JP2015531373A5

JP2015531373A5 -

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Publication number: JP2015531373A5
Authority: JP; Japan
Prior art keywords: methylbenzamide; oxo; fluoro; cyano; diazaspiro
Prior art date: 2013-09-23
Legal status : Granted

Application number

JP2015534582A

Other languages

English (en)

Japanese (ja)

Other versions

JP6351597B2 (ja

JP2015531373A (ja

Filing date

2013-09-23

Publication date

2016-11-04

2013-09-23 Application filed filed Critical

2013-09-23 Priority claimed from PCT/US2013/061197 external-priority patent/WO2014052237A1/en

2015-11-02 Publication of JP2015531373A publication Critical patent/JP2015531373A/ja

2016-11-04 Publication of JP2015531373A5 publication Critical patent/JP2015531373A5/ja

2018-07-04 Application granted granted Critical

2018-07-04 Publication of JP6351597B2 publication Critical patent/JP6351597B2/ja

Status Active legal-status Critical Current

2033-09-23 Anticipated expiration legal-status Critical

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NAGFMACWWJYORB-UHFFFAOYSA-N 2-fluoro-n-methylbenzamide Chemical compound CNC(=O)C1=CC=CC=C1F NAGFMACWWJYORB-UHFFFAOYSA-N 0.000 claims description 28
-1 6-cyano-5-trifluoromethylpyridin-3-yl Chemical group 0.000 claims description 24
238000000034 method Methods 0.000 claims description 24
206010060862 Prostate cancer Diseases 0.000 claims description 21
208000000236 Prostatic Neoplasms Diseases 0.000 claims description 21
230000000683 nonmetastatic effect Effects 0.000 claims description 15
239000000051 antiandrogen Substances 0.000 claims description 9
206010027476 Metastases Diseases 0.000 claims description 5
230000004083 survival effect Effects 0.000 claims description 5
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
102000007066 Prostate-Specific Antigen Human genes 0.000 claims description 2
108010072866 Prostate-Specific Antigen Proteins 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims 20
150000001875 compounds Chemical class 0.000 claims 15
239000000579 Gonadotropin-Releasing Hormone Substances 0.000 claims 14
101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 claims 14
XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 claims 14
229940035638 gonadotropin-releasing hormone Drugs 0.000 claims 14
BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 claims 8
108010069236 Goserelin Proteins 0.000 claims 8
108010000817 Leuprolide Proteins 0.000 claims 8
229960002913 goserelin Drugs 0.000 claims 8
GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 claims 8
229960004338 leuprorelin Drugs 0.000 claims 8
239000000556 agonist Substances 0.000 claims 7
HJBWBFZLDZWPHF-UHFFFAOYSA-N apalutamide Chemical compound C1=C(F)C(C(=O)NC)=CC=C1N1C2(CCC2)C(=O)N(C=2C=C(C(C#N)=NC=2)C(F)(F)F)C1=S HJBWBFZLDZWPHF-UHFFFAOYSA-N 0.000 claims 5
108010037003 Buserelin Proteins 0.000 claims 4
GJKXGJCSJWBJEZ-XRSSZCMZSA-N Deslorelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CNC2=CC=CC=C12 GJKXGJCSJWBJEZ-XRSSZCMZSA-N 0.000 claims 4
108010021717 Nafarelin Proteins 0.000 claims 4
229960002719 buserelin Drugs 0.000 claims 4
CUWODFFVMXJOKD-UVLQAERKSA-N buserelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 CUWODFFVMXJOKD-UVLQAERKSA-N 0.000 claims 4
229960005408 deslorelin Drugs 0.000 claims 4
108700025485 deslorelin Proteins 0.000 claims 4
HHXHVIJIIXKSOE-QILQGKCVSA-N histrelin Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC(N=C1)=CN1CC1=CC=CC=C1 HHXHVIJIIXKSOE-QILQGKCVSA-N 0.000 claims 4
108700020746 histrelin Proteins 0.000 claims 4
229960002193 histrelin Drugs 0.000 claims 4
RWHUEXWOYVBUCI-ITQXDASVSA-N nafarelin Chemical compound C([C@@H](C(=O)N[C@H](CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 RWHUEXWOYVBUCI-ITQXDASVSA-N 0.000 claims 4
229960002333 nafarelin Drugs 0.000 claims 4
JPQFGMYHKSKKGW-UHFFFAOYSA-N 4-[7-[4-cyano-3-(trifluoromethyl)phenyl]-8-oxo-6-sulfanylidene-5,7-diazaspiro[3.4]octan-5-yl]-2-fluoro-n-methylbenzamide Chemical compound C1=C(F)C(C(=O)NC)=CC=C1N1C2(CCC2)C(=O)N(C=2C=C(C(C#N)=CC=2)C(F)(F)F)C1=S JPQFGMYHKSKKGW-UHFFFAOYSA-N 0.000 claims 3
239000003814 drug Substances 0.000 claims 3
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 2
238000004519 manufacturing process Methods 0.000 claims 2
XXUNIGZDNWWYED-UHFFFAOYSA-N 2-methylbenzamide Chemical compound CC1=CC=CC=C1C(N)=O XXUNIGZDNWWYED-UHFFFAOYSA-N 0.000 claims 1
239000000203 mixture Substances 0.000 claims 1
230000002280 anti-androgenic effect Effects 0.000 description 4
102000001307 androgen receptors Human genes 0.000 description 1
108010080146 androgen receptors Proteins 0.000 description 1
108020001756 ligand binding domains Proteins 0.000 description 1
239000003956 nonsteroidal anti androgen Substances 0.000 description 1

JP2015534582A 2012-09-26 2013-09-23 非転移性去勢抵抗性前立腺癌の治療のための抗アンドロゲン剤 Active JP6351597B2 (ja)