ZA200508080B - 4,4-difluoro-1,2,3,4-tetrhydro-5H-1-benzazepine derivative or salt thereof - Google Patents
4,4-difluoro-1,2,3,4-tetrhydro-5H-1-benzazepine derivative or salt thereof Download PDFInfo
- Publication number
- ZA200508080B ZA200508080B ZA200508080A ZA200508080A ZA200508080B ZA 200508080 B ZA200508080 B ZA 200508080B ZA 200508080 A ZA200508080 A ZA 200508080A ZA 200508080 A ZA200508080 A ZA 200508080A ZA 200508080 B ZA200508080 B ZA 200508080B
- Authority
- ZA
- South Africa
- Prior art keywords
- tetrahydro
- benzazepin
- ylidene
- trifluoromethyl
- benzoyl
- Prior art date
Links
- 150000003839 salts Chemical class 0.000 title claims description 15
- DTSDJGNXLLPHFA-UHFFFAOYSA-N 4,4-difluoro-1,2,3,5-tetrahydro-1-benzazepine Chemical class C1C(F)(F)CCNC2=CC=CC=C21 DTSDJGNXLLPHFA-UHFFFAOYSA-N 0.000 title claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 35
- 150000001875 compounds Chemical class 0.000 claims description 30
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- 208000003450 Neurogenic Diabetes Insipidus Diseases 0.000 claims description 8
- 208000028235 central diabetes insipidus Diseases 0.000 claims description 8
- 201000010064 diabetes insipidus Diseases 0.000 claims description 8
- 201000005119 neurohypophyseal diabetes insipidus Diseases 0.000 claims description 8
- 101800001144 Arg-vasopressin Proteins 0.000 claims description 7
- 102100026383 Vasopressin-neurophysin 2-copeptin Human genes 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 7
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 claims description 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 7
- 206010029446 nocturia Diseases 0.000 claims description 7
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- LKJPYSCBVHEWIU-UHFFFAOYSA-N N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-fluorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide Chemical compound C=1C=C(C#N)C(C(F)(F)F)=CC=1NC(=O)C(O)(C)CS(=O)(=O)C1=CC=C(F)C=C1 LKJPYSCBVHEWIU-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 239000000018 receptor agonist Substances 0.000 claims description 3
- 229940044601 receptor agonist Drugs 0.000 claims description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- AZVGAXMUJCVNIU-PDGQHHTCSA-N 3-[[(2z)-2-[1-[4-(2,2-difluoropropoxy)-2-(trifluoromethyl)benzoyl]-4,4,7-trifluoro-2,3-dihydro-1-benzazepin-5-ylidene]acetyl]amino]propanamide Chemical compound FC(F)(F)C1=CC(OCC(F)(F)C)=CC=C1C(=O)N1C2=CC=C(F)C=C2C(=C/C(=O)NCCC(N)=O)/C(F)(F)CC1 AZVGAXMUJCVNIU-PDGQHHTCSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 description 16
- 102000005962 receptors Human genes 0.000 description 13
- 108020003175 receptors Proteins 0.000 description 13
- -1 (2Z)-2-{1-[4-(2,2-difluoropropoxy)-2-(trifluoromethyl)benzoyl]-4,4,7- trifluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene } acetyl Chemical group 0.000 description 9
- 229940079593 drug Drugs 0.000 description 8
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 6
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 6
- 239000000556 agonist Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- DQFQCHIDRBIESA-UHFFFAOYSA-N 1-benzazepine Chemical group N1C=CC=CC2=CC=CC=C12 DQFQCHIDRBIESA-UHFFFAOYSA-N 0.000 description 3
- 108010000437 Deamino Arginine Vasopressin Proteins 0.000 description 3
- 206010013710 Drug interaction Diseases 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 230000001270 agonistic effect Effects 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 230000002686 anti-diuretic effect Effects 0.000 description 2
- 229940124538 antidiuretic agent Drugs 0.000 description 2
- 239000003160 antidiuretic agent Substances 0.000 description 2
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 150000008038 benzoazepines Chemical class 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 229960004281 desmopressin Drugs 0.000 description 2
- NFLWUMRGJYTJIN-NXBWRCJVSA-N desmopressin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSCCC(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(N)=O)=O)CCC(=O)N)C1=CC=CC=C1 NFLWUMRGJYTJIN-NXBWRCJVSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 125000005842 heteroatom Chemical group 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- JMCFRZPWDILQBV-PDGQHHTCSA-N (2z)-2-[1-[4-(2,2-difluoropropoxy)-2-(trifluoromethyl)benzoyl]-4,4,7-trifluoro-2,3-dihydro-1-benzazepin-5-ylidene]-n-(2-hydroxyethyl)acetamide Chemical compound FC(F)(F)C1=CC(OCC(F)(F)C)=CC=C1C(=O)N1C2=CC=C(F)C=C2C(=C/C(=O)NCCO)/C(F)(F)CC1 JMCFRZPWDILQBV-PDGQHHTCSA-N 0.000 description 1
- FYBNGXISSSDXFG-FPXKJXHESA-N (2z)-2-[4,4-difluoro-1-[4-propoxy-2-(trifluoromethyl)benzoyl]-2,3-dihydro-1-benzazepin-5-ylidene]-n-[(2r)-2,3-dihydroxypropyl]acetamide Chemical compound FC(F)(F)C1=CC(OCCC)=CC=C1C(=O)N1C2=CC=CC=C2C(=C/C(=O)NC[C@@H](O)CO)/C(F)(F)CC1 FYBNGXISSSDXFG-FPXKJXHESA-N 0.000 description 1
- VSXSHTIGQAUGMW-VCRXTVNUSA-N (2z)-n-(2-hydroxyethyl)-2-[4,4,7-trifluoro-1-[4-[(2r)-2-fluoropropoxy]-2-(trifluoromethyl)benzoyl]-2,3-dihydro-1-benzazepin-5-ylidene]acetamide Chemical compound FC(F)(F)C1=CC(OC[C@H](F)C)=CC=C1C(=O)N1C2=CC=C(F)C=C2C(=C/C(=O)NCCO)/C(F)(F)CC1 VSXSHTIGQAUGMW-VCRXTVNUSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000004972 1-butynyl group Chemical group [H]C([H])([H])C([H])([H])C#C* 0.000 description 1
- 125000006039 1-hexenyl group Chemical group 0.000 description 1
- AGLYQHFXGAHYRJ-CCOVPTLTSA-N 2-[[(2z)-2-[4,4,7-trifluoro-1-[4-[(2r)-2-fluoropropoxy]-2-(trifluoromethyl)benzoyl]-2,3-dihydro-1-benzazepin-5-ylidene]acetyl]amino]acetamide Chemical compound FC(F)(F)C1=CC(OC[C@H](F)C)=CC=C1C(=O)N1C2=CC=C(F)C=C2C(=C/C(=O)NCC(N)=O)/C(F)(F)CC1 AGLYQHFXGAHYRJ-CCOVPTLTSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- JIYIAXGCGNHSKR-YQNUULROSA-N 3-[[(2z)-2-[4,4,7-trifluoro-1-[4-[(2s)-2-fluoropropoxy]-2-(trifluoromethyl)benzoyl]-2,3-dihydro-1-benzazepin-5-ylidene]acetyl]amino]propanamide Chemical compound FC(F)(F)C1=CC(OC[C@@H](F)C)=CC=C1C(=O)N1C2=CC=C(F)C=C2C(=C/C(=O)NCCC(N)=O)/C(F)(F)CC1 JIYIAXGCGNHSKR-YQNUULROSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- 125000006041 3-hexenyl group Chemical group 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 108010000543 Cytochrome P-450 CYP2C9 Proteins 0.000 description 1
- 102000004328 Cytochrome P-450 CYP3A Human genes 0.000 description 1
- 108010081668 Cytochrome P-450 CYP3A Proteins 0.000 description 1
- 102100029358 Cytochrome P450 2C9 Human genes 0.000 description 1
- 108090000876 Oxytocin receptors Proteins 0.000 description 1
- 102000004279 Oxytocin receptors Human genes 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 150000001538 azepines Chemical class 0.000 description 1
- 125000002785 azepinyl group Chemical group 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000000392 cycloalkenyl group Chemical group 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 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 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
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000002541 furyl 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
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000005394 methallyl group Chemical group 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003123032 | 2003-04-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200508080B true ZA200508080B (en) | 2007-03-28 |
Family
ID=36770628
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200508080A ZA200508080B (en) | 2003-04-28 | 2004-04-26 | 4,4-difluoro-1,2,3,4-tetrhydro-5H-1-benzazepine derivative or salt thereof |
Country Status (3)
| Country | Link |
|---|---|
| CN (2) | CN100404511C (zh) |
| ES (1) | ES2366641T3 (zh) |
| ZA (1) | ZA200508080B (zh) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012043791A1 (ja) * | 2010-10-01 | 2012-04-05 | 大正製薬株式会社 | １，２，４-トリアゾロン誘導体 |
| US9586905B2 (en) * | 2012-12-26 | 2017-03-07 | Sanwa Kagaku Kenkyusho Co., Ltd. | Benzoazepine derivative and medical use thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL182011B1 (en) * | 1993-08-26 | 2001-10-31 | Yamanouchi Pharma Co Ltd | Benzazepine derivative, pharmaceutic composition and intermediate compounds |
| JP3215910B2 (ja) * | 1994-06-15 | 2001-10-09 | 大塚製薬株式会社 | ベンゾヘテロ環誘導体 |
| JPH09221476A (ja) * | 1995-12-15 | 1997-08-26 | Otsuka Pharmaceut Co Ltd | 医薬組成物 |
| AR011913A1 (es) * | 1997-03-06 | 2000-09-13 | Yamano Masaki | Derivados de 4,4-difluoro-2,3,4,5-tetrahidro-1h-1-benzoazepina y composiciones farmaceuticas de los mismos. |
-
2004
- 2004-04-26 ES ES04729502T patent/ES2366641T3/es not_active Expired - Lifetime
- 2004-04-26 CN CNB2004800113447A patent/CN100404511C/zh not_active Expired - Fee Related
- 2004-04-26 ZA ZA200508080A patent/ZA200508080B/en unknown
- 2004-04-26 CN CNA2008100999960A patent/CN101279971A/zh active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| CN1780819A (zh) | 2006-05-31 |
| CN100404511C (zh) | 2008-07-23 |
| ES2366641T3 (es) | 2011-10-24 |
| CN101279971A (zh) | 2008-10-08 |
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