=O)C(C)=CN1[C@H]1C=C[C@@H](CO)O1 XNKLLVCARDGLGL-JGVFFNPUSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 101000996723 Sus scrofa Gonadotropin-releasing hormone receptor Proteins 0.000 description 1
- 102100027222 T-lymphocyte activation antigen CD80 Human genes 0.000 description 1
- 108010000449 TNF-Related Apoptosis-Inducing Ligand Receptors Proteins 0.000 description 1
- 102000002259 TNF-Related Apoptosis-Inducing Ligand Receptors Human genes 0.000 description 1
- 244000204900 Talipariti tiliaceum Species 0.000 description 1
- YMNZWKHEJQGPIA-CDJQDVQCSA-N Tavulin Chemical compound C/1=C(C)\C(O)CCC(/C)=C/C(O)C2C(=C)C(=O)OC2\1 YMNZWKHEJQGPIA-CDJQDVQCSA-N 0.000 description 1
- 208000024313 Testicular Neoplasms Diseases 0.000 description 1
- 206010057644 Testis cancer Diseases 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-N Thiophosphoric acid Chemical group OP(O)(S)=O RYYWUUFWQRZTIU-UHFFFAOYSA-N 0.000 description 1
- FOCVUCIESVLUNU-UHFFFAOYSA-N Thiotepa Chemical compound C1CN1P(N1CC1)(=S)N1CC1 FOCVUCIESVLUNU-UHFFFAOYSA-N 0.000 description 1
- 102000002938 Thrombospondin Human genes 0.000 description 1
- 108060008245 Thrombospondin Proteins 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 239000004012 Tofacitinib Substances 0.000 description 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 102000011117 Transforming Growth Factor beta2 Human genes 0.000 description 1
- 101800000304 Transforming growth factor beta-2 Proteins 0.000 description 1
- 229930189037 Trapoxin Natural products 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 108010050144 Triptorelin Pamoate Proteins 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 208000035896 Twin-reversed arterial perfusion sequence Diseases 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 108091008605 VEGF receptors Proteins 0.000 description 1
- 229940124674 VEGF-R inhibitor Drugs 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- 108020000999 Viral RNA Proteins 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- WREGKURFCTUGRC-POYBYMJQSA-N Zalcitabine Chemical compound O=C1N=C(N)C=CN1[C@@H]1O[C@H](CO)CC1 WREGKURFCTUGRC-POYBYMJQSA-N 0.000 description 1
- 239000001089 [(2R)-oxolan-2-yl]methanol Substances 0.000 description 1
- FKCMADOPPWWGNZ-YUMQZZPRSA-N [(2r)-1-[(2s)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1B(O)O FKCMADOPPWWGNZ-YUMQZZPRSA-N 0.000 description 1
- RTJVUHUGTUDWRK-CSLCKUBZSA-N [(2r,4ar,6r,7r,8s,8ar)-6-[[(5s,5ar,8ar,9r)-9-(3,5-dimethoxy-4-phosphonooxyphenyl)-8-oxo-5a,6,8a,9-tetrahydro-5h-[2]benzofuro[6,5-f][1,3]benzodioxol-5-yl]oxy]-2-methyl-7-[2-(2,3,4,5,6-pentafluorophenoxy)acetyl]oxy-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]d Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](OC(=O)COC=4C(=C(F)C(F)=C(F)C=4F)F)[C@@H]4O[C@H](C)OC[C@H]4O3)OC(=O)COC=3C(=C(F)C(F)=C(F)C=3F)F)[C@@H]3[C@@H]2C(OC3)=O)=C1 RTJVUHUGTUDWRK-CSLCKUBZSA-N 0.000 description 1
- XJXKGUZINMNEDK-GPJOBVNKSA-L [(4r,5r)-5-(aminomethyl)-2-propan-2-yl-1,3-dioxolan-4-yl]methanamine;platinum(2+);propanedioate Chemical compound [Pt+2].[O-]C(=O)CC([O-])=O.CC(C)C1O[C@H](CN)[C@@H](CN)O1 XJXKGUZINMNEDK-GPJOBVNKSA-L 0.000 description 1
- XMYKNCNAZKMVQN-NYYWCZLTSA-N [(e)-(3-aminopyridin-2-yl)methylideneamino]thiourea Chemical compound NC(=S)N\N=C\C1=NC=CC=C1N XMYKNCNAZKMVQN-NYYWCZLTSA-N 0.000 description 1
- XSMVECZRZBFTIZ-UHFFFAOYSA-M [2-(aminomethyl)cyclobutyl]methanamine;2-oxidopropanoate;platinum(4+) Chemical compound [Pt+4].CC([O-])C([O-])=O.NCC1CCC1CN XSMVECZRZBFTIZ-UHFFFAOYSA-M 0.000 description 1
- PZSXCNWLLFEOPM-UHFFFAOYSA-N [F].C(CC)(=O)O Chemical compound [F].C(CC)(=O)O PZSXCNWLLFEOPM-UHFFFAOYSA-N 0.000 description 1
- XNPAKGMQCVYQAO-UHFFFAOYSA-N [F].CC(O)=O Chemical compound [F].CC(O)=O XNPAKGMQCVYQAO-UHFFFAOYSA-N 0.000 description 1
- QVSITNJKGHUCGD-UHFFFAOYSA-N [O].FC=1C=CC=C(C1)F Chemical compound [O].FC=1C=CC=C(C1)F QVSITNJKGHUCGD-UHFFFAOYSA-N 0.000 description 1
- 229960004748 abacavir Drugs 0.000 description 1
- MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 1
- 229960003697 abatacept Drugs 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 229940028652 abraxane Drugs 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- DEXPIBGCLCPUHE-UISHROKMSA-N acetic acid;(4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-n-[(2s,3r)-1-amino-3-hydroxy-1-oxobutan-2-yl]-19-[[(2r)-2-amino-3-naphthalen-2-ylpropanoyl]amino]-16-[(4-hydroxyphenyl)methyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-7-propan-2-yl-1,2-dithia-5, Chemical compound CC(O)=O.C([C@H]1C(=O)N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)[C@H](N)CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(N)=O)=O)C(C)C)C1=CC=C(O)C=C1 DEXPIBGCLCPUHE-UISHROKMSA-N 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
- WDJHALXBUFZDSR-UHFFFAOYSA-N acetoacetic acid Chemical compound CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 1
- 229960001466 acetohexamide Drugs 0.000 description 1
- VGZSUPCWNCWDAN-UHFFFAOYSA-N acetohexamide Chemical compound C1=CC(C(=O)C)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 VGZSUPCWNCWDAN-UHFFFAOYSA-N 0.000 description 1
- 108010052004 acetyl-2-naphthylalanyl-3-chlorophenylalanyl-1-oxohexadecyl-seryl-4-aminophenylalanyl(hydroorotyl)-4-aminophenylalanyl(carbamoyl)-leucyl-ILys-prolyl-alaninamide Proteins 0.000 description 1
- 108010014659 acetyl-glycyl-valyl-allo-isoleucyl-seryl-glutaminyl-isoleucyl-arginyl-prolyl-cysteinamide Proteins 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 229940099550 actimmune Drugs 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229960005310 aldesleukin Drugs 0.000 description 1
- 229960004343 alendronic acid Drugs 0.000 description 1
- 229940060515 aleve Drugs 0.000 description 1
- 229940060516 alferon n Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229940110282 alimta Drugs 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 229940098174 alkeran Drugs 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 108010004614 allotrap Proteins 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 229910021502 aluminium hydroxide Inorganic materials 0.000 description 1
- 229950010817 alvocidib Drugs 0.000 description 1
- BIIVYFLTOXDAOV-YVEFUNNKSA-N alvocidib Chemical compound O[C@@H]1CN(C)CC[C@@H]1C1=C(O)C=C(O)C2=C1OC(C=1C(=CC=CC=1)Cl)=CC2=O BIIVYFLTOXDAOV-YVEFUNNKSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- FQPFAHBPWDRTLU-UHFFFAOYSA-N aminophylline Chemical compound NCCN.O=C1N(C)C(=O)N(C)C2=C1NC=N2.O=C1N(C)C(=O)N(C)C2=C1NC=N2 FQPFAHBPWDRTLU-UHFFFAOYSA-N 0.000 description 1
- 229960003556 aminophylline Drugs 0.000 description 1
- 229940113720 aminosalicylate Drugs 0.000 description 1
- 229960000836 amitriptyline Drugs 0.000 description 1
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 229960000510 ammonia Drugs 0.000 description 1
- SWLVFNYSXGMGBS-UHFFFAOYSA-N ammonium bromide Chemical compound [NH4+].[Br-] SWLVFNYSXGMGBS-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229960004701 amonafide Drugs 0.000 description 1
- 229960002550 amrubicin Drugs 0.000 description 1
- VJZITPJGSQKZMX-XDPRQOKASA-N amrubicin Chemical compound O([C@H]1C[C@](CC2=C(O)C=3C(=O)C4=CC=CC=C4C(=O)C=3C(O)=C21)(N)C(=O)C)[C@H]1C[C@H](O)[C@H](O)CO1 VJZITPJGSQKZMX-XDPRQOKASA-N 0.000 description 1
- 229960001220 amsacrine Drugs 0.000 description 1
- XCPGHVQEEXUHNC-UHFFFAOYSA-N amsacrine Chemical compound COC1=CC(NS(C)(=O)=O)=CC=C1NC1=C(C=CC=C2)C2=NC2=CC=CC=C12 XCPGHVQEEXUHNC-UHFFFAOYSA-N 0.000 description 1
- 229960004238 anakinra Drugs 0.000 description 1
- 229960002932 anastrozole Drugs 0.000 description 1
- 230000033115 angiogenesis Effects 0.000 description 1
- CIDNKDMVSINJCG-GKXONYSUSA-N annamycin Chemical compound I[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(=O)CO)C1 CIDNKDMVSINJCG-GKXONYSUSA-N 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- NUZWLKWWNNJHPT-UHFFFAOYSA-N anthralin Chemical compound C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O NUZWLKWWNNJHPT-UHFFFAOYSA-N 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 229940127217 antithrombotic drug Drugs 0.000 description 1
- 229950002465 apaziquone Drugs 0.000 description 1
- 238000003782 apoptosis assay Methods 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
- UVJYAKBJSGRTHA-ZCRGAIPPSA-N arglabin Chemical compound C1C[C@H]2C(=C)C(=O)O[C@@H]2[C@@H]2C(C)=CC[C@]32O[C@]31C UVJYAKBJSGRTHA-ZCRGAIPPSA-N 0.000 description 1
- UVJYAKBJSGRTHA-UHFFFAOYSA-N arglabin Natural products C1CC2C(=C)C(=O)OC2C2C(C)=CCC32OC31C UVJYAKBJSGRTHA-UHFFFAOYSA-N 0.000 description 1
- 229940078010 arimidex Drugs 0.000 description 1
- 229940087620 aromasin Drugs 0.000 description 1
- 229950004810 atamestane Drugs 0.000 description 1
- PEPMWUSGRKINHX-TXTPUJOMSA-N atamestane Chemical compound C1C[C@@H]2[C@@]3(C)C(C)=CC(=O)C=C3CC[C@H]2[C@@H]2CCC(=O)[C@]21C PEPMWUSGRKINHX-TXTPUJOMSA-N 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000002238 attenuated effect Effects 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 229940054720 avage Drugs 0.000 description 1
- 229940003504 avonex Drugs 0.000 description 1
- KLNFSAOEKUDMFA-UHFFFAOYSA-N azanide;2-hydroxyacetic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OCC(O)=O KLNFSAOEKUDMFA-UHFFFAOYSA-N 0.000 description 1
- 229960000190 bacillus calmette–guérin vaccine Drugs 0.000 description 1
- 229960004168 balsalazide Drugs 0.000 description 1
- IPOKCKJONYRRHP-FMQUCBEESA-N balsalazide Chemical compound C1=CC(C(=O)NCCC(=O)O)=CC=C1\N=N\C1=CC=C(O)C(C(O)=O)=C1 IPOKCKJONYRRHP-FMQUCBEESA-N 0.000 description 1
- 229960000560 balsalazide disodium Drugs 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 229950001429 batabulin Drugs 0.000 description 1
- 229950008356 becatecarin Drugs 0.000 description 1
- MAFMQEKGGFWBAB-UHFFFAOYSA-N benzonatate Chemical compound CCCCNC1=CC=C(C(=O)OCCOCCOCCOCCOCCOCCOCCOCCOCCOC)C=C1 MAFMQEKGGFWBAB-UHFFFAOYSA-N 0.000 description 1
- 229960003789 benzonatate Drugs 0.000 description 1
- 229940017687 beta-d-ribose Drugs 0.000 description 1
- 102000014974 beta2-adrenergic receptor activity proteins Human genes 0.000 description 1
- 108040006828 beta2-adrenergic receptor activity proteins Proteins 0.000 description 1
- 229960004311 betamethasone valerate Drugs 0.000 description 1
- 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 description 1
- 229940021459 betaseron Drugs 0.000 description 1
- PYXFVCFISTUSOO-UHFFFAOYSA-N betulafolienetriol Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC(C(C)(O)CCC=C(C)C)C4C(O)CC3C21C PYXFVCFISTUSOO-UHFFFAOYSA-N 0.000 description 1
- 229940110331 bextra Drugs 0.000 description 1
- 229960000997 bicalutamide Drugs 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- ACWZRVQXLIRSDF-UHFFFAOYSA-N binimetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1F ACWZRVQXLIRSDF-UHFFFAOYSA-N 0.000 description 1
- 230000008512 biological response Effects 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 229910052797 bismuth Inorganic materials 0.000 description 1
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 1
- JAONZGLTYYUPCT-UHFFFAOYSA-K bismuth subgallate Chemical compound OC(=O)C1=CC(O)=C2O[Bi](O)OC2=C1 JAONZGLTYYUPCT-UHFFFAOYSA-K 0.000 description 1
- 229960000199 bismuth subgallate Drugs 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- JSKFWUPVIZYJMR-UDOAKELVSA-N bmy-27557 Chemical compound O=C1N(CCN(CC)CC)C(=O)C(C2=C3[CH]C=CC(Cl)=C3NC2=C23)=C1C2=C1C=CC=C(Cl)[C]1N3[C@@H]1O[C@H](CO)[C@@H](OC)[C@H](O)[C@H]1O JSKFWUPVIZYJMR-UDOAKELVSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229960002645 boric acid Drugs 0.000 description 1
- 229960003065 bosentan Drugs 0.000 description 1
- 238000002725 brachytherapy Methods 0.000 description 1
- 229960000455 brentuximab vedotin Drugs 0.000 description 1
- FNXLCIKXHOPCKH-UHFFFAOYSA-N bromamine Chemical compound BrN FNXLCIKXHOPCKH-UHFFFAOYSA-N 0.000 description 1
- 229940074995 bromine Drugs 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 229940125763 bromodomain inhibitor Drugs 0.000 description 1
- 229950004271 brostallicin Drugs 0.000 description 1
- RXOVOXFAAGIKDQ-UHFFFAOYSA-N brostallicin Chemical compound C1=C(C(=O)NCCN=C(N)N)N(C)C=C1NC(=O)C1=CC(NC(=O)C=2N(C=C(NC(=O)C=3N(C=C(NC(=O)C(Br)=C)C=3)C)C=2)C)=CN1C RXOVOXFAAGIKDQ-UHFFFAOYSA-N 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- MAEIEVLCKWDQJH-UHFFFAOYSA-N bumetanide Chemical compound CCCCNC1=CC(C(O)=O)=CC(S(N)(=O)=O)=C1OC1=CC=CC=C1 MAEIEVLCKWDQJH-UHFFFAOYSA-N 0.000 description 1
- 229960004064 bumetanide Drugs 0.000 description 1
- 229960002719 buserelin Drugs 0.000 description 1
- 229960002092 busulfan Drugs 0.000 description 1
- 229910052792 caesium Inorganic materials 0.000 description 1
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
- 239000004227 calcium gluconate Substances 0.000 description 1
- 229960004494 calcium gluconate Drugs 0.000 description 1
- 235000013927 calcium gluconate Nutrition 0.000 description 1
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 description 1
- 229940112129 campath Drugs 0.000 description 1
- 229940088954 camptosar Drugs 0.000 description 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 229930003827 cannabinoid Natural products 0.000 description 1
- 239000003557 cannabinoid Substances 0.000 description 1
- 229960004117 capecitabine Drugs 0.000 description 1
- 229960001631 carbomer Drugs 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 229960002115 carboquone Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 229960003261 carmofur Drugs 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 229940097647 casodex Drugs 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229960002412 cediranib Drugs 0.000 description 1
- 229960002580 cefprozil Drugs 0.000 description 1
- 230000006369 cell cycle progression Effects 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 229940107810 cellcept Drugs 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229950001357 celmoleukin Drugs 0.000 description 1
- 229940106164 cephalexin Drugs 0.000 description 1
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 1
- 229960003115 certolizumab pegol Drugs 0.000 description 1
- 229960001803 cetirizine Drugs 0.000 description 1
- 229960004342 cetirizine hydrochloride Drugs 0.000 description 1
- 229960003230 cetrorelix Drugs 0.000 description 1
- 229940112106 cetrotide Drugs 0.000 description 1
- CKMOQBVBEGCJGW-UHFFFAOYSA-L chembl1200760 Chemical compound [Na+].[Na+].C1=C(C([O-])=O)C(O)=CC=C1N=NC1=CC=C(C(=O)NCCC([O-])=O)C=C1 CKMOQBVBEGCJGW-UHFFFAOYSA-L 0.000 description 1
- IQCIQDNWBGEGRL-UHFFFAOYSA-N chembl1614651 Chemical compound O=C1C2=C(O)C=CC(O)=C2N2N=C(CNCCO)C3=CC=C(NCCCN)C1=C32 IQCIQDNWBGEGRL-UHFFFAOYSA-N 0.000 description 1
- RCTCWZRPYFBGLQ-KVBIMOIYSA-N chembl2105639 Chemical compound C([C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 RCTCWZRPYFBGLQ-KVBIMOIYSA-N 0.000 description 1
- ZFVRYNYOPQZKDG-MQMHXKEQSA-N chembl560895 Chemical compound O=C1CC(C)(C)CC2=C1C(C(F)(F)F)=NN2C(C=1)=CC=C(C(N)=O)C=1N[C@H]1CC[C@H](O)CC1 ZFVRYNYOPQZKDG-MQMHXKEQSA-N 0.000 description 1
- 150000005829 chemical entities Chemical class 0.000 description 1
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 description 1
- 229960004630 chlorambucil Drugs 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 229960003677 chloroquine Drugs 0.000 description 1
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 1
- 229960001761 chlorpropamide Drugs 0.000 description 1
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 229950010810 cintredekin besudotox Drugs 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- 229960001229 ciprofloxacin hydrochloride Drugs 0.000 description 1
- DIOIOSKKIYDRIQ-UHFFFAOYSA-N ciprofloxacin hydrochloride Chemical compound Cl.C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 DIOIOSKKIYDRIQ-UHFFFAOYSA-N 0.000 description 1
- 229960002626 clarithromycin Drugs 0.000 description 1
- AGOYDEPGAOXOCK-KCBOHYOISA-N clarithromycin 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)([C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)OC)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 AGOYDEPGAOXOCK-KCBOHYOISA-N 0.000 description 1
- 229960004299 clocortolone Drugs 0.000 description 1
- YMTMADLUXIRMGX-RFPWEZLHSA-N clocortolone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(Cl)[C@@H]2[C@@H]2C[C@@H](C)[C@H](C(=O)CO)[C@@]2(C)C[C@@H]1O YMTMADLUXIRMGX-RFPWEZLHSA-N 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 239000011280 coal tar Substances 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 229960004415 codeine phosphate Drugs 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 229950007276 conatumumab Drugs 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 229940031670 conjugate vaccine Drugs 0.000 description 1
- 229940038717 copaxone Drugs 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 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 description 1
- CZZLLDDFQKSALH-UHFFFAOYSA-N cpg 8954 Chemical compound O=C1NC(=O)C(C)=CN1C1OC(COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C(NC(=O)C(C)=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C(N=C(N)C=C2)=O)COP(O)(=O)OC2C(OC(C2)N2C3=NC=NC(N)=C3N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)COP(O)(=O)OC2C(OC(C2)N2C3=C(C(NC(N)=N3)=O)N=C2)CO)C(OP(O)(=O)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)OP(O)(=O)OCC2C(CC(O2)N2C3=C(C(NC(N)=N3)=O)N=C2)O)C1 CZZLLDDFQKSALH-UHFFFAOYSA-N 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229940109248 cromoglycate Drugs 0.000 description 1
- 239000002875 cyclin dependent kinase inhibitor Substances 0.000 description 1
- 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 description 1
- 229950006614 cytarabine ocfosfate Drugs 0.000 description 1
- YJTVZHOYBAOUTO-URBBEOKESA-N cytarabine ocfosfate Chemical compound O[C@H]1[C@H](O)[C@@H](COP(O)(=O)OCCCCCCCCCCCCCCCCCC)O[C@H]1N1C(=O)N=C(N)C=C1 YJTVZHOYBAOUTO-URBBEOKESA-N 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 229960003901 dacarbazine Drugs 0.000 description 1
- 229950006418 dactolisib Drugs 0.000 description 1
- JOGKUKXHTYWRGZ-UHFFFAOYSA-N dactolisib Chemical compound O=C1N(C)C2=CN=C3C=CC(C=4C=C5C=CC=CC5=NC=4)=CC3=C2N1C1=CC=C(C(C)(C)C#N)C=C1 JOGKUKXHTYWRGZ-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 229960005107 darunavir Drugs 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 229940070230 daypro Drugs 0.000 description 1
- 229960003603 decitabine Drugs 0.000 description 1
- 230000008260 defense mechanism Effects 0.000 description 1
- 229960000958 deferoxamine Drugs 0.000 description 1
- 229960002272 degarelix Drugs 0.000 description 1
- MEUCPCLKGZSHTA-XYAYPHGZSA-N degarelix Chemical compound C([C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CC=1C=CC(NC(=O)[C@H]2NC(=O)NC(=O)C2)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(NC(N)=O)C=C1 MEUCPCLKGZSHTA-XYAYPHGZSA-N 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 210000000852 deltoid muscle Anatomy 0.000 description 1
- 229960001251 denosumab Drugs 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229960003314 deracoxib Drugs 0.000 description 1
- 229940051427 deramaxx Drugs 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 229960003662 desonide Drugs 0.000 description 1
- 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 description 1
- 229960002593 desoximetasone Drugs 0.000 description 1
- VWVSBHGCDBMOOT-IIEHVVJPSA-N desoximetasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@H](C(=O)CO)[C@@]1(C)C[C@@H]2O VWVSBHGCDBMOOT-IIEHVVJPSA-N 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229960002344 dexamethasone sodium phosphate Drugs 0.000 description 1
- PLCQGRYPOISRTQ-FCJDYXGNSA-L dexamethasone 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-FCJDYXGNSA-L 0.000 description 1
- SSQJFGMEZBFMNV-PMACEKPBSA-N dexanabinol Chemical compound C1C(CO)=CC[C@@H]2C(C)(C)OC3=CC(C(C)(C)CCCCCC)=CC(O)=C3[C@H]21 SSQJFGMEZBFMNV-PMACEKPBSA-N 0.000 description 1
- 229960001985 dextromethorphan Drugs 0.000 description 1
- LRCZQSDQZJBHAF-PUBGEWHCSA-N dha-paclitaxel Chemical compound N([C@H]([C@@H](OC(=O)CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CC)C(=O)O[C@@H]1C(=C2[C@@H](OC(C)=O)C(=O)[C@]3(C)[C@@H](O)C[C@H]4OC[C@]4([C@H]3[C@H](OC(=O)C=3C=CC=CC=3)[C@](C2(C)C)(O)C1)OC(C)=O)C)C=1C=CC=CC=1)C(=O)C1=CC=CC=C1 LRCZQSDQZJBHAF-PUBGEWHCSA-N 0.000 description 1
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- KPHWPUGNDIVLNH-UHFFFAOYSA-M diclofenac sodium Chemical compound [Na+].[O-]C(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl KPHWPUGNDIVLNH-UHFFFAOYSA-M 0.000 description 1
- 229960002656 didanosine Drugs 0.000 description 1
- 229960004154 diflorasone Drugs 0.000 description 1
- WXURHACBFYSXBI-XHIJKXOTSA-N diflorasone 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](C)[C@@](C(=O)CO)(O)[C@@]2(C)C[C@@H]1O WXURHACBFYSXBI-XHIJKXOTSA-N 0.000 description 1
- 229960000616 diflunisal Drugs 0.000 description 1
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- HYPPXZBJBPSRLK-UHFFFAOYSA-N diphenoxylate Chemical compound C1CC(C(=O)OCC)(C=2C=CC=CC=2)CCN1CCC(C#N)(C=1C=CC=CC=1)C1=CC=CC=C1 HYPPXZBJBPSRLK-UHFFFAOYSA-N 0.000 description 1
- 229960004192 diphenoxylate Drugs 0.000 description 1
- 206010013023 diphtheria Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 229960002311 dithranol Drugs 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 229940030606 diuretics Drugs 0.000 description 1
- 229960003668 docetaxel Drugs 0.000 description 1
- 229940072701 dolobid Drugs 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- MVCOAUNKQVWQHZ-UHFFFAOYSA-N doramapimod Chemical compound C1=CC(C)=CC=C1N1C(NC(=O)NC=2C3=CC=CC=C3C(OCCN3CCOCC3)=CC=2)=CC(C(C)(C)C)=N1 MVCOAUNKQVWQHZ-UHFFFAOYSA-N 0.000 description 1
- ZWAOHEXOSAUJHY-ZIYNGMLESA-N doxifluridine Chemical compound O[C@@H]1[C@H](O)[C@@H](C)O[C@H]1N1C(=O)NC(=O)C(F)=C1 ZWAOHEXOSAUJHY-ZIYNGMLESA-N 0.000 description 1
- 229950005454 doxifluridine Drugs 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- GVGYEFKIHJTNQZ-RFQIPJPRSA-N ecgonine benzoate Chemical compound O([C@@H]1[C@@H]([C@H]2CC[C@@H](C1)N2C)C(O)=O)C(=O)C1=CC=CC=C1 GVGYEFKIHJTNQZ-RFQIPJPRSA-N 0.000 description 1
- 229950001287 edotecarin Drugs 0.000 description 1
- 229960001776 edrecolomab Drugs 0.000 description 1
- 229960002759 eflornithine Drugs 0.000 description 1
- VLCYCQAOQCDTCN-UHFFFAOYSA-N eflornithine Chemical compound NCCCC(N)(C(F)F)C(O)=O VLCYCQAOQCDTCN-UHFFFAOYSA-N 0.000 description 1
- 229940121647 egfr inhibitor Drugs 0.000 description 1
- 108010039262 elastatinal Proteins 0.000 description 1
- 229940020485 elidel Drugs 0.000 description 1
- 229940087477 ellence Drugs 0.000 description 1
- 229940120655 eloxatin Drugs 0.000 description 1
- 229960003586 elvitegravir Drugs 0.000 description 1
- JUZYLCPPVHEVSV-LJQANCHMSA-N elvitegravir Chemical compound COC1=CC=2N([C@H](CO)C(C)C)C=C(C(O)=O)C(=O)C=2C=C1CC1=CC=CC(Cl)=C1F JUZYLCPPVHEVSV-LJQANCHMSA-N 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 150000002081 enamines Chemical class 0.000 description 1
- 229940073621 enbrel Drugs 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- JOZGNYDSEBIJDH-UHFFFAOYSA-N eniluracil Chemical compound O=C1NC=C(C#C)C(=O)N1 JOZGNYDSEBIJDH-UHFFFAOYSA-N 0.000 description 1
- 229950010213 eniluracil Drugs 0.000 description 1
- 229950011487 enocitabine Drugs 0.000 description 1
- HKSZLNNOFSGOKW-UHFFFAOYSA-N ent-staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(C)O1 HKSZLNNOFSGOKW-UHFFFAOYSA-N 0.000 description 1
- INVTYAOGFAGBOE-UHFFFAOYSA-N entinostat Chemical compound NC1=CC=CC=C1NC(=O)C(C=C1)=CC=C1CNC(=O)OCC1=CC=CN=C1 INVTYAOGFAGBOE-UHFFFAOYSA-N 0.000 description 1
- 229950002189 enzastaurin Drugs 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- HESCAJZNRMSMJG-HGYUPSKWSA-N epothilone A Natural products O=C1[C@H](C)[C@H](O)[C@H](C)CCC[C@H]2O[C@H]2C[C@@H](/C(=C\c2nc(C)sc2)/C)OC(=O)C[C@H](O)C1(C)C HESCAJZNRMSMJG-HGYUPSKWSA-N 0.000 description 1
- 229950006835 eptaplatin Drugs 0.000 description 1
- 229960001433 erlotinib Drugs 0.000 description 1
- 229960001842 estramustine Drugs 0.000 description 1
- FRPJXPJMRWBBIH-RBRWEJTLSA-N estramustine Chemical compound ClCCN(CCCl)C(=O)OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 FRPJXPJMRWBBIH-RBRWEJTLSA-N 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- MHYCRLGKOZWVEF-UHFFFAOYSA-N ethyl acetate;hydrate Chemical compound O.CCOC(C)=O MHYCRLGKOZWVEF-UHFFFAOYSA-N 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
- 229960005420 etoposide Drugs 0.000 description 1
- 229960005167 everolimus Drugs 0.000 description 1
- 229940085363 evista Drugs 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 229960000255 exemestane Drugs 0.000 description 1
- 229960001519 exenatide Drugs 0.000 description 1
- 230000028023 exocytosis Effects 0.000 description 1
- 238000002710 external beam radiation therapy Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 229940043168 fareston Drugs 0.000 description 1
- 229940087861 faslodex Drugs 0.000 description 1
- 229940065410 feldene Drugs 0.000 description 1
- 229940087476 femara Drugs 0.000 description 1
- 229950003662 fenretinide Drugs 0.000 description 1
- 229960002428 fentanyl Drugs 0.000 description 1
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 1
- 229960003592 fexofenadine Drugs 0.000 description 1
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
- 229950000133 filanesib Drugs 0.000 description 1
- LLXISKGBWFTGEI-FQEVSTJZSA-N filanesib Chemical compound C1([C@]2(CCCN)SC(=NN2C(=O)N(C)OC)C=2C(=CC=C(F)C=2)F)=CC=CC=C1 LLXISKGBWFTGEI-FQEVSTJZSA-N 0.000 description 1
- 229960004177 filgrastim Drugs 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229960004039 finasteride Drugs 0.000 description 1
- 229960000556 fingolimod Drugs 0.000 description 1
- KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229960000390 fludarabine Drugs 0.000 description 1
- 229960005304 fludarabine phosphate Drugs 0.000 description 1
- 229960004511 fludroxycortide Drugs 0.000 description 1
- 229960002074 flutamide Drugs 0.000 description 1
- VVIAGPKUTFNRDU-ABLWVSNPSA-N folinic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 VVIAGPKUTFNRDU-ABLWVSNPSA-N 0.000 description 1
- 235000008191 folinic acid Nutrition 0.000 description 1
- 239000011672 folinic acid Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
- BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 description 1
- 229960002848 formoterol Drugs 0.000 description 1
- 229960000193 formoterol fumarate Drugs 0.000 description 1
- YAKWPXVTIGTRJH-UHFFFAOYSA-N fotemustine Chemical compound CCOP(=O)(OCC)C(C)NC(=O)N(CCCl)N=O YAKWPXVTIGTRJH-UHFFFAOYSA-N 0.000 description 1
- 229960004783 fotemustine Drugs 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 229960002258 fulvestrant Drugs 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 239000000417 fungicide Substances 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 229960003883 furosemide Drugs 0.000 description 1
- 108020001507 fusion proteins Proteins 0.000 description 1
- 102000037865 fusion proteins Human genes 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- 229940044627 gamma-interferon Drugs 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 150000002270 gangliosides Chemical class 0.000 description 1
- 108010063604 gastrin immunogen Proteins 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- QTQAWLPCGQOSGP-GBTDJJJQSA-N geldanamycin Chemical compound N1C(=O)\C(C)=C/C=C\[C@@H](OC)[C@H](OC(N)=O)\C(C)=C/[C@@H](C)[C@@H](O)[C@H](OC)C[C@@H](C)CC2=C(OC)C(=O)C=C1C2=O QTQAWLPCGQOSGP-GBTDJJJQSA-N 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- 229910052732 germanium Inorganic materials 0.000 description 1
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940042385 glatiramer Drugs 0.000 description 1
- 229940080856 gleevec Drugs 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- 229960004346 glimepiride Drugs 0.000 description 1
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
- 229960001381 glipizide Drugs 0.000 description 1
- ZJJXGWJIGJFDTL-UHFFFAOYSA-N glipizide Chemical compound C1=NC(C)=CN=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZJJXGWJIGJFDTL-UHFFFAOYSA-N 0.000 description 1
- 229960003468 gliquidone Drugs 0.000 description 1
- 206010061989 glomerulosclerosis Diseases 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 235000001727 glucose Nutrition 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 229960003180 glutathione Drugs 0.000 description 1
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
- RBNPOMFGQQGHHO-UHFFFAOYSA-N glyceric acid Chemical compound OCC(O)C(O)=O RBNPOMFGQQGHHO-UHFFFAOYSA-N 0.000 description 1
- XLXSAKCOAKORKW-UHFFFAOYSA-N gonadorelin Chemical compound C1CCC(C(=O)NCC(N)=O)N1C(=O)C(CCCN=C(N)N)NC(=O)C(CC(C)C)NC(=O)CNC(=O)C(NC(=O)C(CO)NC(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C(CC=1NC=NC=1)NC(=O)C1NC(=O)CC1)CC1=CC=C(O)C=C1 XLXSAKCOAKORKW-UHFFFAOYSA-N 0.000 description 1
- 229960002913 goserelin Drugs 0.000 description 1
- QBKSWRVVCFFDOT-UHFFFAOYSA-N gossypol Chemical compound CC(C)C1=C(O)C(O)=C(C=O)C2=C(O)C(C=3C(O)=C4C(C=O)=C(O)C(O)=C(C4=CC=3C)C(C)C)=C(C)C=C21 QBKSWRVVCFFDOT-UHFFFAOYSA-N 0.000 description 1
- 229960002383 halcinonide Drugs 0.000 description 1
- 229940115747 halobetasol Drugs 0.000 description 1
- 239000003481 heat shock protein 90 inhibitor Substances 0.000 description 1
- 229940062743 hectorol Drugs 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- PPZMYIBUHIPZOS-UHFFFAOYSA-N histamine dihydrochloride Chemical compound Cl.Cl.NCCC1=CN=CN1 PPZMYIBUHIPZOS-UHFFFAOYSA-N 0.000 description 1
- 108010040030 histidinoalanine Proteins 0.000 description 1
- 229940121372 histone deacetylase inhibitor Drugs 0.000 description 1
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 1
- 239000004030 hiv protease inhibitor Substances 0.000 description 1
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
- 229940116978 human epidermal growth factor Drugs 0.000 description 1
- 229940048921 humira Drugs 0.000 description 1
- 229940088013 hycamtin Drugs 0.000 description 1
- LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 description 1
- 229960000240 hydrocodone Drugs 0.000 description 1
- 229960000631 hydrocortisone valerate Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]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
- 229930005342 hyoscyamine Natural products 0.000 description 1
- 229960003210 hyoscyamine Drugs 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 229960002751 imiquimod Drugs 0.000 description 1
- DOUYETYNHWVLEO-UHFFFAOYSA-N imiquimod Chemical compound C1=CC=CC2=C3N(CC(C)C)C=NC3=C(N)N=C21 DOUYETYNHWVLEO-UHFFFAOYSA-N 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 230000002434 immunopotentiative effect Effects 0.000 description 1
- 229960001936 indinavir Drugs 0.000 description 1
- CBVCZFGXHXORBI-PXQQMZJSSA-N indinavir Chemical compound C([C@H](N(CC1)C[C@@H](O)C[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H]2C3=CC=CC=C3C[C@H]2O)C(=O)NC(C)(C)C)N1CC1=CC=CN=C1 CBVCZFGXHXORBI-PXQQMZJSSA-N 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 229960004461 interferon beta-1a Drugs 0.000 description 1
- 229960003161 interferon beta-1b Drugs 0.000 description 1
- 229940095009 interferon gamma-1a Drugs 0.000 description 1
- 108010042414 interferon gamma-1b Proteins 0.000 description 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
- 201000002313 intestinal cancer Diseases 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007919 intrasynovial administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229960005386 ipilimumab Drugs 0.000 description 1
- 229940084651 iressa Drugs 0.000 description 1
- 229960000779 irinotecan hydrochloride Drugs 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 229960004125 ketoconazole Drugs 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229960004752 ketorolac Drugs 0.000 description 1
- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 1
- BWHLPLXXIDYSNW-UHFFFAOYSA-N ketorolac tromethamine Chemical compound OCC(N)(CO)CO.OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 BWHLPLXXIDYSNW-UHFFFAOYSA-N 0.000 description 1
- 229960004958 ketotifen Drugs 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229960001627 lamivudine Drugs 0.000 description 1
- JTEGQNOMFQHVDC-NKWVEPMBSA-N lamivudine Chemical compound O=C1N=C(N)C=CN1[C@H]1O[C@@H](CO)SC1 JTEGQNOMFQHVDC-NKWVEPMBSA-N 0.000 description 1
- 229960002437 lanreotide Drugs 0.000 description 1
- 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 description 1
- 229950000340 laromustine Drugs 0.000 description 1
- 229950005692 larotaxel Drugs 0.000 description 1
- 229960002367 lasofoxifene Drugs 0.000 description 1
- GXESHMAMLJKROZ-IAPPQJPRSA-N lasofoxifene Chemical compound C1([C@@H]2[C@@H](C3=CC=C(C=C3CC2)O)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 GXESHMAMLJKROZ-IAPPQJPRSA-N 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 229960002618 lenograstim Drugs 0.000 description 1
- 229940115286 lentinan Drugs 0.000 description 1
- 229950001845 lestaurtinib Drugs 0.000 description 1
- 229960003881 letrozole Drugs 0.000 description 1
- 229960001691 leucovorin Drugs 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- MKXZASYAUGDDCJ-CGTJXYLNSA-N levomethorphan Chemical compound C([C@H]12)CCC[C@@]11CCN(C)[C@@H]2CC2=CC=C(OC)C=C21 MKXZASYAUGDDCJ-CGTJXYLNSA-N 0.000 description 1
- 229950008204 levosalbutamol Drugs 0.000 description 1
- 229950006761 lexacalcitol Drugs 0.000 description 1
- 229960004393 lidocaine hydrochloride Drugs 0.000 description 1
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 1
- MPVGZUGXCQEXTM-UHFFFAOYSA-N linifanib Chemical compound CC1=CC=C(F)C(NC(=O)NC=2C=CC(=CC=2)C=2C=3C(N)=NNC=3C=CC=2)=C1 MPVGZUGXCQEXTM-UHFFFAOYSA-N 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 229950002950 lintuzumab Drugs 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000000940 lipogenetic effect Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 229950008991 lobaplatin Drugs 0.000 description 1
- 229940063718 lodine Drugs 0.000 description 1
- 229960002247 lomustine Drugs 0.000 description 1
- 229950001750 lonafarnib Drugs 0.000 description 1
- DHMTURDWPRKSOA-RUZDIDTESA-N lonafarnib Chemical compound C1CN(C(=O)N)CCC1CC(=O)N1CCC([C@@H]2C3=C(Br)C=C(Cl)C=C3CCC3=CC(Br)=CN=C32)CC1 DHMTURDWPRKSOA-RUZDIDTESA-N 0.000 description 1
- 229960001571 loperamide Drugs 0.000 description 1
- RDOIQAHITMMDAJ-UHFFFAOYSA-N loperamide Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C(=O)N(C)C)CCN(CC1)CCC1(O)C1=CC=C(Cl)C=C1 RDOIQAHITMMDAJ-UHFFFAOYSA-N 0.000 description 1
- 229960004525 lopinavir Drugs 0.000 description 1
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 1
- 229960003088 loratadine Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229950002654 lurtotecan Drugs 0.000 description 1
- RVFGKBWWUQOIOU-NDEPHWFRSA-N lurtotecan Chemical compound O=C([C@]1(O)CC)OCC(C(N2CC3=4)=O)=C1C=C2C3=NC1=CC=2OCCOC=2C=C1C=4CN1CCN(C)CC1 RVFGKBWWUQOIOU-NDEPHWFRSA-N 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 208000003747 lymphoid leukemia Diseases 0.000 description 1
- 229940124302 mTOR inhibitor Drugs 0.000 description 1
- 229940092110 macugen Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 229950002736 marizomib Drugs 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229940090004 megace Drugs 0.000 description 1
- 229960004296 megestrol acetate Drugs 0.000 description 1
- 229960001924 melphalan Drugs 0.000 description 1
- LMOINURANNBYCM-UHFFFAOYSA-N metaproterenol Chemical compound CC(C)NCC(O)C1=CC(O)=CC(O)=C1 LMOINURANNBYCM-UHFFFAOYSA-N 0.000 description 1
- FBOZXECLQNJBKD-UHFFFAOYSA-N methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-UHFFFAOYSA-N 0.000 description 1
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 1
- 229940099246 mevacor Drugs 0.000 description 1
- 239000002679 microRNA Substances 0.000 description 1
- 229960002853 midazolam hydrochloride Drugs 0.000 description 1
- PLYSCVSCYOQVRP-UHFFFAOYSA-N midazolam hydrochloride Chemical compound Cl.C12=CC(Cl)=CC=C2N2C(C)=NC=C2CN=C1C1=CC=CC=C1F PLYSCVSCYOQVRP-UHFFFAOYSA-N 0.000 description 1
- 229960001110 miglitol Drugs 0.000 description 1
- UQRORFVVSGFNRO-UTINFBMNSA-N miglustat Chemical compound CCCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO UQRORFVVSGFNRO-UTINFBMNSA-N 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 229960003775 miltefosine Drugs 0.000 description 1
- DYKFCLLONBREIL-KVUCHLLUSA-N minocycline Chemical compound C([C@H]1C2)C3=C(N(C)C)C=CC(O)=C3C(=O)C1=C(O)[C@@]1(O)[C@@H]2[C@H](N(C)C)C(O)=C(C(N)=O)C1=O DYKFCLLONBREIL-KVUCHLLUSA-N 0.000 description 1
- 229960004023 minocycline Drugs 0.000 description 1
- 229960005485 mitobronitol Drugs 0.000 description 1
- 239000003226 mitogen Substances 0.000 description 1
- 229950010913 mitolactol Drugs 0.000 description 1
- VFKZTMPDYBFSTM-GUCUJZIJSA-N mitolactol Chemical compound BrC[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)CBr VFKZTMPDYBFSTM-GUCUJZIJSA-N 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 229960003063 molgramostim Drugs 0.000 description 1
- 108010032806 molgramostim Proteins 0.000 description 1
- VYGYNVZNSSTDLJ-HKCOAVLJSA-N monorden Natural products CC1CC2OC2C=C/C=C/C(=O)CC3C(C(=CC(=C3Cl)O)O)C(=O)O1 VYGYNVZNSSTDLJ-HKCOAVLJSA-N 0.000 description 1
- 229960001951 montelukast sodium Drugs 0.000 description 1
- LBFBRXGCXUHRJY-HKHDRNBDSA-M montelukast sodium Chemical compound [Na+].CC(C)(O)C1=CC=CC=C1CC[C@H](C=1C=C(\C=C\C=2N=C3C=C(Cl)C=CC3=CC=2)C=CC=1)SCC1(CC([O-])=O)CC1 LBFBRXGCXUHRJY-HKHDRNBDSA-M 0.000 description 1
- 229960004715 morphine sulfate Drugs 0.000 description 1
- GRVOTVYEFDAHCL-RTSZDRIGSA-N morphine sulfate pentahydrate Chemical compound O.O.O.O.O.OS(O)(=O)=O.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O.O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O GRVOTVYEFDAHCL-RTSZDRIGSA-N 0.000 description 1
- AARXZCZYLAFQQU-UHFFFAOYSA-N motexafin gadolinium Chemical compound [Gd].CC(O)=O.CC(O)=O.C1=C([N-]2)C(CC)=C(CC)C2=CC(C(=C2C)CCCO)=NC2=CN=C2C=C(OCCOCCOCCOC)C(OCCOCCOCCOC)=CC2=NC=C2C(C)=C(CCCO)C1=N2 AARXZCZYLAFQQU-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 229940072709 motrin Drugs 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- ZTFBIUXIQYRUNT-MDWZMJQESA-N mubritinib Chemical compound C1=CC(C(F)(F)F)=CC=C1\C=C\C1=NC(COC=2C=CC(CCCCN3N=NC=C3)=CC=2)=CO1 ZTFBIUXIQYRUNT-MDWZMJQESA-N 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 229960000951 mycophenolic acid Drugs 0.000 description 1
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 description 1
- 208000017708 myomatous neoplasm Diseases 0.000 description 1
- ISGGVCWFTPTHIX-UHFFFAOYSA-N n'-(2-hydroxy-3-piperidin-1-ylpropoxy)pyridine-3-carboximidamide;dihydrochloride Chemical compound Cl.Cl.C1CCCCN1CC(O)CONC(=N)C1=CC=CN=C1 ISGGVCWFTPTHIX-UHFFFAOYSA-N 0.000 description 1
- SMFXSYMLJDHGIE-UHFFFAOYSA-N n-(3-aminopropyl)-n-[1-(5-benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide Chemical compound N=1C=2SN=C(C)C=2C(=O)N(CC=2C=CC=CC=2)C=1C(C(C)C)N(CCCN)C(=O)C1=CC=C(C)C=C1 SMFXSYMLJDHGIE-UHFFFAOYSA-N 0.000 description 1
- OHDXDNUPVVYWOV-UHFFFAOYSA-N n-methyl-1-(2-naphthalen-1-ylsulfanylphenyl)methanamine Chemical compound CNCC1=CC=CC=C1SC1=CC=CC2=CC=CC=C12 OHDXDNUPVVYWOV-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-M naphthalene-1-sulfonate Chemical compound C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-M 0.000 description 1
- 229940090008 naprosyn Drugs 0.000 description 1
- 229960003940 naproxen sodium Drugs 0.000 description 1
- CDBRNDSHEYLDJV-FVGYRXGTSA-M naproxen sodium Chemical compound [Na+].C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CDBRNDSHEYLDJV-FVGYRXGTSA-M 0.000 description 1
- 229960000698 nateglinide Drugs 0.000 description 1
- OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 1
- 229950004847 navitoclax Drugs 0.000 description 1
- JLYAXFNOILIKPP-KXQOOQHDSA-N navitoclax Chemical compound C([C@@H](NC1=CC=C(C=C1S(=O)(=O)C(F)(F)F)S(=O)(=O)NC(=O)C1=CC=C(C=C1)N1CCN(CC1)CC1=C(CCC(C1)(C)C)C=1C=CC(Cl)=CC=1)CSC=1C=CC=CC=1)CN1CCOCC1 JLYAXFNOILIKPP-KXQOOQHDSA-N 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 229950007221 nedaplatin Drugs 0.000 description 1
- RQTOOFIXOKYGAN-UHFFFAOYSA-N nedocromil Chemical compound CCN1C(C(O)=O)=CC(=O)C2=C1C(CCC)=C1OC(C(O)=O)=CC(=O)C1=C2 RQTOOFIXOKYGAN-UHFFFAOYSA-N 0.000 description 1
- 229960004398 nedocromil Drugs 0.000 description 1
- 229950010159 nemorubicin Drugs 0.000 description 1
- CTMCWCONSULRHO-UHQPFXKFSA-N nemorubicin Chemical compound C1CO[C@H](OC)CN1[C@@H]1[C@H](O)[C@H](C)O[C@@H](O[C@@H]2C3=C(O)C=4C(=O)C5=C(OC)C=CC=C5C(=O)C=4C(O)=C3C[C@](O)(C2)C(=O)CO)C1 CTMCWCONSULRHO-UHQPFXKFSA-N 0.000 description 1
- QZGIWPZCWHMVQL-UIYAJPBUSA-N neocarzinostatin chromophore Chemical compound O1[C@H](C)[C@H](O)[C@H](O)[C@@H](NC)[C@H]1O[C@@H]1C/2=C/C#C[C@H]3O[C@@]3([C@@H]3OC(=O)OC3)C#CC\2=C[C@H]1OC(=O)C1=C(O)C=CC2=C(C)C=C(OC)C=C12 QZGIWPZCWHMVQL-UIYAJPBUSA-N 0.000 description 1
- GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 1
- 229940029345 neupogen Drugs 0.000 description 1
- 229940063708 neutrexin Drugs 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229940080607 nexavar Drugs 0.000 description 1
- 229940099637 nilandron Drugs 0.000 description 1
- 229960002653 nilutamide Drugs 0.000 description 1
- 229960001420 nimustine Drugs 0.000 description 1
- VFEDRRNHLBGPNN-UHFFFAOYSA-N nimustine Chemical compound CC1=NC=C(CNC(=O)N(CCCl)N=O)C(N)=N1 VFEDRRNHLBGPNN-UHFFFAOYSA-N 0.000 description 1
- 229940109551 nipent Drugs 0.000 description 1
- XHWRWCSCBDLOLM-UHFFFAOYSA-N nolatrexed Chemical compound CC1=CC=C2NC(N)=NC(=O)C2=C1SC1=CC=NC=C1 XHWRWCSCBDLOLM-UHFFFAOYSA-N 0.000 description 1
- 229950000891 nolatrexed Drugs 0.000 description 1
- 229940085033 nolvadex Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- ZWLPBLYKEWSWPD-UHFFFAOYSA-N o-toluic acid Chemical compound CC1=CC=CC=C1C(O)=O ZWLPBLYKEWSWPD-UHFFFAOYSA-N 0.000 description 1
- 229950006584 obatoclax Drugs 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
- 229960002450 ofatumumab Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 235000021313 oleic acid Nutrition 0.000 description 1
- 229950003600 ombrabulin Drugs 0.000 description 1
- IXWNTLSTOZFSCM-YVACAVLKSA-N ombrabulin Chemical compound C1=C(NC(=O)[C@@H](N)CO)C(OC)=CC=C1\C=C/C1=CC(OC)=C(OC)C(OC)=C1 IXWNTLSTOZFSCM-YVACAVLKSA-N 0.000 description 1
- 229960002657 orciprenaline Drugs 0.000 description 1
- 229950007283 oregovomab Drugs 0.000 description 1
- 229940035567 orencia Drugs 0.000 description 1
- 230000002188 osteogenic effect Effects 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 description 1
- 150000004880 oxines Chemical class 0.000 description 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 1
- 229960002239 paclitaxel poliglumex Drugs 0.000 description 1
- 229960003978 pamidronic acid Drugs 0.000 description 1
- 229940096763 panretin Drugs 0.000 description 1
- 208000003154 papilloma Diseases 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229950007460 patupilone Drugs 0.000 description 1
- 229960001744 pegaspargase Drugs 0.000 description 1
- 108010001564 pegaspargase Proteins 0.000 description 1
- 230000006320 pegylation Effects 0.000 description 1
- WVUNYSQLFKLYNI-AATRIKPKSA-N pelitinib Chemical compound C=12C=C(NC(=O)\C=C\CN(C)C)C(OCC)=CC2=NC=C(C#N)C=1NC1=CC=C(F)C(Cl)=C1 WVUNYSQLFKLYNI-AATRIKPKSA-N 0.000 description 1
- 229950003819 pelitrexol Drugs 0.000 description 1
- 229960005079 pemetrexed Drugs 0.000 description 1
- 229960005570 pemtumomab Drugs 0.000 description 1
- 229960001639 penicillamine Drugs 0.000 description 1
- 229950003180 peplomycin Drugs 0.000 description 1
- QIMGFXOHTOXMQP-GFAGFCTOSA-N peplomycin Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCCN[C@@H](C)C=1C=CC=CC=1)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1NC=NC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C QIMGFXOHTOXMQP-GFAGFCTOSA-N 0.000 description 1
- 210000002824 peroxisome Anatomy 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 210000003800 pharynx Anatomy 0.000 description 1
- 229940107333 phenergan Drugs 0.000 description 1
- 150000007965 phenolic acids Chemical class 0.000 description 1
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 1
- 150000003009 phosphonic acids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 102000020233 phosphotransferase Human genes 0.000 description 1
- LHNIIDJUOCFXAP-UHFFFAOYSA-N pictrelisib Chemical compound C1CN(S(=O)(=O)C)CCN1CC1=CC2=NC(C=3C=4C=NNC=4C=CC=3)=NC(N3CCOCC3)=C2S1 LHNIIDJUOCFXAP-UHFFFAOYSA-N 0.000 description 1
- KASDHRXLYQOAKZ-XDSKOBMDSA-N pimecrolimus Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@H](Cl)[C@H](OC)C1 KASDHRXLYQOAKZ-XDSKOBMDSA-N 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 229960005414 pirbuterol Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 210000002706 plastid Anatomy 0.000 description 1
- 229950005134 polycarbophil Drugs 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 108010001062 polysaccharide-K Proteins 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- MREOOEFUTWFQOC-UHFFFAOYSA-M potassium;5-chloro-4-hydroxy-1h-pyridin-2-one;4,6-dioxo-1h-1,3,5-triazine-2-carboxylate;5-fluoro-1-(oxolan-2-yl)pyrimidine-2,4-dione Chemical compound [K+].OC1=CC(=O)NC=C1Cl.[O-]C(=O)C1=NC(=O)NC(=O)N1.O=C1NC(=O)C(F)=CN1C1OCCC1 MREOOEFUTWFQOC-UHFFFAOYSA-M 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000001144 powder X-ray diffraction data Methods 0.000 description 1
- 229960001896 pramocaine Drugs 0.000 description 1
- DQKXQSGTHWVTAD-UHFFFAOYSA-N pramocaine Chemical compound C1=CC(OCCCC)=CC=C1OCCCN1CCOCC1 DQKXQSGTHWVTAD-UHFFFAOYSA-N 0.000 description 1
- JDOZJEUDSLGTLU-VWUMJDOOSA-N prednisolone phosphate Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COP(O)(O)=O)[C@@H]4[C@@H]3CCC2=C1 JDOZJEUDSLGTLU-VWUMJDOOSA-N 0.000 description 1
- 229960002943 prednisolone sodium phosphate Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 229940068586 prezista Drugs 0.000 description 1
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 description 1
- 229960000624 procarbazine Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000005522 programmed cell death Effects 0.000 description 1
- 229940087463 proleukin Drugs 0.000 description 1
- XXPDBLUZJRXNNZ-UHFFFAOYSA-N promethazine hydrochloride Chemical compound Cl.C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 XXPDBLUZJRXNNZ-UHFFFAOYSA-N 0.000 description 1
- 229960002244 promethazine hydrochloride Drugs 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 210000004765 promyelocyte Anatomy 0.000 description 1
- 229940117382 propecia Drugs 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 201000001514 prostate carcinoma Diseases 0.000 description 1
- 239000003528 protein farnesyltransferase inhibitor Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 229940034080 provenge Drugs 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 239000003379 purinergic P1 receptor agonist Substances 0.000 description 1
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 1
- 235000008160 pyridoxine Nutrition 0.000 description 1
- 239000011677 pyridoxine Substances 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 229940030966 pyrrole Drugs 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- WVTKBKWTSCPRNU-UHFFFAOYSA-N rac-Tetrandrin Natural products O1C(C(=CC=2CCN3C)OC)=CC=2C3CC(C=C2)=CC=C2OC(=C2)C(OC)=CC=C2CC2N(C)CCC3=CC(OC)=C(OC)C1=C23 WVTKBKWTSCPRNU-UHFFFAOYSA-N 0.000 description 1
- 239000002534 radiation-sensitizing agent Substances 0.000 description 1
- AECPBJMOGBFQDN-YMYQVXQQSA-N radicicol Chemical compound C1CCCC(=O)C[C@H]2[C@H](Cl)C(=O)CC(=O)[C@H]2C(=O)O[C@H](C)C[C@H]2O[C@@H]21 AECPBJMOGBFQDN-YMYQVXQQSA-N 0.000 description 1
- 229930192524 radicicol Natural products 0.000 description 1
- 229960004622 raloxifene Drugs 0.000 description 1
- 229960004742 raltegravir Drugs 0.000 description 1
- CZFFBEXEKNGXKS-UHFFFAOYSA-N raltegravir Chemical compound O1C(C)=NN=C1C(=O)NC(C)(C)C1=NC(C(=O)NCC=2C=CC(F)=CC=2)=C(O)C(=O)N1C CZFFBEXEKNGXKS-UHFFFAOYSA-N 0.000 description 1
- 108010061338 ranpirnase Proteins 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 229960005567 rebeccamycin Drugs 0.000 description 1
- INSACQSBHKIWNS-QZQSLCQPSA-N rebeccamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](OC)[C@@H](CO)O[C@H]1N1C2=C3N=C4[C](Cl)C=CC=C4C3=C3C(=O)NC(=O)C3=C2C2=CC=CC(Cl)=C21 INSACQSBHKIWNS-QZQSLCQPSA-N 0.000 description 1
- 229950005950 rebimastat Drugs 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 230000006798 recombination Effects 0.000 description 1
- 238000005215 recombination Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229940087462 relafen Drugs 0.000 description 1
- 229940020428 renagel Drugs 0.000 description 1
- 229960002354 repaglinide Drugs 0.000 description 1
- OAKGNIRUXAZDQF-TXHRRWQRSA-N retaspimycin Chemical compound N1C(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@@H](O)[C@@H](OC)C[C@H](C)CC2=C(O)C1=CC(O)=C2NCC=C OAKGNIRUXAZDQF-TXHRRWQRSA-N 0.000 description 1
- 229940002683 retin-a Drugs 0.000 description 1
- 229940064914 retrovir Drugs 0.000 description 1
- 229940120975 revlimid Drugs 0.000 description 1
- 229960000329 ribavirin Drugs 0.000 description 1
- HZCAHMRRMINHDJ-DBRKOABJSA-N ribavirin Natural products O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1N=CN=C1 HZCAHMRRMINHDJ-DBRKOABJSA-N 0.000 description 1
- 239000002342 ribonucleoside Substances 0.000 description 1
- 229960000759 risedronic acid Drugs 0.000 description 1
- 229960000311 ritonavir Drugs 0.000 description 1
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 1
- 229920002477 rna polymer Polymers 0.000 description 1
- OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- HHJUWIANJFBDHT-ZVTSDNJWSA-N rsa8ko39wh Chemical compound C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 HHJUWIANJFBDHT-ZVTSDNJWSA-N 0.000 description 1
- 101150024074 rub1 gene Proteins 0.000 description 1
- HMABYWSNWIZPAG-UHFFFAOYSA-N rucaparib Chemical compound C1=CC(CNC)=CC=C1C(N1)=C2CCNC(=O)C3=C2C1=CC(F)=C3 HMABYWSNWIZPAG-UHFFFAOYSA-N 0.000 description 1
- 229960000215 ruxolitinib Drugs 0.000 description 1
- HFNKQEVNSGCOJV-OAHLLOKOSA-N ruxolitinib Chemical compound C1([C@@H](CC#N)N2N=CC(=C2)C=2C=3C=CNC=3N=CN=2)CCCC1 HFNKQEVNSGCOJV-OAHLLOKOSA-N 0.000 description 1
- 235000012045 salad Nutrition 0.000 description 1
- NGWSFRIPKNWYAO-SHTIJGAHSA-N salinosporamide A Chemical compound C([C@@H]1[C@H](O)[C@]23C(=O)O[C@]2([C@H](C(=O)N3)CCCl)C)CCC=C1 NGWSFRIPKNWYAO-SHTIJGAHSA-N 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000003566 sealing material Substances 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229950000055 seliciclib Drugs 0.000 description 1
- CYOHGALHFOKKQC-UHFFFAOYSA-N selumetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1Cl CYOHGALHFOKKQC-UHFFFAOYSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229960003693 sevelamer Drugs 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229960000714 sipuleucel-t Drugs 0.000 description 1
- 229960004034 sitagliptin Drugs 0.000 description 1
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 description 1
- 229950001403 sizofiran Drugs 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 229950010372 sobuzoxane Drugs 0.000 description 1
- YRWWOAFMPXPHEJ-OFBPEYICSA-K sodium L-ascorbic acid 2-phosphate Chemical compound [Na+].[Na+].[Na+].OC[C@H](O)[C@H]1OC(=O)C(OP([O-])([O-])=O)=C1[O-] YRWWOAFMPXPHEJ-OFBPEYICSA-K 0.000 description 1
- 229940048058 sodium ascorbyl phosphate Drugs 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- JSMHQMIPUOPQLR-UHFFFAOYSA-M sodium;dioctadecyl phosphate Chemical compound [Na+].CCCCCCCCCCCCCCCCCCOP([O-])(=O)OCCCCCCCCCCCCCCCCCC JSMHQMIPUOPQLR-UHFFFAOYSA-M 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 229940078986 somatuline Drugs 0.000 description 1
- 229940072291 soriatane Drugs 0.000 description 1
- VIDRYROWYFWGSY-UHFFFAOYSA-N sotalol hydrochloride Chemical compound Cl.CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 VIDRYROWYFWGSY-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- HKSZLNNOFSGOKW-FYTWVXJKSA-N staurosporine Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@H]1C[C@@H](NC)[C@@H](OC)[C@]4(C)O1 HKSZLNNOFSGOKW-FYTWVXJKSA-N 0.000 description 1
- CGPUWJWCVCFERF-UHFFFAOYSA-N staurosporine Natural products C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1C1CC(NC)C(OC)C4(OC)O1 CGPUWJWCVCFERF-UHFFFAOYSA-N 0.000 description 1
- 229960001203 stavudine Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- GPTONYMQFTZPKC-UHFFFAOYSA-N sulfamethoxydiazine Chemical compound N1=CC(OC)=CN=C1NS(=O)(=O)C1=CC=C(N)C=C1 GPTONYMQFTZPKC-UHFFFAOYSA-N 0.000 description 1
- 229960002229 sulfametoxydiazine Drugs 0.000 description 1
- MPUQHZXIXSTTDU-QXGSTGNESA-N sulfamic acid [(1S,2S,4R)-4-[4-[[(1S)-2,3-dihydro-1H-inden-1-yl]amino]-7-pyrrolo[2,3-d]pyrimidinyl]-2-hydroxycyclopentyl]methyl ester Chemical compound C1[C@H](O)[C@H](COS(=O)(=O)N)C[C@H]1N1C2=NC=NC(N[C@@H]3C4=CC=CC=C4CC3)=C2C=C1 MPUQHZXIXSTTDU-QXGSTGNESA-N 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 1
- 229960001796 sunitinib Drugs 0.000 description 1
- 239000000516 sunscreening agent Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 235000019605 sweet taste sensations Nutrition 0.000 description 1
- 239000012622 synthetic inhibitor Substances 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- 229950003999 tafluposide Drugs 0.000 description 1
- 108010009573 talabostat Proteins 0.000 description 1
- 229950010637 talabostat Drugs 0.000 description 1
- ZMELOYOKMZBMRB-DLBZAZTESA-N talmapimod Chemical compound C([C@@H](C)N(C[C@@H]1C)C(=O)C=2C(=CC=3N(C)C=C(C=3C=2)C(=O)C(=O)N(C)C)Cl)N1CC1=CC=C(F)C=C1 ZMELOYOKMZBMRB-DLBZAZTESA-N 0.000 description 1
- 229960003454 tamoxifen citrate Drugs 0.000 description 1
- 229950007866 tanespimycin Drugs 0.000 description 1
- 239000011269 tar Substances 0.000 description 1
- 229940120982 tarceva Drugs 0.000 description 1
- 229960003102 tasonermin Drugs 0.000 description 1
- 108010048573 taspoglutide Proteins 0.000 description 1
- WRGVLTAWMNZWGT-VQSPYGJZSA-N taspoglutide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NC(C)(C)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)C(C)(C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 WRGVLTAWMNZWGT-VQSPYGJZSA-N 0.000 description 1
- 229950007151 taspoglutide Drugs 0.000 description 1
- YMNZWKHEJQGPIA-UHFFFAOYSA-N tatridin-A Natural products C1=C(C)C(O)CCC(C)=CC(O)C2C(=C)C(=O)OC21 YMNZWKHEJQGPIA-UHFFFAOYSA-N 0.000 description 1
- 229940063683 taxotere Drugs 0.000 description 1
- 229960001674 tegafur Drugs 0.000 description 1
- WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 description 1
- 229940061353 temodar Drugs 0.000 description 1
- QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 description 1
- 229960004556 tenofovir Drugs 0.000 description 1
- VCMJCVGFSROFHV-WZGZYPNHSA-N tenofovir disoproxil fumarate Chemical compound OC(=O)\C=C\C(O)=O.N1=CN=C2N(C[C@@H](C)OCP(=O)(OCOC(=O)OC(C)C)OCOC(=O)OC(C)C)C=NC2=C1N VCMJCVGFSROFHV-WZGZYPNHSA-N 0.000 description 1
- 229960000195 terbutaline Drugs 0.000 description 1
- 229950007967 tesmilifene Drugs 0.000 description 1
- 201000003120 testicular cancer Diseases 0.000 description 1
- BSYVTEYKTMYBMK-UHFFFAOYSA-N tetrahydrofurfuryl alcohol Chemical compound OCC1CCCO1 BSYVTEYKTMYBMK-UHFFFAOYSA-N 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 229940110675 theracys Drugs 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 229940015849 thiophene Drugs 0.000 description 1
- 229960001196 thiotepa Drugs 0.000 description 1
- RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 1
- 208000013066 thyroid gland cancer Diseases 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- XFYDIVBRZNQMJC-UHFFFAOYSA-N tizanidine Chemical compound ClC=1C=CC2=NSN=C2C=1NC1=NCCN1 XFYDIVBRZNQMJC-UHFFFAOYSA-N 0.000 description 1
- 229960000488 tizanidine Drugs 0.000 description 1
- 229960003989 tocilizumab Drugs 0.000 description 1
- 229960001350 tofacitinib Drugs 0.000 description 1
- 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 description 1
- QGUALMNFRILWRA-UHFFFAOYSA-M tolmetin sodium Chemical compound [Na+].C1=CC(C)=CC=C1C(=O)C1=CC=C(CC([O-])=O)N1C QGUALMNFRILWRA-UHFFFAOYSA-M 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229940019127 toradol Drugs 0.000 description 1
- 229960004167 toremifene citrate Drugs 0.000 description 1
- AKCRNFFTGXBONI-UHFFFAOYSA-N torin 1 Chemical compound C1CN(C(=O)CC)CCN1C1=CC=C(N2C(C=CC3=C2C2=CC(=CC=C2N=C3)C=2C=C3C=CC=CC3=NC=2)=O)C=C1C(F)(F)F AKCRNFFTGXBONI-UHFFFAOYSA-N 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 229960000977 trabectedin Drugs 0.000 description 1
- 229940118436 tracleer Drugs 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 229960004380 tramadol Drugs 0.000 description 1
- LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 description 1
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000002103 transcriptional effect Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 108010060597 trapoxin A Proteins 0.000 description 1
- 229940066958 treanda Drugs 0.000 description 1
- 229940032510 trelstar Drugs 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 229960005526 triapine Drugs 0.000 description 1
- KVSKGMLNBAPGKH-UHFFFAOYSA-N tribromosalicylanilide Chemical compound OC1=C(Br)C=C(Br)C=C1C(=O)NC1=CC=C(Br)C=C1 KVSKGMLNBAPGKH-UHFFFAOYSA-N 0.000 description 1
- IEDVJHCEMCRBQM-UHFFFAOYSA-N trimethoprim Chemical compound COC1=C(OC)C(OC)=CC(CC=2C(=NC(N)=NC=2)N)=C1 IEDVJHCEMCRBQM-UHFFFAOYSA-N 0.000 description 1
- 229960001082 trimethoprim Drugs 0.000 description 1
- 229960001099 trimetrexate Drugs 0.000 description 1
- NOYPYLRCIDNJJB-UHFFFAOYSA-N trimetrexate Chemical compound COC1=C(OC)C(OC)=CC(NCC=2C(=C3C(N)=NC(N)=NC3=CC=2)C)=C1 NOYPYLRCIDNJJB-UHFFFAOYSA-N 0.000 description 1
- 229960000538 trimetrexate glucuronate Drugs 0.000 description 1
- VXKHXGOKWPXYNA-PGBVPBMZSA-N triptorelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 VXKHXGOKWPXYNA-PGBVPBMZSA-N 0.000 description 1
- 229940086984 trisenox Drugs 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
- 210000005239 tubule Anatomy 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- 229950008396 ulobetasol propionate Drugs 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 238000002628 unsealed source radiotherapy Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 229940045136 urea Drugs 0.000 description 1
- AUFUWRKPQLGTGF-FMKGYKFTSA-N uridine triacetate Chemical compound CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@@H](COC(=O)C)O[C@H]1N1C(=O)NC(=O)C=C1 AUFUWRKPQLGTGF-FMKGYKFTSA-N 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 1
- 229960000604 valproic acid Drugs 0.000 description 1
- 229940054937 valstar Drugs 0.000 description 1
- 229940097704 vantas Drugs 0.000 description 1
- 229940099039 velcade Drugs 0.000 description 1
- LQBVNQSMGBZMKD-UHFFFAOYSA-N venetoclax Chemical compound C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN(CC1)CCN1C(C=C1OC=2C=C3C=CNC3=NC=2)=CC=C1C(=O)NS(=O)(=O)C(C=C1[N+]([O-])=O)=CC=C1NCC1CCOCC1 LQBVNQSMGBZMKD-UHFFFAOYSA-N 0.000 description 1
- 229960001183 venetoclax Drugs 0.000 description 1
- 229940094450 vetoryl Drugs 0.000 description 1
- 229960001254 vildagliptin Drugs 0.000 description 1
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- NMDYYWFGPIMTKO-HBVLKOHWSA-N vinflunine Chemical compound C([C@@](C1=C(C2=CC=CC=C2N1)C1)(C2=C(OC)C=C3N(C)[C@@H]4[C@@]5(C3=C2)CCN2CC=C[C@]([C@@H]52)([C@H]([C@]4(O)C(=O)OC)OC(C)=O)CC)C(=O)OC)[C@H]2C[C@@H](C(C)(F)F)CN1C2 NMDYYWFGPIMTKO-HBVLKOHWSA-N 0.000 description 1
- 229960000922 vinflunine Drugs 0.000 description 1
- GBABOYUKABKIAF-GHYRFKGUSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-GHYRFKGUSA-N 0.000 description 1
- 229960002066 vinorelbine Drugs 0.000 description 1
- 229940087652 vioxx Drugs 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 108010069784 vitespin Proteins 0.000 description 1
- 229940063674 voltaren Drugs 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- QDLHCMPXEPAAMD-QAIWCSMKSA-N wortmannin Chemical compound C1([C@]2(C)C3=C(C4=O)OC=C3C(=O)O[C@@H]2COC)=C4[C@@H]2CCC(=O)[C@@]2(C)C[C@H]1OC(C)=O QDLHCMPXEPAAMD-QAIWCSMKSA-N 0.000 description 1
- QDLHCMPXEPAAMD-UHFFFAOYSA-N wortmannin Natural products COCC1OC(=O)C2=COC(C3=O)=C2C1(C)C1=C3C2CCC(=O)C2(C)CC1OC(C)=O QDLHCMPXEPAAMD-UHFFFAOYSA-N 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- 229940053867 xeloda Drugs 0.000 description 1
- UGOMMVLRQDMAQQ-UHFFFAOYSA-N xphos Chemical group CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 UGOMMVLRQDMAQQ-UHFFFAOYSA-N 0.000 description 1
- 229940004212 yondelis Drugs 0.000 description 1
- 229960000523 zalcitabine Drugs 0.000 description 1
- 229950009002 zanolimumab Drugs 0.000 description 1
- 229940099072 zavesca Drugs 0.000 description 1
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 1
- 229950009268 zinostatin Drugs 0.000 description 1
- 229940033942 zoladex Drugs 0.000 description 1
- 229960004276 zoledronic acid Drugs 0.000 description 1
- 229940002005 zometa Drugs 0.000 description 1
- 229960000641 zorubicin Drugs 0.000 description 1
- FBTUMDXHSRTGRV-ALTNURHMSA-N zorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(\C)=N\NC(=O)C=1C=CC=CC=1)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 FBTUMDXHSRTGRV-ALTNURHMSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- 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
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/16—Masculine contraceptives
-
- 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
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/06—Antigout agents, e.g. antihyperuricemic or uricosuric agents
-
- 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
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/14—Drugs for disorders of the endocrine system of the thyroid hormones, e.g. T3, T4
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Immunology (AREA)
- Oncology (AREA)
- Virology (AREA)
- Diabetes (AREA)
- Endocrinology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Cardiology (AREA)
- Communicable Diseases (AREA)
- Reproductive Health (AREA)
- Hematology (AREA)
- Physical Education & Sports Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Dermatology (AREA)
- AIDS & HIV (AREA)
- Pain & Pain Management (AREA)
- Molecular Biology (AREA)
- Obesity (AREA)
- Gastroenterology & Hepatology (AREA)
- Emergency Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Transplantation (AREA)
Abstract
N‑[4‑(2,4‑二氟苯氧基)‑3‑(6‑甲基‑7‑氧代‑6,7‑二氢‑1H‑吡咯并[2,3‑c]吡啶‑4‑基)苯基]乙磺酰胺和其结晶形式,是用于治疗疾病(例如,癌症)的药物组合物的合适药用组分。
Description
发明背景
溴结构域(Bromodomain)指的是保守蛋白结构沟(structural folds),它与一些蛋白中存在的N-乙酰化的赖氨酸残基结合。含有蛋白的溴结构域的BET家族由四个成员(BRD2、BRD3、BRD4和BRDt)组成。BET家族的每个成员使用两个溴结构域,以辨别主要(但不是唯一)存在于组蛋白的氨基端尾部上的N-乙酰化的赖氨酸残基。这些相互作用通过将转录因子补充至染色质内的特定基因组位置来调节基因表达。例如,组蛋白结合的BRD4对启动子补充转录因子P-TEFb,引起与细胞周期进程有关的基因亚型的表达(Yang等人,Mol.Cell. Biol. 28: 967-976(2008))。BRD2和BRD3还起到生长促进基因的转录调节剂的作用(LeRoy等人,Mol. Cell 30: 51-60(2008))。最近,确定了BET家族成员对于维持一些癌症类型是很重要的(Zuber等人,Nature 478: 524-528(2011); Mertz等人,Proc. Nat’l.Acad. Sci. 108: 16669-16674(2011); Delmore等人,Cell 146: 1-14,(2011); Dawson等人,Nature 478: 529-533(2011))。BET家族成员还涉及通过典型的NF-KB途径来介导急性炎症性响应(Huang等人,Mol. Cell. Biol. 29: 1375-1387(2009)),引起与细胞素的产生相关的基因的上调(Nicodeme等人,Nature 468: 1119-1123,(2010))。已经证明,通过BET溴结构域抑制剂来抑制细胞素诱导,是在动物模型中治疗炎症介导的肾病的有效手段(Zhang等人,J. Biol. Chem. 287: 28840-28851(2012))。BRD2功能与血脂异常的诱因或脂肪生成的异常控制、炎症性的升高和对自身免疫疾病的敏感性提高有关(Denis,Discovery Medicine 10: 489-499(2010))。人类免疫缺陷性病毒使用BRD4启动由稳定整合的病毒RNA来转录病毒DNA(Jang等人,Mol. Cell, 19: 523-534(2005))。用BET特异性溴结构域抑制剂治疗db/db小鼠,显示出蛋白尿减少,由此为糖尿病性肾病的新的治疗法提供了可能性(Liu等人, “Role of Transcription Factor Acetylation in DiabeticKidney Disease” Diabetes, DOI: 10.2337/db13-1810(2014))。还已表明,在潜在的T细胞感染和潜在的单核白细胞感染的模型中,BET溴结构域抑制剂可重新激活HIV转录(Banerjee等人,J. Leukocyte Biol. 92(6): 1147-1154(2012))。在被BET溴结构域抑制剂阻断的精子生成过程中,BRDt具有重要的作用(Matzuk等人,Cell 150: 673-684(2012))。在败血症和内毒素性休克的动物模型中用BET抑制剂进行的研究,已经证明了概念验证(proof-of-concept)效能(Nicodeme等人,Nature 468: 1119-1123(2010))、胰岛素抗性和肝脂质沉着症(Bradner等人,Composition and methods for modulating metabolism. WO2011/143651A1)、特发性肺纤维化(Tang等人,Am. J. Pathol. 183: 470-479(2013))和心力衰竭(Spiltoir等人,J. Mol. Cellular Cardiol. 63: 175-179(2013), Anand等人,Cell 154: 569-582(2013))。相应地,为了治疗这些适应症,还有开发新药和其结晶形式的医学需要。
附图的简要说明
图1提供了N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺I型的粉末X射线衍射(PXRD)扫描。
图2提供了N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺I型的差示扫描量热(DSC)热像图。
图3提供了N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺I型的TGA曲线。
图4提供了N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺II型的粉末X射线衍射(PXRD)扫描。
图5提供了N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺II型的差示扫描量热(DSC)热像图。
图6提供了N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺II型的TGA曲线。
概述
在一方面,本发明涉及N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的分离的结晶形式,其中,所述结晶形式具有包含三个或更多个选自下列2θ峰值±0.2的粉末X射线衍射图∶6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。在一方面,本发明涉及N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的分离的结晶形式,其中,所述结晶形式具有包含下列2θ峰值±0.2的粉末X射线衍射图∶6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。在某些实施方案中,粉末X射线衍射图包含下列2θ峰值±0.2∶6.2°、9.0°、11.0°、12.3°、12.6°、13.1°、14.1°、15.6°、16.4°、16.5°、16.9°、17.8°、18.1°、18.3°、18.9°、20.4°、21.1°、21.6°、21.8°、22.1°、22.9°、23.2°、24.4°、24.7°、25.6°、26.3°、27.0°和27.3°。在某些实施方案中,粉末X射线衍射图包含三个、四个、五个或六个选自下列的2θ峰值±0.2:6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。在某些实施方案中,粉末X射线衍射图包含六个选自下列的2θ峰值±0.2∶6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。在某些实施方案中,粉末X射线衍射图包含五个选自下列的2θ峰值±0.2∶6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。在某些实施方案中,粉末X射线衍射图包含四个选自下列的2θ峰值±0.2∶6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。在某些实施方案中,粉末X射线衍射图包含三个选自下列的2θ峰值±0.2∶6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。在某些实施方案中,粉末X射线衍射图包含下列2θ峰值±0.2∶6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。在某些实施方案中,粉末X射线衍射图包含下列2θ峰值±0.2∶6.2°、9.0°、12.3°、12.6°和15.6°。在某些实施方案中,粉末X射线衍射图包含下列2θ峰值±0.2∶22.1°、25.6°、26.3°、27.0°和27.3°。在某些实施方案中,粉末X射线衍射图在下列2θ位置包含峰值±0.2∶6.2°、9.0°、12.3°、12.6°、13.1°、14.1°、16.4°、16.5°、16.9°、17.8°、18.1°、18.3°和18.9°。在某些实施方案中,粉末X射线衍射图在下列2θ位置包含峰值±0.2∶6.2°、9.0°、12.3°、12.6°、13.1°、14.1°、18.1°和18.9°。在某些实施方案中,粉末X射线衍射图在下列2θ位置包含峰值±0.2∶6.2°、9.0°、12.3°、12.6°、13.1°和18.1°。在某些实施方案中,粉末X射线衍射图在下列2θ位置包含峰值±0.2∶9.0°、12.3°、12.6°、13.1°和18.1°。在某些实施方案中,结晶形式II在240和242℃之间具有差示扫描量热图吸热线。在某些实施方案中,结晶形式II在大约241℃具有差示扫描量热图吸热线。在某些实施方案中,使用DSC测定吸热线,加热速率为10℃/分钟。在某些实施方案中,粉末X射线衍射图在下列2θ位置包含峰值±0.2∶6.2°、9.0°、11.0°、12.2°、12.6°、13.1°、14.1°、15.5°、16.3°、16.5°、16.9°、17.8°、18.0°、18.3°、18.9°、20.4°、21.0°、21.6°、21.8°、22.1°、22.9°、23.2°、24.4°、24.6°、25.5°、26.3°、26.9°和27.2。在某些实施方案中,粉末X射线衍射图在选自下列的2θ位置±0.2包含峰值±0.2∶6.2°、9.0°、12.2°、12.6°、15.5°、22.1°、25.5°、26.3°、26.9°和27.2°。
在另一个方面,本发明涉及药物组合物,所述药物组合物含有N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II,以及至少一种药用载体。在某些实施方案中,所述药物组合物是固体剂型。
在另一个方面,本发明涉及治疗患者的癌症的方法,所述方法包括:给予需要其的患者治疗有效量的、含有N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II以及至少一种可药用载体的药物组合物。在一些实施方案中,癌症选自∶听神经瘤、急性白血病、急性淋巴细胞性白血病、急性髓细胞性白血病(单核细胞、成髓细胞、腺癌、血管肉瘤、星形细胞瘤、髓单核细胞和前髓细胞)、急性的T细胞白血病、基底细胞癌、胆管癌、膀胱癌、脑癌、乳腺癌、支气管癌、子宫颈癌、软骨肉瘤、脊索瘤、绒膜癌、慢性白血病、慢性淋巴细胞性白血病、慢性髓细胞(粒细胞)白血病、慢性粒性白血病、结肠癌、结肠直肠癌、颅咽管瘤、囊腺癌、扩散性大B细胞淋巴瘤、增殖异常性(dysproliferative)变化(发育异常和组织变形)、胚胎性癌、子宫内膜癌、内皮肉瘤、室管膜瘤、上皮癌、红白血病、食道癌、雌激素-受体阳性乳腺癌、特发性血小板增多症、尤因氏瘤、纤维肉瘤、滤泡性淋巴瘤、生殖细胞睾丸癌、胶质瘤、恶性胶质瘤、胶质肉瘤、重链病、成血管细胞瘤、肝癌、肝细胞癌、激素不敏感的前列腺癌、平滑肌肉瘤、白血病、脂肉瘤、肺癌、淋巴管内皮肉瘤、淋巴管肉瘤、淋巴细胞性白血病、淋巴瘤(霍奇金氏和非霍奇金氏)、膀胱、乳房、结肠、肺、卵巢、胰腺、前列腺、皮肤和子宫和恶性肿瘤和高增殖病症、起源于T细胞或B细胞的淋巴恶性肿瘤、白血病、淋巴瘤、髓样癌、成髓细胞瘤、黑素瘤、脑膜瘤、间皮瘤、多发性骨髓瘤、粒细胞性白血病、骨髓瘤、粘液肉瘤、神经母细胞瘤、NUT中线癌(NMC)、非小细胞肺癌、寡枝神经胶质细胞瘤、口腔癌、骨原性肉瘤、卵巢癌、胰腺癌、乳头状腺癌、乳头状癌、松果体瘤、真性红细胞增多症、前列腺癌、直肠癌、肾细胞癌、成视网膜细胞瘤、横纹肌肉瘤、肉瘤、皮脂腺癌、精原细胞瘤、皮肤癌、小细胞肺癌、实质固态瘤(癌和肉瘤)、小细胞肺癌、胃癌、鳞状细胞癌、滑膜瘤、汗腺癌、甲状腺癌、Waldenström’s巨球蛋白血症、睾丸肿瘤、子宫癌和Wilms'肿瘤。在某些实施方案中,所述方法进一步包括:给予治疗有效量的至少一种其它治疗剂。在某些实施方案中,其它治疗剂选自阿糖胞苷、硼替佐米(Bortezomib)和5-阿扎胞苷。
在另一个方面,本发明涉及治疗患者的疾病或病症的方法,所述方法包括:给予需要其的患者治疗有效量的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II,其中,所述疾病或病症选自∶阿狄森氏病、急性痛风、强直性脊柱炎、哮喘、动脉粥样硬化、贝切特氏病、大疱性皮肤病、心脏肌病、心脏肥大、慢性阻塞性肺病(COPD)、克罗恩氏病、皮炎、湿疹、巨细胞性动脉炎、肾小球肾炎、心力衰竭、肝炎、垂体炎、炎症性肠病、川崎氏病、狼疮肾炎、多发性硬化、心肌炎、肌炎、肾炎、器官移植排斥、骨关节炎、胰腺炎、心包炎、结节性动脉周围炎、肺炎、夏科氏肝硬变、牛皮癣、牛皮癣关节炎、类风湿性关节炎、巩膜炎、硬化性胆管炎、败血症、系统性红斑狼疮、Takayasu's动脉炎、中毒性休克、甲状腺炎、I型糖尿病、溃疡性结肠炎、葡萄膜炎、白癜风、血管炎和眶坏死性肉芽肿病。在某些实施方案中,所述方法进一步包括:给予治疗有效量的至少一种其它治疗剂。
在另一个方面,本发明涉及治疗患者的慢性肾疾病或病症的方法,所述方法包括:给予需要其的患者治疗有效量的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II,其中,所述疾病或病症选自∶糖尿病性的肾病、高血压肾病、HIV相关的肾病、肾小球肾炎、狼疮肾炎、IgA肾病、局灶性节段性肾小球硬化症、膜性肾小球肾炎、微小病变疾病、多囊肾疾病和管状间质性肾炎。在某些实施方案中,所述方法进一步包括:给予治疗有效量的至少一种其它治疗剂。
在另一个方面,本发明涉及治疗患者的急性肾损伤或疾病或病症的方法,所述方法包括:给予需要其的患者治疗有效量的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II,其中,所述急性肾损伤或疾病或病症选自∶缺血-再灌注诱导的肾病、心脏和大外科诱导的肾病、经皮的冠状动脉干预诱导的肾病、放射造影剂诱导的肾病、败血症诱导的肾病、肺炎诱导的肾病和药物毒性诱导的肾病。在某些实施方案中,所述方法进一步包括:给予治疗有效量的至少一种其它治疗剂。
在另一个方面,本发明涉及治疗患者的AIDS的方法,所述方法包括:给予需要其的患者治疗有效量的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II。在某些实施方案中,所述方法进一步包括:给予治疗有效量的至少一种其它治疗剂。
在另一个方面,本发明涉及治疗患者的肥胖症、血脂异常、高胆固醇血症、阿尔海默氏疾病、代谢综合征、肝脂质沉着症、II型糖尿病、胰岛素抗性、糖尿病性视网膜病或糖尿病性神经病变的方法,所述方法包括:给予需要其的患者治疗有效量的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II。在某些实施方案中,所述方法进一步包括:给予治疗有效量的至少一种其它治疗剂。
在另一个方面,本发明涉及男性患者避孕的方法,所述方法包括:给予需要其的患者治疗有效量的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II。在某些实施方案中,所述方法进一步包括:给予治疗有效量的至少一种其它治疗剂。
本发明的进一步方面提供了单独的或与至少一种其它治疗剂联用的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II在制备药物中的用途,所述药物用于治疗或预防本文公开的病症和病症,所述药物可以含有或不含药用载体。
在某些实施方案中,本发明提供了单独的或与至少一种其它治疗剂联用的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II在制备药物中的用途,所述药物用于治疗癌症,所述药物可以含有或不含药用载体。
如上所述,N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II可以在配制药物组合物过程中提供优点。相应地,本发明的一个方面涉及药物组合物,其含有结晶形式的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺,以及药用载体。在进一步的实施方案中,按照本发明的组合物含有单独的或与第二个治疗剂联用的上述II型N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺,以及药用载体。
另一个方面涉及制备N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II的方法。
在另一个方面,本发明涉及制备含有N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺和药用载体的药物组合物的方法,所述方法包括∶将分离的结晶形式的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺与可药用载体混合,其中,所述结晶形式具有包含三个或更多个选自下列2θ峰值±0.2的粉末X射线衍射图∶6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。
在另一个方面,本发明涉及组合物,其含有大于90%(w/w)的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II,其中,所述结晶形式具有包含三个或更多个选自下列2θ峰值±0.2的粉末X射线衍射图∶6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。在某些实施方案中,所述组合物含有90-99%(w/w)之间的结晶形式II。
详细说明
可以将N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺制备为结晶形式,称为结晶形式II。本文使用的化合物的结晶形式是指相同化学个体,但晶体排列不同。N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺是人类BRD4的抑制剂,而且是乳腺癌细胞系MX-1的增殖的抑制剂。
需要指出的是,在本说明书和权利要求中使用的单数形式“一种(a)”、“一个(an)”和“该(the)”包括多个对象,除非另外在文中清楚地规定范围。由此,例如,“化合物”包括单个化合物以及一个或多个相同或不同的化合物,“药用载体”是指单个药用载体以及一或多种药用载体,等等。
当使用N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II时,它的纯度高于大约90%。这意味着N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺结晶形式II不会含有多于大约10%的任何其它化合物,尤其是不会含有多于大约10%的结晶形式I。更优选,术语“基本上纯的”是指结晶形式II的纯度高于大约95%。这意味着结晶形式II不会含有多于大约5%的任何其它化合物,尤其是不会含有多于大约5%的结晶形式I。更加优选,术语“基本上纯的”是指结晶形式II的纯度高于大约97%。这意味着结晶形式II不会含有多于大约3%的任何其它化合物,尤其是不会含有多于大约3%的结晶形式I。
N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式I还可以被称为“I型N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺”,或类似的术语,并且具有本文列出的生理化学参数。N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II还可以被称为“II型N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺”,或类似的术语,并且具有本文列出的生理化学参数。
在某些方面,本发明进一步涉及含有II型N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺和药用载体的药物组合物。
N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式,例如,II型,在适合于给予需要其的患者的任何给药途径(包括口服)的药物组合物的制备中,可以用作活性药用组分(API)。其它给药途径包括但不限于:肠胃外、舌下、口腔、鼻内、肺、局部、透皮、皮内、眼、耳、直肠、阴道、胃内、颅内、滑膜内和关节内途径。
当按照合适的方案给予需要其的患者时,N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺以治疗有效数量存在于本发明的药物组合物中。一般情况下,根据所述化合物,可以以合适的频率(例如,每天两次至每周一次)给予的单位剂量(单次给予的数量)为大约10至大约1,000 mg。在每天给药一次(q.d.)的频率下,单位剂量和日剂量相同。例如,单位剂量典型地是大约25至大约1,000mg,更典型地是大约50至大约500 mg,例如,大约50、大约100、大约150、大约200、大约250、大约300、大约350、大约400、大约450或大约500 mg。
本文使用的术语“药用载体”是指无毒的惰性固体、半固体或液体填料、稀释剂、密封材料或任何类型的制剂助剂。药用载体包括但不局限于,例如,密封材料和添加剂,例如,吸收促进剂、抗氧化剂、粘合剂、缓冲剂、载体、涂布剂、着色剂、稀释剂、崩解剂、乳化剂、膨胀剂、填料、调味剂、助流剂、保湿剂、润滑剂、香料、防腐剂、发射剂、防粘剂、杀菌剂、甜味剂、增溶剂、润湿剂、其混合物,等等。
在制备含有N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II或用它制备的口服给药的固体剂型制剂中使用的药用载体包括,例如,琼脂、褐藻酸、氢氧化铝、苯甲醇、苯甲酸苄酯、1,3-丁二醇、卡波姆、蓖麻油、纤维素、醋酸纤维素、可可脂、共聚维酮、玉米淀粉、玉米油、棉子油、交聚维酮、甘油二酯、乙醇、乙基纤维素、月桂酸乙酯、油酸乙酯、脂肪酸酯、明胶、胚芽油、葡萄糖、甘油、花生油、羟基丙基甲基纤维素、异丙醇、等渗盐水、乳糖、氢氧化镁、硬脂酸镁、麦芽、甘露糖醇、甘油一酯、橄榄油、聚维酮、花生油、磷酸钾盐、马铃薯淀粉、聚维酮、丙二醇、林格溶液、红花油、芝麻油、二氧化硅、羧甲基纤维素钠、磷酸钠盐、月桂基硫酸钠、山梨糖醇钠、硬脂酰富马酸钠、大豆油、硬脂酸、硬脂酰富马酸盐、蔗糖、表面活性剂、滑石粉、黄芪胶、四氢糠醇、甘油三酯、维生素E和它们的衍生物、水、其混合物,等等。
在制备含有N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II或用它制备的眼部或口服给药的液体剂型制剂中使用的药用载体包括,例如,1,3-丁二醇、蓖麻油、玉米油、棉子油、乙醇、脱水山梨糖醇的脂肪酸酯、胚芽油、花生油、甘油、异丙醇、橄榄油、聚乙二醇、丙二醇、芝麻油、水、其混合物,等等。
在制备含有N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II或用它制备的渗透给药的制剂中使用的药用载体包括,例如,氯氟烃、乙醇、水、其混合物,等等。
在制备含有N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II或用它制备的胃肠外给药的制剂中使用的药用载体包括,例如,1,3-丁二醇、蓖麻油、玉米油、棉子油、葡萄糖、胚芽油、花生油、脂质体、油酸、橄榄油、花生油、林格溶液、红花油、芝麻油、大豆油、U.S.P.或等渗氯化钠溶液、水、其混合物,等等。
在制备含有N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II或用它制备的直肠或阴道给药的制剂中使用的药用载体包括但不局限于:可可脂、聚乙二醇、石蜡、其混合物,等等。
通常,以能够提供药物的治疗有效日剂量的数量给予所述组合物。本文的术语“日剂量”是指每天给予的药物数量,与给药频率无关。例如,如果患者每天两次接受150 mg的单位剂量,则日剂量是300 mg。应该理解,使用术语“日剂量”不意味着具体剂量必须每天一次给予。然而,在一个具体实施方案中,给药频率是每天一次(q.d.),并且在该实施方案中,日剂量和单位剂量相同。
构成治疗有效剂量的内容取决于具体化合物、患者(包括患者的种类和体重)、所治疗的疾病(例如,癌症的具体类型)、疾病的阶段和/或严重程度、个体患者对化合物的耐受性,是以单一治疗形式或是以与一或多种其它药物(例如,治疗癌症的其它化疗)的联用药形式给予化合物,及其它因素。由此,日剂量可以在很宽的范围内变化,例如,大约10至大约1,000 mg。在特殊情况下,日剂量可以更多或更少可能是合适的。可以理解,如果只单一给予这种剂量,本文讲述的“治疗有效”剂量不一定要求药物有治疗效果;典型地,治疗效能取决于按照方案(包括给药的合适频率和时间)所反复给予的组合物。不用过度实验,普通医生可以选择合适的治疗有效剂量。例如,在治疗期间,医生可以用相对低的日剂量开始治疗癌症患者,并且在几天或几周期间内向上调节剂量,以便降低不利的副作用的危险。
例如,N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的合适剂量通常是大约10至大约1,000 mg/天,更典型地是大约50至大约500 mg/天或大约200至大约400 mg/天,例如,大约50、大约100、大约150、大约200、大约250、大约300、大约350、大约400、大约450或大约500 mg/天,以3至10天或大约4至8天或大约7天的平均剂量间隔时间给药。
含有晶体N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺II型的组合物,适合用于单一治疗或联合治疗,例如,与其它化学疗法或电离辐射的联合治疗。
N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II,以及含有N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II的药物组合物,可以给予患有溴结构域介导的障碍或病症的患者。术语“给药”是指化合物与患者接触的方法。由此,可以通过注射形式来给予N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II,即,静脉内、肌肉内、皮内、皮下、十二指肠内、肠胃外(parentally)或腹膜内给药。还可以通过吸入形式给药,例如,鼻内给药。另外,可以透皮、局部、通过植入法、透皮、局部和通过植入法给予N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II。在某些实施方案中,可以口服递送N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II。在其它实施方案中,还可以通过直肠、经颊、阴道内、眼部或吹入形式递送N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II。根据障碍或病症的性质,可以预防性、急性和长期使用N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II,治疗溴结构域介导的障碍和病症。
“溴结构域介导的障碍或病症”的特征在于:一个或多个溴结构域(例如,BRD4)在初期的参与、一或多种症状或疾病标志的表现、障碍或病症的严重程度或进程。
相应地,N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II可以用于治疗癌症,包括但不限于:听神经瘤、急性白血病、急性淋巴细胞性白血病、急性髓细胞性白血病(单核细胞、成髓细胞、腺癌、血管肉瘤、星形细胞瘤、髓单核细胞和前髓细胞)、急性的T细胞白血病、基底细胞癌、胆管癌、膀胱癌、脑癌、乳腺癌、支气管癌、子宫颈癌、软骨肉瘤、脊索瘤、绒膜癌、慢性白血病、慢性淋巴细胞性白血病、慢性髓细胞(粒细胞)白血病、慢性粒性白血病、结肠癌、结肠直肠癌、颅咽管瘤、囊腺癌、扩散性大B细胞淋巴瘤、增殖异常性(dysproliferative)变化(发育异常和组织变形)、胚胎性癌、子宫内膜癌、内皮肉瘤、室管膜瘤、上皮癌、红白血病、食道癌、雌激素-受体阳性乳腺癌、特发性血小板增多症、尤因氏瘤、纤维肉瘤、滤泡性淋巴瘤、生殖细胞睾丸癌、胶质瘤、恶性胶质瘤、胶质肉瘤、重链病、成血管细胞瘤、肝癌、肝细胞癌、激素不敏感的前列腺癌、平滑肌肉瘤、白血病、脂肉瘤、肺癌、淋巴管内皮肉瘤、淋巴管肉瘤、淋巴细胞性白血病、淋巴瘤(霍奇金氏和非霍奇金氏)、膀胱、乳房、结肠、肺、卵巢、胰腺、前列腺、皮肤和子宫和恶性肿瘤和高增殖病症、起源于T细胞或B细胞的淋巴恶性肿瘤、白血病、淋巴瘤、髓样癌、成髓细胞瘤、黑素瘤、脑膜瘤、间皮瘤、多发性骨髓瘤、粒细胞性白血病、骨髓瘤、粘液肉瘤、神经母细胞瘤、NUT中线癌(NMC)、非小细胞肺癌、寡枝神经胶质细胞瘤、口腔癌、骨原性肉瘤、卵巢癌、胰腺癌、乳头状腺癌、乳头状癌、松果体瘤、真性红细胞增多症、前列腺癌、直肠癌、肾细胞癌、成视网膜细胞瘤、横纹肌肉瘤、肉瘤、皮脂腺癌、精原细胞瘤、皮肤癌、小细胞肺癌、实质固态瘤(癌和肉瘤)、小细胞肺癌、胃癌、鳞状细胞癌、滑膜瘤、汗腺癌、甲状腺癌、Waldenström’s巨球蛋白血症、睾丸肿瘤、子宫癌和Wilms'肿瘤。
另外,N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II可以用于治疗炎症性疾病、炎症性病症和自身免疫疾病,包括但不限于:阿狄森氏病、急性痛风、强直性脊柱炎、哮喘、动脉粥样硬化、贝切特氏病、大疱性皮肤病、心脏肌病、心脏肥大、慢性阻塞性肺病(COPD)、克罗恩氏病、皮炎、湿疹、巨细胞性动脉炎、肾小球肾炎、心力衰竭、肝炎、垂体炎、炎症性肠病、川崎氏病、狼疮肾炎、多发性硬化、心肌炎、肌炎、肾炎、器官移植排斥、骨关节炎、胰腺炎、心包炎、结节性动脉周围炎、肺炎、夏科氏肝硬变、牛皮癣、牛皮癣关节炎、类风湿性关节炎、巩膜炎、硬化性胆管炎、败血症、系统性红斑狼疮、Takayasu's动脉炎、中毒性休克、甲状腺炎、I型糖尿病、溃疡性结肠炎、葡萄膜炎、白癜风、血管炎和眶坏死性肉芽肿病。
N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II可以用于治疗AIDS。
N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II可以用于治疗慢性肾病或病症,包括但不局限于∶糖尿病性的肾病、高血压肾病、HIV相关的肾病、肾小球肾炎、狼疮肾炎、IgA肾病、局灶性节段性肾小球硬化症、膜性肾小球肾炎、微小病变疾病、多囊肾疾病和管状间质性肾炎。
N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II可以用于治疗急性肾损伤或疾病或病症,包括但不局限于∶缺血-再灌注诱导的肾病、心脏和大外科诱导的肾病、经皮的冠状动脉干预诱导的肾病、放射造影剂诱导的肾病、败血症诱导的肾病、肺炎诱导的肾病和药物毒性诱导的肾病。
N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II可以用于治疗肥胖症、血脂异常、高胆固醇血症、阿尔海默氏疾病、代谢综合征、肝脂质沉着症、II型糖尿病、胰岛素抗性、糖尿病性视网膜病或糖尿病性神经病变。
N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II通过抑制精子生成,可以用于预防患者受孕,包括给予需要其的患者治疗有效量的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II。
N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II可以共同给予患者。术语“共同给予”是指给予两种或多种不同的药剂或治疗(例如,辐射治疗),也就是说,利用相同药物组合物中的联用药或独立药物组合物的联用药形式给予患者。由此,共同给予包括同时给予含有两种或多种治疗剂的单一药物组合物,或在相同或不同的时间给予同一患者两种或多种不同的组合物。
N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II,可以与治疗有效量的一或多种治疗癌症的药剂共同给予,其中,所述药剂的例子包括,例如,辐射、烷基化剂、血管生成抑制剂、抗体、代谢拮抗剂、抗有丝分裂剂、抗增殖剂、抗病毒剂、极光激酶抑制剂、细胞程序死亡促进剂(例如,Bcl-xL、Bcl-w和Bfl-1)抑制剂、死亡受体途径的活化剂、Bcr-Abl激酶抑制剂、BiTE(双-特异性T细胞衔接物)抗体、抗体药物共轭物、生物反应调节剂、依赖细胞周期蛋白的激酶抑制剂、细胞周期抑制剂、环加氧酶-2抑制剂、DVD(双重变域抗体)、白血病病毒癌基因同系物(ErbB2)受体抑制剂、生长因子抑制剂、热休克蛋白(HSP)-90抑制剂、组蛋白脱乙酰基酶(HDAC)抑制剂、激素治疗、免疫、细胞程序死亡蛋白的抑制剂(IAP)、插入抗生素、激酶抑制剂、驱动蛋白抑制剂、Jak2抑制剂、雷帕霉素抑制剂的哺乳动物靶向、microRNA's、丝裂原活化的胞外信号调节激酶抑制剂、多价结合蛋白、非甾体抗炎症的药物(NSAID)、聚ADP(腺苷二磷酸)-核糖聚合酶(PARP)抑制剂、铂化学疗法、polo类激酶(Plk)抑制剂、磷酸肌醇-3激酶(溴结构域)抑制剂、蛋白体抑制剂、嘌呤类似物、嘧啶类似物、受体酪氨酸激酶抑制剂、类视黄醇(etinoids)/三角肌(deltoids)植物生物碱、小抑制性的核醣核酸(siRNA)、拓扑异构酶抑制剂、泛素连接酶抑制剂,等等,以及这些药剂的一或多种药剂的联用药。
BiTE抗体是双特异性抗体,通过同时结合两个细胞,它引导T细胞,攻击癌细胞。然后,T细胞攻击靶向癌细胞。BiTE抗体的例子包括:阿德木单抗(adecatumumab)(MicrometMT201)、blinatumomab(Micromet MT103),等等。不受理论限制,T细胞引起靶向癌细胞的细胞程序死亡的一个机理是溶细胞颗粒的组分(包括穿孔素和粒酶B)的胞吐作用。在这方面,已经证明,Bcl-2通过穿孔素和粒酶B,使细胞程序死亡的诱导减弱。这些数据说明,抑制Bcl-2可以增强T细胞靶向癌细胞时所引起的细胞毒素效果(V.R. Sutton, D.L. Vaux和J.A. Trapani, J. of Immunology 1997, 158(12), 5783)。
SiRNA是具有内源RNA碱基或化学修饰的核苷酸的分子。这种修饰不会消除细胞活性,相反,使稳定性提高和/或细胞效能增加。化学修饰的例子包括:硫代磷酸基团、2'-脱氧核苷酸、含有2'-OCH3的核糖核苷酸、2'-F-核糖核苷酸、2'-甲氧基乙基核糖核苷酸、其组合,等等。siRNA可以具有变化的长度(例如,10-200 bps)和结构(例如,发夹形、单/双链、凸、凹/缺口、错配),并且在细胞中加工,提供活性基因沉默。双链siRNA(dsRNA)在每个链上(钝端)或非对称端(突出端)上可以具有相同数量的核苷酸。1-2个核苷酸的突出端可以存在于有义链和/或反义链上,而且还存在于所给定链的5'-和/或3'-端。
多价结合蛋白是含有两个或多个抗原结合位点的结合蛋白。设计多价结合蛋白,使其具有三个或更多个抗原结合位点,并且通常不是天然存在的抗体。术语“多特异性结合蛋白”是指能够结合两个或多个相关或无关靶向的结合蛋白。双重变域(DVD)结合蛋白是四价或多价结合蛋白,其结合含有两个或多个抗原结合位点的蛋白。这种DVD可以是单特异性的(即,能够结合一个抗原)或多特异性的(即,能够结合两个或多个抗原)。含有两个重链DVD多肽和两个轻链DVD多肽的DVD结合蛋白称为DVD Ig's。DVD Ig的每一半含有重链DVD多肽、轻链DVD多肽和两个抗原结合位点。每个结合位点含有重链变域和轻链变域,每个抗原结合位点总共有6个涉及抗原结合的CDR。多特异性DVD包括DVD结合蛋白,其结合DLL4和VEGF、或C-met和EFGR或ErbB3以及EGFR。
烷基化剂包括:六甲蜜胺、AMD-473、AP-5280、apaziquone、苯达莫司汀、溴他利星(brostallicin)、白消安、卡波醌、卡莫司汀(BCNU)、苯丁酸氮芥、CLORETAZINE®(拉莫司汀(laromustine)、VNP 40101M)、环磷酰胺、去氯羟嗪、雌莫司汀、福莫司汀、葡膦酰胺、异环磷酰胺、KW-2170、环己亚硝脲(CCNU)、马磷酰胺(mafosfamide)、苯丙氨酸氮芥、二溴甘露醇、二溴卫矛醇、嘧啶亚硝脲、氮芥N-氧化物、雷莫司汀(Ranimustine)、替莫唑胺、硫替派、TREANDA®(苯达莫司汀)、曲奥舒凡(treosulfan)、rofosfamide,等等。
血管生成抑制剂包括:内皮特异性受体酪氨酸激酶(Tie-2)抑制剂、表皮生长因子受体(EGFR)抑制剂、胰岛素生长因子-2受体(Tie-2)抑制剂、基质金属蛋白酶-2(MMP-2)抑制剂、基质金属蛋白酶-9(MMP-9)抑制剂、血小板生长因子受体(PDGFR)抑制剂、凝血栓蛋白类似物、血管内皮生长因子受体酪氨酸激酶(VEGFR)抑制剂,等等。
代谢拮抗剂包括:ALIMTA®(培美曲唑(Pemetrexed)二钠、LY231514、MTA)、5-阿扎胞苷、XELODA® (卡培他滨)、卡莫氟、LEUSTAT®(克拉屈滨)、氯法拉滨(clofarabine)、阿糖胞苷、阿糖胞苷十八烷基磷酸钠、阿糖胞苷、地西他滨、去铁胺、去氧氟尿苷、依氟鸟氨酸、EICAR(5-乙炔基-1-β-D-呋喃核糖基咪唑-4-甲酰胺)、依诺他滨、ethnylcytidine、氟达拉滨、单独或与亚叶酸联用的5-氟尿嘧啶、GEMZAR®(吉西他滨)、羟基脲、ALKERAN®(苯丙氨酸氮芥)、巯基嘌呤、6-巯基嘌呤核糖核苷、氨甲喋呤、霉酚酸、奈拉滨(nelarabine)、诺拉曲特(nolatrexed)、十八烷基磷酸钠、吡利曲索(pelitrexol)、喷司他丁、雷替曲塞(raltitrexed)、利巴韦林、triapine、三甲曲沙、S-1、噻唑呋啉、替加氟、TS-1、阿糖腺苷、UFT,等等。
抗病毒剂包括利托那韦、羟氯奎,等等。
极光激酶抑制剂包括:ABT-348、AZD-1152、MLN-8054、VX-680、极光A-特异性激酶抑制剂、极光B-特异性激酶抑制剂和pan-极光激酶抑制剂,等等。
Bcl-2蛋白抑制剂包括:AT-101((-)棉子酚)、GENASENSE®(G3139或奥利默森(oblimersen)(Bcl-2-靶向反义寡核苷酸))、IPI-194、IPI-565、N(4-(4-((4'-氯(1,1'-联苯)-2-基)甲基)哌嗪-1-基)苯甲酰基)-4-(((1R)-3-(二甲基氨基)-1-((苯硫基)甲基)丙基)氨基)-3-硝基苯磺酰胺)(ABT-737)、N(4-(4-((2-(4-氯苯基)-5,5-二甲基-1-环己-1-烯-1-基)甲基)哌嗪-1-基)苯甲酰基)-4-(((1R)-3-(吗啉-4-基)-1-((苯硫基)甲基)丙基)氨基)-3-((三氟甲基)磺酰基)苯磺酰胺(ABT-263)、GX-070(obatoclax)、ABT-199,等等。
Bcr-Abl激酶抑制剂包括:DASATINIB®(BMS-354825)、GLEEVEC®(伊马替尼),等等。
CDK抑制剂包括:AZD-5438、BMI-1040、BMS-032、BMS-387、CVT-2584、夫拉平度(flavopyridol)、GPC-286199、MCS-5A、PD0332991、PHA-690509、塞利西利(seliciclib)(CYC-202、R-roscovitine)、ZK-304709,等等。
COX-2抑制剂包括:ABT-963、ARCOXIA®(艾托考昔)、BEXTRA®(伐地考昔)、BMS347070、CELEBREX®(西乐葆)、COX-189(罗美昔布(lumiracoxib))、CT-3、DERAMAXX®(德拉昔布(deracoxib))、JTE-522、4-甲基-2-(3,4-二甲基苯基)-1-(4-氨磺酰基苯基-1H-吡咯)、MK-663(艾托考昔)、NS-398、帕瑞考营、RS-57067、SC-58125、SD-8381、SVT-2016、S-2474、T-614、VIOXX®(罗非考昔),等等。
EGFR抑制剂包括:EGFR抗体、ABX-EGF、抗EGFR免疫脂质体、EGF-疫苗、EMD-7200、ERBITUX®(西妥昔单抗(cetuximab))、HR3、IgA抗体、IRESSA®(吉非替尼)、TARCEVA®(埃洛替尼或OSI-774)、TP-38、EGFR融合蛋白、TYKERB®(拉帕替尼(lapatinib)),等等。
ErbB2受体抑制剂包括:CP-724-714、CI-1033(卡拉替尼(canertinib))、HERCEPTIN®(曲妥珠单抗(trastuzumab))、TYKERB®(拉帕替尼(lapatinib))、OMNITARG®(2C4,帕妥珠单抗(petuzumab))、TAK-165、GW-572016(ionafarnib)、GW-282974、EKB-569、PI-166、dHER2(HER2疫苗)、APC-8024(HER-2疫苗)、抗HER/2neu双特异性抗体、B7.her2IgG3、AS HER2三功能双特异性抗体、mAB AR-209、mAB 2B-1,等等。
组蛋白脱乙酰基酶抑制剂包括:缩酚酸肽、LAQ-824、MS-275、trapoxin、辛二酰苯胺异羟肟酸(SAHA)、TSA、丙戊酸,等等。
HSP-90抑制剂包括:17-AAG-nab、17-AAG、CNF-101、CNF-1010、CNF-2024、17-DMAG、格尔德霉素、IPI-504、KOS-953、MYCOGRAB®(对于HSP-90的人类重组抗体)、NCS-683664、PU24FCl、PU-3、根赤壳菌素、SNX-2112、STA-9090 VER49009,等等。
细胞程序死亡蛋白的抑制剂包括:HGS1029、GDC-0145、GDC-0152、LCL-161、LBW-242,等等。
抗体药物共轭物包括:抗-CD22-MC-MMAF、抗-CD22-MC-MMAE、抗-CD22-MCC-DM1、CR-011-vcMMAE、PSMA-ADC、MEDI-547、SGN-19Am SGN-35、SGN-75,等等。
死亡受体途径的活化剂包括:TRAIL、抗体或靶向TRAIL或死亡受体的其它药剂(例如,DR4和DR5),例如Apomab、conatumumab、ETR2-ST01、GDC0145(来沙木单抗(lexatumumab))、HGS-1029、LBY-135、PRO-1762和曲妥珠单抗(trastuzumab)。
驱动蛋白抑制剂包括:Eg5抑制剂,例如,AZD4877、ARRY-520;CENPE抑制剂,例如,GSK923295A,等等。
JAK-2抑制剂包括:CEP-701(来他替尼(lesaurtinib))、XL019和INCB018424,等等。
MEK抑制剂包括:ARRY-142886、ARRY-438162 PD-325901、PD-98059,等等。
mTOR抑制剂包括:AP-23573、CCI-779、依维莫司、RAD-001、雷帕霉素、西罗莫司(temsirolimus)、ATP竞争性的TORC1/TORC2抑制剂,包括PI-103、PP242、PP30、Torin 1,等等。
非甾体抗炎症的药物包括:AMIGESIC®(双水杨酯)、DOLOBID®(二氟尼柳)、MOTRIN®(布洛芬)、ORUDIS®(酮洛芬)、RELAFEN®(萘丁美酮)、FELDENE®(吡罗昔康)、布洛芬乳膏剂、ALEVE®(萘普生)和NAPROSYN®(萘普生)、VOLTAREN®(双氯芬酸)、INDOCIN®(消炎痛)、CLINORIL®(舒林酸)、TOLECTIN®(甲苯酰吡酸)、LODINE®(依托度酸)、TORADOL®(酮咯酸)、DAYPRO®(奥沙普秦),等等。
PDGFR抑制剂包括:C-451、CP-673、CP-868596,等等。
铂化疗药物包括:顺铂、ELOXATIN®(奥沙利铂)、依他铂、乐铂、奈达铂、PARAPLATIN®(卡铂)、沙铂(satraplatin)、皮卡铂(picoplatin),等等。
Polo类激酶抑制剂包括BI-2536,等等。
磷酸肌醇-3激酶(PI3K)抑制剂包括:渥曼青霉素、LY294002、XL-147、CAL-120、ONC-21、AEZS-127、ETP-45658、PX-866、GDC-0941、BGT226、BEZ235、XL765,等等。
凝血酶敏感蛋白类似物包括:ABT-510、ABT-567、ABT-898、TSP-1,等等。
VEGFR抑制剂包括:AVASTIN®(贝伐单抗(bevacizumab))、ABT-869、AEE-788、ANGIOZYME™(抑制血管生成的核糖酶(Ribozyme Pharmaceuticals(Boulder, CO.)andChiron,(Emeryville, CA))、阿西替尼(axitinib)(AG-13736)、AZD-2171、CP-547,632、IM-862、MACUGEN(哌加他尼(pegaptamib))、NEXAVAR®(索拉非尼(sorafenib),BAY43-9006)、帕唑帕尼(pazopanib)(GW-786034)、瓦他拉尼(vatalanib)(PTK-787,ZK-222584)、SUTENT®(舒尼替尼(Sunitinib),SU-11248)、VEGF trap、ZACTIMA™(凡德他尼(vandetanib),ZD-6474)、GA101、奥法木单抗(ofatumumab)、ABT-806(mAb-806)、ErbB3特异性抗体、BSG2特异性抗体、DLL4特异性抗体和C-met特异性抗体,等等。
抗生素包括:插入抗生素阿柔比星、放线菌素D、氨柔比星、蒽环霉素(annamycin)、多柔比星、BLENOXANE®(博来霉素)、柔红霉素、CAELYX®或MYOCET®(脂质体多柔比星)、依沙芦星、表阿霉素(epirbucin)、glarbuicin、ZAVEDOS®(伊达比星)、丝裂霉素C、奈莫柔比星、新制癌菌素、硫酸培洛霉素、吡柔比星、蝴蝶霉素(rebeccamycin)、净司他丁(stimalamer)、链脲霉素、VALSTAR®(戊柔比星(valrubicin))、新制癌菌素,等等。
拓扑异构酶抑制剂包括:阿柔比星、9-氨基喜树碱、氨萘非特、安吖啶、becatecarin、贝洛替康(belotecan)、BN-80915、CAMPTOSAR®(盐酸依立替康)、喜树碱、CARDIOXANE®(右旋丙亚胺(dexrazoxine))、二氟替康(diflomotecan)、伊朵堤卡林(edotecarin)、ELLENCE®或PHARMORUBICIN®(表柔比星)、依托泊苷、依沙替康(exatecan)、10-羟基喜树碱、吉马替康、勒托替康、米托蒽醌、卢比替康(orathecin)、吡柔比星(pirarbucin)、匹杉琼(pixantrone)、鲁比替康、索布佐生、SN-38、tafluposide、托泊替康,等等。
抗体包括:AVASTIN®(贝伐单抗(bevacizumab))、CD40-特异性抗体、chTNT-1/B、地诺塞麦(denosumab)、ERBITUX®(西妥昔单抗(cetuximab))、HUMAX-CD4®(扎木单抗(zanolimumab))、IGF1R-特异性抗体、林妥珠单抗、PANOREX®(依决洛单抗)、RENCAREX®(WXG250)、RITUXAN®(利妥昔单抗(rituximab))、ticilimumab、trastuzimab、CD20抗体I和II型,等等。
激素治疗包括:ARIMIDEX®(阿那曲唑)、AROMASIN®(依西美坦)、阿佐昔芬(arzoxifene)、CASODEX®(比卡鲁胺)、CETROTIDE®(西曲瑞克)、地盖瑞利(degarelix)、地洛瑞林、DESOPAN®(曲洛司坦)、地塞米松、DROGENIL®(氟他胺)、EVISTA®(雷诺昔酚)、AFEMA™(法屈唑)、FARESTON®(枸橼酸托瑞米芬)、FASLODEX®(氟维司群)、FEMARA®(来曲唑)、福美坦、糖皮质激素、HECTOROL®(度骨化醇(doxercalciferol))、RENAGEL®(碳酸司维拉姆(sevelamer))、拉索昔芬、乙酸亮丙瑞林、MEGACE®(甲地孕酮)、MIFEPREX®(美服培酮)、NILANDRON™(尼鲁米特)、NOLVADEX®(枸橼酸它莫西芬)、PLENAXIS™(阿倍瑞克(Abarelix))、脱氢可的松、PROPECIA®(非那雄胺)、rilostane、SUPREFACT®(布舍瑞林)、TRELSTAR®(促黄体素释放激素(LHRH))、VANTAS®(组氨瑞林(Histrelin)植入物)、VETORYL®(曲洛司坦或modrastane)、ZOLADEX®(fosrelin、戈舍瑞林),等等。
三角叶杨(Deltoids)和类视黄醇包括:西奥骨化醇(seocalcitol)(EB1089、CB1093)、来沙骨化醇(lexacalcitrol)(KH1060)、芬维A胺(fenretinide)、PANRETIN®(阿利维A酸(aliretinoin))、ATRAGEN®(脂质体维甲酸)、TARGRETIN®(贝沙罗汀(bexarotene))、LGD-1550,等等。
PARP抑制剂包括:ABT-888(veliparib)、奥拉帕尼(olaparib)、KU-59436、AZD-2281、AG-014699、BSI-201、BGP-15、INO-1001、ONO-2231,等等。
植物生物碱包括但不局限于:长春新碱、长春碱、去乙酰长春酰胺、长春瑞滨,等等。
蛋白酶体抑制剂包括:VELCADE®(硼替佐米(Bortezomib))、MG132、NPI-0052、PR-171,等等。
免疫的例子包括干扰素及其它免疫增强药剂。干扰素包括:干扰素α、干扰素α-2a、干扰素α-2b、干扰素β、干扰素γ-1a、ACTIMMUNE®(干扰素γ-1b)或干扰素γ-n1、其联用药,等等。其它药剂包括:ALFAFERONE®(IFN-α)、BAM-002(氧化型谷胱甘肽)、BEROMUN®(他索纳明(tasonermin))、BEXXAR®(托西莫单抗(tositumomab))、CAMPATH®(阿仑单抗(alemtuzumab))、CTLA4(细胞毒素淋巴细胞抗原4)、去氯羟嗪、地尼白介素(denileukin)、依帕珠单抗(epratuzumab)、GRANOCYTE®(来格司亭)、蘑菇多糖、白细胞α干扰素、咪喹莫特、MDX-010(抗CTLA-4)、黑素瘤疫苗、米妥莫单抗(mitumomab)、莫拉司亭、MYLOTARG™(吉妥珠单抗奥唑米星(gemtuzumab ozogamicin))、NEUPOGEN®(非格司亭)、OncoVAC-CL、OVAREX®(奥戈伏单抗(oregovomab))、pemtumomab(Y-muHMFG1)、PROVENGE® (sipuleucel-T)、sargaramostim、sizofilan、替西白介素(teceleukin)、THERACYS®(Bacillus Calmette-Guerin)、乌苯美司、VIRULIZIN®(免疫治疗剂,Lorus Pharmaceuticals)、Z-100(Maruyama的特异物质(SSM))、WF-10(四氯十氧化物(Tetrachlorodecaoxide)(TCDO))、PROLEUKIN®(阿地白介素)、ZADAXIN®(胸腺法新(thymalfasin))、ZENAPAX®(达(克)珠单抗)、ZEVALIN®(90Y-替伊莫单抗(Ibritumomab tiuxetan)),等等。
生物反应调节剂是修饰活性有机体的防卫机理或生物学响应的药剂,例如,组织细胞的存活、生长或分化,使它们具有抗肿瘤活性,并且包括云芝多糖K(krestin)、蘑菇多糖、西佐喃、溶链菌制剂(picibanil)PF-3512676(CpG-8954)、乌苯美司,等等。
嘧啶类似物包括:阿糖胞苷(ara C或阿拉伯糖苷C)、胞嘧啶阿拉伯糖苷、去氧氟尿苷、FLUDARA® (氟达拉滨)、5-FU(5-氟尿嘧啶)、氮尿苷、GEMZAR®(吉西他滨)、TOMUDEX®(雷替曲塞(ratitrexed))、TROXATYL™(三乙酰尿苷曲沙他滨(troxacitabine)),等等。
嘌呤类似物包括:LANVIS®(硫鸟嘌呤)和PURI-NETHOL®(巯基嘌呤)。
抗有丝分裂剂包括:巴他布林(batabulin)、埃坡霉素D(KOS-862)、N-(2-((4-羟基苯基)氨基)吡啶-3-基)-4-甲氧基苯磺酰胺、伊沙匹隆(ixabepilone)(BMS 247550)、太平洋紫杉醇、TAXOTERE®(多西他赛)、PNU100940(109881)、伊沙匹隆(patupilone)、XRP-9881(拉洛他赛(larotaxel))、长春氟宁、ZK-EPO(合成的埃坡霉素),等等。
泛素连接酶抑制剂包括MDM2抑制剂,例如,nutlins,NEDD8抑制剂,例如,MLN4924,等等。
N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II还可以用作增强放疗效能的放射致敏剂。放疗的例子包括:外束放疗、远距放射疗法、近距放射疗法和封闭、非封闭源放疗,等等。
另外,N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II可以与其它化学治疗剂联用,例如,ABRAXANE™(ABI-007)、ABT-100(法尼基转移酶抑制剂)、ADVEXIN®(Ad5CMV-p53疫苗)、ALTOCOR®或MEVACOR®(洛伐他汀)、AMPLIGEN®(poly I:poly C12U,合成的RNA)、APTOSYN®(依昔舒林(exisulind))、AREDIA®(帕米膦酸)、arglabin、L-门冬酰胺酶、阿他美坦(1-甲基-3,17-二酮-雄烷-1,4-二烯)、AVAGE®(维生素A酸(tazarotene))、AVE-8062(考布他汀(combreastatin)衍生物)BEC2(米妥莫单抗(mitumomab))、恶液质素或cachexin(肿瘤坏死因子)、canvaxin(疫苗)、CEAVAC®(癌症疫苗)、CELEUK® (西莫白介素)、CEPLENE®(二盐酸组按)、CERVARIX®(人乳头瘤病毒疫苗)、CHOP®(C: CYTOXAN®(环磷酰胺);H: ADRIAMYCIN®(羟基多柔比星);O: 长春新碱(ONCOVIN®); P:脱氢可的松)、CYPAT™(乙酸赛普龙)、考布他汀(combrestatin)A4P、DAB(389)EGF(通过His-Ala连接基与人类表皮生长因子融合的白喉毒素的催化和迁移域)或TransMID-107R™(白喉毒素)、达卡巴嗪、放线菌素、5,6-二甲基呫吨酮-4-乙酸(DMXAA)、恩尿嘧啶、EVIZON™(角鲨胺(squalamine)乳酸盐)、DIMERICINE®(T4N5脂质体洗剂)、discodermolide、DX-8951f(依沙替康(exatecan)甲磺酸盐)、enzastaurin、EPO906(埃博霉素(epithilone)B)、GARDASIL® (四价人乳头瘤病毒(6、11、16、18类型)重组疫苗)、GASTRIMMUNE®、GENASENSE®、GMK(神经节糖苷共轭疫苗)、GVAX®(前列腺癌症疫苗)、卤夫酮(halofuginone)、组氨瑞林(histerelin)、羟基脲、依班膦酸、IGN-101、IL-13-PE38、IL-13-PE38QQR (贝辛白介素(cintredekin besudotox))、IL-13-假单胞菌属外毒素、干扰素-α、干扰素-γ、JUNOVAN™或MEPACT™ (米伐木肽(mifamurtide))、洛那法尼(lonafarnib)、5,10-亚甲基四氢叶酸、米特福辛(十六烷基磷酸胆碱)、NEOVASTAT®(AE-941)、NEUTREXIN®(三甲曲沙葡糖醛酸盐)、NIPENT®(喷司他丁)、ONCONASE®(核糖核酸酶)、ONCOPHAGE®(黑素瘤疫苗治疗)、ONCOVAX®(IL-2疫苗)、ORATHECIN™(鲁比替康)、OSIDEM®(基于抗体的细胞药物)、OVAREX® MAb(鼠的单克隆抗体)、太平洋紫杉醇、PANDIMEX™(从含有20(S)原人参萜二醇(aPPD)和20(S)原人参萜三醇(aPPT)的人参中获得的糖苷配基皂草苷)、帕尼单抗(panitumumab)、PANVAC®-VF(调查研究的癌症疫苗)、培加帕酶、PEG干扰素A、苯妥帝尔(phenoxodiol)、普鲁苄肼、瑞马司他(rebimastat)、REMOVAB® (卡妥索单抗(catumaxomab))、REVLIMID® (来那度胺(lenalidomide))、RSR13(乙丙昔罗(efaproxiral))、SOMATULINE® LA(兰瑞肽)、SORIATANE®(阿维A)、星孢菌素(链霉菌属星状孢子)、talabostat(PT100)、TARGRETIN® (贝沙罗汀(bexarotene))、TAXOPREXIN®(DHA-太平洋紫杉醇)、TELCYTA®(canfosfamide,TLK286)、temilifene、TEMODAR®(替莫唑胺)、替米利芬(tesmilifene)、反应停、THERATOPE®(STn-KLH)、thymitaq(2-氨基-3,4-二氢-6-甲基-4-氧代-5-(4-吡啶基硫基)喹唑啉二盐酸盐)、TNFERADE™(腺病毒载体∶含有肿瘤坏死因子-α的基因的DNA载体)、TRACLEER®或ZAVESCA®(波生坦)、维甲酸(Retin-A)、粉防已碱、TRISENOX®(三氧化二砷)、VIRULIZIN®、ukrain(从白屈菜植物获得的生物碱的衍生物)、vitaxin抗alphavbeta3抗体)、XCYTRIN®(莫特沙芬(motexafin)钆)、XINLAY™(阿曲生坦(atrasentan))、XYOTAX™(聚谷氨酸紫杉醇(paclitaxel poliglumex))、YONDELIS®(曲贝替定(trabectedin))、ZD-6126、ZINECARD®(右雷佐生)、ZOMETA®(唑来膦酸)、佐柔比星,等等。
N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II,还可以与治疗有效量的一或多种治疗炎性疾病或病症或自身免疫疾病的药剂共同给予,其中,所述药剂的例子包括,例如,氨甲喋呤、托法替尼(tofacitinib)、6-巯基嘌呤、硫唑嘌呤、柳氮磺吡啶(sulphasalazine)、美沙拉嗪、奥沙拉秦、氯喹(chloroquinine)/羟氯奎、青霉胺(pencillamine)、金硫苹果酸盐(肌内和口服)、硫唑嘌呤、秋水仙碱(cochicine)、皮质类甾醇(口服、吸入和局部注射)、β-2肾上腺素受体激动剂(柳丁氨醇、叔丁喘宁、沙美特罗(salmeteral))、黄嘌呤(茶碱、氨茶碱)、色甘酸盐、萘多罗米、酮替酚、异丙托品和氧托品、环孢菌素、FK506、雷帕霉素、麦考酚酸莫酯、来氟米特、NSAID,例如,布洛芬,皮质类甾醇,例如,氢化泼尼松,磷酸二酯酶抑制剂、腺苷(adensosine)激动剂、抗血栓形成药剂、补体抑制剂、肾上腺素能药剂、通过促炎细胞因子(例如,TNFα或IL-1)妨碍信号的药剂(例如,NIK、IKK、p38或MAP激酶抑制剂)、IL-1β转化酶抑制剂、T细胞信号抑制剂,例如,激酶抑制剂、金属蛋白酶抑制剂、柳氮磺吡啶、6-巯基嘌呤、血管紧张肽转化酶抑制剂、可溶性细胞素受体和它们的衍生物(例如,可溶性p55或p75TNF受体和衍生物p75TNFRIgG(依那西普),以及p55TNFRIgG(来那西普(Lenercept))、sIL-1RI、sIL-1RII、sIL-6R)、抗炎细胞素(例如,IL-4、IL-10、IL-11、IL-13和TGFb)、西乐葆、叶酸、硫酸羟氯奎、罗非考昔、依那西普、因福利美、阿达木单抗、塞妥珠单抗(certolizumab)、托珠单抗(tocilizumab)、阿巴西普(abatacept)、萘普生、伐地考昔、柳氮磺吡啶、甲基强的松龙、美洛昔康、醋酸甲基强的松龙、硫代苹果酸金钠、阿司匹林、曲安奈德(triamcinoloneacetonide)、丙氧吩萘磺酸盐/apap、叶酸、萘丁美酮、双氯芬酸、吡罗昔康、依托度酸、双氯灭痛、奥沙普秦、氧可酮HCl、重酒石酸二氢可待因酮/apap、双氯灭痛/迷索前列醇、芬太尼、阿那白滞素、反胺苯环醇HCl、双水杨酯、舒林酸、氰钴维生素/fa/吡哆醇、醋氨酚、阿仑膦酸钠、氢化泼尼松、皮质酮、倍他米松、硫酸吗啡、盐酸利多卡因、消炎痛、硫酸氨基葡萄糖(glucosamine sulf)/软骨素、阿米替林HCl、磺胺嘧啶、氧可酮HCl/醋氨酚、奥洛他定(olopatadine)HCl迷索前列醇、萘普生钠、奥美拉唑、环磷酰胺、利妥昔单抗(rituximab)、IL-1 TRAP、MRA、CTLA4-IG、IL-18 BP、抗IL-12、抗IL15、BIRB-796、SCIO-469、VX-702、AMG-548、VX-740、罗氟司特、IC-485、CDC-801、S1P1激动剂(例如,FTY720)、PKC家族抑制剂(例如,鲁伯斯塔或AEB-071)和美索普兰(Mesopram)。在某些实施方案中,联用药包括氨甲喋呤或来氟米特,并且在中度或严重的类风湿性关节炎病例中,包括如上所述的环孢灵和抗TNF抗体。
可以与N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II共同给药的炎症性肠病的治疗剂的非限制性例子包括下列治疗剂∶布地奈德(budenoside);表皮生长因子;皮质类甾醇;环孢菌素、柳氮磺吡啶;氨基水杨酸盐;6-巯基嘌呤;硫唑嘌呤;甲硝哒唑;脂氧合酶抑制剂;5-氨基水杨酸(mesalamine);奥沙拉秦;巴柳氮;抗氧化剂;血栓烷抑制剂;IL-1受体拮抗剂;抗IL-1β单克隆抗体;抗IL-6单克隆抗体;生长因子;弹性酶抑制剂;吡啶基-咪唑化合物;其它人类细胞素或生长因子的抗体或拮抗剂,例如,TNF、LT、IL-1、IL-2、IL-6、IL-7、IL-8、IL-12、IL-15、IL-16、IL-23、EMAP-II、GM-CSF、FGF和PDGF;细胞表面分子,例如,CD2、CD3、CD4、CD8、CD25、CD28、CD30、CD40、CD45、CD69、CD90或它们的配体;氨甲喋呤;环孢灵;FK506;雷帕霉素;麦考酚酸莫酯;来氟米特;NSAID,例如,布洛芬;皮质类甾醇,例如,氢化泼尼松;磷酸二酯酶抑制剂;腺苷激动剂;抗血栓形成的药剂;补体抑制剂;肾上腺素能药剂;通过促炎细胞因子(例如,TNFα或IL-1)妨碍信号的药剂(例如,NIK、IKK、p38或MAP激酶抑制剂);IL-1β转化酶抑制剂;TNFα转化酶抑制剂;T细胞信号抑制剂,例如,激酶抑制剂;金属蛋白酶抑制剂;柳氮磺吡啶;硫唑嘌呤;6-巯基嘌呤;血管紧张肽转化酶抑制剂;可溶性细胞素受体和它们的衍生物(例如,可溶性p55或p75 TNF受体、sIL-1RI、sIL-1RII、sIL-6R)和抗炎细胞素(例如,IL-4、IL-10、IL-11、IL-13和TGFβ)。可以与N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II联用的、治疗克罗恩氏病的药剂的优选例子包括下列药剂∶TNF拮抗剂,例如,抗TNF抗体、D2E7(阿达木单抗)、CA2(因福利美)、CDP 571、TNFR-Ig 构成物、(p75TNFRIgG(依那西普)和p55TNFRIgG(LenerceptTM)抑制剂和PDE4抑制剂。N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II可以与皮质类甾醇联用,例如,布地奈德(budenoside)和地塞米松;柳氮磺吡啶、5-对氨水杨酸;奥沙拉秦;以及妨碍促炎细胞因子(例如,IL-1)的合成或作用的药剂,例如,IL – 1β转化酶抑制剂和IL-1ra;T细胞信号抑制剂、例如,酪氨酸激酶抑制剂;6-巯基嘌呤;IL-11;5-氨基水杨酸(mesalamine);脱氢可的松;硫唑嘌呤;巯基嘌呤;因福利美;甲基泼尼松龙琥珀酸酯钠;地芬诺酯/atrop硫酸盐;盐酸洛哌丁胺;氨甲喋呤;奥美拉唑;叶酸;环丙沙星/葡萄糖-水;重酒石酸二氢可待因酮/apap;盐酸四环素;醋酸氟轻松;甲硝哒唑;硫汞撒/硼酸;考来烯胺/蔗糖;盐酸环丙沙星;硫酸莨菪碱;利多尔;盐酸咪达唑仑;氧可酮HCl/醋氨酚;盐酸异丙嗪;磷酸钠;磺胺甲基异噁唑/三甲氧苄二氨嘧啶;西乐葆;聚卡波菲;萘磺酸丙氧吩;氢化可的松;多种维生素;巴柳氮二钠;磷酸可待因/apap;考来维仑(colesevelam)HCl;氰钴维生素;叶酸;左氧氟沙星;甲基强的松龙;那他珠单抗(natalizumab)和干扰素-γ。
可以与N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II共同给药的、治疗多发性硬化的药剂的非限制性例子包括下列药剂∶皮质类甾醇;氢化泼尼松;甲基强的松龙;硫唑嘌呤;环磷酰胺;环孢灵;氨甲喋呤;4-氨基吡啶;替扎尼定;干扰素-β1a(Avonex®;Biogen);干扰素-β1b(Betaseron®;Chiron/Berlex);干扰素α-n3)(Interferon Sciences/Fujimoto)、干扰素-α(Alfa Wassermann/J&J)、干扰素β1A-IF(Serono/Inhale Therapeutics)、聚乙二醇化干扰素α2b(Enzon/Schering-Plough)、共聚物1(Cop-1;Copaxone®;Teva PharmaceuticalIndustries, Inc.);高压氧;静脉内免疫球蛋白;克拉屈滨;其它人类细胞素或生长因子和它们的受体的抗体或拮抗剂,例如,TNF、LT、IL-1、IL-2、IL-6、IL-7、IL-8、IL-12、IL-23、IL-15、IL-16、EMAP-II、GM-CSF、FGF和PDGF。N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II可以与细胞表面分子的抗体联用,例如,CD2、CD3、CD4、CD8、CD19、CD20、CD25、CD28、CD30、CD40、CD45、CD69、CD80、CD86、CD90或它们的配体。N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II可以与下列药剂联用,例如,氨甲喋呤、环孢灵、FK506、雷帕霉素、麦考酚酸莫酯、来氟米特、S1P1激动剂、NSAID,例如,布洛芬,皮质类甾醇,例如,氢化泼尼松,磷酸二酯酶抑制剂、腺苷(adensosine)激动剂、抗血栓形成药剂、补体抑制剂、肾上腺素能药剂、通过促炎细胞因子(例如,TNFα或IL-1)妨碍信号的药剂(例如,NIK、IKK、p38或MAP激酶抑制剂)、IL – 1β转化酶抑制剂、TACE抑制剂、T细胞信号抑制剂,例如,激酶抑制剂、金属蛋白酶抑制剂、柳氮磺吡啶、硫唑嘌呤、6-巯基嘌呤、血管紧张肽转化酶抑制剂、可溶性细胞素受体和它们的衍生物(例如,可溶性p55或p75 TNF受体、sIL-1RI、sIL-1RII、sIL-6R)和抗炎细胞素(例如,IL-4、IL-10、IL-13和TGFβ)。
N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II还可以与下列药剂共同给药,例如,阿仑单抗(alemtuzumab)、屈大麻酚、达(克)珠单抗、米托蒽醌、盐酸扎利罗登(xaliproden)、氨吡啶、乙酸格拉默(glatiramer)、那他珠单抗(natalizumab)、sinnabidol、α-immunokineNNSO3、ABR-215062、AnergiX.MS、趋化因子受体拮抗剂、BBR-2778、calagualine、CPI-1189、LEM(脂质体密封的米托蒽醌)、THC.CBD(大麻素激动剂)、MBP-8298、美索普兰(mesopram)(PDE4抑制剂)、MNA-715、抗IL-6受体抗体、neurovax、吡非尼酮(pirfenidone)allotrap 1258(RDP-1258)、sTNF-R1、他仑帕奈(talampanel)、特立氟胺(teriflunomide)、TGF-beta2、替利莫肽(tiplimotide)、VLA-4拮抗剂(例如,TR-14035、VLA4 Ultrahaler、Antegran-ELAN/Biogen)、干扰素γ拮抗剂和IL-4激动剂。
可以与N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II共同给药的强直性脊柱炎的治疗剂的非限制性例子包括下列治疗剂∶布洛芬、双氯芬酸、迷索前列醇、萘普生、美洛昔康、消炎痛、双氯芬酸、西乐葆、罗非考昔、柳氮磺吡啶、氨甲喋呤、硫唑嘌呤、米诺环素(minocyclin)、脱氢可的松和抗TNF抗体、D2E7(HUMIRA®)、CA2(因福利美)、CDP 571、TNFR-Ig构成物、(p75TNFRIgG(ENBREL®)和p55TNFRIgG(Lenercept®)。
可以与N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II共同给药的、治疗哮喘的药剂的非限制性例子包括下列药剂∶沙丁胺醇、沙美特罗/氟替卡松、孟鲁司特钠、丙酸氟替卡松、布地奈德、脱氢可的松、沙美特罗羟萘甲酸盐、左沙丁胺醇()HCl、硫酸沙丁胺醇/异丙托品、强的松龙磷酸钠酯、曲安奈德(triamcinolone acetonide)、二丙酸氯地米松、异丙托溴铵、阿奇毒素、乙酸吡布特罗、氢化泼尼松、无水茶碱、甲基泼尼松龙琥珀酸酯钠、克拉霉素、扎鲁司特、富马酸福莫特罗、流感病毒疫苗、阿莫西林三水合物、氟尼缩松、过敏注射剂、色甘酸钠、盐酸非索非那定、氟尼缩松/薄荷醇、阿莫西林/克拉维酸盐、左氧氟沙星、吸入辅助装置、愈创甘油醚、地塞米松磷酸钠、莫西沙星(moxifloxacin)HCl、盐酸多西环素(doxycyclinehyclate)、愈创甘油醚/d-美沙芬(methorphan)、对位麻黄碱/cod/chlorphenir、加替沙星(gatifloxacin)、盐酸西替利嗪、糠酸莫美松、沙美特罗羟萘甲酸盐、苯佐那酯、头孢氨苄、pe/氢可酮/chlorphenir、西替利嗪HCl/假麻黄硷(pseudoephed)、苯肾上腺素/cod/普鲁米近、可待因/普鲁米近、头孢丙烯、地塞米松、愈创甘油醚/假麻黄碱、扑尔敏/氢可酮、萘多罗米钠、硫酸叔丁喘宁、肾上腺素、甲基强的松龙、抗IL-13抗体和硫酸二羟苯基异丙氨基乙醇。
可以与N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II共同给药的、治疗COPD的药剂的非限制性例子包括下列药剂∶硫酸沙丁胺醇/异丙托品、异丙托溴铵、沙美特罗/氟替卡松、沙丁胺醇、沙美特罗羟萘甲酸盐、丙酸氟替卡松、脱氢可的松、无水茶碱、甲基泼尼松龙琥珀酸酯钠、孟鲁司特钠、布地奈德、富马酸福莫特罗、曲安奈德(triamcinolone acetonide)、左氧氟沙星、愈创甘油醚、阿奇毒素、二丙酸氯地米松、左沙丁胺醇(levalbuterol)HCl、氟尼缩松、头孢曲松钠、阿莫西林三水合物、加替沙星(gatifloxacin)、扎鲁司特、阿莫西林/克拉维酸盐、氟尼缩松/薄荷醇、扑尔敏/氢可酮、硫酸二羟苯基异丙氨基乙醇、甲基强的松龙、糠酸莫美松、对位麻黄碱/cod/chlorphenir、乙酸吡布特罗、对位麻黄碱/氯雷他定、硫酸叔丁喘宁、噻托溴胺、(R,R)-福莫特罗、TgAAT、西洛司特(cilomilast)和罗氟司特。
可以与N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II共同给药的牛皮癣的治疗剂的非限制性例子包括下列治疗剂∶卡泊三烯(calcipotriene)、丙酸氯氟美松、曲安奈德(triamcinoloneacetonide)、丙酸卤倍他索(halobetasol)、维生素A酸(tazarotene)、氨甲喋呤、醋酸氟轻松、倍他米松diprop增强型、氟轻松、阿维A、焦油香波、戊酸倍他米松、糠酸莫美松、酮康唑、普拉莫星/肤轻松、戊酸氢化可的松、氟氢缩松、脲、倍他米松、丙酸氯氟美松/emoll、丙酸氟替卡松、阿奇毒素、氢化可的松、滋润配方(moisturizing formula)、叶酸、地奈德、吡美莫司、煤焦油、双乙酸二氟拉松、叶酸依那西普、乳酸、甲氧呋豆素、hc/次没食子酸铋(bismuthsubgal)/znox/resor、醋酸甲基强的松龙、脱氢可的松、防晒霜、哈西缩松、水杨酸、地蒽酚、特戊酸氯可托龙、煤馏出物、煤焦油/水杨酸、煤焦油/水杨酸/硫、去羟米松、地西泮、软化剂、醋酸氟轻松/软化剂、矿物油/蓖麻油/乳酸钠、矿物油/花生油、石油产品/十四烷酸异丙酯、补骨脂素、水杨酸、皂/三溴水杨酰苯胺、硫汞撒/硼酸、西乐葆、因福利美、环孢灵、阿法赛特(alefacept)、依法利珠(efalizumab)、他克莫司、吡美莫司、PUVA、UVB、柳氮磺吡啶、ABT-874和ustekinamab。
可以与N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II共同给药的、牛皮癣关节炎的治疗剂的非限制性例子包括下列治疗剂∶氨甲喋呤、依那西普、罗非考昔、西乐葆、叶酸、柳氮磺吡啶、萘普生、来氟米特、醋酸甲基强的松龙、消炎痛、硫酸羟氯奎、脱氢可的松、舒林酸、倍他米松diprop增强型、因福利美、氨甲喋呤、叶酸、曲安奈德(triamcinolone acetonide)、双氯芬酸、二甲亚砜、吡罗昔康、双氯灭痛、酮洛芬、美洛昔康、甲基强的松龙、萘丁美酮、甲苯酰吡酸钠、卡泊三烯(calcipotriene)、环孢灵、双氯灭痛/迷索前列醇、醋酸氟轻松、氨基葡糖硫酸盐、硫代苹果酸金钠、重酒石酸二氢可待因酮/apap、布洛芬、利塞膦酸钠、磺胺嘧啶、硫鸟嘌呤、伐地考昔、阿法赛特(alefacept)、D2E7(阿达木单抗)和依法利珠(efalizumab)。
可以与N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II共同给药的、SLE(狼疮)的治疗剂的例子包括下列治疗剂∶NSAID,例如,双氯芬酸、萘普生、布洛芬、吡罗昔康、消炎痛;COX2抑制剂,例如,西乐葆、罗非考昔、伐地考昔;抗疟剂,例如,羟氯奎;类固醇,例如,脱氢可的松、氢化泼尼松、布地奈德(budenoside)、地塞米松;细胞毒素,例如,硫唑嘌呤、环磷酰胺、麦考酚酸莫酯、氨甲喋呤;PDE4的抑制剂或嘌呤合成抑制剂,例如,Cellcept®。N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II可以与下列药剂联用,例如,柳氮磺吡啶、5-对氨水杨酸、奥沙拉秦、Imuran®以及妨碍促炎细胞因子(例如,IL-1)的合成、产生或作用的药剂,例如,半胱天冬酶抑制剂,例如,IL-1β转化酶抑制剂和IL-1ra。N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II还可以和T细胞信号抑制剂一起使用,例如,酪氨酸激酶抑制剂;或靶向T细胞活化分子的分子,例如,CTLA-4-IgG或抗B7家族抗体、抗PD-1家族抗体。N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II可以与IL-11或抗细胞素抗体联用,例如,fonotolizumab(抗IFNg抗体)或抗受体抗体,例如,抗IL-6受体抗体和B细胞表面分子的抗体。N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II还可以和消耗B细胞或使B细胞失活的药剂LJP 394(阿贝莫司(abetimus))一起使用,例如,利妥昔单抗(Rituximab)(抗CD20抗体)、lymphostat-B(抗BlyS抗体)、TNF拮抗剂,例如,抗TNF抗体、D2E7(阿达木单抗)、CA2(因福利美)、CDP 571、TNFR-Ig构成物、(p75TNFRIgG(依那西普)和p55TNFRIgG(LenerceptTM)。
N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II还可以与治疗有效量的预防或治疗AIDS所使用的一或多种药剂共同给药,其中,所述药剂的例子包括:HIV逆转录酶抑制剂、HIV蛋白酶抑制剂、免疫调节剂及其它逆转录病毒药物。逆转录酶抑制剂的例子包括但不局限于:阿巴卡韦、阿德福韦、去羟肌苷、地拉韦啶酯(dipivoxil delavirdine)、依法韦恩茨、恩曲他滨(emtricitabine)、拉夫米定、内维拉平、利匹韦林(rilpivirine)、双脱氧胸苷、泰诺福韦、扎西他滨和叠氮胸苷。蛋白酶抑制剂的例子包括但不局限于:安普那韦、阿扎那韦(atazanavir)、达芦那韦(darunavir)、茚地那韦、佛萨普那韦、洛匹那韦、奈非那韦、利托那韦、沙奎那维和替拉那韦(tipranavir)。其它逆转录病毒药物的例子包括但不局限于:埃替拉韦(elvitegravir)、恩夫韦地、马拉维若(maraviroc)和雷特格韦(raltegravir)。
N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II,还可以与治疗有效量的预防或治疗II型糖尿病、肝脂质沉着症、胰岛素耐受性、代谢综合征和相关病症的一或多种治疗剂共同给予,其中,所述药剂的例子包括但不局限于:胰岛素以及为了提高体内作用时间而修饰的胰岛素;刺激胰岛素分泌的药剂,例如,醋酸己脲、氯磺丙脲、优降糖、格列美脲、格列甲嗪、达美康、吡喃葡萄糖苷(glycopyramide)、格列喹酮、瑞格列奈(rapaglinide)、那格列奈(nataglinide)、甲磺吖庚脲和甲苯磺丁脲;作为胰高血糖素样肽激动剂的药剂,例如,艾塞那肽(exanatide)、利拉鲁肽(liraglutide)和他司鲁泰(taspoglutide);抑制二肽基-肽酶IV的药剂,例如,维格列汀(vildagliptin)、西他列汀、沙格列汀(saxagliptin)、利拉利汀(linagliptin)、阿格列汀(allogliptin)和septagliptin;与过氧物酶体增殖因子活化的受体γ结合的药剂,例如,罗格列酮和吡格列酮;降低胰岛素抗性的药剂,例如,二甲双胍;降低葡萄糖在小肠中吸收的药剂,例如,阿卡波糖、米格列醇和伏格列醇。
N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II,还可以与治疗有效量的预防或治疗急性肾脏病症和慢性肾脏疾病的一或多种治疗剂共同给予,其中,所述药剂的例子包括但不局限于:多巴胺、利尿剂,例如,利尿磺胺、布美他尼、噻嗪等等、甘露糖醇、葡萄糖酸钙、碳酸氢钠、沙丁胺醇、帕立骨化醇(paricalcitol)、度骨化醇(doxercalciferol)、西那卡塞(cinacalcet)和bardoxalone methyl。
术语“治疗”指的是减轻或消除疾病和/或它的伴随症状的方法。
术语“预防”指的是防止疾病和/或它的伴随症状发作或避免患者得病的方法。本文使用的“预防”还包括延迟疾病和/或它的伴随症状的发作,以及降低患者得病的危险。
短语“治疗有效量”是指,当单独给予或与其它药剂或治疗法结合给予具体患者或目标人群时,足以防止所治疗的病症或障碍的一或多种症状发展或使其减轻至某种程度的化合物或其可药用盐的数量。例如,在人或其它哺乳动物中,对于所治疗的具体疾病和患者,可以在实验室或临床条件下用实验方法确定治疗有效量,或可以是美国食品与药物管理局或同等的国外代理处的规则所要求的数量。
本文所定义的术语“患者”指的是动物,例如,哺乳动物,包括但不限于:灵长类(例如,人)、牛、羊、山羊、马、狗、猫、兔、大鼠、小鼠,等等。在优选实施方案中,患者是人。
下列实施例可以用于说明性的目的,不应该认为其限制本发明的范围。
实施例
粉末X射线衍射(PXRD)
使用配备有曲线位置灵敏探测器和平行光束的G3000衍射器(Inel Corp.,Artenay, France),收集PXRD数据。在40 kV和30 mA下,用铜阳极管(1.5 kW细焦)操作衍射器。入射束锗单色仪提供单色辐射。使用衰减的直射光束(一度间隔),校正衍射器。使用硅粉线位置参考标准(NIST 640c),对刻度进行检测。使用Symphonix软件(Inel Corp.,Artenay,France),用电脑控制仪器,并使用Jade软件(version 9,Materials Data,Inc.,Livermore,CA)分析数据。将样品加载到铝样品座上,并用载玻片整平。使用在40 kV和30mA下操作的X射线管,用铜Kα1 X射线照射样品。
PXRD图示于图1和4中。下表包括分析,并且提供下列近似数据:2θ位置和相对强度,使用峰高,测定高度%(H%)(每秒钟计数)。
差示扫描量热(DSC)
配备有通用分析2000软件(Version 4.5A,TA Instruments,New Castle,DE)的DSC(Q-2000,TA Instruments,New Castle,DE)用于测定DSC热示踪。用联苯、铟和锡标准校正温度轴。用铟校正电池常数。除非另作说明,否则,在研究期间,将样品(2-5 mg)密封在通风的铝盘中,并在50 mL/min的氮气流中,以10℃/分钟的速度加热。
热解重量分析(TGA)
在配备有数据分析仪(Universal Analysis 2000,version 4.5A,TAInstruments,New Castle,DE)的热天平(Q-500,TA Instruments,New Castle,DE)上收集TGA痕量。在实验期间,用60 mL/min的氮气吹扫加热炉,同时,以40 mL/min吹扫天平舱。使用铝和镍的居里点,校正TGA加热炉的温度。试样量在2至20 mg的范围,使用10℃/min的加热速度。
制备N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]
吡啶-4-基)苯基]乙磺酰胺I型
步骤1A
将2-溴-1-氟-4-硝基苯(15 g,68 mmol)、2,4-二氟苯酚(7.82 ml,82 mmol)和碳酸铯(26.7 g,82 mmol)在二甲亚砜(75 ml)中的混合物在110℃下加热1小时。将该反应混合物冷却至环境温度,并加入水(1000 ml)和饱和氯化钠水溶液(1000 ml)。将该混合物用乙酸乙酯(3x200 ml)提取。将合并的有机物用饱和氯化钠水溶液洗涤,干燥(无水硫酸镁),过滤,减压浓缩,提供2-溴-1-(2,4-二氟苯氧基)-4-硝基苯(22.5 g,定量)。
步骤2A
将2-溴-1-(2,4-二氟苯氧基)-4-硝基苯(22.5 g,68.2 mmol)、铁粉(19.04 g,341mmol)和氯化铵(7.30 g,136 mmol)在四氢呋喃(117 ml)、乙醇(117 ml)和水(39.0 ml)中的混合物在回流下、在100℃下加热2小时。将该反应混合物冷却至刚好低于回流温度,通过硅藻土过滤,并将滤饼用温热甲醇(3 x 50 ml)洗涤。将得到的溶液减压浓缩,而后用饱和碳酸氢钠(150 ml)中和至pH8。将该混合物用乙酸乙酯(3 x 100 ml)提取。将合并的有机物用饱和氯化钠水溶液洗涤,用无水硫酸镁干燥,过滤,并浓缩。将残余物用快速色谱纯化(硅胶,乙酸乙酯/己烷梯度,0-15%),提供3-溴-4-(2,4-二氟苯氧基)苯胺(16.8 g,产率82%)。
步骤3A
将5-溴-2-甲氧基-4-甲基-3-硝基吡啶(15.0 g,60.7 mmol)溶于二甲基甲酰胺(300 ml)中,并加入甲醇化锂(6.07 ml,6.07 mmol,1M)。将该反应混合物加热至100℃。用10分钟向该混合物中加入1,1-二甲氧基-N,N-二甲基甲胺(64.5 ml,486 mmol)。将该反应混合物在95℃下搅拌16小时。将该反应混合物冷却至室温,并小心地加入水(300 ml,放热)。真空过滤,收集产生的沉淀,用水洗涤,干燥,提供(E)-2-(5-溴-2-甲氧基-3-硝基吡啶-4-基)-N,N-二甲基乙烯胺(13.9 g,45.9 mmol,产率76%)。
步骤4A
在不锈钢耐压瓶中,将(E)-2-(5-溴-2-甲氧基-3-硝基吡啶-4-基)-N,N-二甲基乙烯胺(13.9 g,45.8 mmol)和乙酸乙酯(150 ml)加入到Ra-Ni 2800(预先用乙醇洗涤)、水浆(6.9 g,118 mmol)中,并在30 psi的氢气氛围中、在室温下搅拌30分钟。过滤该反应混合物,并浓缩。将残余物与二氯甲烷一起研磨,过滤收集固体,提供4-溴-7-甲氧基-1H-吡咯并[2,3-c]吡啶(5.82 g)。蒸发母液,并将残余物再次与二氯甲烷一起研磨,过滤,额外提供1.63 g的4-溴-7-甲氧基-1H-吡咯并[2,3-c]吡啶。总产率=7.45 g,产率72%。
步骤5A
将4-溴-7-甲氧基-1H-吡咯并[2,3-c]吡啶(7.42 g,32.7 mmol)的二甲基甲酰胺(235 ml)溶液在室温下搅拌。向此溶液中加入氢化钠(1.18 g,1.96 g,60%分散体,在油中,49.0 mmol),并将该反应混合物搅拌10分钟。然后逐份加入对甲苯磺酰氯(9.35 g,49.0mmol),并将该混合物在室温下、在氮气氛围中搅拌16小时。将该反应混合物小心地用水淬灭,并在布氏漏斗上真空过滤,收集所得到的米色固体,并用水洗涤。收集固体,并在真空烘箱中、在50℃下干燥,提供12.4 g(100%)的4-溴-7-甲氧基-1-甲苯磺酰基-1H-吡咯并[2,3-c]吡啶。
步骤6A
将4-溴-7-甲氧基-1-甲苯磺酰基-1H-吡咯并[2,3-c]吡啶(12.4 g,32.6 mmol)的二噁烷(140 ml)溶液在室温下搅拌。向此溶液中加入4M HCl/二噁烷(140 ml)。将该反应混合物在40℃下搅拌16小时。将该反应混合物冷却至室温,并浓缩。将残余物与二乙醚一起研磨,过滤,用额外的二乙醚冲洗,干燥,提供4-溴-1-甲苯磺酰基-1H-吡咯并[2,3-c]吡啶-7(6H)-酮(11.23 g,30.6 mmol,产率94%)的米色固体。
步骤7A
在氮气氛围中,将氢化钠(0.875 g,36.5 mmol,1.46 g,60%分散体,在油中)加入到4-溴-1-甲苯磺酰基-1H-吡咯并[2,3-c]吡啶-7(6H)-酮(11.2 g,30.4 mmol)的二甲基甲酰胺(217 ml)搅拌溶液中。30分钟之后,加入碘甲烷(2.27 ml,36.5 mmol),并将该溶液在室温下搅拌3小时。加入水(250 ml),形成沉淀。真空过滤,收集沉淀,用水(50 ml)冲洗,在真空烘箱中、在55℃下干燥过夜,提供11.2 g的4-溴-6-甲基-1-甲苯磺酰基-1H-吡咯并[2,3-c]吡啶-7(6H)-酮(96%)。
步骤8A
将4-溴-6-甲基-1-甲苯磺酰基-1H-吡咯并[2,3-c]吡啶-7(6H)-酮(6.55 g,17.2mmol)、4,4,4',4',5,5,5',5'-八甲基-2,2'-双(1,3,2-二氧杂硼杂环戊烷)(8.73 g,34.4mmol)、乙酸钾(3.71 g,37.8 mmol)、三(二亚苄基丙酮)二钯(0)(0.393 g,0.430 mmol)和2-二环己基膦基-2',4',6'-三异丙基联苯(X-PHOS,0.819 g,1.72 mmol)混合,并在搅拌下,用氩气吹扫1小时。将二噁烷(86 ml)用氮气吹扫1小时,在氮气氛围中,通过小管转移到固体组分中,并将该混合物在氩气氛围中、在80℃下加热5小时。将该反应混合物冷却至室温,在乙酸乙酯和水之间分配,并通过硅藻土过滤。将乙酸乙酯层用盐水洗涤两次,干燥(Na2SO4),过滤,并浓缩。将残余物色谱纯化(硅胶,25-80%乙酸乙酯/己烷)。将色谱得到的物质与最小数量的己烷(30 ml)一起研磨,并过滤收集颗粒状固体,用最小数量己烷冲洗,干燥至恒定质量,提供6-甲基-4-(4,4,5,5-四甲基-1,3,2-二氧杂硼杂环戊烷-2-基)-1-甲苯磺酰基-1H-吡咯并[2,3-c]吡啶-7(6H)-酮(5.4 g,73%)。
步骤9A
将3-溴-4-(2,4-二氟苯氧基)苯胺(5.0 g,11.67 mmol)、6-甲基-4-(4,4,5,5-四甲基-1,3,2-二氧杂硼杂环戊烷-2-基)-1-甲苯磺酰基-1H-吡咯并[2,3-c]吡啶-7(6H)-酮(3.85 g,12.84 mmol)、1,3,5,7-四甲基-6-苯基-2,4,8-三氧杂-6-磷杂金刚烷(0.399 g,1.366 mmol)、三(二亚苄基丙酮)二钯(0)(0.321 g,0.350 mmol)和磷酸钾(6.19 g,29.2mmol)在二噁烷(50 ml)和水(12.5 ml)中的混合物脱气,并用氮气反填充若干次。将该反应混合物在60℃下加热16小时,而后冷却至环境温度。将该反应混合物在水和乙酸乙酯之间分配。用额外的乙酸乙酯提取水层三次。用盐水洗涤合并的有机层,用无水硫酸镁干燥,过滤,并浓缩。用快速柱色谱纯化残余物(硅胶,60%乙酸乙酯/己烷),提供4-(5-氨基-2-(2,4-二氟苯氧基)苯基)-6-甲基-1-甲苯磺酰基-1H-吡咯并[2,3-c]吡啶-7(6H)-酮(4.40 g,产率72.3%)。
步骤10A
将4-(5-氨基-2-(2,4-二氟苯氧基)苯基)-6-甲基-1-甲苯磺酰基-1H-吡咯并[2,3-c]吡啶-7(6H)-酮(4.35 g,8.34 mmol)的二氯甲烷(50 ml)溶液冷却至0℃。向此溶液中加入乙磺酰基氯(2.37 ml,25.0 mmol)。将该反应混合物在室温下搅拌2小时。蒸发溶剂,并将残余物在乙酸乙酯和水之间分配。用额外的乙酸乙酯提取水层两次。将合并的有机层用饱和氯化钠水溶液洗涤,用无水硫酸镁干燥,过滤,并浓缩。用快速色谱纯化残余物(硅胶,80%乙酸乙酯/己烷),提供N-(4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-1-甲苯磺酰基-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基)-N-(乙磺酰基)乙磺酰胺(5.34 g,产率91%)。
步骤11A
将N-(4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-1-甲苯磺酰基-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基)-N-(乙磺酰基)乙磺酰胺(5.3 g,7.5 mmol)、氢氧化钾(8.43g,150 mmol)和N,N,N-三甲基十六烷-1-基溴化铵(0.137 g,0.375 mmol)在四氢呋喃(60ml)和水(30 ml)中的混合物在90℃下加热16小时。减压除去四氢呋喃,并将残余物在水和乙酸乙酯之间分配。使用10% HCl,将水层中和至pH7。然后,用乙酸乙酯提取水层。将合并的有机层用饱和氯化钠水溶液洗涤,用无水硫酸镁干燥,过滤,并浓缩。用快速色谱纯化残余物(硅胶,乙酸乙酯)。将目标级分合并,并浓缩。将残余物与20 ml乙腈一起研磨,提供N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺I型(2.82 g,产率82%)。1H NMR(300 MHz, DMSO-d 6)δ 1.23(t, J=7.3 Hz, 3H),3.11(q, J=7.3 Hz, 2H), 3.53(s, 3H), 6.27-6.22(m, 1H), 6.91(d, J=8.7 Hz, 1H),7.13-6.93(m, 2H), 7.19(dd, J=8.8, 2.7 Hz, 1H), 7.32-7.25(m, 2H), 7.42-7.31(m,2H), 9.77(s, 1H), 12.04(bs, 1H)。MS(ESI+)m/z 460.1(M+H)+。
I型固体的PXRD分析提供了列于表1中的X射线衍射峰。取出一部分I型固体,加热到190℃,而后冷却至室温。当用PXRD分析时,所得到的物质提供了列于表2中的X射线衍射峰。该物质的DSC热像图描述在图2中。在大约238.30℃,I型熔化。该物质的TGA曲线描述在图3中。
II型的代表性的热特性示于图5和6中。在大约241.15℃,II型熔化。
表1∶N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]
吡啶-4-基)苯基]乙磺酰胺I型的峰列表
峰位置(° 2θ) | 相对强度 |
8.5 | 100.0 |
10.8 | 23.0 |
11.1 | 7.9 |
11.3 | 12.5 |
11.7 | 12.0 |
12.9 | 7.4 |
13.8 | 3.7 |
14.4 | 18.7 |
15.0 | 2.0 |
16.2 | 3.0 |
16.5 | 3.6 |
17.1 | 11.4 |
17.3 | 15.0 |
17.4 | 6.2 |
17.8 | 4.3 |
18.5 | 13.9 |
18.8 | 14.1 |
19.3 | 9.0 |
19.5 | 26.8 |
20.2 | 8.7 |
20.6 | 30.2 |
21.5 | 18.8 |
22.6 | 19.5 |
23.2 | 9.8 |
23.5 | 20.7 |
23.9 | 3.4 |
24.4 | 12.3 |
25.1 | 15.2 |
表2∶N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]
吡啶-4-基)苯基]乙磺酰胺I型的峰列表
峰位置(° 2θ) | 相对强度 |
8.5 | 100.0 |
10.8 | 22.0 |
11.1 | 8.5 |
11.3 | 14.9 |
11.7 | 13.2 |
13.0 | 6.2 |
13.8 | 3.2 |
14.5 | 21.7 |
15.1 | 3.1 |
16.2 | 2.8 |
16.6 | 3.3 |
17.1 | 12.3 |
17.4 | 18.4 |
17.5 | 7.6 |
17.9 | 4.6 |
18.5 | 14.9 |
18.9 | 16.1 |
19.4 | 10.0 |
19.6 | 33.9 |
20.3 | 8.5 |
20.7 | 35.6 |
21.6 | 20.5 |
22.7 | 21.7 |
23.3 | 10.6 |
23.6 | 21.5 |
23.9 | 3.8 |
24.5 | 10.1 |
25.2 | 18.7 |
制备N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]
吡啶-4-基)苯基]乙磺酰胺II型
步骤1B
在环境温度下,将3-溴-4-(2,4-二氟苯氧基)苯胺(3.24 g,10.80 mmol)和三乙胺(4.37 g,43.2 mmol)在二氯甲烷(48.1 ml)中搅拌。逐滴加入乙磺酰基氯(4.16 g,32.4mmol),并将该溶液在环境温度下搅拌1小时。将该反应混合物减压浓缩,加入二噁烷(24ml)和氢氧化钠(10% w/v,12 ml,0.427 mmol),并将该溶液加热至70℃下,保持1小时。使用饱和NH4Cl水溶液(200 ml),将该溶液中和至大约pH7。用乙酸乙酯(3x125 mL)提取水相。将合并的有机物用盐水洗涤,干燥(无水MgSO4),过滤,而后减压浓缩。用快速色谱纯化残余物(硅胶,0-50%乙酸乙酯/石油醚梯度),提供N-(3-溴-4-(2,4-二氟苯氧基)苯基)乙磺酰胺(1.4 g,3.57 mmol,产率33.1%)。
步骤2B
将6-甲基-4-(4,4,5,5-四甲基-1,3,2-二氧杂硼杂环戊烷-2-基)-1-甲苯磺酰基-1H-吡咯并[2,3-c]吡啶-7(6H)-酮(6.00 g,14.0 mmol)、N-(3-溴-4-(2,4-二氟苯氧基)苯基)乙磺酰胺(5.77 g,14.7 mmol)、1,3,5,7-四甲基-6-苯基-2,4,8-三氧杂-6-磷杂金刚烷(0.205 g,0.700 mmol)、三(二亚苄基丙酮)二钯(0)(0.321 g,0.350 mmol)和磷酸钾(2.97g,14.0 mmol)的混合物合并,并用氩气吹扫30分钟。将二噁烷(60 ml)和水(15 ml)的混合物用氮气吹扫30分钟,并在氩气氛围中,用注射器转移到反应容器中。将该反应混合物在60℃下搅拌2小时,冷却至环境温度,并在乙酸乙酯和水之间分配。将有机层用盐水洗涤,干燥(无水硫酸钠),用硅胶(2-4 g)处理45分钟,过滤,浓缩,提供N-(4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-1-甲苯磺酰基-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基)乙磺酰胺(8 g,13.04 mmol,产率93%)。
步骤3B
将N-(4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-1-甲苯磺酰基-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基)乙磺酰胺(8.0 g,13 mmol)、N,N,N-三甲基十六烷-1-基溴化铵(0.238 g,0.652 mmol)和氢氧化钾(11.9 g,211 mmol)在四氢呋喃(66 ml)和水(22 ml)中混合,并将该混合物在100℃下加热14小时。将该反应混合物冷却至环境温度,在乙酸乙酯和水之间分配,并通过小心地加入浓HCl,将pH值调节至大约7。分离有机层,用饱和氯化钠水溶液洗涤三次,干燥(无水Na2SO4),过滤,浓缩。将残余物悬浮在二氯甲烷中,在回流下加热四个小时,而后冷却至室温。过滤分离所得到的固体,并用二氯甲烷和己烷冲洗,提供N-(4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基)乙磺酰胺I型和II型的混合物(4.2 g,9.14 mmol,产率70.1%)。
步骤4B
将一部分从步骤3B获得的I型和II型的混合物(7.5 g,16.32 mmol)溶于沸腾的乙酸乙酯(1500 ml)和乙醇(50 ml)的溶剂混合物中。停止加热,并将该热溶液用3-巯丙基功能化的硅胶(Aldrich,目录号:538086,10 g)和Darco G-60(10 g)处理,搅拌20分钟,通过0.5英寸厚的硅藻土垫过滤,并浓缩滤液。将得到的固体在回流乙醇(150 ml)中搅拌两个小时,冷却至环境温度,并过滤收集固体,干燥至恒定质量(6.517 g,回收率87%),提供N-(4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基)乙磺酰胺II型。
II型固体给出了列于表3中的X射线衍射峰。取出一部分上面步骤4B得到的II型固体,加热到190℃,而后冷却至室温。当用PXRD分析时,所得到的固体提供了列于表4中的X射线衍射峰。该物质的DSC热像图描述在图5中。在大约241.15℃,II型熔化。该物质的TGA曲线描述在图6中。
表3∶N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]
吡啶-4-基)苯基]乙磺酰胺II型的峰列表
峰位置(° 2θ) | 相对强度 |
6.2 | 11.7 |
9.0 | 6.7 |
11.0 | 5.4 |
12.2 | 18.4 |
12.6 | 16.2 |
13.1 | 48.1 |
14.1 | 12.1 |
15.5 | 5.8 |
16.3 | 13.0 |
16.5 | 16.9 |
16.9 | 23.2 |
17.8 | 32.7 |
18.0 | 100.0 |
18.3 | 15.3 |
18.9 | 60.1 |
20.4 | 8.7 |
21.0 | 13.5 |
21.6 | 13.5 |
21.8 | 29.7 |
22.1 | 24.3 |
22.9 | 8.9 |
23.2 | 6.2 |
24.4 | 11.0 |
24.6 | 16.0 |
25.5 | 19.6 |
26.3 | 30.1 |
26.9 | 20.2 |
27.2 | 12.1 |
表4∶N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]
吡啶-4-基)苯基]乙磺酰胺II型的峰列表
峰位置(° 2θ) | 相对强度 |
6.2 | 10.1 |
9.0 | 6.9 |
11.0 | 5.1 |
12.3 | 20.3 |
12.6 | 19.7 |
13.1 | 50.5 |
14.1 | 13.5 |
15.6 | 5.1 |
16.4 | 17.5 |
16.5 | 20.3 |
16.9 | 24.1 |
17.8 | 33.2 |
18.1 | 100.0 |
18.3 | 14.2 |
18.9 | 70.0 |
20.4 | 8.3 |
21.1 | 15.8 |
21.6 | 14.9 |
21.8 | 36.2 |
22.1 | 25.5 |
22.9 | 10.3 |
23.2 | 6.1 |
24.4 | 13.2 |
24.7 | 17.0 |
25.6 | 26.4 |
26.3 | 41.9 |
27.0 | 21.9 |
27.3 | 12.4 |
Claims (29)
1.N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的分离的结晶形式,其中,所述结晶形式具有包含三个或更多个选自下列的2θ峰值±0.2的粉末X射线衍射图:6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。
2.N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的分离的结晶形式,其中,所述结晶形式具有包含下列2θ峰值±0.2的粉末X射线衍射图:6.2°、9.0°、11.0°、12.3°、12.6°、13.1°、14.1°、15.6°、16.4°、16.5°、16.9°、17.8°、18.1°、18.3°、18.9°、20.4°、21.1°、21.6°、21.8°、22.1°、22.9°、23.2°、24.4°、24.7°、25.6°、26.3°、27.0°和27.3°。
3.权利要求1的结晶形式,具有包含三个、四个、五个或六个选自下列的2θ峰值±0.2的粉末X射线衍射图:6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。
4.权利要求1的结晶形式,具有包含六个选自下列的2θ峰值±0.2的粉末X射线衍射图:6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。
5.权利要求1的结晶形式,具有包含五个选自下列的2θ峰值±0.2的粉末X射线衍射图:6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。
6.权利要求1的结晶形式,具有包含四个选自下列的2θ峰值±0.2的粉末X射线衍射图:6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。
7.权利要求1的结晶形式,具有包含三个选自下列的2θ峰值±0.2的粉末X射线衍射图:6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。
8.权利要求1的结晶形式,具有包含下列2θ峰值±0.2的粉末X射线衍射图:6.2°、9.0°、12.3°、12.6°和15.6°。
9.权利要求1的结晶形式,具有包含下列2θ峰值±0.2的粉末X射线衍射图:22.1°、25.6°、26.3°、27.0°和27.3°。
10.权利要求2的结晶形式,具有包含在下列2θ位置的峰值±0.2的粉末X射线衍射图:6.2°、9.0°、12.3°、12.6°、13.1°、14.1°、16.4°、16.5°、16.9°、17.8°、18.1°、18.3°和18.9°。
11.权利要求2的结晶形式,具有包含在下列2θ位置的峰值±0.2的粉末X射线衍射图:6.2°、9.0°、12.3°、12.6°、13.1°、14.1°、18.1°和18.9°。
12.权利要求2的结晶形式,具有包含在下列2θ位置的峰值±0.2的粉末X射线衍射图:6.2°、9.0°、12.3°、12.6°、13.1°和18.1°。
13.权利要求2的结晶形式,具有包含在下列2θ位置的峰值±0.2的粉末X射线衍射图:9.0°、12.3°、12.6°、13.1°和18.1°。
14.权利要求1的结晶形式,在240和242℃之间具有差示扫描量热图吸热线。
15.权利要求1的结晶形式,在大约241℃具有差示扫描量热图吸热线。
16.药物组合物,其含有按照权利要求1的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的分离的结晶形式,以及至少一种可药用载体。
17.药物组合物在制备治疗个体癌症的药物中的用途,所述药物组合物含有按照权利要求1的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式,以及至少一种可药用载体。
18.权利要求17的用途,其中,所述癌症选自:听神经瘤、基底细胞癌、胆管癌、膀胱癌、脑癌、乳腺癌、支气管癌、子宫颈癌、软骨肉瘤、脊索瘤、绒膜癌、结肠癌、结肠直肠癌、颅咽管瘤、囊腺癌、扩散性大B细胞淋巴瘤、增殖异常性变化、胚胎性癌、子宫内膜癌、内皮肉瘤、室管膜瘤、上皮癌、食道癌、雌激素-受体阳性乳腺癌、特发性血小板增多症、尤因氏瘤、纤维肉瘤、滤泡性淋巴瘤、生殖细胞睾丸癌、胶质瘤、恶性胶质瘤、胶质肉瘤、重链病、成血管细胞瘤、肝癌、肝细胞癌、激素不敏感的前列腺癌、平滑肌肉瘤、白血病、脂肉瘤、肺癌、淋巴管内皮肉瘤、淋巴管肉瘤、淋巴瘤、膀胱、乳房、结肠、肺、卵巢、胰腺、前列腺、皮肤和子宫的恶性肿瘤和高增殖病症、起源于T细胞或B细胞的淋巴恶性肿瘤、髓样癌、成髓细胞瘤、黑素瘤、脑膜瘤、间皮瘤、多发性骨髓瘤、骨髓瘤、粘液肉瘤、神经母细胞瘤、NUT中线癌、非小细胞肺癌、寡枝神经胶质细胞瘤、口腔癌、骨原性肉瘤、卵巢癌、胰腺癌、乳头状腺癌、乳头状癌、松果体瘤、真性红细胞增多症、前列腺癌、直肠癌、肾细胞癌、成视网膜细胞瘤、横纹肌肉瘤、肉瘤、皮脂腺癌、精原细胞瘤、皮肤癌、小细胞肺癌、实质固态瘤、小细胞肺癌、胃癌、鳞状细胞癌、滑膜瘤、汗腺癌、甲状腺癌、Waldenström’s巨球蛋白血症、睾丸肿瘤、子宫癌和Wilms'肿瘤。
19.权利要求18的用途,其中,所述癌症选自:急性白血病、慢性白血病、红白血病、淋巴细胞性白血病、粒细胞性白血病、发育异常、组织变形、霍奇金氏淋巴瘤和非霍奇金氏淋巴瘤。
20.权利要求18的用途,其中,所述癌症选自:急性淋巴细胞性白血病、急性髓细胞性白血病、急性T细胞白血病、慢性淋巴细胞性白血病、慢性髓细胞白血病和慢性粒性白血病。
21.权利要求18的用途,其中,所述癌症选自:急性单核细胞白血病、急性成髓细胞白血病、腺癌、血管肉瘤、星形细胞瘤、急性髓单核细胞白血病、急性前髓细胞白血病和慢性粒细胞白血病。
22.制备含有N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺和可药用载体的药物组合物的方法,所述方法包括:
将N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的分离的结晶形式与可药用载体混合,其中,所述结晶形式具有包含三个或更多个选自下列的2θ峰值±0.2的粉末X射线衍射图:6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。
23.含有大于90%(w/w)的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式II的组合物,其中,所述结晶形式具有包含三个或更多个选自下列的2θ峰值±0.2的粉末X射线衍射图:6.2°、9.0°、12.3°、12.6°、15.6°、22.1°、25.6°、26.3°、27.0°和27.3°。
24.药物组合物在制备治疗个体的急性肾疾病或病症的药物中的用途,所述药物组合物包含按照权利要求1的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式,以及至少一种可药用载体,其中,所述急性肾疾病或病症选自:缺血-再灌注诱导的肾病、心脏和大外科诱导的肾病、经皮的冠状动脉干预诱导的肾病、放射造影剂诱导的肾病、败血症诱导的肾病、肺炎诱导的肾病和药物毒性诱导的肾病。
25.药物组合物在制备治疗个体的慢性肾疾病或病症的药物中的用途,所述药物组合物包含按照权利要求1的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式,以及至少一种可药用载体,其中,所述慢性肾疾病或病症选自:糖尿病性的肾病、高血压肾病、HIV相关的肾病、肾小球肾炎、狼疮肾炎、IgA肾病、局灶性节段性肾小球硬化症、膜性肾小球肾炎、微小病变疾病、多囊肾疾病和管状间质性肾炎。
26.药物组合物在制备治疗个体的疾病或病症的药物中的用途,所述药物组合物包含按照权利要求1的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式,以及至少一种可药用载体,其中,所述疾病或病症选自:阿狄森氏病、急性痛风、强直性脊柱炎、哮喘、动脉粥样硬化、贝切特氏病、大疱性皮肤病、心脏肌病、心脏肥大、慢性阻塞性肺病(COPD)、克罗恩氏病、皮炎、湿疹、巨细胞性动脉炎、肾小球肾炎、心力衰竭、肝炎、垂体炎、炎症性肠病、川崎氏病、狼疮肾炎、多发性硬化、心肌炎、肌炎、肾炎、器官移植排斥、骨关节炎、胰腺炎、心包炎、结节性动脉周围炎、肺炎、夏科氏肝硬变、牛皮癣、牛皮癣关节炎、类风湿性关节炎、巩膜炎、硬化性胆管炎、败血症、系统性红斑狼疮、Takayasu's动脉炎、中毒性休克、甲状腺炎、I型糖尿病、溃疡性结肠炎、葡萄膜炎、白癜风、血管炎和眶坏死性肉芽肿病。
27.药物组合物在制备治疗个体获得性免疫缺陷综合征(AIDS)的药物中的用途,所述药物组合物含有按照权利要求1的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式,以及至少一种可药用载体。
28.药物组合物在制备治疗个体的疾病或病症的药物中的用途,所述药物组合物包含按照权利要求1的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式,以及至少一种可药用载体,其中,所述疾病或病症选自:肥胖症、血脂异常、高胆固醇血症、阿尔茨海默氏疾病、代谢综合征、肝脂质沉着症、II型糖尿病、胰岛素抗性、糖尿病性视网膜病和糖尿病性神经病变。
29.药物组合物在制备使雄性个体避孕的药物中的用途,所述药物组合物包含按照权利要求1的N-[4-(2,4-二氟苯氧基)-3-(6-甲基-7-氧代-6,7-二氢-1H-吡咯并[2,3-c]吡啶-4-基)苯基]乙磺酰胺的结晶形式,以及至少一种可药用载体。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201361840777P | 2013-06-28 | 2013-06-28 | |
US61/840777 | 2013-06-28 | ||
PCT/US2014/044513 WO2014210425A1 (en) | 2013-06-28 | 2014-06-27 | Crystalline bromodomain inhibitors |
Publications (2)
Publication Number | Publication Date |
---|---|
CN105473586A CN105473586A (zh) | 2016-04-06 |
CN105473586B true CN105473586B (zh) | 2019-11-05 |
Family
ID=51261220
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201480042976.3A Active CN105473586B (zh) | 2013-06-28 | 2014-06-27 | 晶体溴结构域抑制剂 |
Country Status (33)
Country | Link |
---|---|
US (3) | US9321765B2 (zh) |
EP (1) | EP3013826B1 (zh) |
JP (1) | JP6423425B2 (zh) |
KR (1) | KR102323829B1 (zh) |
CN (1) | CN105473586B (zh) |
AR (1) | AR096758A1 (zh) |
AU (2) | AU2014302252B2 (zh) |
BR (1) | BR112015032736A2 (zh) |
CA (1) | CA2916221C (zh) |
CL (1) | CL2015003722A1 (zh) |
CR (1) | CR20160036A (zh) |
CY (1) | CY1119066T1 (zh) |
DK (1) | DK3013826T3 (zh) |
DO (1) | DOP2015000304A (zh) |
ES (1) | ES2636939T3 (zh) |
HK (2) | HK1223354A1 (zh) |
HR (1) | HRP20171154T1 (zh) |
IL (1) | IL243202B (zh) |
LT (1) | LT3013826T (zh) |
ME (1) | ME02801B (zh) |
MX (1) | MX360065B (zh) |
NZ (1) | NZ631112A (zh) |
PE (1) | PE20160287A1 (zh) |
PH (1) | PH12015502792A1 (zh) |
PL (1) | PL3013826T3 (zh) |
PT (1) | PT3013826T (zh) |
RS (1) | RS56318B1 (zh) |
RU (1) | RU2675268C2 (zh) |
SG (1) | SG11201510692TA (zh) |
SI (1) | SI3013826T1 (zh) |
TW (1) | TWI639594B (zh) |
UY (1) | UY35632A (zh) |
WO (1) | WO2014210425A1 (zh) |
Families Citing this family (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014096965A2 (en) | 2012-12-21 | 2014-06-26 | Rvx Therapeutics Inc. | Novel heterocyclic compounds as bromodomain inhibitors |
EP2970282B1 (en) | 2013-03-15 | 2019-08-21 | Incyte Holdings Corporation | Tricyclic heterocycles as bet protein inhibitors |
JP6599852B2 (ja) | 2013-06-21 | 2019-10-30 | ゼニス・エピジェネティクス・リミテッド | ブロモドメイン阻害剤としての新規の置換された二環式化合物 |
NZ714669A (en) | 2013-06-21 | 2021-07-30 | Zenith Epigenetics Ltd | Novel bicyclic bromodomain inhibitors |
WO2015006193A1 (en) | 2013-07-08 | 2015-01-15 | Incyte Corporation | Tricyclic heterocycles as bet protein inhibitors |
AU2014298051B2 (en) | 2013-07-31 | 2018-11-15 | Zenith Epigenetics Ltd. | Novel quinazolinones as bromodomain inhibitors |
SI3640241T1 (sl) | 2013-10-18 | 2023-01-31 | Celgene Quanticel Research, Inc. | Inhibitorji bromodomene |
US9315501B2 (en) | 2013-11-26 | 2016-04-19 | Incyte Corporation | Bicyclic heterocycles as BET protein inhibitors |
WO2015081203A1 (en) | 2013-11-26 | 2015-06-04 | Incyte Corporation | Bicyclic heterocycles as bet protein inhibitors |
WO2015095492A1 (en) | 2013-12-19 | 2015-06-25 | Incyte Corporation | Tricyclic heterocycles as bet protein inhibitors |
PL3134403T3 (pl) | 2014-04-23 | 2020-07-13 | Incyte Corporation | 1H-pirolo[2,3-c]pirydyn-7(6H)-ony i pirazolo[3,4-c]pirydyn-7(6H)-ony jako inhibitory białek BET |
ES2855225T3 (es) | 2014-09-15 | 2021-09-23 | Incyte Corp | Heterociclos tricíclicos para su uso como inhibidores de proteínas BET |
WO2016087936A1 (en) | 2014-12-01 | 2016-06-09 | Zenith Epigenetics Corp. | Substituted pyridinones as bromodomain inhibitors |
US10179125B2 (en) | 2014-12-01 | 2019-01-15 | Zenith Epigenetics Ltd. | Substituted pyridines as bromodomain inhibitors |
CN107207474B (zh) | 2014-12-11 | 2021-05-07 | 恒翼生物医药科技(上海)有限公司 | 被取代的杂环作为溴结构域抑制剂 |
EP3233846A4 (en) | 2014-12-17 | 2018-07-18 | Zenith Epigenetics Ltd. | Inhibitors of bromodomains |
WO2017015027A1 (en) * | 2015-07-20 | 2017-01-26 | Mayo Foundation For Medical Education And Research | Methods and materials for treating cancer |
TW201722966A (zh) | 2015-10-29 | 2017-07-01 | 英塞特公司 | Bet蛋白質抑制劑之非晶固體形式 |
CN109071534B (zh) | 2016-04-15 | 2021-11-23 | 艾伯维公司 | 布罗莫结构域抑制剂 |
CA3220975A1 (en) | 2016-06-20 | 2017-12-28 | Incyte Corporation | Crystalline solid forms of a bet inhibitor |
WO2018106988A1 (en) * | 2016-12-09 | 2018-06-14 | Smet Pharmaceutical Inc. | Biologically active compositions containing two different classes of chemical compounds for treating solid tumors |
CN109384784B (zh) * | 2017-08-10 | 2021-01-12 | 浙江海正药业股份有限公司 | 磺酰胺类衍生物、其制备方法及其在医药上的用途 |
AU2019268333A1 (en) | 2018-05-15 | 2020-10-29 | Abbvie Inc. | Treating solid tumors with bromodomain inhibitors |
US11633399B2 (en) | 2018-12-25 | 2023-04-25 | Sol-Gel Technologies Ltd. | Treatment of skin disorders with compositions comprising an EGFR inhibitor |
WO2020232214A1 (en) * | 2019-05-14 | 2020-11-19 | Abbvie Inc. | Treating acute myeloid leukemia (aml) with mivebresib, a bromodomain inhibitor |
KR20220101099A (ko) * | 2019-11-13 | 2022-07-19 | 랩트 테라퓨틱스, 인크. | C-c 케모카인 수용체 유형 4 길항제의 결정 형태 및 이의 용도 |
CN110964691B (zh) * | 2019-12-31 | 2020-10-30 | 深圳新赛尔生物科技有限公司 | 子宫内膜干细胞的定向成脂分化培养 |
JP2023510610A (ja) * | 2020-01-19 | 2023-03-14 | チア タイ ティエンチン ファーマシューティカル グループ カンパニー リミテッド | ブロモドメインタンパク質阻害剤の結晶形、塩形態及びその製造方法 |
US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
US11746932B2 (en) | 2020-07-02 | 2023-09-05 | Hempvana, Llc | Expandable and retractable hose reinforced with hemp |
US11583602B2 (en) | 2021-06-23 | 2023-02-21 | Kimtron, Inc. | System and method for ultra-close proximity irradiation of rotating biomass |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6271380B1 (en) * | 1998-12-30 | 2001-08-07 | Dupont Pharmaceuticals Company | 1H-imidazo[4,5-d]pyridazin-7-ones, 3H-imidazo-[4,5-c]pyridin-4-ones and corresponding thiones as corticotropin releasing factor (CRF) receptor ligands |
WO2011143669A2 (en) * | 2010-05-14 | 2011-11-17 | Dana-Farber Cancer Institute, Inc | Compositions and methods for treating neoplasia, inflammatory disease and other disorders |
CN104136435A (zh) * | 2011-12-30 | 2014-11-05 | 艾伯维公司 | 溴结构域抑制剂 |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1514552A4 (en) * | 2002-06-06 | 2008-04-02 | Eisai R&D Man Co Ltd | NEW MILED IMIDAZOLE DERIVATIVE |
TWI339206B (en) * | 2003-09-04 | 2011-03-21 | Vertex Pharma | Compositions useful as inhibitors of protein kinases |
AU2010314395B2 (en) * | 2009-11-05 | 2015-04-09 | Glaxosmithkline Llc | Benzodiazepine bromodomain inhibitor |
GB0919434D0 (en) * | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Novel compounds |
US20130252331A1 (en) | 2010-05-14 | 2013-09-26 | James Elliott Bradner | Compositions and methods for modulating metabolism |
AT510136B1 (de) * | 2010-07-12 | 2016-11-15 | Primetals Technologies Austria GmbH | Verfahren zur herstellung von kohlepartikeln enthaltenden presslingen |
-
2014
- 2014-06-26 AR ARP140102431A patent/AR096758A1/es unknown
- 2014-06-27 ME MEP-2017-170A patent/ME02801B/me unknown
- 2014-06-27 EP EP14745267.6A patent/EP3013826B1/en active Active
- 2014-06-27 KR KR1020167002396A patent/KR102323829B1/ko active IP Right Grant
- 2014-06-27 MX MX2015017435A patent/MX360065B/es active IP Right Grant
- 2014-06-27 WO PCT/US2014/044513 patent/WO2014210425A1/en active Application Filing
- 2014-06-27 PT PT147452676T patent/PT3013826T/pt unknown
- 2014-06-27 CA CA2916221A patent/CA2916221C/en active Active
- 2014-06-27 NZ NZ631112A patent/NZ631112A/en unknown
- 2014-06-27 ES ES14745267.6T patent/ES2636939T3/es active Active
- 2014-06-27 AU AU2014302252A patent/AU2014302252B2/en active Active
- 2014-06-27 US US14/317,029 patent/US9321765B2/en active Active
- 2014-06-27 SG SG11201510692TA patent/SG11201510692TA/en unknown
- 2014-06-27 RU RU2016102591A patent/RU2675268C2/ru active
- 2014-06-27 UY UY0001035632A patent/UY35632A/es not_active Application Discontinuation
- 2014-06-27 RS RS20170763A patent/RS56318B1/sr unknown
- 2014-06-27 PL PL14745267T patent/PL3013826T3/pl unknown
- 2014-06-27 CN CN201480042976.3A patent/CN105473586B/zh active Active
- 2014-06-27 LT LTEP14745267.6T patent/LT3013826T/lt unknown
- 2014-06-27 JP JP2016524230A patent/JP6423425B2/ja active Active
- 2014-06-27 BR BR112015032736A patent/BR112015032736A2/pt not_active Application Discontinuation
- 2014-06-27 PE PE2015002664A patent/PE20160287A1/es not_active Application Discontinuation
- 2014-06-27 DK DK14745267.6T patent/DK3013826T3/en active
- 2014-06-27 SI SI201430310T patent/SI3013826T1/sl unknown
- 2014-06-27 TW TW103122417A patent/TWI639594B/zh active
-
2015
- 2015-12-16 PH PH12015502792A patent/PH12015502792A1/en unknown
- 2015-12-17 IL IL243202A patent/IL243202B/en active IP Right Grant
- 2015-12-22 DO DO2015000304A patent/DOP2015000304A/es unknown
- 2015-12-23 CL CL2015003722A patent/CL2015003722A1/es unknown
-
2016
- 2016-01-19 CR CR20160036A patent/CR20160036A/es unknown
- 2016-04-25 US US15/137,816 patent/US20160237085A1/en not_active Abandoned
- 2016-10-04 HK HK16111525.3A patent/HK1223354A1/zh unknown
- 2016-11-04 HK HK16112718.8A patent/HK1224298A1/zh unknown
- 2016-11-18 US US15/355,876 patent/US20170066765A1/en not_active Abandoned
-
2017
- 2017-07-03 CY CY20171100702T patent/CY1119066T1/el unknown
- 2017-07-27 HR HRP20171154TT patent/HRP20171154T1/hr unknown
-
2018
- 2018-03-20 AU AU2018201986A patent/AU2018201986A1/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6271380B1 (en) * | 1998-12-30 | 2001-08-07 | Dupont Pharmaceuticals Company | 1H-imidazo[4,5-d]pyridazin-7-ones, 3H-imidazo-[4,5-c]pyridin-4-ones and corresponding thiones as corticotropin releasing factor (CRF) receptor ligands |
WO2011143669A2 (en) * | 2010-05-14 | 2011-11-17 | Dana-Farber Cancer Institute, Inc | Compositions and methods for treating neoplasia, inflammatory disease and other disorders |
CN104136435A (zh) * | 2011-12-30 | 2014-11-05 | 艾伯维公司 | 溴结构域抑制剂 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN105473586B (zh) | 晶体溴结构域抑制剂 | |
CN105189504B (zh) | 稠合四环溴结构域抑制剂 | |
US10633379B2 (en) | Bromodomain inhibitors | |
CN105164113B (zh) | 吡咯酰胺抑制剂 | |
CN105026403B (zh) | 四环布罗莫结构域抑制剂 | |
US9776990B2 (en) | Isoindolone derivatives | |
US20150158873A1 (en) | Bromodomain inhibitors | |
CN106986872A (zh) | 溴结构域抑制剂 | |
US20210253551A1 (en) | Bromodomain Inhibitors |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1223354 Country of ref document: HK |
|
GR01 | Patent grant | ||
GR01 | Patent grant |