KR20170047397A - 치환된 피페리딘 화합물 - Google Patents
치환된 피페리딘 화합물 Download PDFInfo
- Publication number
- KR20170047397A KR20170047397A KR1020177009316A KR20177009316A KR20170047397A KR 20170047397 A KR20170047397 A KR 20170047397A KR 1020177009316 A KR1020177009316 A KR 1020177009316A KR 20177009316 A KR20177009316 A KR 20177009316A KR 20170047397 A KR20170047397 A KR 20170047397A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- cancer
- cell
- carcinoma
- tumor
- 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.)
- Withdrawn
Links
- 150000003053 piperidines Chemical class 0.000 title claims abstract description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 333
- 150000003839 salts Chemical class 0.000 claims abstract description 167
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 130
- 239000012453 solvate Substances 0.000 claims abstract description 81
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 60
- 201000011510 cancer Diseases 0.000 claims abstract description 49
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 41
- 102000004169 proteins and genes Human genes 0.000 claims abstract description 39
- 208000035475 disorder Diseases 0.000 claims abstract description 28
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 445
- -1 piperazin-4-yl Chemical group 0.000 claims description 200
- 239000000203 mixture Substances 0.000 claims description 127
- 238000000034 method Methods 0.000 claims description 120
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 91
- 125000003282 alkyl amino group Chemical group 0.000 claims description 82
- 125000001072 heteroaryl group Chemical group 0.000 claims description 82
- 239000001257 hydrogen Substances 0.000 claims description 78
- 229910052739 hydrogen Inorganic materials 0.000 claims description 78
- 125000005843 halogen group Chemical group 0.000 claims description 64
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 63
- 150000002431 hydrogen Chemical class 0.000 claims description 52
- 201000009030 Carcinoma Diseases 0.000 claims description 50
- 208000009956 adenocarcinoma Diseases 0.000 claims description 49
- 229910052799 carbon Inorganic materials 0.000 claims description 48
- 150000004677 hydrates Chemical class 0.000 claims description 46
- 125000003118 aryl group Chemical group 0.000 claims description 44
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 44
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 39
- 206010018338 Glioma Diseases 0.000 claims description 38
- 210000004027 cell Anatomy 0.000 claims description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 38
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 37
- 229910052757 nitrogen Inorganic materials 0.000 claims description 36
- 208000032612 Glial tumor Diseases 0.000 claims description 35
- 208000032839 leukemia Diseases 0.000 claims description 33
- 201000010099 disease Diseases 0.000 claims description 32
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 32
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 29
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 27
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 125000001188 haloalkyl group Chemical group 0.000 claims description 26
- 208000003950 B-cell lymphoma Diseases 0.000 claims description 24
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 24
- LKYNGTHMKCTTQC-UHFFFAOYSA-N 1,2-oxazole-3-carboxamide Chemical compound NC(=O)C=1C=CON=1 LKYNGTHMKCTTQC-UHFFFAOYSA-N 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 23
- 125000006652 (C3-C12) cycloalkyl group Chemical group 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 206010042971 T-cell lymphoma Diseases 0.000 claims description 21
- 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 claims description 21
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 19
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 201000002510 thyroid cancer Diseases 0.000 claims description 19
- 206010025323 Lymphomas Diseases 0.000 claims description 18
- 206010039491 Sarcoma Diseases 0.000 claims description 18
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 18
- 125000000304 alkynyl group Chemical group 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 239000003814 drug Substances 0.000 claims description 17
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 17
- 208000026310 Breast neoplasm Diseases 0.000 claims description 16
- 201000000274 Carcinosarcoma Diseases 0.000 claims description 16
- 208000005718 Stomach Neoplasms Diseases 0.000 claims description 16
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 206010017758 gastric cancer Diseases 0.000 claims description 16
- 201000001441 melanoma Diseases 0.000 claims description 16
- 201000011549 stomach cancer Diseases 0.000 claims description 16
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 15
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 14
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 14
- 208000035269 cancer or benign tumor Diseases 0.000 claims description 14
- 208000005017 glioblastoma Diseases 0.000 claims description 14
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
- 241000894007 species Species 0.000 claims description 14
- NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 14
- 208000024893 Acute lymphoblastic leukemia Diseases 0.000 claims description 13
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims description 13
- 206010029260 Neuroblastoma Diseases 0.000 claims description 13
- 208000006664 Precursor Cell Lymphoblastic Leukemia-Lymphoma Diseases 0.000 claims description 13
- 125000005518 carboxamido group Chemical group 0.000 claims description 13
- 206010000830 Acute leukaemia Diseases 0.000 claims description 12
- 201000003076 Angiosarcoma Diseases 0.000 claims description 12
- 208000001258 Hemangiosarcoma Diseases 0.000 claims description 12
- 206010006187 Breast cancer Diseases 0.000 claims description 11
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 11
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 11
- 208000009091 myxoma Diseases 0.000 claims description 11
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 10
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 10
- 201000000053 blastoma Diseases 0.000 claims description 10
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 10
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 10
- 201000008184 embryoma Diseases 0.000 claims description 10
- 201000007270 liver cancer Diseases 0.000 claims description 10
- 208000014018 liver neoplasm Diseases 0.000 claims description 10
- 230000001404 mediated effect Effects 0.000 claims description 10
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 9
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 9
- 206010033128 Ovarian cancer Diseases 0.000 claims description 9
- 206010038389 Renal cancer Diseases 0.000 claims description 9
- 208000033781 Thyroid carcinoma Diseases 0.000 claims description 9
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 9
- 210000000481 breast Anatomy 0.000 claims description 9
- 201000010881 cervical cancer Diseases 0.000 claims description 9
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
- 208000013077 thyroid gland carcinoma Diseases 0.000 claims description 9
- 210000004881 tumor cell Anatomy 0.000 claims description 9
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 8
- 206010005003 Bladder cancer Diseases 0.000 claims description 8
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 8
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 8
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 8
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 8
- 206010047741 Vulval cancer Diseases 0.000 claims description 8
- 230000001154 acute effect Effects 0.000 claims description 8
- 125000001153 fluoro group Chemical group F* 0.000 claims description 8
- 125000003709 fluoroalkyl group Chemical group 0.000 claims description 8
- 201000010982 kidney cancer Diseases 0.000 claims description 8
- 210000003491 skin Anatomy 0.000 claims description 8
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 8
- 229910052717 sulfur Inorganic materials 0.000 claims description 8
- 208000011691 Burkitt lymphomas Diseases 0.000 claims description 7
- 208000006332 Choriocarcinoma Diseases 0.000 claims description 7
- 201000003741 Gastrointestinal carcinoma Diseases 0.000 claims description 7
- 201000004404 Neurofibroma Diseases 0.000 claims description 7
- 208000021712 Soft tissue sarcoma Diseases 0.000 claims description 7
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 7
- 208000000260 Warts Diseases 0.000 claims description 7
- 206010016629 fibroma Diseases 0.000 claims description 7
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 7
- 206010024627 liposarcoma Diseases 0.000 claims description 7
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 7
- 208000027500 optic nerve neoplasm Diseases 0.000 claims description 7
- 208000003154 papilloma Diseases 0.000 claims description 7
- 201000010153 skin papilloma Diseases 0.000 claims description 7
- 201000003120 testicular cancer Diseases 0.000 claims description 7
- 230000001982 uveitic effect Effects 0.000 claims description 7
- 208000002008 AIDS-Related Lymphoma Diseases 0.000 claims description 6
- 206010003571 Astrocytoma Diseases 0.000 claims description 6
- 206010004146 Basal cell carcinoma Diseases 0.000 claims description 6
- 206010004593 Bile duct cancer Diseases 0.000 claims description 6
- 206010005949 Bone cancer Diseases 0.000 claims description 6
- 208000018084 Bone neoplasm Diseases 0.000 claims description 6
- 208000007690 Brenner tumor Diseases 0.000 claims description 6
- 206010073258 Brenner tumour Diseases 0.000 claims description 6
- 206010070487 Brown tumour Diseases 0.000 claims description 6
- 208000009798 Craniopharyngioma Diseases 0.000 claims description 6
- 208000008334 Dermatofibrosarcoma Diseases 0.000 claims description 6
- 206010014714 Endocrine neoplasms Diseases 0.000 claims description 6
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 6
- 208000022072 Gallbladder Neoplasms Diseases 0.000 claims description 6
- 208000005234 Granulosa Cell Tumor Diseases 0.000 claims description 6
- 208000017604 Hodgkin disease Diseases 0.000 claims description 6
- 208000021519 Hodgkin lymphoma Diseases 0.000 claims description 6
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 6
- 208000006404 Large Granular Lymphocytic Leukemia Diseases 0.000 claims description 6
- 206010023825 Laryngeal cancer Diseases 0.000 claims description 6
- 206010024612 Lipoma Diseases 0.000 claims description 6
- 206010025312 Lymphoma AIDS related Diseases 0.000 claims description 6
- 208000003445 Mouth Neoplasms Diseases 0.000 claims description 6
- 208000034578 Multiple myelomas Diseases 0.000 claims description 6
- 206010029488 Nodular melanoma Diseases 0.000 claims description 6
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 6
- 208000007913 Pituitary Neoplasms Diseases 0.000 claims description 6
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 6
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 6
- 201000000582 Retinoblastoma Diseases 0.000 claims description 6
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 6
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims description 6
- 208000002495 Uterine Neoplasms Diseases 0.000 claims description 6
- 208000008383 Wilms tumor Diseases 0.000 claims description 6
- 210000000683 abdominal cavity Anatomy 0.000 claims description 6
- 208000020990 adrenal cortex carcinoma Diseases 0.000 claims description 6
- 208000007128 adrenocortical carcinoma Diseases 0.000 claims description 6
- 208000015230 aggressive NK-cell leukemia Diseases 0.000 claims description 6
- 201000008275 breast carcinoma Diseases 0.000 claims description 6
- 208000020719 chondrogenic neoplasm Diseases 0.000 claims description 6
- 208000030748 clear cell sarcoma of kidney Diseases 0.000 claims description 6
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 6
- 201000004101 esophageal cancer Diseases 0.000 claims description 6
- 201000010175 gallbladder cancer Diseases 0.000 claims description 6
- 210000002768 hair cell Anatomy 0.000 claims description 6
- 201000010536 head and neck cancer Diseases 0.000 claims description 6
- 201000002222 hemangioblastoma Diseases 0.000 claims description 6
- 125000005191 hydroxyalkylamino group Chemical group 0.000 claims description 6
- 206010073096 invasive lobular breast carcinoma Diseases 0.000 claims description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
- 201000007211 kidney clear cell sarcoma Diseases 0.000 claims description 6
- 206010023841 laryngeal neoplasm Diseases 0.000 claims description 6
- 231100000518 lethal Toxicity 0.000 claims description 6
- 230000001665 lethal effect Effects 0.000 claims description 6
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 claims description 6
- 201000001117 malignant triton tumor Diseases 0.000 claims description 6
- 208000000516 mast-cell leukemia Diseases 0.000 claims description 6
- 208000029586 mediastinal germ cell tumor Diseases 0.000 claims description 6
- 201000000032 nodular malignant melanoma Diseases 0.000 claims description 6
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 6
- 201000008968 osteosarcoma Diseases 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 201000006845 reticulosarcoma Diseases 0.000 claims description 6
- 208000029922 reticulum cell sarcoma Diseases 0.000 claims description 6
- 201000000849 skin cancer Diseases 0.000 claims description 6
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 6
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 6
- 206010046766 uterine cancer Diseases 0.000 claims description 6
- 230000002792 vascular Effects 0.000 claims description 6
- 206010005969 Bone giant cell tumour Diseases 0.000 claims description 5
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 5
- 208000025205 Mantle-Cell Lymphoma Diseases 0.000 claims description 5
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 claims description 5
- 201000005746 Pituitary adenoma Diseases 0.000 claims description 5
- 206010061538 Pituitary tumour benign Diseases 0.000 claims description 5
- 208000026149 Primary peritoneal carcinoma Diseases 0.000 claims description 5
- 102000005157 Somatostatin Human genes 0.000 claims description 5
- 108010056088 Somatostatin Proteins 0.000 claims description 5
- 206010057644 Testis cancer Diseases 0.000 claims description 5
- 208000004354 Vulvar Neoplasms Diseases 0.000 claims description 5
- 201000011143 bone giant cell tumor Diseases 0.000 claims description 5
- 208000018554 digestive system carcinoma Diseases 0.000 claims description 5
- 201000005202 lung cancer Diseases 0.000 claims description 5
- 208000020816 lung neoplasm Diseases 0.000 claims description 5
- 208000021310 pituitary gland adenoma Diseases 0.000 claims description 5
- 230000001185 psoriatic effect Effects 0.000 claims description 5
- NHXLMOGPVYXJNR-ATOGVRKGSA-N somatostatin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CSSC[C@@H](C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@@H](CCCCN)C(=O)N[C@H](C(=O)N1)[C@@H](C)O)NC(=O)CNC(=O)[C@H](C)N)C(O)=O)=O)[C@H](O)C)C1=CC=CC=C1 NHXLMOGPVYXJNR-ATOGVRKGSA-N 0.000 claims description 5
- 229960000553 somatostatin Drugs 0.000 claims description 5
- 206010062261 spinal cord neoplasm Diseases 0.000 claims description 5
- 125000004434 sulfur atom Chemical group 0.000 claims description 5
- 230000001573 trophoblastic effect Effects 0.000 claims description 5
- 206010046885 vaginal cancer Diseases 0.000 claims description 5
- 208000013139 vaginal neoplasm Diseases 0.000 claims description 5
- 201000005102 vulva cancer Diseases 0.000 claims description 5
- 208000021309 Germ cell tumor Diseases 0.000 claims description 4
- 208000033559 Waldenström macroglobulinemia Diseases 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 201000000564 macroglobulinemia Diseases 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 230000001605 fetal effect Effects 0.000 claims description 3
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 230000002611 ovarian Effects 0.000 claims description 3
- 206010007953 Central nervous system lymphoma Diseases 0.000 claims description 2
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 claims description 2
- 201000010915 Glioblastoma multiforme Diseases 0.000 claims description 2
- 201000004462 Leydig Cell Tumor Diseases 0.000 claims description 2
- 206010025219 Lymphangioma Diseases 0.000 claims description 2
- 206010052178 Lymphocytic lymphoma Diseases 0.000 claims description 2
- 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 claims description 2
- 206010064281 Malignant atrophic papulosis Diseases 0.000 claims description 2
- 208000033014 Plasma cell tumor Diseases 0.000 claims description 2
- 208000007452 Plasmacytoma Diseases 0.000 claims description 2
- 206010065857 Primary Effusion Lymphoma Diseases 0.000 claims description 2
- 208000034541 Rare lymphatic malformation Diseases 0.000 claims description 2
- 208000025316 Richter syndrome Diseases 0.000 claims description 2
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 claims description 2
- 230000002490 cerebral effect Effects 0.000 claims description 2
- 210000002808 connective tissue Anatomy 0.000 claims description 2
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical group [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 claims description 2
- 201000011523 endocrine gland cancer Diseases 0.000 claims description 2
- 208000012804 lymphangiosarcoma Diseases 0.000 claims description 2
- 208000011645 metastatic carcinoma Diseases 0.000 claims description 2
- 208000025189 neoplasm of testis Diseases 0.000 claims description 2
- 208000027831 neuroepithelial neoplasm Diseases 0.000 claims description 2
- 230000002093 peripheral effect Effects 0.000 claims description 2
- 208000010626 plasma cell neoplasm Diseases 0.000 claims description 2
- 208000016800 primary central nervous system lymphoma Diseases 0.000 claims description 2
- 206010033701 Papillary thyroid cancer Diseases 0.000 claims 15
- 208000030045 thyroid gland papillary carcinoma Diseases 0.000 claims 15
- 210000002919 epithelial cell Anatomy 0.000 claims 9
- 201000001514 prostate carcinoma Diseases 0.000 claims 9
- 230000002485 urinary effect Effects 0.000 claims 9
- 201000010260 leiomyoma Diseases 0.000 claims 8
- 230000002710 gonadal effect Effects 0.000 claims 7
- 206010027406 Mesothelioma Diseases 0.000 claims 6
- 230000003211 malignant effect Effects 0.000 claims 6
- 208000000649 small cell carcinoma Diseases 0.000 claims 6
- 208000036762 Acute promyelocytic leukaemia Diseases 0.000 claims 5
- 208000003200 Adenoma Diseases 0.000 claims 5
- 206010001233 Adenoma benign Diseases 0.000 claims 5
- 208000016683 Adult T-cell leukemia/lymphoma Diseases 0.000 claims 5
- 208000036170 B-Cell Marginal Zone Lymphoma Diseases 0.000 claims 5
- 206010008583 Chloroma Diseases 0.000 claims 5
- 208000010126 Chondromatosis Diseases 0.000 claims 5
- 206010058314 Dysplasia Diseases 0.000 claims 5
- 206010061850 Extranodal marginal zone B-cell lymphoma (MALT type) Diseases 0.000 claims 5
- 208000007569 Giant Cell Tumors Diseases 0.000 claims 5
- 208000028018 Lymphocytic leukaemia Diseases 0.000 claims 5
- 201000003791 MALT lymphoma Diseases 0.000 claims 5
- 208000002231 Muscle Neoplasms Diseases 0.000 claims 5
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims 5
- 208000033826 Promyelocytic Acute Leukemia Diseases 0.000 claims 5
- 206010043276 Teratoma Diseases 0.000 claims 5
- 201000006966 adult T-cell leukemia Diseases 0.000 claims 5
- 230000003325 follicular Effects 0.000 claims 5
- 208000003747 lymphoid leukemia Diseases 0.000 claims 5
- 206010027191 meningioma Diseases 0.000 claims 5
- 230000001394 metastastic effect Effects 0.000 claims 5
- 208000022669 mucinous neoplasm Diseases 0.000 claims 5
- 201000009368 muscle benign neoplasm Diseases 0.000 claims 5
- 201000005987 myeloid sarcoma Diseases 0.000 claims 5
- 208000017708 myomatous neoplasm Diseases 0.000 claims 5
- 201000008026 nephroblastoma Diseases 0.000 claims 5
- 208000015768 polyposis Diseases 0.000 claims 5
- 206010044412 transitional cell carcinoma Diseases 0.000 claims 5
- 208000002699 Digestive System Neoplasms Diseases 0.000 claims 4
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims 4
- 206010018341 Gliosis Diseases 0.000 claims 4
- 102000051325 Glucagon Human genes 0.000 claims 4
- 108060003199 Glucagon Proteins 0.000 claims 4
- 206010061336 Pelvic neoplasm Diseases 0.000 claims 4
- 206010043515 Throat cancer Diseases 0.000 claims 4
- 206010046798 Uterine leiomyoma Diseases 0.000 claims 4
- 230000001580 bacterial effect Effects 0.000 claims 4
- 230000007395 cerebral gliosis Effects 0.000 claims 4
- 208000027858 endometrioid tumor Diseases 0.000 claims 4
- 201000010972 female reproductive endometrioid cancer Diseases 0.000 claims 4
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=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](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)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(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims 4
- 229960004666 glucagon Drugs 0.000 claims 4
- 238000011065 in-situ storage Methods 0.000 claims 4
- 208000028774 intestinal disease Diseases 0.000 claims 4
- 201000002524 peritoneal carcinoma Diseases 0.000 claims 4
- 208000029824 high grade glioma Diseases 0.000 claims 3
- 201000011614 malignant glioma Diseases 0.000 claims 3
- 201000004916 vulva carcinoma Diseases 0.000 claims 3
- 208000013013 vulvar carcinoma Diseases 0.000 claims 3
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims 1
- SWKPZDCGFSPUIV-UHFFFAOYSA-N C12CC(CC(CC1)N2)NC(=O)C1=NOC(=C1)C1CC1 Chemical compound C12CC(CC(CC1)N2)NC(=O)C1=NOC(=C1)C1CC1 SWKPZDCGFSPUIV-UHFFFAOYSA-N 0.000 claims 1
- 125000005974 C6-C14 arylcarbonyl group Chemical group 0.000 claims 1
- 201000008808 Fibrosarcoma Diseases 0.000 claims 1
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 claims 1
- 208000012018 Yolk sac tumor Diseases 0.000 claims 1
- 210000001015 abdomen Anatomy 0.000 claims 1
- 208000025188 carcinoma of pharynx Diseases 0.000 claims 1
- 208000001991 endodermal sinus tumor Diseases 0.000 claims 1
- 201000003444 follicular lymphoma Diseases 0.000 claims 1
- 230000000574 ganglionic effect Effects 0.000 claims 1
- 201000003115 germ cell cancer Diseases 0.000 claims 1
- 210000003292 kidney cell Anatomy 0.000 claims 1
- MPNJWRNRFVACPL-UHFFFAOYSA-N n-(1-benzoylpiperidin-4-yl)-5-cyclopropyl-1,2-oxazole-3-carboxamide Chemical compound C1=C(C2CC2)ON=C1C(=O)NC(CC1)CCN1C(=O)C1=CC=CC=C1 MPNJWRNRFVACPL-UHFFFAOYSA-N 0.000 claims 1
- MUDAEPOBGDXNPN-UHFFFAOYSA-N n-(1-benzylpiperidin-4-yl)-5-cyclopropyl-1,2-oxazole-3-carboxamide Chemical compound C1=C(C2CC2)ON=C1C(=O)NC(CC1)CCN1CC1=CC=CC=C1 MUDAEPOBGDXNPN-UHFFFAOYSA-N 0.000 claims 1
- YAYBWGALIACAPN-UHFFFAOYSA-N n-[1-(2-amino-2-oxoethyl)piperidin-4-yl]-5-cyclopropyl-1,2-oxazole-3-carboxamide Chemical compound C1CN(CC(=O)N)CCC1NC(=O)C1=NOC(C2CC2)=C1 YAYBWGALIACAPN-UHFFFAOYSA-N 0.000 claims 1
- XILPKXKYJPWLPW-UHFFFAOYSA-N n-[1-(4-acetamidophenyl)sulfonylpiperidin-4-yl]-5-cyclopropyl-1,2-oxazole-3-carboxamide Chemical compound C1=CC(NC(=O)C)=CC=C1S(=O)(=O)N1CCC(NC(=O)C2=NOC(=C2)C2CC2)CC1 XILPKXKYJPWLPW-UHFFFAOYSA-N 0.000 claims 1
- 201000002628 peritoneum cancer Diseases 0.000 claims 1
- 210000004560 pineal gland Anatomy 0.000 claims 1
- 230000001817 pituitary effect Effects 0.000 claims 1
- 208000010916 pituitary tumor Diseases 0.000 claims 1
- 230000035935 pregnancy Effects 0.000 claims 1
- 208000023747 urothelial carcinoma Diseases 0.000 claims 1
- 102100032804 Histone-lysine N-methyltransferase SMYD3 Human genes 0.000 abstract description 43
- 101000708574 Homo sapiens Histone-lysine N-methyltransferase SMYD3 Proteins 0.000 abstract description 43
- 102100032806 N-lysine methyltransferase SMYD2 Human genes 0.000 abstract description 39
- 101000708645 Homo sapiens N-lysine methyltransferase SMYD2 Proteins 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 208
- 239000000243 solution Substances 0.000 description 188
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 183
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 108
- 238000003786 synthesis reaction Methods 0.000 description 104
- 230000015572 biosynthetic process Effects 0.000 description 103
- 239000007787 solid Substances 0.000 description 94
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 87
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 77
- 235000019439 ethyl acetate Nutrition 0.000 description 63
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 52
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 50
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 43
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 40
- 239000012071 phase Substances 0.000 description 39
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
- 101710131374 N-lysine methyltransferase SMYD2 Proteins 0.000 description 38
- 239000000741 silica gel Substances 0.000 description 38
- 229910002027 silica gel Inorganic materials 0.000 description 38
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- 125000001424 substituent group Chemical group 0.000 description 36
- 238000005160 1H NMR spectroscopy Methods 0.000 description 35
- 235000018102 proteins Nutrition 0.000 description 33
- 125000003107 substituted aryl group Chemical group 0.000 description 31
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 27
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 27
- 239000012044 organic layer Substances 0.000 description 27
- 239000003208 petroleum Substances 0.000 description 26
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 24
- 239000011541 reaction mixture Substances 0.000 description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 239000003921 oil Substances 0.000 description 21
- 235000019198 oils Nutrition 0.000 description 21
- 230000005764 inhibitory process Effects 0.000 description 20
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 19
- 239000012298 atmosphere Substances 0.000 description 19
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
- DKYIWKDELCEHRP-UHFFFAOYSA-N 5-cyclopropyl-1,2-oxazole-3-carboxamide Chemical compound O1N=C(C(=O)N)C=C1C1CC1 DKYIWKDELCEHRP-UHFFFAOYSA-N 0.000 description 17
- 125000004414 alkyl thio group Chemical group 0.000 description 17
- 239000012267 brine Substances 0.000 description 17
- 150000001721 carbon Chemical group 0.000 description 17
- 238000002360 preparation method Methods 0.000 description 17
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 17
- 238000002953 preparative HPLC Methods 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 239000012043 crude product Substances 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 14
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 14
- 125000004438 haloalkoxy group Chemical group 0.000 description 14
- 239000011734 sodium Substances 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 125000001691 aryl alkyl amino group Chemical group 0.000 description 13
- 239000000460 chlorine Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 13
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
- 241000124008 Mammalia Species 0.000 description 12
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 12
- 125000004104 aryloxy group Chemical group 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 125000005129 aryl carbonyl group Chemical group 0.000 description 11
- 125000000392 cycloalkenyl group Chemical group 0.000 description 11
- XYYBFARHMVZMDR-UHFFFAOYSA-N 1,2-oxazole-3-carboxamide hydrochloride Chemical compound Cl.O1N=C(C=C1)C(=O)N XYYBFARHMVZMDR-UHFFFAOYSA-N 0.000 description 10
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 10
- 239000007821 HATU Substances 0.000 description 10
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 10
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 10
- 125000004404 heteroalkyl group Chemical group 0.000 description 10
- 239000003112 inhibitor Substances 0.000 description 10
- 230000002401 inhibitory effect Effects 0.000 description 10
- 125000005358 mercaptoalkyl group Chemical group 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 239000012074 organic phase Substances 0.000 description 10
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 10
- 125000000547 substituted alkyl group Chemical group 0.000 description 10
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 9
- 125000000623 heterocyclic group Chemical group 0.000 description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
- 125000003277 amino group Chemical group 0.000 description 8
- 125000004429 atom Chemical group 0.000 description 8
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 125000004181 carboxyalkyl group Chemical group 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 125000004430 oxygen atom Chemical group O* 0.000 description 7
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 7
- 239000003643 water by type Substances 0.000 description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- OGIPSHDJYIEDKG-IENPIDJESA-N NC1C[C@@H](N(CC1)C(=O)OC(C)(C)C)C Chemical compound NC1C[C@@H](N(CC1)C(=O)OC(C)(C)C)C OGIPSHDJYIEDKG-IENPIDJESA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 230000008878 coupling Effects 0.000 description 6
- 238000010168 coupling process Methods 0.000 description 6
- 238000005859 coupling reaction Methods 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 238000011161 development Methods 0.000 description 6
- 230000018109 developmental process Effects 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- 206010061534 Oesophageal squamous cell carcinoma Diseases 0.000 description 5
- 206010060862 Prostate cancer Diseases 0.000 description 5
- 208000036765 Squamous cell carcinoma of the esophagus Diseases 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 5
- 208000007276 esophageal squamous cell carcinoma Diseases 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000001294 propane Substances 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 125000001544 thienyl group Chemical group 0.000 description 5
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
- OWMVXHFZCCPOTD-UHFFFAOYSA-N 5-cyclopropyl-1,2-oxazole-3-carboxylic acid Chemical compound O1N=C(C(=O)O)C=C1C1CC1 OWMVXHFZCCPOTD-UHFFFAOYSA-N 0.000 description 4
- GRBRENNBXLOEOX-GNAZCLTHSA-N Cl.C[C@H]1C[C@H](CCN1)NC(=O)c1cc(on1)C1CC1 Chemical compound Cl.C[C@H]1C[C@H](CCN1)NC(=O)c1cc(on1)C1CC1 GRBRENNBXLOEOX-GNAZCLTHSA-N 0.000 description 4
- 206010009944 Colon cancer Diseases 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
- 108010033040 Histones Proteins 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 150000007942 carboxylates Chemical class 0.000 description 4
- 238000004296 chiral HPLC Methods 0.000 description 4
- 239000008298 dragée Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000008273 gelatin Substances 0.000 description 4
- 229920000159 gelatin Polymers 0.000 description 4
- 235000019322 gelatine Nutrition 0.000 description 4
- 235000011852 gelatine desserts Nutrition 0.000 description 4
- 230000014509 gene expression Effects 0.000 description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 210000004185 liver Anatomy 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- SNMVRZFUUCLYTO-UHFFFAOYSA-N n-propyl chloride Chemical compound CCCCl SNMVRZFUUCLYTO-UHFFFAOYSA-N 0.000 description 4
- 230000003287 optical effect Effects 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 230000002062 proliferating effect Effects 0.000 description 4
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 4
- 125000004076 pyridyl group Chemical group 0.000 description 4
- 230000002829 reductive effect Effects 0.000 description 4
- NZJKEPNCNBWESN-UHFFFAOYSA-N tert-butyl 3-amino-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1C(N)CC2CCC1N2C(=O)OC(C)(C)C NZJKEPNCNBWESN-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- BGZUFEVTVCKYMP-UHFFFAOYSA-N 1,4-dioxa-8-azaspiro[4.5]decane-8-sulfonyl chloride Chemical compound C1CN(S(=O)(=O)Cl)CCC21OCCO2 BGZUFEVTVCKYMP-UHFFFAOYSA-N 0.000 description 3
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 3
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 3
- RXAQOLMDSYHIER-UHFFFAOYSA-N CC1NCC(C(C1)NC(OC(C)(C)C)=O)C Chemical compound CC1NCC(C(C1)NC(OC(C)(C)C)=O)C RXAQOLMDSYHIER-UHFFFAOYSA-N 0.000 description 3
- KFWLJFWRWUMYKY-MOGJOVFKSA-N Cl.O=C(N[C@H]1CCN[C@@H](Cc2ccccc2)C1)c1cc(on1)C1CC1 Chemical compound Cl.O=C(N[C@H]1CCN[C@@H](Cc2ccccc2)C1)c1cc(on1)C1CC1 KFWLJFWRWUMYKY-MOGJOVFKSA-N 0.000 description 3
- 229940126062 Compound A Drugs 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 241000725643 Respiratory syncytial virus Species 0.000 description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- JOQRDARBUIIJCV-UHFFFAOYSA-N benzyl 4-(chlorosulfonylmethyl)piperidine-1-carboxylate Chemical compound C1CC(CS(=O)(=O)Cl)CCN1C(=O)OCC1=CC=CC=C1 JOQRDARBUIIJCV-UHFFFAOYSA-N 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 3
- 150000003857 carboxamides Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 125000004990 dihydroxyalkyl group Chemical group 0.000 description 3
- HRBVVSOFSLPAOY-JXMROGBWSA-N ethyl (e)-2-cyano-3-(4-hydroxyphenyl)prop-2-enoate Chemical compound CCOC(=O)C(\C#N)=C\C1=CC=C(O)C=C1 HRBVVSOFSLPAOY-JXMROGBWSA-N 0.000 description 3
- MHKXVJFDESXWFH-UHFFFAOYSA-N ethyl 4-cyclopropyl-2,4-dioxobutanoate Chemical compound CCOC(=O)C(=O)CC(=O)C1CC1 MHKXVJFDESXWFH-UHFFFAOYSA-N 0.000 description 3
- XMKHEATVFWAIMD-UHFFFAOYSA-N ethyl 5-cyclopropyl-1,2-oxazole-3-carboxylate Chemical compound O1N=C(C(=O)OCC)C=C1C1CC1 XMKHEATVFWAIMD-UHFFFAOYSA-N 0.000 description 3
- UBWKBDZVYQXLBF-UHFFFAOYSA-N ethyl 5-ethyl-1,2-oxazole-3-carboxylate Chemical compound CCOC(=O)C=1C=C(CC)ON=1 UBWKBDZVYQXLBF-UHFFFAOYSA-N 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000003197 gene knockdown Methods 0.000 description 3
- 125000005553 heteroaryloxy group Chemical group 0.000 description 3
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 3
- 125000001786 isothiazolyl group Chemical group 0.000 description 3
- 125000000842 isoxazolyl group Chemical group 0.000 description 3
- 230000000670 limiting effect Effects 0.000 description 3
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 201000002528 pancreatic cancer Diseases 0.000 description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 3
- 230000035755 proliferation Effects 0.000 description 3
- 125000005493 quinolyl group Chemical group 0.000 description 3
- 125000006413 ring segment Chemical group 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- HYIVCRFCFBKXBK-UHFFFAOYSA-N tert-butyl 4-amino-2-benzylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(N)CC1CC1=CC=CC=C1 HYIVCRFCFBKXBK-UHFFFAOYSA-N 0.000 description 3
- UMBWKSXEVUZEMI-UHFFFAOYSA-N tert-butyl 4-amino-3-methylpiperidine-1-carboxylate Chemical compound CC1CN(C(=O)OC(C)(C)C)CCC1N UMBWKSXEVUZEMI-UHFFFAOYSA-N 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 description 2
- KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 2
- 125000006002 1,1-difluoroethyl group Chemical group 0.000 description 2
- HOMQGAKTXAZZTC-UHFFFAOYSA-N 1,2-oxazole-3-carboxamide dihydrochloride Chemical compound Cl.Cl.O1N=C(C=C1)C(=O)N HOMQGAKTXAZZTC-UHFFFAOYSA-N 0.000 description 2
- DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 2
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 2
- DMUXSGAKEXSNGN-UHFFFAOYSA-N 2-ethyloctanoic acid Chemical compound CCCCCCC(CC)C(O)=O DMUXSGAKEXSNGN-UHFFFAOYSA-N 0.000 description 2
- OQHQOOLVQDEIGL-UHFFFAOYSA-N 2-methyl-2,7-diazaspiro[4.4]nonane Chemical compound C1N(C)CCC11CNCC1 OQHQOOLVQDEIGL-UHFFFAOYSA-N 0.000 description 2
- GPKDGVXBXQTHRY-UHFFFAOYSA-N 3-chloropropane-1-sulfonyl chloride Chemical compound ClCCCS(Cl)(=O)=O GPKDGVXBXQTHRY-UHFFFAOYSA-N 0.000 description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- DGGKXQQCVPAUEA-UHFFFAOYSA-N 8-azabicyclo[3.2.1]octane Chemical compound C1CCC2CCC1N2 DGGKXQQCVPAUEA-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- GRBRENNBXLOEOX-UHFFFAOYSA-N Cl.CC1CC(CCN1)NC(=O)c1cc(on1)C1CC1 Chemical compound Cl.CC1CC(CCN1)NC(=O)c1cc(on1)C1CC1 GRBRENNBXLOEOX-UHFFFAOYSA-N 0.000 description 2
- KFWLJFWRWUMYKY-RCPFAERMSA-N Cl.O=C(N[C@@H]1CCN[C@@H](Cc2ccccc2)C1)c1cc(on1)C1CC1 Chemical compound Cl.O=C(N[C@@H]1CCN[C@@H](Cc2ccccc2)C1)c1cc(on1)C1CC1 KFWLJFWRWUMYKY-RCPFAERMSA-N 0.000 description 2
- KFWLJFWRWUMYKY-QNBGGDODSA-N Cl.O=C(N[C@@H]1CCN[C@H](Cc2ccccc2)C1)c1cc(on1)C1CC1 Chemical compound Cl.O=C(N[C@@H]1CCN[C@H](Cc2ccccc2)C1)c1cc(on1)C1CC1 KFWLJFWRWUMYKY-QNBGGDODSA-N 0.000 description 2
- KFWLJFWRWUMYKY-IDVLALEDSA-N Cl.O=C(N[C@H]1CCN[C@H](Cc2ccccc2)C1)c1cc(on1)C1CC1 Chemical compound Cl.O=C(N[C@H]1CCN[C@H](Cc2ccccc2)C1)c1cc(on1)C1CC1 KFWLJFWRWUMYKY-IDVLALEDSA-N 0.000 description 2
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 102100032801 Histone-lysine N-methyltransferase SMYD1 Human genes 0.000 description 2
- 102100025663 Histone-lysine N-trimethyltransferase SMYD5 Human genes 0.000 description 2
- 102000006947 Histones Human genes 0.000 description 2
- 101000708638 Homo sapiens Histone-lysine N-methyltransferase SMYD1 Proteins 0.000 description 2
- 101000835819 Homo sapiens Histone-lysine N-trimethyltransferase SMYD5 Proteins 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 108060004795 Methyltransferase Proteins 0.000 description 2
- 102000016397 Methyltransferase Human genes 0.000 description 2
- 150000001204 N-oxides Chemical class 0.000 description 2
- OGIPSHDJYIEDKG-VEDVMXKPSA-N NC1C[C@H](N(CC1)C(=O)OC(C)(C)C)C Chemical compound NC1C[C@H](N(CC1)C(=O)OC(C)(C)C)C OGIPSHDJYIEDKG-VEDVMXKPSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 108091030071 RNAI Proteins 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001447 alkali salts Chemical class 0.000 description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 2
- 125000005122 aminoalkylamino group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 201000001531 bladder carcinoma Diseases 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 230000024245 cell differentiation Effects 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- GHVNFZFCNZKVNT-UHFFFAOYSA-N decanoic acid Chemical compound CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 2
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 208000037765 diseases and disorders Diseases 0.000 description 2
- 239000010685 fatty oil Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 108700039708 galantide Proteins 0.000 description 2
- 230000009368 gene silencing by RNA Effects 0.000 description 2
- 230000002068 genetic effect Effects 0.000 description 2
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 2
- 210000003128 head Anatomy 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 201000005787 hematologic cancer Diseases 0.000 description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- 210000002602 induced regulatory T cell Anatomy 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 201000002313 intestinal cancer Diseases 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- QXNCRJVBIMSYRT-UHFFFAOYSA-N isoindole-1,3-dione;hydrochloride Chemical compound Cl.C1=CC=C2C(=O)NC(=O)C2=C1 QXNCRJVBIMSYRT-UHFFFAOYSA-N 0.000 description 2
- 210000003734 kidney Anatomy 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- VOBKQNGOMCDLPT-UHFFFAOYSA-N n-propyl-1,2-oxazole-3-carboxamide Chemical compound CCCNC(=O)C=1C=CON=1 VOBKQNGOMCDLPT-UHFFFAOYSA-N 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- 239000003791 organic solvent mixture Substances 0.000 description 2
- 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- KBOGICFUPOMDKS-UHFFFAOYSA-N piperidin-4-ylcarbamic acid Chemical compound OC(=O)NC1CCNCC1 KBOGICFUPOMDKS-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 230000019639 protein methylation Effects 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- 239000003381 stabilizer Substances 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 125000004426 substituted alkynyl group Chemical group 0.000 description 2
- 239000000829 suppository Substances 0.000 description 2
- 239000002511 suppository base Substances 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- GZOHWMOHDHOZOR-QMMMGPOBSA-N tert-butyl (2s)-2-methyl-3-oxopiperidine-1-carboxylate Chemical compound C[C@@H]1N(C(=O)OC(C)(C)C)CCCC1=O GZOHWMOHDHOZOR-QMMMGPOBSA-N 0.000 description 2
- DFFSDMXABHKMRG-UHFFFAOYSA-N tert-butyl N-(2,5-dimethylpyridin-4-yl)carbamate Chemical compound CC1=NC=C(C(=C1)NC(OC(C)(C)C)=O)C DFFSDMXABHKMRG-UHFFFAOYSA-N 0.000 description 2
- 125000003396 thiol group Chemical class [H]S* 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 150000003626 triacylglycerols Chemical class 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 2
- 208000010570 urinary bladder carcinoma Diseases 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 description 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
- 125000005869 (methoxyethoxy)methanyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- UXYRXGFUANQKTA-UHFFFAOYSA-N 1,2-oxazole-3-carboxylic acid Chemical compound OC(=O)C=1C=CON=1 UXYRXGFUANQKTA-UHFFFAOYSA-N 0.000 description 1
- CQHYICHMGNSGQH-UHFFFAOYSA-N 1,3-oxazole-2-carboxylic acid Chemical compound OC(=O)C1=NC=CO1 CQHYICHMGNSGQH-UHFFFAOYSA-N 0.000 description 1
- KPKNTUUIEVXMOH-UHFFFAOYSA-N 1,4-dioxa-8-azaspiro[4.5]decane Chemical compound O1CCOC11CCNCC1 KPKNTUUIEVXMOH-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 1
- HVCFCNAITDHQFX-UHFFFAOYSA-N 1-cyclopropylethanone Chemical compound CC(=O)C1CC1 HVCFCNAITDHQFX-UHFFFAOYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- HMBHAQMOBKLWRX-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-3-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)COC2=C1 HMBHAQMOBKLWRX-UHFFFAOYSA-N 0.000 description 1
- KQCWCIYVDIVYAB-UHFFFAOYSA-N 2,5-dimethylpyridin-4-amine Chemical compound CC1=CC(N)=C(C)C=N1 KQCWCIYVDIVYAB-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- HZLCGUXUOFWCCN-UHFFFAOYSA-N 2-hydroxynonadecane-1,2,3-tricarboxylic acid Chemical compound CCCCCCCCCCCCCCCCC(C(O)=O)C(O)(C(O)=O)CC(O)=O HZLCGUXUOFWCCN-UHFFFAOYSA-N 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- FYZUENZXIZCLAZ-UHFFFAOYSA-N 2-methylhept-2-enoic acid Chemical compound CCCCC=C(C)C(O)=O FYZUENZXIZCLAZ-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical class CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- KDFDOINBXBEOLZ-UHFFFAOYSA-N 2-phenylpropan-2-amine Chemical compound CC(C)(N)C1=CC=CC=C1 KDFDOINBXBEOLZ-UHFFFAOYSA-N 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 1
- SZMPXSZRPMZQPS-UHFFFAOYSA-N 2h-1,3-oxazole-3-carboxamide Chemical compound NC(=O)N1COC=C1 SZMPXSZRPMZQPS-UHFFFAOYSA-N 0.000 description 1
- RDXUBBUYWZAROQ-UHFFFAOYSA-N 3-(1,3-dioxoisoindol-2-yl)propane-1-sulfonyl chloride Chemical compound C1=CC=C2C(=O)N(CCCS(=O)(=O)Cl)C(=O)C2=C1 RDXUBBUYWZAROQ-UHFFFAOYSA-N 0.000 description 1
- PNYRDVBFYVDJJI-UHFFFAOYSA-N 3-cyano-5-[2-[4-[2-(3-methylindol-1-yl)ethyl]piperazin-1-yl]phenyl]-n-(3-pyrrolidin-1-ylpropyl)benzamide Chemical compound C12=CC=CC=C2C(C)=CN1CCN(CC1)CCN1C1=CC=CC=C1C(C=1)=CC(C#N)=CC=1C(=O)NCCCN1CCCC1 PNYRDVBFYVDJJI-UHFFFAOYSA-N 0.000 description 1
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 1
- VJESMUKSQGXQDB-UHFFFAOYSA-N 3-tert-butyl-2,5-dimethylpyridine Chemical compound CC1=CN=C(C)C(C(C)(C)C)=C1 VJESMUKSQGXQDB-UHFFFAOYSA-N 0.000 description 1
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- KMMHZIBWCXYAAH-UHFFFAOYSA-N 4-bromobenzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=C(Br)C=C1 KMMHZIBWCXYAAH-UHFFFAOYSA-N 0.000 description 1
- WSCSCUFHNZNZOU-UHFFFAOYSA-N 4-cyclopropyl-1,2-oxazole-3-carboxamide Chemical compound NC(=O)C1=NOC=C1C1CC1 WSCSCUFHNZNZOU-UHFFFAOYSA-N 0.000 description 1
- MHNWFTRAAHXXBP-UHFFFAOYSA-N 4-cyclopropyl-1,2-oxazole-3-carboxamide hydrochloride Chemical compound Cl.C1(CC1)C=1C(=NOC1)C(=O)N MHNWFTRAAHXXBP-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- SXIFAEWFOJETOA-UHFFFAOYSA-N 4-hydroxy-butyl Chemical group [CH2]CCCO SXIFAEWFOJETOA-UHFFFAOYSA-N 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- GDYYZWFHNRVHCC-UHFFFAOYSA-N 4-methylpiperazine-1-sulfonyl chloride Chemical compound CN1CCN(S(Cl)(=O)=O)CC1 GDYYZWFHNRVHCC-UHFFFAOYSA-N 0.000 description 1
- IJOOLKIYFVIJNU-UHFFFAOYSA-N 4-oxocyclohexane-1-sulfonyl chloride Chemical compound ClS(=O)(=O)C1CCC(=O)CC1 IJOOLKIYFVIJNU-UHFFFAOYSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- TULZZUANLRGWPM-UHFFFAOYSA-N 5-ethyl-1,2-oxazole-3-carboxylic acid Chemical compound CCC1=CC(C(O)=O)=NO1 TULZZUANLRGWPM-UHFFFAOYSA-N 0.000 description 1
- DENNCEQUAZKJGC-UHFFFAOYSA-N 6-azabicyclo[3.1.1]heptane Chemical compound C1CCC2CC1N2 DENNCEQUAZKJGC-UHFFFAOYSA-N 0.000 description 1
- ZIJAZUBWHAZHPL-UHFFFAOYSA-N 6-chloropyridine-3-carboxamide Chemical compound NC(=O)C1=CC=C(Cl)N=C1 ZIJAZUBWHAZHPL-UHFFFAOYSA-N 0.000 description 1
- QXZKKHONVQGXAK-UHFFFAOYSA-N 6-chloropyridine-3-sulfonyl chloride Chemical compound ClC1=CC=C(S(Cl)(=O)=O)C=N1 QXZKKHONVQGXAK-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 description 1
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 description 1
- 208000001794 Adipose Tissue Neoplasms Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 229910018072 Al 2 O 3 Inorganic materials 0.000 description 1
- 241001439211 Almeida Species 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000037540 Alveolar soft tissue sarcoma Diseases 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 241000937413 Axia Species 0.000 description 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- JXJDWUZYXNMVOI-HOTGVXAUSA-N C(C1=CC=CC=C1)[C@@H]1NCC[C@@H](C1)NC(=O)C1=NOC(=C1)C1CC1 Chemical compound C(C1=CC=CC=C1)[C@@H]1NCC[C@@H](C1)NC(=O)C1=NOC(=C1)C1CC1 JXJDWUZYXNMVOI-HOTGVXAUSA-N 0.000 description 1
- OVBMCCHLPUATCC-UHFFFAOYSA-N C1(CC1)C1=CC(=NO1)C(=O)NC1CC(N(CC1)S(=O)(=O)CC1CCNCC1)C Chemical compound C1(CC1)C1=CC(=NO1)C(=O)NC1CC(N(CC1)S(=O)(=O)CC1CCNCC1)C OVBMCCHLPUATCC-UHFFFAOYSA-N 0.000 description 1
- WSLSIFGLYKRFKV-WCBMZHEXSA-N C1(CC1)C1=CC(=NO1)C(=O)N[C@H]1C[C@@H](NCC1)C Chemical compound C1(CC1)C1=CC(=NO1)C(=O)N[C@H]1C[C@@H](NCC1)C WSLSIFGLYKRFKV-WCBMZHEXSA-N 0.000 description 1
- UFSHPRQKVBTSKO-WCQYABFASA-N C1(CC1)C1=CC(=NO1)C(=O)N[C@H]1[C@H](CN(CC1)C(=O)OC(C)(C)C)C Chemical compound C1(CC1)C1=CC(=NO1)C(=O)N[C@H]1[C@H](CN(CC1)C(=O)OC(C)(C)C)C UFSHPRQKVBTSKO-WCQYABFASA-N 0.000 description 1
- QSIIYOAQFCULHV-WCBMZHEXSA-N C1(CC1)C1=CC(=NO1)C(=O)N[C@H]1[C@H](CNCC1)C Chemical compound C1(CC1)C1=CC(=NO1)C(=O)N[C@H]1[C@H](CNCC1)C QSIIYOAQFCULHV-WCBMZHEXSA-N 0.000 description 1
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 1
- DSSXWZJKILIKDX-UHFFFAOYSA-N CC1CN(CCN1S(Cl)(=O)=O)NC(=O)C1=NOC(=C1)C1CC1 Chemical compound CC1CN(CCN1S(Cl)(=O)=O)NC(=O)C1=NOC(=C1)C1CC1 DSSXWZJKILIKDX-UHFFFAOYSA-N 0.000 description 1
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 1
- 101100180402 Caenorhabditis elegans jun-1 gene Proteins 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- RENMDAKOXSCIGH-UHFFFAOYSA-N Chloroacetonitrile Chemical compound ClCC#N RENMDAKOXSCIGH-UHFFFAOYSA-N 0.000 description 1
- 108010077544 Chromatin Proteins 0.000 description 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- GRBRENNBXLOEOX-GHXDPTCOSA-N Cl.C[C@@H]1C[C@@H](CCN1)NC(=O)c1cc(on1)C1CC1 Chemical compound Cl.C[C@@H]1C[C@@H](CCN1)NC(=O)c1cc(on1)C1CC1 GRBRENNBXLOEOX-GHXDPTCOSA-N 0.000 description 1
- GRBRENNBXLOEOX-SCYNACPDSA-N Cl.C[C@@H]1C[C@H](CCN1)NC(=O)c1cc(on1)C1CC1 Chemical compound Cl.C[C@@H]1C[C@H](CCN1)NC(=O)c1cc(on1)C1CC1 GRBRENNBXLOEOX-SCYNACPDSA-N 0.000 description 1
- GRBRENNBXLOEOX-KXNXZCPBSA-N Cl.C[C@H]1C[C@@H](CCN1)NC(=O)c1cc(on1)C1CC1 Chemical compound Cl.C[C@H]1C[C@@H](CCN1)NC(=O)c1cc(on1)C1CC1 GRBRENNBXLOEOX-KXNXZCPBSA-N 0.000 description 1
- VEINOHULGNFPBZ-YJBOKZPZSA-N ClCC(=O)NC(C)(C)C1=CC=C(C=C1)S(=O)(=O)N1[C@H](C[C@H](CC1)NC(=O)C1=NOC(=C1)C1CC1)C Chemical compound ClCC(=O)NC(C)(C)C1=CC=C(C=C1)S(=O)(=O)N1[C@H](C[C@H](CC1)NC(=O)C1=NOC(=C1)C1CC1)C VEINOHULGNFPBZ-YJBOKZPZSA-N 0.000 description 1
- RARLULDKUQSRQB-AAEUAGOBSA-N ClCCCS(=O)(=O)N1[C@H](C[C@H](CC1)NC(=O)C1=NOC(=C1)C1CC1)C Chemical compound ClCCCS(=O)(=O)N1[C@H](C[C@H](CC1)NC(=O)C1=NOC(=C1)C1CC1)C RARLULDKUQSRQB-AAEUAGOBSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 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
- 108020004414 DNA Proteins 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-VVKOMZTBSA-N Dideuterium Chemical compound [2H][2H] UFHFLCQGNIYNRP-VVKOMZTBSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- JGFBKJBAYISHAG-UHFFFAOYSA-N Ethyl 2,4-dioxohexanoate Chemical compound CCOC(=O)C(=O)CC(=O)CC JGFBKJBAYISHAG-UHFFFAOYSA-N 0.000 description 1
- 208000009849 Female Genital Neoplasms Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 108010036115 Histone Methyltransferases Proteins 0.000 description 1
- 102000011787 Histone Methyltransferases Human genes 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000708835 Homo sapiens SET and MYND domain-containing protein 4 Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- WZELXJBMMZFDDU-UHFFFAOYSA-N Imidazol-2-one Chemical compound O=C1N=CC=N1 WZELXJBMMZFDDU-UHFFFAOYSA-N 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102000000717 Lysine methyltransferases Human genes 0.000 description 1
- 108050008120 Lysine methyltransferases Proteins 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive 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
- VTBTYIXBHVXHBT-UHFFFAOYSA-N N,N-dimethylformamide isoindole-1,3-dione Chemical compound C1(C=2C(C(N1)=O)=CC=CC2)=O.CN(C=O)C VTBTYIXBHVXHBT-UHFFFAOYSA-N 0.000 description 1
- HXAUFKNVZJETMU-UHFFFAOYSA-N N12NC(CC(CC1)C2)C(=O)O Chemical compound N12NC(CC(CC1)C2)C(=O)O HXAUFKNVZJETMU-UHFFFAOYSA-N 0.000 description 1
- WNSLCVLJGPNBMY-UHFFFAOYSA-N N1CCCCC1.O1N=C(C=C1)C(=O)N Chemical compound N1CCCCC1.O1N=C(C=C1)C(=O)N WNSLCVLJGPNBMY-UHFFFAOYSA-N 0.000 description 1
- LRMHFTKQCYRREO-WCQYABFASA-N NCCCS(=O)(=O)N1C[C@@H]([C@@H](CC1)NC(=O)C1=NOC(=C1)C1CC1)C Chemical compound NCCCS(=O)(=O)N1C[C@@H]([C@@H](CC1)NC(=O)C1=NOC(=C1)C1CC1)C LRMHFTKQCYRREO-WCQYABFASA-N 0.000 description 1
- 201000004253 NUT midline carcinoma Diseases 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 208000006994 Precancerous Conditions Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 108700040121 Protein Methyltransferases Proteins 0.000 description 1
- 102000055027 Protein Methyltransferases Human genes 0.000 description 1
- 208000015634 Rectal Neoplasms Diseases 0.000 description 1
- 102100032725 SET and MYND domain-containing protein 4 Human genes 0.000 description 1
- 102000051614 SET domains Human genes 0.000 description 1
- 108700039010 SET domains Proteins 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 201000011648 T-cell childhood lymphoblastic lymphoma Diseases 0.000 description 1
- 208000000389 T-cell leukemia Diseases 0.000 description 1
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
- 208000020982 T-lymphoblastic lymphoma Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical class OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- SMEGJBVQLJJKKX-HOTMZDKISA-N [(2R,3S,4S,5R,6R)-5-acetyloxy-3,4,6-trihydroxyoxan-2-yl]methyl acetate Chemical compound CC(=O)OC[C@@H]1[C@H]([C@@H]([C@H]([C@@H](O1)O)OC(=O)C)O)O SMEGJBVQLJJKKX-HOTMZDKISA-N 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 229940081735 acetylcellulose Drugs 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 208000026562 adenomatoid odontogenic tumor Diseases 0.000 description 1
- 201000008395 adenosquamous carcinoma Diseases 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 229940040563 agaric acid 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
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000004688 alkyl sulfonyl alkyl group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 206010065867 alveolar rhabdomyosarcoma Diseases 0.000 description 1
- 208000008524 alveolar soft part sarcoma Diseases 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 125000003828 azulenyl group Chemical group 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical class C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 1
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 125000002529 biphenylenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C12)* 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 125000005392 carboxamide group Chemical group NC(=O)* 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000004709 cell invasion Effects 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 230000033077 cellular process Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 208000019065 cervical carcinoma Diseases 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 159000000006 cesium salts Chemical class 0.000 description 1
- 208000018805 childhood acute lymphoblastic leukemia Diseases 0.000 description 1
- 238000010568 chiral column chromatography Methods 0.000 description 1
- 150000003841 chloride salts Chemical class 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 208000006990 cholangiocarcinoma Diseases 0.000 description 1
- 229940075419 choline hydroxide Drugs 0.000 description 1
- 210000003483 chromatin Anatomy 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000008876 conformational transition Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229940099112 cornstarch Drugs 0.000 description 1
- 150000003950 cyclic amides Chemical group 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 239000000824 cytostatic agent Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- DIOQZVSQGTUSAI-NJFSPNSNSA-N decane Chemical group CCCCCCCCC[14CH3] DIOQZVSQGTUSAI-NJFSPNSNSA-N 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 125000004431 deuterium atom Chemical group 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 229940120124 dichloroacetate Drugs 0.000 description 1
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 230000006718 epigenetic regulation Effects 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 150000002169 ethanolamines Chemical class 0.000 description 1
- KFOZNPPBKHYHQD-UHFFFAOYSA-N ethenesulfonyl chloride Chemical compound ClS(=O)(=O)C=C KFOZNPPBKHYHQD-UHFFFAOYSA-N 0.000 description 1
- 125000006232 ethoxy propyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 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
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 208000028149 female reproductive system neoplasm Diseases 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 1
- 229960004884 fluconazole Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
- 125000004785 fluoromethoxy group Chemical group [H]C([H])(F)O* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000003838 furazanyl group Chemical group 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 231100000118 genetic alteration Toxicity 0.000 description 1
- 230000004077 genetic alteration Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 208000006359 hepatoblastoma Diseases 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 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
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- YAMHXTCMCPHKLN-UHFFFAOYSA-N imidazolidin-2-one Chemical compound O=C1NCCN1 YAMHXTCMCPHKLN-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 201000006747 infectious mononucleosis Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940100601 interleukin-6 Drugs 0.000 description 1
- 230000017306 interleukin-6 production Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001793 isothiazol-3-yl group Chemical group [H]C1=C([H])C(*)=NS1 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 125000004498 isoxazol-4-yl group Chemical group O1N=CC(=C1)* 0.000 description 1
- 125000004499 isoxazol-5-yl group Chemical group O1N=CC=C1* 0.000 description 1
- 239000004922 lacquer Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 238000011866 long-term treatment Methods 0.000 description 1
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 238000009115 maintenance therapy Methods 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 210000005075 mammary gland Anatomy 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- KWKAKUADMBZCLK-UHFFFAOYSA-N methyl heptene Natural products CCCCCCC=C KWKAKUADMBZCLK-UHFFFAOYSA-N 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 201000010879 mucinous adenocarcinoma Diseases 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 210000003739 neck Anatomy 0.000 description 1
- 230000009826 neoplastic cell growth Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 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
- WIVNTNLDTMNDNO-UHFFFAOYSA-N octane-1-sulfonyl chloride Chemical compound CCCCCCCCS(Cl)(=O)=O WIVNTNLDTMNDNO-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000008106 ocular cancer Diseases 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 210000000496 pancreas Anatomy 0.000 description 1
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000008063 pharmaceutical solvent Substances 0.000 description 1
- 239000008180 pharmaceutical surfactant Substances 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- ONYMIKVHDIYIDG-UHFFFAOYSA-N piperidin-4-ylmethyl hydrogen sulfate Chemical compound C1CNCCC1COS(=O)(=O)O ONYMIKVHDIYIDG-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940116317 potato starch Drugs 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000007112 pro inflammatory response Effects 0.000 description 1
- 230000001686 pro-survival effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000006233 propoxy propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])OC([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006225 propoxyethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000005767 propoxymethyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])[#8]C([H])([H])* 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 229940121649 protein inhibitor Drugs 0.000 description 1
- 239000012268 protein inhibitor Substances 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 206010038038 rectal cancer Diseases 0.000 description 1
- 201000001275 rectum cancer Diseases 0.000 description 1
- 210000003289 regulatory T cell Anatomy 0.000 description 1
- 201000010174 renal carcinoma Diseases 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000028617 response to DNA damage stimulus Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 229940100486 rice starch Drugs 0.000 description 1
- 210000003079 salivary gland Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000002027 skeletal muscle Anatomy 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000012439 solid excipient Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 201000011096 spinal cancer Diseases 0.000 description 1
- 208000037959 spinal tumor Diseases 0.000 description 1
- LBJQKYPPYSCCBH-UHFFFAOYSA-N spiro[3.3]heptane Chemical compound C1CCC21CCC2 LBJQKYPPYSCCBH-UHFFFAOYSA-N 0.000 description 1
- 208000021550 spleen neoplasm Diseases 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000003883 substance clean up Methods 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 206010042863 synovial sarcoma Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- KVTWWCJKAXSUCV-UHFFFAOYSA-N tert-butyl (2-methylpropan-2-yl)oxycarbonyl carbonate methanol Chemical compound OC.CC(C)(C)OC(=O)OC(=O)OC(C)(C)C KVTWWCJKAXSUCV-UHFFFAOYSA-N 0.000 description 1
- HQMYWQCBINPHBB-MRVPVSSYSA-N tert-butyl (2r)-2-methyl-4-oxopiperidine-1-carboxylate Chemical compound C[C@@H]1CC(=O)CCN1C(=O)OC(C)(C)C HQMYWQCBINPHBB-MRVPVSSYSA-N 0.000 description 1
- HVLQURGQQISYSQ-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[3.5]nonane-7-carboxylate;hydrochloride Chemical compound Cl.C1CN(C(=O)OC(C)(C)C)CCC11CNC1 HVLQURGQQISYSQ-UHFFFAOYSA-N 0.000 description 1
- LQBXEVOJCOQNTJ-UHFFFAOYSA-N tert-butyl 2-benzyl-4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1CC1=CC=CC=C1 LQBXEVOJCOQNTJ-UHFFFAOYSA-N 0.000 description 1
- MENILFUADYEXNU-UHFFFAOYSA-N tert-butyl 3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate Chemical compound C1C(=O)CC2CCC1N2C(=O)OC(C)(C)C MENILFUADYEXNU-UHFFFAOYSA-N 0.000 description 1
- OGIPSHDJYIEDKG-UHFFFAOYSA-N tert-butyl 4-amino-2-methylpiperidine-1-carboxylate Chemical compound CC1CC(N)CCN1C(=O)OC(C)(C)C OGIPSHDJYIEDKG-UHFFFAOYSA-N 0.000 description 1
- CKXZPVPIDOJLLM-UHFFFAOYSA-N tert-butyl n-piperidin-4-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1CCNCC1 CKXZPVPIDOJLLM-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 1
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 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
- 238000013518 transcription Methods 0.000 description 1
- 230000035897 transcription Effects 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 229940078499 tricalcium phosphate Drugs 0.000 description 1
- 235000019731 tricalcium phosphate Nutrition 0.000 description 1
- 229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 230000006433 tumor necrosis factor production Effects 0.000 description 1
- 208000025443 tumor of adipose tissue Diseases 0.000 description 1
- 208000024719 uterine cervix neoplasm Diseases 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- DYWSVUBJGFTOQC-UHFFFAOYSA-N xi-2-Ethylheptanoic acid Chemical compound CCCCCC(CC)C(O)=O DYWSVUBJGFTOQC-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4453—Non condensed piperidines, e.g. piperocaine only substituted in position 1, e.g. propipocaine, diperodon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201462048771P | 2014-09-10 | 2014-09-10 | |
| US62/048,771 | 2014-09-10 | ||
| US201462078845P | 2014-11-12 | 2014-11-12 | |
| US62/078,845 | 2014-11-12 | ||
| US201562146790P | 2015-04-13 | 2015-04-13 | |
| US62/146,790 | 2015-04-13 | ||
| PCT/US2015/049235 WO2016040515A1 (en) | 2014-09-10 | 2015-09-09 | Substituted piperidine compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20170047397A true KR20170047397A (ko) | 2017-05-04 |
Family
ID=55459535
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020177009316A Withdrawn KR20170047397A (ko) | 2014-09-10 | 2015-09-09 | 치환된 피페리딘 화합물 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US10577363B2 (enExample) |
| EP (1) | EP3193605A4 (enExample) |
| JP (1) | JP2017528464A (enExample) |
| KR (1) | KR20170047397A (enExample) |
| CN (1) | CN107072207A (enExample) |
| AU (1) | AU2015315182A1 (enExample) |
| BR (1) | BR112017004589A2 (enExample) |
| CA (1) | CA2960280A1 (enExample) |
| EA (1) | EA201790327A1 (enExample) |
| IL (1) | IL250888A0 (enExample) |
| MX (1) | MX2017002986A (enExample) |
| SG (2) | SG10201901189SA (enExample) |
| WO (1) | WO2016040515A1 (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102496364B1 (ko) | 2014-09-10 | 2023-02-06 | 에피자임, 인코포레이티드 | Smyd 억제제 |
| JP2017526706A (ja) | 2014-09-10 | 2017-09-14 | エピザイム,インコーポレイティド | イソオキサゾールカルボキサミド化合物 |
| AU2015315171A1 (en) | 2014-09-10 | 2017-03-16 | Epizyme, Inc. | Substituted cyclohexylamine compounds |
| JP2017528460A (ja) * | 2014-09-10 | 2017-09-28 | エピザイム インコーポレイテッド | 不可逆的smyd阻害剤としてのイソオキサゾールカルボキサミド |
| EP3263572B1 (en) | 2015-02-27 | 2021-12-15 | Seed Research Institute Co., Ltd. | Method for producing kakeromycin and derivatives thereof |
| HUE057315T2 (hu) * | 2016-07-28 | 2022-04-28 | Idorsia Pharmaceuticals Ltd | Piperidin cxcr7 receptor modulátorok |
| WO2018151678A1 (en) * | 2017-02-15 | 2018-08-23 | Agency For Science, Technology And Research | Compounds for treatment of cancer and epigenetics |
| MA51664B1 (fr) * | 2018-01-26 | 2024-05-31 | Idorsia Pharmaceuticals Ltd | Formes cristallines de l'antagoniste du récepteur cxcr7 d'acide (3s,4s)-1-cyclopropylméthyl-4-([5-(2,4-difluoro-phényl)-isoxazole-3-carbonyl]-amino)-pipéridine-3-carboxylique (1-pyrimidin-2-yl-cyclopropyl)-amide |
| CN112955214B (zh) | 2018-10-29 | 2024-05-07 | 勃林格殷格翰国际有限公司 | 吡啶基磺酰胺衍生物、药物组合物及其用途 |
| FI3873600T3 (fi) | 2018-10-29 | 2023-12-07 | Boehringer Ingelheim Int | Pyridinyylisulfonamidijohdannaisia, farmaseuttisia koostumuksia ja niiden käytöt |
| JP7678756B2 (ja) | 2019-09-30 | 2025-05-16 | 日本ケミファ株式会社 | アゼパン誘導体 |
| CN114702552B (zh) * | 2022-03-11 | 2024-05-31 | 苏州思萃免疫技术研究所有限公司 | mTORC2抑制剂 |
| CN117800895A (zh) * | 2022-09-30 | 2024-04-02 | 苏州阿尔脉生物科技有限公司 | 草酸胺类衍生物、包含其的药物组合物及其医药用途 |
| WO2025133989A1 (en) * | 2023-12-20 | 2025-06-26 | Alt-Bio Pte. Ltd. | Smyd modulators and uses thereof |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1228288B (it) * | 1989-01-09 | 1991-06-07 | Zambon Spa | Composti ad attivita' antiserotoninica |
| SE9902987D0 (sv) | 1999-08-24 | 1999-08-24 | Astra Pharma Prod | Novel compounds |
| SE0403106D0 (sv) * | 2004-12-20 | 2004-12-20 | Astrazeneca Ab | Chemical compounds |
| WO2008137834A2 (en) * | 2007-05-04 | 2008-11-13 | Osi Pharmaceuticals, Inc. | Crystal structure of smyd3 protein |
| PE20091093A1 (es) * | 2007-12-03 | 2009-08-25 | Takeda Pharmaceutical | Compuesto heterociclico que contiene nitrogeno y su uso |
| TWI535712B (zh) | 2010-08-06 | 2016-06-01 | 阿斯特捷利康公司 | 化合物 |
| US9045485B2 (en) * | 2010-12-16 | 2015-06-02 | Convergence Pharmaceuticals Limited | ASK 1 inhibiting pyrrolopyrimidine derivatives |
| JP2017528460A (ja) * | 2014-09-10 | 2017-09-28 | エピザイム インコーポレイテッド | 不可逆的smyd阻害剤としてのイソオキサゾールカルボキサミド |
| KR102496364B1 (ko) | 2014-09-10 | 2023-02-06 | 에피자임, 인코포레이티드 | Smyd 억제제 |
| AU2015315171A1 (en) | 2014-09-10 | 2017-03-16 | Epizyme, Inc. | Substituted cyclohexylamine compounds |
| US20170247326A1 (en) | 2014-09-10 | 2017-08-31 | Epizyme, Inc. | Substituted Pyrrolidine Carboxamide Compounds |
| JP2017526706A (ja) * | 2014-09-10 | 2017-09-14 | エピザイム,インコーポレイティド | イソオキサゾールカルボキサミド化合物 |
| US20170253601A1 (en) | 2014-09-10 | 2017-09-07 | Epizyme, Inc. | Substituted Pyrrolidine Compounds |
-
2015
- 2015-09-09 MX MX2017002986A patent/MX2017002986A/es unknown
- 2015-09-09 AU AU2015315182A patent/AU2015315182A1/en not_active Abandoned
- 2015-09-09 SG SG10201901189SA patent/SG10201901189SA/en unknown
- 2015-09-09 JP JP2017513207A patent/JP2017528464A/ja active Pending
- 2015-09-09 BR BR112017004589A patent/BR112017004589A2/pt not_active Application Discontinuation
- 2015-09-09 EP EP15840497.0A patent/EP3193605A4/en not_active Withdrawn
- 2015-09-09 CN CN201580060918.8A patent/CN107072207A/zh active Pending
- 2015-09-09 US US15/510,588 patent/US10577363B2/en active Active
- 2015-09-09 KR KR1020177009316A patent/KR20170047397A/ko not_active Withdrawn
- 2015-09-09 SG SG11201701597RA patent/SG11201701597RA/en unknown
- 2015-09-09 EA EA201790327A patent/EA201790327A1/ru unknown
- 2015-09-09 CA CA2960280A patent/CA2960280A1/en not_active Abandoned
- 2015-09-09 WO PCT/US2015/049235 patent/WO2016040515A1/en not_active Ceased
-
2017
- 2017-03-02 IL IL250888A patent/IL250888A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP3193605A4 (en) | 2018-04-18 |
| SG11201701597RA (en) | 2017-03-30 |
| CN107072207A (zh) | 2017-08-18 |
| EA201790327A1 (ru) | 2017-10-31 |
| JP2017528464A (ja) | 2017-09-28 |
| CA2960280A1 (en) | 2016-03-17 |
| WO2016040515A1 (en) | 2016-03-17 |
| US20170362217A1 (en) | 2017-12-21 |
| MX2017002986A (es) | 2017-10-24 |
| US10577363B2 (en) | 2020-03-03 |
| EP3193605A1 (en) | 2017-07-26 |
| AU2015315182A1 (en) | 2017-03-16 |
| SG10201901189SA (en) | 2019-03-28 |
| BR112017004589A2 (pt) | 2018-01-23 |
| IL250888A0 (en) | 2017-04-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR20170047397A (ko) | 치환된 피페리딘 화합물 | |
| KR102496364B1 (ko) | Smyd 억제제 | |
| US10435399B2 (en) | HDAC6 inhibitory heterocyclic compound | |
| JP7249950B2 (ja) | ヘテロ環化合物 | |
| EP3468960B1 (en) | Chemical compounds as atf4 pathway inhibitors | |
| AU2014287471C1 (en) | Fused piperidine amides as modulators of ion channels | |
| TWI577674B (zh) | 二氫-苯并-及二氫-吡啶并-衍生物 | |
| JP2021520350A (ja) | Brm標的化化合物および関連使用方法 | |
| CA2921959A1 (en) | Furo- and thieno-pyridine carboxamide compounds useful as pim kinase inhibitors | |
| CA2896187A1 (en) | 3-substituted pyrazoles and use as dlk inhibitors | |
| MX2014003612A (es) | Compuestos de pirazol-4-il-heterociclil-carboxamida y metodos de uso. | |
| TW201100385A (en) | Substituted isoquinoline derivative | |
| CA3234429A1 (en) | Ras inhibitors, compositions and methods of use thereof | |
| WO2016040498A1 (en) | Isoxazole carboxamide compounds | |
| JP2017527576A (ja) | 置換シクロヘキシルアミン化合物 | |
| WO2025076088A1 (en) | Lactams for use as sarm1 inhibitors | |
| CN117425654A (zh) | 2,8-二氮杂螺[4.5]癸烷化合物 | |
| EA047011B1 (ru) | Производные сульфонилмочевины в качестве модуляторов nlrp3 инфламмасомы |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20170405 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination |