JP2009506034A5 - - Google Patents
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- Publication number
- JP2009506034A5 JP2009506034A5 JP2008528020A JP2008528020A JP2009506034A5 JP 2009506034 A5 JP2009506034 A5 JP 2009506034A5 JP 2008528020 A JP2008528020 A JP 2008528020A JP 2008528020 A JP2008528020 A JP 2008528020A JP 2009506034 A5 JP2009506034 A5 JP 2009506034A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- aryl
- formula
- cycloalkyl
- heterocyclyl
- 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
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- 150000001875 compounds Chemical class 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 16
- 210000002027 skeletal muscle Anatomy 0.000 claims description 8
- 206010019280 Heart failures Diseases 0.000 claims description 7
- 206010003119 arrhythmia Diseases 0.000 claims description 6
- 206010049418 Sudden Cardiac Death Diseases 0.000 claims description 5
- 230000006870 function Effects 0.000 claims description 5
- 206010047302 ventricular tachycardia Diseases 0.000 claims description 5
- 206010049993 Cardiac death Diseases 0.000 claims description 3
- 206010011906 Death Diseases 0.000 claims description 3
- 206010049565 Muscle fatigue Diseases 0.000 claims description 3
- 208000014321 polymorphic ventricular tachycardia Diseases 0.000 claims description 3
- 206010047281 Ventricular arrhythmia Diseases 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 45
- 125000003118 aryl group Chemical group 0.000 claims 45
- 125000000623 heterocyclic group Chemical group 0.000 claims 36
- 125000000753 cycloalkyl group Chemical group 0.000 claims 35
- 125000003342 alkenyl group Chemical group 0.000 claims 30
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 24
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims 24
- 125000001072 heteroaryl group Chemical group 0.000 claims 22
- 125000002252 acyl group Chemical group 0.000 claims 20
- 125000003545 alkoxy group Chemical group 0.000 claims 16
- 125000003282 alkyl amino group Chemical group 0.000 claims 16
- 125000002877 alkyl aryl group Chemical group 0.000 claims 16
- 150000003839 salts Chemical class 0.000 claims 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 14
- -1 -OS (= O) 2 CF 3 Chemical group 0.000 claims 11
- 125000000304 alkynyl group Chemical group 0.000 claims 10
- 150000007657 benzothiazepines Chemical group 0.000 claims 9
- 201000010099 disease Diseases 0.000 claims 7
- 208000035475 disorder Diseases 0.000 claims 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 6
- 125000005110 aryl thio group Chemical group 0.000 claims 6
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- 125000004414 alkyl thio group Chemical group 0.000 claims 5
- 125000001769 aryl amino group Chemical group 0.000 claims 5
- 229910052736 halogen Inorganic materials 0.000 claims 5
- 208000019622 heart disease Diseases 0.000 claims 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 5
- 229910052757 nitrogen Inorganic materials 0.000 claims 5
- 239000012453 solvate Substances 0.000 claims 5
- 230000002194 synthesizing effect Effects 0.000 claims 5
- 230000006793 arrhythmia Effects 0.000 claims 4
- 230000001746 atrial effect Effects 0.000 claims 4
- 208000010877 cognitive disease Diseases 0.000 claims 4
- 208000013363 skeletal muscle disease Diseases 0.000 claims 4
- 208000020446 Cardiac disease Diseases 0.000 claims 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 3
- 125000005843 halogen group Chemical group 0.000 claims 3
- 229910052760 oxygen Inorganic materials 0.000 claims 3
- 229910052717 sulfur Inorganic materials 0.000 claims 3
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims 2
- 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 claims 2
- 208000000044 Amnesia Diseases 0.000 claims 2
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- 108090000312 Calcium Channels Proteins 0.000 claims 2
- 102000003922 Calcium Channels Human genes 0.000 claims 2
- 208000026139 Memory disease Diseases 0.000 claims 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- 125000004947 alkyl aryl amino group Chemical group 0.000 claims 2
- 150000001412 amines Chemical class 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 150000004820 halides Chemical class 0.000 claims 2
- 150000002367 halogens Chemical class 0.000 claims 2
- 150000004677 hydrates Chemical class 0.000 claims 2
- 230000003834 intracellular effect Effects 0.000 claims 2
- 230000006984 memory degeneration Effects 0.000 claims 2
- 208000023060 memory loss Diseases 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims 2
- 229940002612 prodrug Drugs 0.000 claims 2
- 239000000651 prodrug Substances 0.000 claims 2
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims 2
- 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 claims 1
- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims 1
- HFMBFIQYVXGXHJ-UHFFFAOYSA-N 3,5-dihydro-2h-1,4-benzothiazepin-4-ylmethylphosphonic acid Chemical compound C1N(CP(O)(=O)O)CCSC2=CC=CC=C21 HFMBFIQYVXGXHJ-UHFFFAOYSA-N 0.000 claims 1
- ZGGBEERDYFLGPW-UHFFFAOYSA-N 3-(3,5-dihydro-2h-1,4-benzothiazepin-4-yl)-1-phenylpropan-1-one Chemical compound C1CSC2=CC=CC=C2CN1CCC(=O)C1=CC=CC=C1 ZGGBEERDYFLGPW-UHFFFAOYSA-N 0.000 claims 1
- YATRGOHCGMMZRB-UHFFFAOYSA-N 4-(2,3-dihydrobenzotriazol-1-ylmethyl)-3,5-dihydro-2h-1,4-benzothiazepine Chemical compound C1CSC2=CC=CC=C2CN1CN1C2=CC=CC=C2NN1 YATRGOHCGMMZRB-UHFFFAOYSA-N 0.000 claims 1
- KDVFIRDMILUCHV-UHFFFAOYSA-N 4-(3-phenylprop-2-ynyl)-3,5-dihydro-2h-1,4-benzothiazepine Chemical compound C1CSC2=CC=CC=C2CN1CC#CC1=CC=CC=C1 KDVFIRDMILUCHV-UHFFFAOYSA-N 0.000 claims 1
- YMEMBEJIXHGPGI-UHFFFAOYSA-N 4-(benzotriazol-1-ylmethyl)-3,5-dihydro-2h-1,4-benzothiazepine Chemical compound C1CSC2=CC=CC=C2CN1CN1C2=CC=CC=C2N=N1 YMEMBEJIXHGPGI-UHFFFAOYSA-N 0.000 claims 1
- WLJDAPBDQIXNAI-UHFFFAOYSA-N 4-[(4-chlorophenyl)methyl]-3,5-dihydro-2h-1,4-benzothiazepine Chemical compound C1=CC(Cl)=CC=C1CN1CC2=CC=CC=C2SCC1 WLJDAPBDQIXNAI-UHFFFAOYSA-N 0.000 claims 1
- KWFXDSKKCIWDFV-UHFFFAOYSA-N 4-[(4-methoxyphenyl)methyl]-3,5-dihydro-2h-1,4-benzothiazepine Chemical compound C1=CC(OC)=CC=C1CN1CC2=CC=CC=C2SCC1 KWFXDSKKCIWDFV-UHFFFAOYSA-N 0.000 claims 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical group N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 1
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims 1
- VCOWGXFQDYCGJU-UHFFFAOYSA-N 4-ethyl-3,5-dihydro-2h-1,4-benzothiazepine Chemical compound C1N(CC)CCSC2=CC=CC=C21 VCOWGXFQDYCGJU-UHFFFAOYSA-N 0.000 claims 1
- XRHNTUDLOFKUFB-UHFFFAOYSA-N 4-ethylsulfonyl-3,5-dihydro-2h-1,4-benzothiazepine Chemical compound C1N(S(=O)(=O)CC)CCSC2=CC=CC=C21 XRHNTUDLOFKUFB-UHFFFAOYSA-N 0.000 claims 1
- MVONUVDATWXOLI-UHFFFAOYSA-N 4-methylsulfonyl-3,5-dihydro-2h-1$l^{4},4-benzothiazepine 1-oxide Chemical compound C1N(S(=O)(=O)C)CCS(=O)C2=CC=CC=C21 MVONUVDATWXOLI-UHFFFAOYSA-N 0.000 claims 1
- GQKWMROFTREIMB-UHFFFAOYSA-N 4-methylsulfonyl-3,5-dihydro-2h-1,4-benzothiazepine Chemical compound C1N(S(=O)(=O)C)CCSC2=CC=CC=C21 GQKWMROFTREIMB-UHFFFAOYSA-N 0.000 claims 1
- YJWORHPBMHBZEI-UHFFFAOYSA-N 4-pentyl-3,5-dihydro-2h-1,4-benzothiazepine Chemical compound C1N(CCCCC)CCSC2=CC=CC=C21 YJWORHPBMHBZEI-UHFFFAOYSA-N 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 206010003658 Atrial Fibrillation Diseases 0.000 claims 1
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- 206010020844 Hyperthermia malignant Diseases 0.000 claims 1
- 208000018717 Malignant hyperthermia of anesthesia Diseases 0.000 claims 1
- 208000034972 Sudden Infant Death Diseases 0.000 claims 1
- 206010042440 Sudden infant death syndrome Diseases 0.000 claims 1
- 206010046543 Urinary incontinence Diseases 0.000 claims 1
- 239000002253 acid Substances 0.000 claims 1
- 239000003963 antioxidant agent Substances 0.000 claims 1
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- 239000007884 disintegrant Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 239000003995 emulsifying agent Substances 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 239000000796 flavoring agent Substances 0.000 claims 1
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- 125000005842 heteroatom Chemical group 0.000 claims 1
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- 201000006938 muscular dystrophy Diseases 0.000 claims 1
- GKBMXTYBSIKIQE-UHFFFAOYSA-N n-butyl-3,5-dihydro-2h-1,4-benzothiazepine-4-carbothioamide Chemical compound C1N(C(=S)NCCCC)CCSC2=CC=CC=C21 GKBMXTYBSIKIQE-UHFFFAOYSA-N 0.000 claims 1
- SHLXIBJVRTYBJU-UHFFFAOYSA-N n-phenyl-3,5-dihydro-2h-1,4-benzothiazepine-4-carboxamide Chemical compound C1CSC2=CC=CC=C2CN1C(=O)NC1=CC=CC=C1 SHLXIBJVRTYBJU-UHFFFAOYSA-N 0.000 claims 1
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- REQCZEXYDRLIBE-UHFFFAOYSA-N procainamide Chemical compound CCN(CC)CCNC(=O)C1=CC=C(N)C=C1 REQCZEXYDRLIBE-UHFFFAOYSA-N 0.000 claims 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 claims 1
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- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
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- 108010012219 Ryanodine Receptor Calcium Release Channel Proteins 0.000 description 54
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- KCWGETCFOVJEPI-UHFFFAOYSA-N jtv-519 Chemical compound C1C2=CC(OC)=CC=C2SCCN1C(=O)CCN(CC1)CCC1CC1=CC=CC=C1 KCWGETCFOVJEPI-UHFFFAOYSA-N 0.000 description 41
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- FPWBHFYYVSNIFZ-UHFFFAOYSA-N 2-(7-methoxy-3,5-dihydro-2h-1,4-benzothiazepin-4-yl)-2-oxoacetic acid Chemical compound S1CCN(C(=O)C(O)=O)CC2=CC(OC)=CC=C21 FPWBHFYYVSNIFZ-UHFFFAOYSA-N 0.000 description 4
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- DKKLXCRMAXNIJF-UHFFFAOYSA-N 3-(4-benzylpiperidin-1-yl)-1-(7-methoxy-3,5-dihydro-2h-1,4-benzothiazepin-4-yl)propan-1-one;hydrochloride Chemical compound Cl.C1C2=CC(OC)=CC=C2SCCN1C(=O)CCN(CC1)CCC1CC1=CC=CC=C1 DKKLXCRMAXNIJF-UHFFFAOYSA-N 0.000 description 1
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- QSVICPLKGCIIQP-UHFFFAOYSA-N COc(cc1CN(CC2)C(CCN3CCC(Cc4ccccc4)CC3)=O)ccc1S2(=O)=O Chemical compound COc(cc1CN(CC2)C(CCN3CCC(Cc4ccccc4)CC3)=O)ccc1S2(=O)=O QSVICPLKGCIIQP-UHFFFAOYSA-N 0.000 description 1
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- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/212,413 | 2005-08-25 | ||
| US11/212,413 US7704990B2 (en) | 2005-08-25 | 2005-08-25 | Agents for preventing and treating disorders involving modulation of the RyR receptors |
| PCT/US2006/032405 WO2007024717A2 (en) | 2005-08-25 | 2006-08-17 | Agents for preventing and treating disorders involving modulation of the ryr receptors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2009506034A JP2009506034A (ja) | 2009-02-12 |
| JP2009506034A5 true JP2009506034A5 (https=) | 2012-05-17 |
| JP5342877B2 JP5342877B2 (ja) | 2013-11-13 |
Family
ID=37772221
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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