JP2020536965A5 - - Google Patents

Info

Publication number

JP2020536965A5

JP2020536965A5 JP2020541641A JP2020541641A JP2020536965A5 JP 2020536965 A5 JP2020536965 A5 JP 2020536965A5 JP 2020541641 A JP2020541641 A JP 2020541641A JP 2020541641 A JP2020541641 A JP 2020541641A JP 2020536965 A5 JP2020536965 A5 JP 2020536965A5

Authority

JP

Japan

Prior art keywords

approved

formulation

preparation

appartamide

prostate cancer

Prior art date

2018-04-30

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

• Espacenet
• Global Dossier
• Discuss

• 238000009472 formulation Methods 0.000 claims description 61
• 239000000203 mixture Substances 0.000 claims description 61
• 238000000034 method Methods 0.000 claims description 55
• 230000000683 nonmetastatic effect Effects 0.000 claims description 27
• 206010060862 Prostate cancer Diseases 0.000 claims description 26
• 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 26
• 230000004083 survival effect Effects 0.000 claims description 26
• 206010027476 Metastases Diseases 0.000 claims description 20
• 239000000051 antiandrogen Substances 0.000 claims description 19
• 229940079593 drug Drugs 0.000 claims description 18
• 239000003814 drug Substances 0.000 claims description 18
• 238000010317 ablation therapy Methods 0.000 claims description 10
• 239000003098 androgen Substances 0.000 claims description 10
• 230000002280 anti-androgenic effect Effects 0.000 claims description 6
• 229960004671 enzalutamide Drugs 0.000 claims description 6
• WXCXUHSOUPDCQV-UHFFFAOYSA-N enzalutamide Chemical compound C1=C(F)C(C(=O)NC)=CC=C1N1C(C)(C)C(=O)N(C=2C=C(C(C#N)=CC=2)C(F)(F)F)C1=S WXCXUHSOUPDCQV-UHFFFAOYSA-N 0.000 claims description 6
• 239000000758 substrate Substances 0.000 claims description 6
• 206010028980 Neoplasm Diseases 0.000 claims description 5
• 201000011510 cancer Diseases 0.000 claims description 5
• IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 claims description 4
• NIJJYAXOARWZEE-UHFFFAOYSA-N Valproic acid Chemical compound CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 230000001394 metastastic effect Effects 0.000 claims description 4
• 206010061289 metastatic neoplasm Diseases 0.000 claims description 4
• 238000011282 treatment Methods 0.000 claims description 4
• XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 claims description 2
• SUBDBMMJDZJVOS-UHFFFAOYSA-N 5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole Chemical compound N=1C2=CC(OC)=CC=C2NC=1S(=O)CC1=NC=C(C)C(OC)=C1C SUBDBMMJDZJVOS-UHFFFAOYSA-N 0.000 claims description 2
• RZTAMFZIAATZDJ-HNNXBMFYSA-N 5-o-ethyl 3-o-methyl (4s)-4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound CCOC(=O)C1=C(C)NC(C)=C(C(=O)OC)[C@@H]1C1=CC=CC(Cl)=C1Cl RZTAMFZIAATZDJ-HNNXBMFYSA-N 0.000 claims description 2
• 239000005552 B01AC04 - Clopidogrel Substances 0.000 claims description 2
• 102100022595 Broad substrate specificity ATP-binding cassette transporter ABCG2 Human genes 0.000 claims description 2
• 108010026925 Cytochrome P-450 CYP2C19 Proteins 0.000 claims description 2
• 208000006619 Cytochrome P-450 CYP2C8 Inhibitors Diseases 0.000 claims description 2
• 108010000543 Cytochrome P-450 CYP2C9 Proteins 0.000 claims description 2
• 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 claims description 2
• 208000009011 Cytochrome P-450 CYP3A Inhibitors Diseases 0.000 claims description 2
• 102100029363 Cytochrome P450 2C19 Human genes 0.000 claims description 2
• 102100029358 Cytochrome P450 2C9 Human genes 0.000 claims description 2
• 102100039205 Cytochrome P450 3A4 Human genes 0.000 claims description 2
• LTMHDMANZUZIPE-AMTYYWEZSA-N Digoxin Natural products O([C@H]1[C@H](C)O[C@H](O[C@@H]2C[C@@H]3[C@@](C)([C@@H]4[C@H]([C@]5(O)[C@](C)([C@H](O)C4)[C@H](C4=CC(=O)OC4)CC5)CC3)CC2)C[C@@H]1O)[C@H]1O[C@H](C)[C@@H](O[C@H]2O[C@@H](C)[C@H](O)[C@@H](O)C2)[C@@H](O)C1 LTMHDMANZUZIPE-AMTYYWEZSA-N 0.000 claims description 2
• HEMJJKBWTPKOJG-UHFFFAOYSA-N Gemfibrozil Chemical compound CC1=CC=C(C)C(OCCCC(C)(C)C(O)=O)=C1 HEMJJKBWTPKOJG-UHFFFAOYSA-N 0.000 claims description 2
• 101000823298 Homo sapiens Broad substrate specificity ATP-binding cassette transporter ABCG2 Proteins 0.000 claims description 2
• FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims description 2
• XUIIKFGFIJCVMT-LBPRGKRZSA-N L-thyroxine Chemical compound IC1=CC(C[C@H]([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-LBPRGKRZSA-N 0.000 claims description 2
• 239000002136 L01XE07 - Lapatinib Substances 0.000 claims description 2
• CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 claims description 2
• 102000007066 Prostate-Specific Antigen Human genes 0.000 claims description 2
• 108010072866 Prostate-Specific Antigen Proteins 0.000 claims description 2
• NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 claims description 2
• RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 2
• 108091006731 SLCO1B1 Proteins 0.000 claims description 2
• 102100027233 Solute carrier organic anion transporter family member 1B1 Human genes 0.000 claims description 2
• 230000000259 anti-tumor effect Effects 0.000 claims description 2
• 239000003795 chemical substances by application Substances 0.000 claims description 2
• GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 claims description 2
• 229960003009 clopidogrel Drugs 0.000 claims description 2
• 229960001338 colchicine Drugs 0.000 claims description 2
• 238000011393 cytotoxic chemotherapy Methods 0.000 claims description 2
• 229960000288 dabigatran etexilate Drugs 0.000 claims description 2
• KSGXQBZTULBEEQ-UHFFFAOYSA-N dabigatran etexilate Chemical compound C1=CC(C(N)=NC(=O)OCCCCCC)=CC=C1NCC1=NC2=CC(C(=O)N(CCC(=O)OCC)C=3N=CC=CC=3)=CC=C2N1C KSGXQBZTULBEEQ-UHFFFAOYSA-N 0.000 claims description 2
• 229960005107 darunavir Drugs 0.000 claims description 2
• CJBJHOAVZSMMDJ-HEXNFIEUSA-N darunavir Chemical compound C([C@@H]([C@H](O)CN(CC(C)C)S(=O)(=O)C=1C=CC(N)=CC=1)NC(=O)O[C@@H]1[C@@H]2CCO[C@@H]2OC1)C1=CC=CC=C1 CJBJHOAVZSMMDJ-HEXNFIEUSA-N 0.000 claims description 2
• 229960003529 diazepam Drugs 0.000 claims description 2
• AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims description 2
• 229960005156 digoxin Drugs 0.000 claims description 2
• LTMHDMANZUZIPE-PUGKRICDSA-N digoxin Chemical compound C1[C@H](O)[C@H](O)[C@@H](C)O[C@H]1O[C@@H]1[C@@H](C)O[C@@H](O[C@@H]2[C@H](O[C@@H](O[C@@H]3C[C@@H]4[C@]([C@@H]5[C@H]([C@]6(CC[C@@H]([C@@]6(C)[C@H](O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)C[C@@H]2O)C)C[C@@H]1O LTMHDMANZUZIPE-PUGKRICDSA-N 0.000 claims description 2
• LTMHDMANZUZIPE-UHFFFAOYSA-N digoxine Natural products C1C(O)C(O)C(C)OC1OC1C(C)OC(OC2C(OC(OC3CC4C(C5C(C6(CCC(C6(C)C(O)C5)C=5COC(=O)C=5)O)CC4)(C)CC3)CC2O)C)CC1O LTMHDMANZUZIPE-UHFFFAOYSA-N 0.000 claims description 2
• 229960003580 felodipine Drugs 0.000 claims description 2
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 2
• 229960003592 fexofenadine Drugs 0.000 claims description 2
• 229960002074 flutamide Drugs 0.000 claims description 2
• MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 claims description 2
• 229960003627 gemfibrozil Drugs 0.000 claims description 2
• 229960004125 ketoconazole Drugs 0.000 claims description 2
• BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 claims description 2
• 229960004891 lapatinib Drugs 0.000 claims description 2
• 229950008325 levothyroxine Drugs 0.000 claims description 2
• 230000009401 metastasis Effects 0.000 claims description 2
• 229960000485 methotrexate Drugs 0.000 claims description 2
• 229960003793 midazolam Drugs 0.000 claims description 2
• DDLIGBOFAVUZHB-UHFFFAOYSA-N midazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NC=C2CN=C1C1=CC=CC=C1F DDLIGBOFAVUZHB-UHFFFAOYSA-N 0.000 claims description 2
• 229960000381 omeprazole Drugs 0.000 claims description 2
• 229960002036 phenytoin Drugs 0.000 claims description 2
• 229960000311 ritonavir Drugs 0.000 claims description 2
• NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 claims description 2
• 229960000672 rosuvastatin Drugs 0.000 claims description 2
• BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 2
• 229960002855 simvastatin Drugs 0.000 claims description 2
• RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 2
• 239000007909 solid dosage form Substances 0.000 claims description 2
• 208000024891 symptom Diseases 0.000 claims description 2
• XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 claims description 2
• 229960000604 valproic acid Drugs 0.000 claims description 2
• PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 claims description 2
• 229960005080 warfarin Drugs 0.000 claims description 2
• 238000012986 modification Methods 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
• 239000013583 drug formulation Substances 0.000 description 1
• 210000002307 prostate Anatomy 0.000 description 1
• 229960002354 repaglinide Drugs 0.000 description 1