JP2016504289A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2016504289A5 JP2016504289A5 JP2015544036A JP2015544036A JP2016504289A5 JP 2016504289 A5 JP2016504289 A5 JP 2016504289A5 JP 2015544036 A JP2015544036 A JP 2015544036A JP 2015544036 A JP2015544036 A JP 2015544036A JP 2016504289 A5 JP2016504289 A5 JP 2016504289A5
- Authority
- JP
- Japan
- Prior art keywords
- optionally substituted
- substituents selected
- substituted
- cancer
- heteroaryl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 125000001424 substituent group Chemical group 0.000 claims description 302
- 125000001072 heteroaryl group Chemical group 0.000 claims description 112
- 229910052739 hydrogen Inorganic materials 0.000 claims description 112
- 239000001257 hydrogen Substances 0.000 claims description 111
- 125000000217 alkyl group Chemical group 0.000 claims description 107
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 99
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 97
- 125000003118 aryl group Chemical group 0.000 claims description 89
- 150000001875 compounds Chemical class 0.000 claims description 72
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 71
- 229910052736 halogen Inorganic materials 0.000 claims description 68
- 150000002367 halogens Chemical class 0.000 claims description 65
- 150000002431 hydrogen Chemical group 0.000 claims description 39
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 32
- 206010028980 Neoplasm Diseases 0.000 claims description 29
- -1 cyclopropylethyl Chemical group 0.000 claims description 27
- 201000011510 cancer Diseases 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 20
- 208000009956 adenocarcinoma Diseases 0.000 claims description 18
- 206010025323 Lymphomas Diseases 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- 229910052717 sulfur Inorganic materials 0.000 claims description 13
- 125000004434 sulfur atom Chemical group 0.000 claims description 13
- 206010039491 Sarcoma Diseases 0.000 claims description 12
- 125000002619 bicyclic group Chemical group 0.000 claims description 12
- 210000004027 cell Anatomy 0.000 claims description 12
- 125000002950 monocyclic group Chemical group 0.000 claims description 11
- 125000004429 atom Chemical group 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 9
- 206010024612 Lipoma Diseases 0.000 claims description 8
- 206010016629 fibroma Diseases 0.000 claims description 8
- 201000011066 hemangioma Diseases 0.000 claims description 8
- 208000032612 Glial tumor Diseases 0.000 claims description 7
- 206010018338 Glioma Diseases 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 7
- 201000008808 Fibrosarcoma Diseases 0.000 claims description 6
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 6
- 206010043276 Teratoma Diseases 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000002757 morpholinyl group Chemical group 0.000 claims description 6
- 125000004193 piperazinyl group Chemical group 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 6
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 239000003112 inhibitor Substances 0.000 claims description 5
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 5
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 5
- 201000003076 Angiosarcoma Diseases 0.000 claims description 4
- 206010007275 Carcinoid tumour Diseases 0.000 claims description 4
- 208000002927 Hamartoma Diseases 0.000 claims description 4
- 208000001258 Hemangiosarcoma Diseases 0.000 claims description 4
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 4
- 208000018142 Leiomyosarcoma Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 208000034578 Multiple myelomas Diseases 0.000 claims description 4
- 201000004404 Neurofibroma Diseases 0.000 claims description 4
- 208000009905 Neurofibromatoses Diseases 0.000 claims description 4
- 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 4
- 206010033128 Ovarian cancer Diseases 0.000 claims description 4
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 125000002393 azetidinyl group Chemical group 0.000 claims description 4
- 208000002458 carcinoid tumor Diseases 0.000 claims description 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 4
- 201000010260 leiomyoma Diseases 0.000 claims description 4
- 208000032839 leukemia Diseases 0.000 claims description 4
- 201000007270 liver cancer Diseases 0.000 claims description 4
- 208000014018 liver neoplasm Diseases 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 201000004931 neurofibromatosis Diseases 0.000 claims description 4
- 201000008968 osteosarcoma Diseases 0.000 claims description 4
- 125000003566 oxetanyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 201000000849 skin cancer Diseases 0.000 claims description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims description 4
- 208000008383 Wilms tumor Diseases 0.000 claims description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 239000013066 combination product Substances 0.000 claims description 3
- 229940127555 combination product Drugs 0.000 claims description 3
- 125000000723 dihydrobenzofuranyl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 3
- 206010027191 meningioma Diseases 0.000 claims description 3
- 201000008026 nephroblastoma Diseases 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 239000000047 product Substances 0.000 claims description 3
- 210000004291 uterus Anatomy 0.000 claims description 3
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 claims description 2
- 241000321096 Adenoides Species 0.000 claims description 2
- 206010001233 Adenoma benign Diseases 0.000 claims description 2
- 208000020576 Adrenal disease Diseases 0.000 claims description 2
- 206010003571 Astrocytoma Diseases 0.000 claims description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 2
- 206010004146 Basal cell carcinoma Diseases 0.000 claims description 2
- 208000019838 Blood disease Diseases 0.000 claims description 2
- 206010005949 Bone cancer Diseases 0.000 claims description 2
- 208000020084 Bone disease Diseases 0.000 claims description 2
- 206010073106 Bone giant cell tumour malignant Diseases 0.000 claims description 2
- 208000018084 Bone neoplasm Diseases 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 208000009458 Carcinoma in Situ Diseases 0.000 claims description 2
- 206010008263 Cervical dysplasia Diseases 0.000 claims description 2
- 206010008342 Cervix carcinoma Diseases 0.000 claims description 2
- 201000005262 Chondroma Diseases 0.000 claims description 2
- 208000005243 Chondrosarcoma Diseases 0.000 claims description 2
- 201000009047 Chordoma Diseases 0.000 claims description 2
- 208000006332 Choriocarcinoma Diseases 0.000 claims description 2
- 206010048832 Colon adenoma Diseases 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 206010010356 Congenital anomaly Diseases 0.000 claims description 2
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 claims description 2
- 229940124087 DNA topoisomerase II inhibitor Drugs 0.000 claims description 2
- 208000000471 Dysplastic Nevus Syndrome Diseases 0.000 claims description 2
- 206010014733 Endometrial cancer Diseases 0.000 claims description 2
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 2
- 206010014967 Ependymoma Diseases 0.000 claims description 2
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 2
- 208000006168 Ewing Sarcoma Diseases 0.000 claims description 2
- 208000007659 Fibroadenoma Diseases 0.000 claims description 2
- 208000000527 Germinoma Diseases 0.000 claims description 2
- 206010018404 Glucagonoma Diseases 0.000 claims description 2
- 206010018691 Granuloma Diseases 0.000 claims description 2
- 206010019629 Hepatic adenoma Diseases 0.000 claims description 2
- 208000017604 Hodgkin disease Diseases 0.000 claims description 2
- 208000010747 Hodgkins lymphoma Diseases 0.000 claims description 2
- 208000002260 Keloid Diseases 0.000 claims description 2
- 206010023330 Keloid scar Diseases 0.000 claims description 2
- 208000002404 Liver Cell Adenoma Diseases 0.000 claims description 2
- 208000019693 Lung disease Diseases 0.000 claims description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 2
- 208000006644 Malignant Fibrous Histiocytoma Diseases 0.000 claims description 2
- 208000000172 Medulloblastoma Diseases 0.000 claims description 2
- 206010027406 Mesothelioma Diseases 0.000 claims description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 2
- 208000014767 Myeloproliferative disease Diseases 0.000 claims description 2
- 206010029260 Neuroblastoma Diseases 0.000 claims description 2
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 2
- 201000010133 Oligodendroglioma Diseases 0.000 claims description 2
- 208000000035 Osteochondroma Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 201000000582 Retinoblastoma Diseases 0.000 claims description 2
- 201000010208 Seminoma Diseases 0.000 claims description 2
- 208000000097 Sertoli-Leydig cell tumor Diseases 0.000 claims description 2
- 208000032383 Soft tissue cancer Diseases 0.000 claims description 2
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 2
- 206010057644 Testis cancer Diseases 0.000 claims description 2
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 claims description 2
- 239000000317 Topoisomerase II Inhibitor Substances 0.000 claims description 2
- 208000015778 Undifferentiated pleomorphic sarcoma Diseases 0.000 claims description 2
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims description 2
- 235000009754 Vitis X bourquina Nutrition 0.000 claims description 2
- 235000012333 Vitis X labruscana Nutrition 0.000 claims description 2
- 240000006365 Vitis vinifera Species 0.000 claims description 2
- 235000014787 Vitis vinifera Nutrition 0.000 claims description 2
- 206010048215 Xanthomatosis Diseases 0.000 claims description 2
- 210000002534 adenoid Anatomy 0.000 claims description 2
- 201000005188 adrenal gland cancer Diseases 0.000 claims description 2
- 208000024447 adrenal gland neoplasm Diseases 0.000 claims description 2
- 230000002152 alkylating effect Effects 0.000 claims description 2
- 229940121369 angiogenesis inhibitor Drugs 0.000 claims description 2
- 239000004037 angiogenesis inhibitor Substances 0.000 claims description 2
- 230000000340 anti-metabolite Effects 0.000 claims description 2
- 230000001946 anti-microtubular Effects 0.000 claims description 2
- 239000002256 antimetabolite Substances 0.000 claims description 2
- 229940100197 antimetabolite Drugs 0.000 claims description 2
- 230000003115 biocidal effect Effects 0.000 claims description 2
- 210000004369 blood Anatomy 0.000 claims description 2
- 239000008280 blood Substances 0.000 claims description 2
- 210000001185 bone marrow Anatomy 0.000 claims description 2
- 210000004556 brain Anatomy 0.000 claims description 2
- 201000003149 breast fibroadenoma Diseases 0.000 claims description 2
- 210000003123 bronchiole Anatomy 0.000 claims description 2
- 201000002143 bronchus adenoma Diseases 0.000 claims description 2
- 210000000845 cartilage Anatomy 0.000 claims description 2
- 230000022131 cell cycle Effects 0.000 claims description 2
- 201000010881 cervical cancer Diseases 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 208000006990 cholangiocarcinoma Diseases 0.000 claims description 2
- 201000005217 chondroblastoma Diseases 0.000 claims description 2
- 230000001684 chronic effect Effects 0.000 claims description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 2
- 208000009060 clear cell adenocarcinoma Diseases 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 claims description 2
- 206010012818 diffuse large B-cell lymphoma Diseases 0.000 claims description 2
- 230000002500 effect on skin Effects 0.000 claims description 2
- 201000004101 esophageal cancer Diseases 0.000 claims description 2
- 208000015419 gastrin-producing neuroendocrine tumor Diseases 0.000 claims description 2
- 201000000052 gastrinoma Diseases 0.000 claims description 2
- 201000003115 germ cell cancer Diseases 0.000 claims description 2
- 201000005787 hematologic cancer Diseases 0.000 claims description 2
- 208000014951 hematologic disease Diseases 0.000 claims description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 2
- 208000018706 hematopoietic system disease Diseases 0.000 claims description 2
- 208000006359 hepatoblastoma Diseases 0.000 claims description 2
- 201000002735 hepatocellular adenoma Diseases 0.000 claims description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
- 239000002944 hormone and hormone analog Substances 0.000 claims description 2
- 239000002955 immunomodulating agent Substances 0.000 claims description 2
- 201000004933 in situ carcinoma Diseases 0.000 claims description 2
- 206010022498 insulinoma Diseases 0.000 claims description 2
- 210000001117 keloid Anatomy 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 208000022013 kidney Wilms tumor Diseases 0.000 claims description 2
- 210000002429 large intestine Anatomy 0.000 claims description 2
- 206010024627 liposarcoma Diseases 0.000 claims description 2
- 208000019423 liver disease Diseases 0.000 claims description 2
- 201000004593 malignant giant cell tumor Diseases 0.000 claims description 2
- 201000000289 malignant teratoma Diseases 0.000 claims description 2
- 210000002418 meninge Anatomy 0.000 claims description 2
- 208000010492 mucinous cystadenocarcinoma Diseases 0.000 claims description 2
- 208000025113 myeloid leukemia Diseases 0.000 claims description 2
- 208000009091 myxoma Diseases 0.000 claims description 2
- 208000007538 neurilemmoma Diseases 0.000 claims description 2
- 208000004649 neutrophil actin dysfunction Diseases 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 208000008798 osteoma Diseases 0.000 claims description 2
- 210000001672 ovary Anatomy 0.000 claims description 2
- 210000003101 oviduct Anatomy 0.000 claims description 2
- 210000000496 pancreas Anatomy 0.000 claims description 2
- 208000021255 pancreatic insulinoma Diseases 0.000 claims description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Substances [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 2
- 229910052697 platinum Inorganic materials 0.000 claims description 2
- 230000000861 pro-apoptotic effect Effects 0.000 claims description 2
- 210000002307 prostate Anatomy 0.000 claims description 2
- 201000006845 reticulosarcoma Diseases 0.000 claims description 2
- 208000029922 reticulum cell sarcoma Diseases 0.000 claims description 2
- 206010039667 schwannoma Diseases 0.000 claims description 2
- 208000004548 serous cystadenocarcinoma Diseases 0.000 claims description 2
- 230000019491 signal transduction Effects 0.000 claims description 2
- 230000011664 signaling Effects 0.000 claims description 2
- 208000017520 skin disease Diseases 0.000 claims description 2
- 210000003625 skull Anatomy 0.000 claims description 2
- 210000000813 small intestine Anatomy 0.000 claims description 2
- 210000000278 spinal cord Anatomy 0.000 claims description 2
- 210000002784 stomach Anatomy 0.000 claims description 2
- 210000002536 stromal cell Anatomy 0.000 claims description 2
- 208000001608 teratocarcinoma Diseases 0.000 claims description 2
- 201000003120 testicular cancer Diseases 0.000 claims description 2
- 210000001550 testis Anatomy 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 206010044412 transitional cell carcinoma Diseases 0.000 claims description 2
- 208000022271 tubular adenoma Diseases 0.000 claims description 2
- 210000003708 urethra Anatomy 0.000 claims description 2
- 210000003905 vulva Anatomy 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 4
- 125000005809 3,4,5-trimethoxyphenyl group Chemical group [H]C1=C(OC([H])([H])[H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 3
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 claims 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 3
- 201000009030 Carcinoma Diseases 0.000 claims 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical group [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 claims 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 claims 1
- 108091000080 Phosphotransferase Proteins 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 208000005017 glioblastoma Diseases 0.000 claims 1
- 201000010536 head and neck cancer Diseases 0.000 claims 1
- 208000014829 head and neck neoplasm Diseases 0.000 claims 1
- 125000000623 heterocyclic group Chemical group 0.000 claims 1
- 210000000653 nervous system Anatomy 0.000 claims 1
- 208000003388 osteoid osteoma Diseases 0.000 claims 1
- 102000020233 phosphotransferase Human genes 0.000 claims 1
- 230000001568 sexual effect Effects 0.000 claims 1
- 210000004085 squamous epithelial cell Anatomy 0.000 claims 1
- 125000003107 substituted aryl group Chemical group 0.000 claims 1
- 238000006467 substitution reaction Methods 0.000 claims 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 1
- 208000009540 villous adenoma Diseases 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- FGRBYDKOBBBPOI-UHFFFAOYSA-N 10,10-dioxo-2-[4-(N-phenylanilino)phenyl]thioxanthen-9-one Chemical compound O=C1c2ccccc2S(=O)(=O)c2ccc(cc12)-c1ccc(cc1)N(c1ccccc1)c1ccccc1 FGRBYDKOBBBPOI-UHFFFAOYSA-N 0.000 description 2
- JPISJKXQLRTSQT-UHFFFAOYSA-N 6-pyridin-3-yl-4-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]pyrimidine-2,4-diamine Chemical compound N1=CC(=CC=C1)C1=CC(=NC(=N1)N)NCC1=CC=C(C=C1)C1=NOC(=N1)C(F)(F)F JPISJKXQLRTSQT-UHFFFAOYSA-N 0.000 description 2
- BAOBSGIEQCYZGK-UHFFFAOYSA-N 6-pyridin-3-yl-4-N-[[5-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]pyridin-2-yl]methyl]pyrimidine-2,4-diamine Chemical compound N1=CC(=CC=C1)C1=CC(=NC(=N1)N)NCC1=NC=C(C=C1)C1=NOC(=N1)C(F)(F)F BAOBSGIEQCYZGK-UHFFFAOYSA-N 0.000 description 2
- WNHNHRQLGSRUIR-UHFFFAOYSA-N 6-pyridin-3-yl-4-N-[[5-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]pyrimidin-2-yl]methyl]pyrimidine-2,4-diamine Chemical compound N1=CC(=CC=C1)C1=CC(=NC(=N1)N)NCC1=NC=C(C=N1)C1=NOC(=N1)C(F)(F)F WNHNHRQLGSRUIR-UHFFFAOYSA-N 0.000 description 2
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 2
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- ILRZEUGHVKBJTL-UHFFFAOYSA-N 4-(2-morpholin-4-ylethyl)-6-(3,4,5-trimethoxyphenyl)-1H-pyrimidine-2,4-diamine Chemical compound N1(CCOCC1)CCC1(NC(=NC(=C1)C1=CC(=C(C(=C1)OC)OC)OC)N)N ILRZEUGHVKBJTL-UHFFFAOYSA-N 0.000 description 1
- QPTQMJAICSDKPV-UHFFFAOYSA-N 4-(3-morpholin-4-ylpropyl)-6-(3,4,5-trimethoxyphenyl)-1H-pyrimidine-2,4-diamine Chemical compound N1(CCOCC1)CCCC1(NC(=NC(=C1)C1=CC(=C(C(=C1)OC)OC)OC)N)N QPTQMJAICSDKPV-UHFFFAOYSA-N 0.000 description 1
- DVAVYGLMVCUYAM-UHFFFAOYSA-N 4-[2-(diethylamino)ethyl]-6-(3,4,5-trimethoxyphenyl)-1H-pyrimidine-2,4-diamine Chemical compound C(C)N(CCC1(NC(=NC(=C1)C1=CC(=C(C(=C1)OC)OC)OC)N)N)CC DVAVYGLMVCUYAM-UHFFFAOYSA-N 0.000 description 1
- VHVBYURMEBZBDN-UHFFFAOYSA-N 4-cyclopropyl-6-(4-methoxy-2-methylphenyl)-1H-pyrimidine-2,4-diamine Chemical compound C1(CC1)C1(NC(=NC(=C1)C1=C(C=C(C=C1)OC)C)N)N VHVBYURMEBZBDN-UHFFFAOYSA-N 0.000 description 1
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 1
- 208000005440 Basal Cell Neoplasms Diseases 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 208000007569 Giant Cell Tumors Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000034176 Neoplasms, Germ Cell and Embryonal Diseases 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- 208000008385 Urogenital Neoplasms Diseases 0.000 description 1
- 208000025609 Urogenital disease Diseases 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000000928 benzodioxinyl group Chemical group O1C(=COC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 201000000053 blastoma Diseases 0.000 description 1
- 238000003570 cell viability assay Methods 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 201000008184 embryoma Diseases 0.000 description 1
- 201000002246 embryonal cancer Diseases 0.000 description 1
- 210000003238 esophagus Anatomy 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 208000018685 gastrointestinal system disease Diseases 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 201000011682 nervous system cancer Diseases 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 208000037964 urogenital cancer Diseases 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261797022P | 2012-11-27 | 2012-11-27 | |
| SE1251332-1 | 2012-11-27 | ||
| SE1251332 | 2012-11-27 | ||
| US61/797,022 | 2012-11-27 | ||
| PCT/SE2013/051387 WO2014084778A1 (en) | 2012-11-27 | 2013-11-26 | Pyrimidine-2,4-diamine derivatives for treatment of cancer |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2016504289A JP2016504289A (ja) | 2016-02-12 |
| JP2016504289A5 true JP2016504289A5 (https=) | 2017-01-05 |
| JP6322205B2 JP6322205B2 (ja) | 2018-05-09 |
Family
ID=50828272
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015544036A Active JP6322205B2 (ja) | 2012-11-27 | 2013-11-26 | がん治療用のピリミジン−２，４−ジアミン誘導体 |
Country Status (19)
| Country | Link |
|---|---|
| US (3) | US9604937B2 (https=) |
| EP (1) | EP2925744B1 (https=) |
| JP (1) | JP6322205B2 (https=) |
| KR (1) | KR102194646B1 (https=) |
| CN (1) | CN105143206B (https=) |
| AU (1) | AU2013353542B2 (https=) |
| BR (1) | BR112015011497B1 (https=) |
| CA (1) | CA2888338C (https=) |
| CL (1) | CL2015001437A1 (https=) |
| IL (1) | IL238942B (https=) |
| MX (1) | MX373786B (https=) |
| MY (1) | MY182386A (https=) |
| PE (1) | PE20151412A1 (https=) |
| PH (1) | PH12015501058A1 (https=) |
| PL (1) | PL2925744T3 (https=) |
| RU (1) | RU2672916C2 (https=) |
| SG (1) | SG11201503783VA (https=) |
| WO (1) | WO2014084778A1 (https=) |
| ZA (1) | ZA201503470B (https=) |
Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8729263B2 (en) | 2012-08-13 | 2014-05-20 | Novartis Ag | 1,4-disubstituted pyridazine analogs there of and methods for treating SMN-deficiency-related conditions |
| US9604937B2 (en) * | 2012-11-27 | 2017-03-28 | Thomas Helledays Stiftelse For Medicinsk Forskning | Pyrimidine-2,4-diamine derivatives for treatment of cancer |
| WO2015172747A1 (en) * | 2014-05-16 | 2015-11-19 | Zhaoyin Wang | Spirocyclic molecules as mth1 inhibitors |
| WO2015187088A1 (en) * | 2014-06-04 | 2015-12-10 | Thomas Helledays Stiftelse För Medicinsk Forskning | Mth1 inhibitors for treatment of cancer |
| CN106794181A (zh) | 2014-06-04 | 2017-05-31 | 托马斯·黑勒戴药物研究基金会 | 用于治疗炎性和自身免疫性病况的mth1抑制剂 |
| US10336768B2 (en) * | 2014-06-13 | 2019-07-02 | Yuma Therapeutics, Inc. | Pyrimidine compounds and methods using the same |
| CN104292213A (zh) * | 2014-09-08 | 2015-01-21 | 湖南华腾制药有限公司 | 一种嘧啶衍生物的制备方法 |
| JP6533997B2 (ja) * | 2014-12-26 | 2019-06-26 | 株式会社ヤクルト本社 | Ｚｎｆ１４３阻害活性を有する化合物およびその利用 |
| US20180118721A1 (en) | 2015-02-13 | 2018-05-03 | Merck Patent Gmbh | Pyrimidine derivatives |
| WO2016135139A1 (en) | 2015-02-23 | 2016-09-01 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | 2,3-dihydrocyclopenta[b]quinoline derivatives as mth1 inhibitors for the therapy of cancer |
| WO2016135138A1 (en) | 2015-02-23 | 2016-09-01 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | Oxoquinoline derivatives as mth1 inhibitors for the therapy of cancer |
| WO2016135137A1 (en) | 2015-02-23 | 2016-09-01 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | Substituted 4-(phenylamino)quinoline derivatives as mth1 inhibitors for the therapy of cancer |
| WO2016135140A1 (en) | 2015-02-23 | 2016-09-01 | Cemm - Forschungszentrum Für Molekulare Medizin Gmbh | 4-aminoquinazoline derivatives as mth1 inhibitors for the therapy of cancer |
| WO2016145383A1 (en) * | 2015-03-11 | 2016-09-15 | Board Of Regents, University Of Texas System | Mth1 inhibitors for treating disease |
| CR20180323A (es) | 2015-11-20 | 2018-08-06 | Idorsia Pharmaceuticals Ltd | Derivados de indol n-sustituídos como moduladores de los receptores de pge2 |
| CN106928192B (zh) * | 2015-12-29 | 2020-11-13 | 中国科学院广州生物医药与健康研究院 | 一种嘧啶类化合物及其制备方法和应用 |
| CN105732516A (zh) * | 2016-03-09 | 2016-07-06 | 哈尔滨医科大学 | 一种合成mth1蛋白抑制剂th287的方法 |
| WO2017190050A1 (en) * | 2016-04-28 | 2017-11-02 | Cornell University | Inhibitors of soluble adenylyl cyclase |
| KR101876514B1 (ko) * | 2016-11-08 | 2018-07-10 | 한국화학연구원 | 신규한 피리미딘화합물, 이의 제조방법 및 이를 유효성분으로 함유하는 암 및 염증질환의 예방 또는 치료용 약학적 조성물 |
| PL3625228T3 (pl) | 2017-05-18 | 2021-12-20 | Idorsia Pharmaceuticals Ltd | Pochodne pirymidyny jako modulatory receptora pge2 |
| CN110621667A (zh) | 2017-05-18 | 2019-12-27 | 爱杜西亚药品有限公司 | 嘧啶衍生物 |
| CN110621671A (zh) | 2017-05-18 | 2019-12-27 | 爱杜西亚药品有限公司 | 作为pge2受体调节剂的苯并呋喃及苯并噻吩衍生物 |
| EA201992676A1 (ru) | 2017-05-18 | 2020-05-06 | Идорсия Фармасьютиклз Лтд | Фенильные производные в качестве модуляторов pge2 рецепторов |
| WO2019134082A1 (en) * | 2018-01-04 | 2019-07-11 | Wuxi Advant Biotechnology Co., Ltd. | Novel pyrimidine derivatives as mth1 inhibitors |
| WO2019166639A1 (en) | 2018-03-01 | 2019-09-06 | Thomas Helledays Stiftelse För Medicinsk Forskning | Substituted benzodiazoles and use thereof in therapy |
| WO2020210521A2 (en) * | 2019-04-12 | 2020-10-15 | The Regents Of The University Of California | Compositions and methods for increasing muscle mass and oxidative metabolism |
| CN114450277A (zh) * | 2019-09-30 | 2022-05-06 | 豪夫迈·罗氏有限公司 | 用于治疗和预防乙型肝炎病毒感染的经取代的嘧啶 |
| CN114728905B (zh) * | 2019-11-13 | 2025-08-01 | 基因泰克公司 | 治疗性化合物及使用方法 |
| CN110872291B (zh) * | 2019-11-26 | 2021-06-25 | 五邑大学 | 一种四氢吡啶并嘧啶类化合物及其制备方法和应用 |
| CN111557940A (zh) * | 2020-05-28 | 2020-08-21 | 青岛大学附属医院 | Mth1抑制剂th588在制备治疗多发性骨髓瘤的药物中的应用 |
| US11787775B2 (en) | 2020-07-24 | 2023-10-17 | Genentech, Inc. | Therapeutic compounds and methods of use |
| GB202108249D0 (en) * | 2021-06-09 | 2021-07-21 | Univ Of Sussex | Compounds |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB681712A (en) * | 1949-09-14 | 1952-10-29 | Burroughs Wellcome Co | Improvements in or relating to therapeutically useful pyrimidine compounds |
| US2691655A (en) * | 1952-05-24 | 1954-10-12 | Burroughs Wellcome Co | 2-amino-4-substituted amino-6-aryl pyrimidines and process of preparing same |
| WO1986004583A1 (en) | 1985-02-05 | 1986-08-14 | The Upjohn Company | 4-substituted-6-aryl pyrimidine compounds |
| US6169086B1 (en) | 1997-01-27 | 2001-01-02 | Daiichi Pharmaceutical Co., Ltd. | Pyrazole derivatives |
| AU4800299A (en) * | 1998-07-24 | 2000-02-14 | Daiichi Pharmaceutical Co., Ltd. | Pyrazole derivatives and salts thereof |
| WO2002096867A2 (en) | 2001-05-30 | 2002-12-05 | Lg Biomedical Institute | Inhibitors of protein kinase for the treatment of disease |
| IL160327A0 (en) | 2001-08-13 | 2004-07-25 | Janssen Pharmaceutica Nv | 2,4,5-trisubstituted thiazolyl derivatives and their antiinflammatory activity |
| US7419984B2 (en) | 2002-10-17 | 2008-09-02 | Cell Therapeutics, Inc. | Pyrimidines and uses thereof |
| WO2004080979A1 (en) * | 2003-03-14 | 2004-09-23 | Lg Life Sciences Ltd. | Novel 3-(2-amino-4-pyrimidinyl)-4-hydroxyphenyl ketone derivatives |
| WO2005026129A1 (en) | 2003-09-15 | 2005-03-24 | Gpc Biotech Ag | Pharmaceutically active 4,6-disubstituted aminopyrimidine derivatives as modulators of protein kinases |
| AU2005225471B2 (en) | 2004-03-26 | 2011-05-12 | Methylgene Inc. | Inhibitors of histone deacetylase |
| WO2006078886A2 (en) * | 2005-01-18 | 2006-07-27 | Irm Llc | Compounds and compositions as wnt signaling pathway modulators |
| CL2008000467A1 (es) * | 2007-02-14 | 2008-08-22 | Janssen Pharmaceutica Nv | Compuestos derivados de 2-aminopirimidina, moduladores del receptor histamina h4; su procedimiento de preparacion; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar un trastorno inflamatorio seleccionado de alegia, asma |
| CA2714743C (en) | 2008-02-19 | 2017-01-17 | Janssen Pharmaceutica N.V. | Aryl-hydroxyethylamino-pyrimidines and triazines as modulators of fatty acid amide hydrolase |
| US8268846B2 (en) | 2008-07-11 | 2012-09-18 | Abbott Laboratories | Amino heterocyclic linked pyrimidine derivatives |
| JP5743897B2 (ja) * | 2008-11-20 | 2015-07-01 | グラクソスミスクライン・リミテッド・ライアビリティ・カンパニーＧｌａｘｏＳｍｉｔｈＫｌｉｎｅ ＬＬＣ | 化合物 |
| AU2010315190A1 (en) * | 2009-11-05 | 2012-05-10 | Lexicon Pharmaceuticals, Inc. | Tryptophan hydroxylase inhibitors for the treatment of cancer |
| CA2789229A1 (en) * | 2010-02-10 | 2011-08-18 | Lexicon Pharmaceuticals, Inc. | Tryptophan hydroxylase inhibitors for the treatment of metastatic bone disease |
| EP2651405A2 (en) | 2010-12-14 | 2013-10-23 | Electrophoretics Limited | Casein kinase 1 (ck1 ) inhibitors |
| GB201215502D0 (en) | 2012-08-31 | 2012-10-17 | Chalkiadakis Spyridon | Medical use |
| US9604937B2 (en) * | 2012-11-27 | 2017-03-28 | Thomas Helledays Stiftelse For Medicinsk Forskning | Pyrimidine-2,4-diamine derivatives for treatment of cancer |
-
2013
- 2013-11-26 US US14/647,400 patent/US9604937B2/en active Active
- 2013-11-26 KR KR1020157015196A patent/KR102194646B1/ko active Active
- 2013-11-26 PE PE2015000650A patent/PE20151412A1/es not_active Application Discontinuation
- 2013-11-26 EP EP13859400.7A patent/EP2925744B1/en active Active
- 2013-11-26 AU AU2013353542A patent/AU2013353542B2/en active Active
- 2013-11-26 CN CN201380061606.XA patent/CN105143206B/zh active Active
- 2013-11-26 RU RU2015125458A patent/RU2672916C2/ru active
- 2013-11-26 CA CA2888338A patent/CA2888338C/en active Active
- 2013-11-26 PL PL13859400T patent/PL2925744T3/pl unknown
- 2013-11-26 MX MX2015006039A patent/MX373786B/es active IP Right Grant
- 2013-11-26 SG SG11201503783VA patent/SG11201503783VA/en unknown
- 2013-11-26 BR BR112015011497-0A patent/BR112015011497B1/pt active IP Right Grant
- 2013-11-26 MY MYPI2015001271A patent/MY182386A/en unknown
- 2013-11-26 JP JP2015544036A patent/JP6322205B2/ja active Active
- 2013-11-26 WO PCT/SE2013/051387 patent/WO2014084778A1/en not_active Ceased
-
2015
- 2015-05-13 PH PH12015501058A patent/PH12015501058A1/en unknown
- 2015-05-18 ZA ZA2015/03470A patent/ZA201503470B/en unknown
- 2015-05-21 IL IL238942A patent/IL238942B/en active IP Right Grant
- 2015-05-27 CL CL2015001437A patent/CL2015001437A1/es unknown
-
2017
- 2017-03-02 US US15/447,818 patent/US9944640B2/en active Active
-
2018
- 2018-02-19 US US15/899,061 patent/US10174029B2/en active Active
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2016504289A5 (https=) | ||
| RU2015125458A (ru) | Производные пиримидин-2,4-диамина для лечения рака | |
| JP7169412B2 (ja) | 抗癌活性及び抗増殖活性を呈する２－アミノピリミジン－６－オン及び類似体 | |
| CN110573500B (zh) | N-(氮杂芳基)环内酰胺-1-甲酰胺衍生物及其制备方法和应用 | |
| JP2020111602A (ja) | 抗がんおよび抗増殖活性を示すｎ−アシル−ｎ’−（ピリジン−２−イル）尿素および類似体 | |
| JP5843861B2 (ja) | Ａｘｌ阻害剤としての薬学的に活性な化合物 | |
| WO2016026445A1 (zh) | 作为fgfr激酶抑制剂的吲唑类化合物及其制备和应用 | |
| JP2020506244A5 (https=) | ||
| JP2018532786A5 (https=) | ||
| CN108779100A (zh) | 3,4-二吡啶基吡唑类衍生物、其制备方法及其在医药上的应用 | |
| WO2017082688A1 (ko) | 소디움 채널 차단제 | |
| WO2025117536A1 (en) | Hormone receptor modulators | |
| ES2860937T3 (es) | Derivados de pirimidina-2,4-diamina para el tratamiento del cáncer | |
| CN104968654B (zh) | 取代的2-氨基吡啶类蛋白激酶抑制剂 | |
| HK1261495A1 (en) | 3,4-bipyridyl pyrazole derivative, and preparation method therefor and medical application thereof | |
| RU2019127886A (ru) | Гетероциклилсульфонил-замещенные пиридины и их применение при лечении рака |