ES2878054T3 - Espiroheptanil hidantoínas como inhibidores de ROCK - Google Patents
Espiroheptanil hidantoínas como inhibidores de ROCK Download PDFInfo
- Publication number
- ES2878054T3 ES2878054T3 ES18752653T ES18752653T ES2878054T3 ES 2878054 T3 ES2878054 T3 ES 2878054T3 ES 18752653 T ES18752653 T ES 18752653T ES 18752653 T ES18752653 T ES 18752653T ES 2878054 T3 ES2878054 T3 ES 2878054T3
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- ES
- Spain
- Prior art keywords
- alkyl
- heptan
- heterocycle
- carbocycle
- oxy
- Prior art date
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- 239000011435 rock Substances 0.000 title description 42
- 239000003112 inhibitor Substances 0.000 title description 12
- 150000001469 hydantoins Chemical class 0.000 title description 9
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 442
- 150000001875 compounds Chemical class 0.000 claims abstract description 146
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 118
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 106
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 67
- 150000002367 halogens Chemical class 0.000 claims abstract description 66
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 61
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 59
- 150000003839 salts Chemical class 0.000 claims abstract description 55
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 48
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 48
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 47
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 45
- 239000012453 solvate Substances 0.000 claims abstract description 41
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 37
- 101100495911 Arabidopsis thaliana CHR10 gene Proteins 0.000 claims abstract description 35
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 28
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 25
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 14
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims abstract description 12
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims abstract description 12
- 150000001721 carbon Chemical group 0.000 claims abstract description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims abstract description 8
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 5
- 229910052701 rubidium Inorganic materials 0.000 claims abstract description 5
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract 5
- -1 carbocycle Chemical group 0.000 claims description 154
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 95
- 235000005152 nicotinamide Nutrition 0.000 claims description 70
- 239000011570 nicotinamide Substances 0.000 claims description 70
- 125000003003 spiro group Chemical group 0.000 claims description 55
- 229910052739 hydrogen Inorganic materials 0.000 claims description 46
- 229910052717 sulfur Inorganic materials 0.000 claims description 38
- 238000011282 treatment Methods 0.000 claims description 28
- 229960003966 nicotinamide Drugs 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
- 229910004013 NO 2 Inorganic materials 0.000 claims description 20
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 19
- 239000003814 drug Substances 0.000 claims description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 14
- 230000000694 effects Effects 0.000 claims description 14
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 12
- 229940079593 drug Drugs 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 10
- 108010041788 rho-Associated Kinases Proteins 0.000 claims description 9
- 102000000568 rho-Associated Kinases Human genes 0.000 claims description 9
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 8
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 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 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 208000035475 disorder Diseases 0.000 claims description 7
- 238000011321 prophylaxis Methods 0.000 claims description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 206010019280 Heart failures Diseases 0.000 claims description 5
- 230000001594 aberrant effect Effects 0.000 claims description 5
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 claims description 5
- 206010002383 Angina Pectoris Diseases 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 230000003176 fibrotic effect Effects 0.000 claims description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 3
- 208000029078 coronary artery disease Diseases 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
- 206010061216 Infarction Diseases 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 230000007574 infarction Effects 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 claims 6
- DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims 6
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims 3
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims 2
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 2
- 125000004282 imidazolidin-2-yl group Chemical group [H]N1C([H])([H])C([H])([H])N([H])C1([H])* 0.000 claims 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
- 125000006516 2-(benzyloxy)ethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 1
- 125000000134 2-(methylsulfanyl)ethyl group Chemical group [H]C([H])([H])SC([H])([H])C([H])([H])[*] 0.000 claims 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims 1
- 125000005916 2-methylpentyl group Chemical group 0.000 claims 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims 1
- 208000023275 Autoimmune disease Diseases 0.000 claims 1
- NRBZGXSYLFWLJH-PSWASXTPSA-N C(C1=CC=CC=C1)[C@H]1NC(N(C1=O)C1CC2(CC(C2)OC2=NC=CC=C2C(=O)N)C1)=O Chemical compound C(C1=CC=CC=C1)[C@H]1NC(N(C1=O)C1CC2(CC(C2)OC2=NC=CC=C2C(=O)N)C1)=O NRBZGXSYLFWLJH-PSWASXTPSA-N 0.000 claims 1
- GIILBOOEKVDWPQ-UHFFFAOYSA-N NC(=O)C1=C(OC2CC3(C2)CC(C3)N2C(=O)CN(C2=O)C2=CC=CC=C2)N=CC=C1 Chemical compound NC(=O)C1=C(OC2CC3(C2)CC(C3)N2C(=O)CN(C2=O)C2=CC=CC=C2)N=CC=C1 GIILBOOEKVDWPQ-UHFFFAOYSA-N 0.000 claims 1
- VIQMCVQBGKFAQN-UHFFFAOYSA-N NC(=O)C1=C(OC2CC3(C2)CC(C3)N2C(=O)CN(CC3=CC=CC=C3)C2=O)N=CC=C1 Chemical compound NC(=O)C1=C(OC2CC3(C2)CC(C3)N2C(=O)CN(CC3=CC=CC=C3)C2=O)N=CC=C1 VIQMCVQBGKFAQN-UHFFFAOYSA-N 0.000 claims 1
- 208000031481 Pathologic Constriction Diseases 0.000 claims 1
- 208000018262 Peripheral vascular disease Diseases 0.000 claims 1
- 206010047163 Vasospasm Diseases 0.000 claims 1
- 230000000747 cardiac effect Effects 0.000 claims 1
- 208000026106 cerebrovascular disease Diseases 0.000 claims 1
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 1
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims 1
- 210000004072 lung Anatomy 0.000 claims 1
- 210000003205 muscle Anatomy 0.000 claims 1
- 230000002981 neuropathic effect Effects 0.000 claims 1
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 claims 1
- 230000000771 oncological effect Effects 0.000 claims 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims 1
- 208000037804 stenosis Diseases 0.000 claims 1
- 230000036262 stenosis Effects 0.000 claims 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 55
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract description 16
- 125000004429 atom Chemical group 0.000 abstract description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 abstract 2
- 229910006074 SO2NH2 Inorganic materials 0.000 abstract 2
- XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 abstract 1
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 abstract 1
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 abstract 1
- 108010081348 HRT1 protein Hairy Proteins 0.000 abstract 1
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 abstract 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 abstract 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 abstract 1
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- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
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- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- PHCBRBWANGJMHS-UHFFFAOYSA-J tetrasodium;disulfate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O PHCBRBWANGJMHS-UHFFFAOYSA-J 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 125000004627 thianthrenyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3SC12)* 0.000 description 1
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- 238000012546 transfer Methods 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
- 235000019798 tripotassium phosphate Nutrition 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- HFNHAPQMXICKCF-USJMABIRSA-N urotensin-ii Chemical compound N([C@@H](CC(O)=O)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@@H](C(C)C)C(O)=O)C(=O)[C@@H]1CCCN1C(=O)[C@@H](NC(=O)[C@@H](N)CCC(O)=O)[C@@H](C)O HFNHAPQMXICKCF-USJMABIRSA-N 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
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- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Heart & Thoracic Surgery (AREA)
- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762531604P | 2017-07-12 | 2017-07-12 | |
| PCT/US2018/041563 WO2019014304A1 (en) | 2017-07-12 | 2018-07-11 | SPIROHEPTANYL HYDANTOIDS AS ROCK INHIBITORS |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2878054T3 true ES2878054T3 (es) | 2021-11-18 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES18752653T Active ES2878054T3 (es) | 2017-07-12 | 2018-07-11 | Espiroheptanil hidantoínas como inhibidores de ROCK |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US11447487B2 (https=) |
| EP (1) | EP3652167B1 (https=) |
| JP (1) | JP7313331B2 (https=) |
| KR (1) | KR102644889B1 (https=) |
| CN (1) | CN110914257B (https=) |
| ES (1) | ES2878054T3 (https=) |
| WO (1) | WO2019014304A1 (https=) |
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| KR102511441B1 (ko) | 2016-11-30 | 2023-03-16 | 브리스톨-마이어스 스큅 컴퍼니 | 트리시클릭 Rho 키나제 억제제 |
| TW201908293A (zh) | 2017-07-12 | 2019-03-01 | 美商必治妥美雅史谷比公司 | 作為rock抑制劑之5員及雙環雜環醯胺 |
| JP7234201B2 (ja) | 2017-07-12 | 2023-03-07 | ブリストル－マイヤーズ スクイブ カンパニー | 心不全の治療のためのｒｏｃｋの５員アミノヘテロ環および５，６－または６，６員二環式アミノヘテロ環の阻害剤 |
| US11306081B2 (en) | 2017-07-12 | 2022-04-19 | Bristol-Myers Squibb Company | Phenylacetamides as inhibitors of rock |
| US12060341B2 (en) * | 2017-07-12 | 2024-08-13 | Bristol-Myers Squibb Company | Spiroheptanyl hydantoins as ROCK inhibitors |
| EP3704121B1 (en) | 2017-11-03 | 2022-12-21 | Bristol-Myers Squibb Company | Diazaspiro rock inhibitors |
| MX2021005273A (es) | 2018-11-06 | 2021-09-08 | Cervello Therapeutics LLC | Inhibidores de quinasa rock. |
| US11248004B2 (en) | 2018-11-06 | 2022-02-15 | Cervello Therapeutics, Llc. | Substituted isoquinolines as rock kinase inhibitors |
| EP4025570A4 (en) * | 2019-09-06 | 2022-11-02 | ONO Pharmaceutical Co., Ltd. | HYDANTOINDIVATIVES |
| EP4431596A4 (en) | 2021-11-11 | 2026-01-14 | The Doshisha | CRYOCONSERVATION PREPARATION FOR CORNIAL ENDOTHELIAL CELLS AND PROCESS FOR PRODUCING SAID CRYOCONSERVATION PREPARATION |
| AU2024265078A1 (en) | 2023-05-04 | 2025-12-11 | Revolution Medicines, Inc. | Combination therapy for a ras related disease or disorder |
| IL326136A (en) | 2023-08-07 | 2026-03-01 | Revolution Medicines Inc | RMC-6291 for use in the treatment of a disease or disorder associated with the RAS protein |
| US20250154171A1 (en) | 2023-10-12 | 2025-05-15 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025150038A1 (en) * | 2024-01-09 | 2025-07-17 | Adama Makhteshim Ltd. | A method for separation of cis and trans isomers of hydantoin-containing spiro-compound from an isomeric mixture |
| WO2025171296A1 (en) | 2024-02-09 | 2025-08-14 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2025240847A1 (en) | 2024-05-17 | 2025-11-20 | Revolution Medicines, Inc. | Ras inhibitors |
| US20250375445A1 (en) | 2024-06-07 | 2025-12-11 | Revolution Medicines, Inc. | Methods of treating a ras protein-related disease or disorder |
| WO2025265060A1 (en) | 2024-06-21 | 2025-12-26 | Revolution Medicines, Inc. | Therapeutic compositions and methods for managing treatment-related effects |
| WO2026006747A1 (en) | 2024-06-28 | 2026-01-02 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026015825A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Use of ras inhibitor for treating pancreatic cancer |
| WO2026015796A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015790A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026015801A1 (en) | 2024-07-12 | 2026-01-15 | Revolution Medicines, Inc. | Methods of treating a ras related disease or disorder |
| WO2026050446A1 (en) | 2024-08-29 | 2026-03-05 | Revolution Medicines, Inc. | Ras inhibitors |
| WO2026072904A2 (en) | 2024-09-26 | 2026-04-02 | Revolution Medicines, Inc. | Compositions and methods for treating lung cancer |
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| WO2007142323A1 (ja) | 2006-06-08 | 2007-12-13 | Ube Industries, Ltd. | 側鎖にスピロ環構造を有する新規インダゾール誘導体 |
| WO2008036540A2 (en) | 2006-09-20 | 2008-03-27 | Boehringer Ingelheim International Gmbh | Rho kinase inhibitors |
| NZ577980A (en) * | 2006-12-27 | 2012-01-12 | Sanofi Aventis | Cycloalkylamine substituted isoquinolone derivatives |
| CL2007003874A1 (es) | 2007-01-03 | 2008-05-16 | Boehringer Ingelheim Int | Compuestos derivados de benzamida; composicion farmaceutica que comprende a dichos compuestos; y su uso para tratar enfermedades cardiovasculares, hipertension, aterosclerosis, reestenosis, ictus, insuficiencia cardiaca, lesion isquemica, hipertensio |
| AU2011329233A1 (en) | 2010-11-15 | 2013-05-23 | Abbvie Deutschland Gmbh & Co Kg | NAMPT and ROCK inhibitors |
| JP6488239B2 (ja) | 2013-01-18 | 2019-03-20 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | Ｒｏｃｋ阻害剤としてのフタラジノンおよびイソキノリノン |
| AR094929A1 (es) | 2013-02-28 | 2015-09-09 | Bristol Myers Squibb Co | Derivados de fenilpirazol como inhibidores potentes de rock1 y rock2 |
| WO2014134391A1 (en) | 2013-02-28 | 2014-09-04 | Bristol-Myers Squibb Company | Phenylpyrazole derivatives as potent rock1 and rock2 inhibitors |
| EP3016950B1 (en) | 2013-07-02 | 2017-06-07 | Bristol-Myers Squibb Company | Tricyclic pyrido-carboxamide derivatives as rock inhibitors |
| US9914740B2 (en) | 2013-07-02 | 2018-03-13 | Bristol-Myers Squibb Company | Tricyclic pyrido-carboxamide derivatives as rock inhibitors |
| US9902702B2 (en) * | 2014-07-15 | 2018-02-27 | Bristol-Myers Squibb Company | Spirocycloheptanes as inhibitors of rock |
| WO2016028971A1 (en) | 2014-08-21 | 2016-02-25 | Bristol-Myers Squibb Company | Tied-back benzamide derivatives as potent rock inhibitors |
| US10123993B2 (en) | 2015-01-09 | 2018-11-13 | Bristol-Myers Squibb Company | Cyclic ureas as inhibitors of rock |
| ES2730112T3 (es) | 2015-03-09 | 2019-11-08 | Bristol Myers Squibb Co | Lactamas como inhibidores de ROCK |
| TWI730032B (zh) | 2016-01-13 | 2021-06-11 | 美商必治妥美雅史谷比公司 | 作為ｒｏｃｋ抑制劑之螺庚烷水楊酸醯胺及相關化合物 |
| WO2017205709A1 (en) | 2016-05-27 | 2017-11-30 | Bristol-Myers Squibb Company | Triazolones and tetrazolones as inhibitors of rock |
| JP6903731B2 (ja) | 2016-07-07 | 2021-07-14 | ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ | 強力で選択的なｒｏｃｋ阻害剤としてのラクタム、環状尿素、およびカルバメート、およびトリアゾロン誘導体 |
| JP7113810B2 (ja) | 2016-07-07 | 2022-08-05 | ブリストル－マイヤーズ スクイブ カンパニー | Ｒｏｃｋ阻害剤としてのスピロラクタム |
| ES2829550T3 (es) | 2016-07-07 | 2021-06-01 | Bristol Myers Squibb Co | Ureas cíclicas espiro-condensadas como inhibidores de ROCK |
| KR102511441B1 (ko) | 2016-11-30 | 2023-03-16 | 브리스톨-마이어스 스큅 컴퍼니 | 트리시클릭 Rho 키나제 억제제 |
| JP7234201B2 (ja) | 2017-07-12 | 2023-03-07 | ブリストル－マイヤーズ スクイブ カンパニー | 心不全の治療のためのｒｏｃｋの５員アミノヘテロ環および５，６－または６，６員二環式アミノヘテロ環の阻害剤 |
| TW201908293A (zh) | 2017-07-12 | 2019-03-01 | 美商必治妥美雅史谷比公司 | 作為rock抑制劑之5員及雙環雜環醯胺 |
| US11306081B2 (en) | 2017-07-12 | 2022-04-19 | Bristol-Myers Squibb Company | Phenylacetamides as inhibitors of rock |
| EP3704121B1 (en) | 2017-11-03 | 2022-12-21 | Bristol-Myers Squibb Company | Diazaspiro rock inhibitors |
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2018
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- 2018-07-11 CN CN201880046379.6A patent/CN110914257B/zh active Active
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Also Published As
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| KR20200027990A (ko) | 2020-03-13 |
| JP2020526565A (ja) | 2020-08-31 |
| JP7313331B2 (ja) | 2023-07-24 |
| CN110914257B (zh) | 2023-05-26 |
| US20210155618A1 (en) | 2021-05-27 |
| KR102644889B1 (ko) | 2024-03-06 |
| EP3652167A1 (en) | 2020-05-20 |
| WO2019014304A1 (en) | 2019-01-17 |
| CN110914257A (zh) | 2020-03-24 |
| US11447487B2 (en) | 2022-09-20 |
| EP3652167B1 (en) | 2021-06-02 |
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