DE10210190A1 - Aza-Spiroverbindungen - Google Patents
Aza-SpiroverbindungenInfo
- Publication number
- DE10210190A1 DE10210190A1 DE10210190A DE10210190A DE10210190A1 DE 10210190 A1 DE10210190 A1 DE 10210190A1 DE 10210190 A DE10210190 A DE 10210190A DE 10210190 A DE10210190 A DE 10210190A DE 10210190 A1 DE10210190 A1 DE 10210190A1
- Authority
- DE
- Germany
- Prior art keywords
- azaspiro
- hydrogen
- amino
- group
- alkyl
- 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.)
- Ceased
Links
- 150000008627 azaspiro compounds Chemical class 0.000 title claims abstract description 42
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 24
- 125000003368 amide group Chemical group 0.000 claims abstract description 22
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 21
- 239000003814 drug Substances 0.000 claims abstract description 21
- 208000002193 Pain Diseases 0.000 claims abstract description 18
- 125000000464 thioxo group Chemical group S=* 0.000 claims abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 7
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 45
- 239000001257 hydrogen Substances 0.000 claims description 45
- -1 hydroxy, formyl Chemical group 0.000 claims description 40
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 150000002431 hydrogen Chemical class 0.000 claims description 19
- 208000004296 neuralgia Diseases 0.000 claims description 18
- 230000001684 chronic effect Effects 0.000 claims description 17
- 208000021722 neuropathic pain Diseases 0.000 claims description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- DMEGYFMYUHOHGS-UHFFFAOYSA-N heptamethylene Natural products C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 claims description 15
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 150000002430 hydrocarbons Chemical group 0.000 claims description 14
- 125000004414 alkyl thio group Chemical group 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 13
- 125000003282 alkyl amino group Chemical group 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 11
- 229920006395 saturated elastomer Polymers 0.000 claims description 11
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 10
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 10
- 125000004043 oxo group Chemical group O=* 0.000 claims description 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 7
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
- 230000002757 inflammatory effect Effects 0.000 claims description 7
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 7
- FHFHJCMWCPQJLQ-UHFFFAOYSA-N 1-(2-azaspiro[4.5]decan-2-yl)ethanone Chemical compound C1N(C(=O)C)CCC21CCCCC2 FHFHJCMWCPQJLQ-UHFFFAOYSA-N 0.000 claims description 6
- QNCQJIYBTSFVTE-UHFFFAOYSA-N C1NC(CC12CCCCCC2)=S.C2NC(CC21CCCC1)=S.C1NC(CC12CCCCC2)=S.C2NCCC21CCCCC1 Chemical compound C1NC(CC12CCCCCC2)=S.C2NC(CC21CCCC1)=S.C1NC(CC12CCCCC2)=S.C2NCCC21CCCCC1 QNCQJIYBTSFVTE-UHFFFAOYSA-N 0.000 claims description 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 5
- 125000005842 heteroatom Chemical group 0.000 claims description 5
- UYUUEEXDJGLCLY-UHFFFAOYSA-N 2-azaspiro[4.6]undecane Chemical compound C1NCCC21CCCCCC2 UYUUEEXDJGLCLY-UHFFFAOYSA-N 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- VQISVGCZRGIOFD-UHFFFAOYSA-N 2-azaspiro[4.5]decane-3-thione Chemical compound C1NC(=S)CC21CCCCC2 VQISVGCZRGIOFD-UHFFFAOYSA-N 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- SQQWBSBBCSFQGC-JLHYYAGUSA-N ubiquinone-2 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CCC=C(C)C)=C(C)C1=O SQQWBSBBCSFQGC-JLHYYAGUSA-N 0.000 claims 1
- 238000012360 testing method Methods 0.000 abstract description 14
- JAWPQJDOQPSNIQ-UHFFFAOYSA-N 2-Azaspiro[4.5]decan-3-one Chemical compound C1NC(=O)CC21CCCCC2 JAWPQJDOQPSNIQ-UHFFFAOYSA-N 0.000 abstract description 13
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 abstract description 10
- 230000000202 analgesic effect Effects 0.000 abstract description 9
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 abstract description 7
- 125000004434 sulfur atom Chemical group 0.000 abstract description 4
- RBRHMJWQHKXACY-UHFFFAOYSA-N 2-azaspiro[4.6]undecane-3-thione Chemical compound C1NC(=S)CC21CCCCCC2 RBRHMJWQHKXACY-UHFFFAOYSA-N 0.000 abstract description 3
- 238000007912 intraperitoneal administration Methods 0.000 abstract description 3
- 125000002947 alkylene group Chemical group 0.000 abstract description 2
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 230000010534 mechanism of action Effects 0.000 abstract description 2
- 125000005843 halogen group Chemical group 0.000 abstract 6
- 125000000896 monocarboxylic acid group Chemical group 0.000 abstract 6
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 2
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 14
- 150000003254 radicals Chemical class 0.000 description 13
- 239000000243 solution Substances 0.000 description 11
- 229960002870 gabapentin Drugs 0.000 description 10
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000203 mixture Substances 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 206010015037 epilepsy Diseases 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 3
- 208000027418 Wounds and injury Diseases 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 208000014674 injury Diseases 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 229940124641 pain reliever Drugs 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 229930195734 saturated hydrocarbon Natural products 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229910052938 sodium sulfate Inorganic materials 0.000 description 3
- 235000011152 sodium sulphate Nutrition 0.000 description 3
- SFCOKGCNIPSUQF-UHFFFAOYSA-N 2-azaspiro[4.5]decane Chemical compound C1NCCC21CCCCC2 SFCOKGCNIPSUQF-UHFFFAOYSA-N 0.000 description 2
- 206010006002 Bone pain Diseases 0.000 description 2
- 208000000094 Chronic Pain Diseases 0.000 description 2
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 238000005677 Lawesson carbonylation reaction Methods 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 208000000112 Myalgia Diseases 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 239000001961 anticonvulsive agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 229930195712 glutamate Natural products 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 208000013465 muscle pain Diseases 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- JONWDDCKNVVMBS-UHFFFAOYSA-N 2-azaspiro[4.4]nonan-3-one Chemical compound C1NC(=O)CC11CCCC1 JONWDDCKNVVMBS-UHFFFAOYSA-N 0.000 description 1
- ZOYWDMBYQNFNDE-UHFFFAOYSA-N 2-azaspiro[4.4]nonane-3-thione Chemical compound C1NC(=S)CC11CCCC1 ZOYWDMBYQNFNDE-UHFFFAOYSA-N 0.000 description 1
- YXTWCCJCYBPHGQ-UHFFFAOYSA-N 2-azaspiro[4.6]undecan-3-one Chemical compound C1NC(=O)CC21CCCCCC2 YXTWCCJCYBPHGQ-UHFFFAOYSA-N 0.000 description 1
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 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 description 1
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- 208000020401 Depressive disease Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
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- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
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- 125000001931 aliphatic group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
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- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- 230000007935 neutral effect Effects 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 231100000028 nontoxic concentration Toxicity 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 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 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 210000001428 peripheral nervous system Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
- 150000004040 pyrrolidinones Chemical class 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 210000000278 spinal cord Anatomy 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 235000011044 succinic acid Nutrition 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000007428 synaptic transmission, GABAergic Effects 0.000 description 1
- 230000007593 synaptic transmission, glutaminergic Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 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
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical class CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/54—Spiro-condensed
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D497/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D497/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D497/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pain & Pain Management (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Indole Compounds (AREA)
Priority Applications (24)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10210190A DE10210190A1 (de) | 2002-03-07 | 2002-03-07 | Aza-Spiroverbindungen |
| CA002477124A CA2477124A1 (en) | 2002-03-07 | 2003-02-27 | Azaspiro compounds for the treatment of pain |
| JP2003572956A JP2005526745A (ja) | 2002-03-07 | 2003-02-27 | 痛みを治療するためのアザスピロ化合物 |
| PL03372431A PL372431A1 (en) | 2002-03-07 | 2003-02-27 | Azaspiro compounds for the treatment of pain |
| PCT/EP2003/001986 WO2003074486A1 (de) | 2002-03-07 | 2003-02-27 | Aza-spiroverbindungen zur behandlug von schmerzen |
| DK03743342T DK1485352T3 (da) | 2002-03-07 | 2003-02-27 | Aza-spiroforbindelser til behandling af smerter |
| AU2003215603A AU2003215603A1 (en) | 2002-03-07 | 2003-02-27 | Azaspiro compounds for the treatment of pain |
| EP03743342A EP1485352B1 (de) | 2002-03-07 | 2003-02-27 | Aza-spiroverbindungen zur behandlug von schmerzen |
| ES03743342T ES2242944T3 (es) | 2002-03-07 | 2003-02-27 | Compuesto azaespiro para el tratamiento del dolor. |
| CNB038054388A CN1324011C (zh) | 2002-03-07 | 2003-02-27 | 用于治疗疼痛的氮杂－螺环化合物 |
| RU2004129769/04A RU2322438C2 (ru) | 2002-03-07 | 2003-02-27 | Азаспиросоединения для лечения болей |
| EP04029311A EP1520854A3 (de) | 2002-03-07 | 2003-02-27 | Aza-spiroverbindungen zur behandlung von schmerzen |
| PT03743342T PT1485352E (pt) | 2002-03-07 | 2003-02-27 | Composto azaspiro para o tratamento da dor |
| UA20041008091A UA78987C2 (en) | 2002-03-07 | 2003-02-27 | Azaspiro compounds for treating pain |
| AT03743342T ATE298745T1 (de) | 2002-03-07 | 2003-02-27 | Aza-spiroverbindungen zur behandlug von schmerzen |
| SI200330039T SI1485352T1 (en) | 2002-03-07 | 2003-02-27 | Azaspiro compounds for the treatment of pain |
| HK06100281.2A HK1080468B (en) | 2002-03-07 | 2003-02-27 | Azaspiro compounds for the treatment of pain |
| KR10-2004-7012680A KR20040091638A (ko) | 2002-03-07 | 2003-02-27 | 아자-스피로 화합물 |
| BR0307922-8A BR0307922A (pt) | 2002-03-07 | 2003-02-27 | Compostos de aza-espiro para tratamento de dores, composição farmacêutica compreendendo os mesmos e uso dos mesmos para produção de um medicamento |
| MXPA04008669A MXPA04008669A (es) | 2002-03-07 | 2003-02-27 | Compuestos azaspiro para el tratamiento de dolores. |
| DE50300710T DE50300710D1 (de) | 2002-03-07 | 2003-02-27 | Aza-spiroverbindungen zur behandlug von schmerzen |
| ZA200406245A ZA200406245B (en) | 2002-03-07 | 2004-08-05 | Azaspiro compounds for the treatment of pain. |
| US10/936,134 US20050288351A1 (en) | 2002-03-07 | 2004-09-07 | Azaspiro compounds for the treatment of pain |
| NO20044239A NO20044239L (no) | 2002-03-07 | 2004-10-06 | Azaspiroforbindelser for behandling av smerter |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10210190A DE10210190A1 (de) | 2002-03-07 | 2002-03-07 | Aza-Spiroverbindungen |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE10210190A1 true DE10210190A1 (de) | 2003-09-25 |
Family
ID=27771112
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE10210190A Ceased DE10210190A1 (de) | 2002-03-07 | 2002-03-07 | Aza-Spiroverbindungen |
| DE50300710T Expired - Fee Related DE50300710D1 (de) | 2002-03-07 | 2003-02-27 | Aza-spiroverbindungen zur behandlug von schmerzen |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE50300710T Expired - Fee Related DE50300710D1 (de) | 2002-03-07 | 2003-02-27 | Aza-spiroverbindungen zur behandlug von schmerzen |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US20050288351A1 (enExample) |
| EP (2) | EP1520854A3 (enExample) |
| JP (1) | JP2005526745A (enExample) |
| KR (1) | KR20040091638A (enExample) |
| CN (1) | CN1324011C (enExample) |
| AT (1) | ATE298745T1 (enExample) |
| AU (1) | AU2003215603A1 (enExample) |
| BR (1) | BR0307922A (enExample) |
| CA (1) | CA2477124A1 (enExample) |
| DE (2) | DE10210190A1 (enExample) |
| ES (1) | ES2242944T3 (enExample) |
| MX (1) | MXPA04008669A (enExample) |
| NO (1) | NO20044239L (enExample) |
| PL (1) | PL372431A1 (enExample) |
| PT (1) | PT1485352E (enExample) |
| RU (1) | RU2322438C2 (enExample) |
| UA (1) | UA78987C2 (enExample) |
| WO (1) | WO2003074486A1 (enExample) |
| ZA (1) | ZA200406245B (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW201607923A (zh) * | 2014-07-15 | 2016-03-01 | 歌林達有限公司 | 被取代之氮螺環（４．５）癸烷衍生物 |
| CN107216335B (zh) * | 2017-06-29 | 2019-04-30 | 上海药明康德新药开发有限公司 | 一种叔丁基1-(羟甲基)-3-氧杂-9-氮杂螺[5.5]十一烷-9-甲酸基酯制法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0116347A1 (en) * | 1983-02-09 | 1984-08-22 | Hoechst-Roussel Pharmaceuticals Incorporated | Substituted 1-azaspiro(4.5)decanes and 1-azaspiro(5.5)-undecanes, intermediates and a process for their preparation, and their use as medicaments |
| EP0894497A1 (de) * | 1997-07-31 | 1999-02-03 | Grünenthal GmbH | Verwendung substituierter Imidazolidin-2,4-dion-Verbindungen als Schmerzmittel |
| WO1999025683A1 (de) * | 1997-11-18 | 1999-05-27 | KLINIKUM DER ALBERT-LUDWIGS-UNIVERSITäT FREIBURG | An 4-stellung substituierte 2-pyrrolidinon-derivate zur verringerung des extrazellulären glutamat-spiegels |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2866734A (en) * | 1956-12-05 | 1958-12-30 | Us Vitamin Corp | 3-pyridylethyl 2, 4-oxazolidinediones and process |
| US3150143A (en) * | 1960-07-19 | 1964-09-22 | Geschicketer Fund For Medical | Therapeutically active nu-substituted azaspiranes |
| US3398151A (en) * | 1966-02-01 | 1968-08-20 | Mead Johnson & Co | Azaspirodecanediones and azaspiroundecanediones |
| US3629276A (en) * | 1969-07-16 | 1971-12-21 | Abbott Lab | 2-amino-5-spiro-substituted-oxazo compounds |
| GB8916447D0 (en) * | 1989-07-19 | 1989-09-06 | Ici Plc | Composition,process and use |
| US5319135A (en) * | 1989-08-25 | 1994-06-07 | Warner-Lambert Company | Process for cyclic amino acid anticonvulsant compounds |
| US5132451A (en) * | 1989-08-25 | 1992-07-21 | Warner-Lambert Company | Process for cyclic amino acid anticonvulsant compounds |
| RU95114363A (ru) * | 1992-11-09 | 1997-03-20 | Дзе Бутс Компани ПЛС. (GB) | Производные азаспиросоединений, способ их получения, фармацевтическая композиция, средства для лечения ожирения, средства для лечения аффективных расстройств |
| US5925672A (en) * | 1996-12-06 | 1999-07-20 | Neurosciences Research Foundation, Inc. | Methods of treating mental diseases, inflammation and pain |
| GB9708484D0 (en) * | 1997-04-25 | 1997-06-18 | Merck Sharp & Dohme | Therapeutic agents |
| US5948807A (en) * | 1997-09-03 | 1999-09-07 | Regents Of The University Of Minnesota | Spiroindanamines and Spiroindanimides |
| JP2002516312A (ja) * | 1998-05-26 | 2002-06-04 | ワーナー−ランバート・カンパニー | カルシウムチャンネルのα２δサブユニットに対する親和性を有する立体配座的に制約されたアミノ酸化合物 |
-
2002
- 2002-03-07 DE DE10210190A patent/DE10210190A1/de not_active Ceased
-
2003
- 2003-02-27 RU RU2004129769/04A patent/RU2322438C2/ru not_active IP Right Cessation
- 2003-02-27 AU AU2003215603A patent/AU2003215603A1/en not_active Abandoned
- 2003-02-27 DE DE50300710T patent/DE50300710D1/de not_active Expired - Fee Related
- 2003-02-27 WO PCT/EP2003/001986 patent/WO2003074486A1/de not_active Ceased
- 2003-02-27 PT PT03743342T patent/PT1485352E/pt unknown
- 2003-02-27 AT AT03743342T patent/ATE298745T1/de not_active IP Right Cessation
- 2003-02-27 JP JP2003572956A patent/JP2005526745A/ja active Pending
- 2003-02-27 KR KR10-2004-7012680A patent/KR20040091638A/ko not_active Ceased
- 2003-02-27 CN CNB038054388A patent/CN1324011C/zh not_active Expired - Fee Related
- 2003-02-27 ES ES03743342T patent/ES2242944T3/es not_active Expired - Lifetime
- 2003-02-27 UA UA20041008091A patent/UA78987C2/uk unknown
- 2003-02-27 CA CA002477124A patent/CA2477124A1/en not_active Abandoned
- 2003-02-27 PL PL03372431A patent/PL372431A1/xx not_active Application Discontinuation
- 2003-02-27 EP EP04029311A patent/EP1520854A3/de not_active Withdrawn
- 2003-02-27 EP EP03743342A patent/EP1485352B1/de not_active Expired - Lifetime
- 2003-02-27 BR BR0307922-8A patent/BR0307922A/pt not_active IP Right Cessation
- 2003-02-27 MX MXPA04008669A patent/MXPA04008669A/es not_active Application Discontinuation
-
2004
- 2004-08-05 ZA ZA200406245A patent/ZA200406245B/xx unknown
- 2004-09-07 US US10/936,134 patent/US20050288351A1/en not_active Abandoned
- 2004-10-06 NO NO20044239A patent/NO20044239L/no not_active Application Discontinuation
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0116347A1 (en) * | 1983-02-09 | 1984-08-22 | Hoechst-Roussel Pharmaceuticals Incorporated | Substituted 1-azaspiro(4.5)decanes and 1-azaspiro(5.5)-undecanes, intermediates and a process for their preparation, and their use as medicaments |
| EP0894497A1 (de) * | 1997-07-31 | 1999-02-03 | Grünenthal GmbH | Verwendung substituierter Imidazolidin-2,4-dion-Verbindungen als Schmerzmittel |
| WO1999025683A1 (de) * | 1997-11-18 | 1999-05-27 | KLINIKUM DER ALBERT-LUDWIGS-UNIVERSITäT FREIBURG | An 4-stellung substituierte 2-pyrrolidinon-derivate zur verringerung des extrazellulären glutamat-spiegels |
Non-Patent Citations (2)
| Title |
|---|
| J. med. Chem. 1963, 6(4), 388-407 * |
| J. med. Chem. 1965, 8(1), 62-73 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1639122A (zh) | 2005-07-13 |
| ZA200406245B (en) | 2005-06-13 |
| RU2004129769A (ru) | 2005-07-10 |
| CA2477124A1 (en) | 2003-09-12 |
| EP1520854A2 (de) | 2005-04-06 |
| MXPA04008669A (es) | 2004-12-06 |
| PT1485352E (pt) | 2005-10-31 |
| UA78987C2 (en) | 2007-05-10 |
| AU2003215603A1 (en) | 2003-09-16 |
| CN1324011C (zh) | 2007-07-04 |
| HK1080468A1 (zh) | 2006-04-28 |
| EP1520854A3 (de) | 2007-02-21 |
| WO2003074486A1 (de) | 2003-09-12 |
| ATE298745T1 (de) | 2005-07-15 |
| NO20044239L (no) | 2004-12-01 |
| EP1485352A1 (de) | 2004-12-15 |
| AU2003215603A2 (en) | 2003-09-16 |
| JP2005526745A (ja) | 2005-09-08 |
| KR20040091638A (ko) | 2004-10-28 |
| PL372431A1 (en) | 2005-07-25 |
| BR0307922A (pt) | 2004-12-21 |
| RU2322438C2 (ru) | 2008-04-20 |
| US20050288351A1 (en) | 2005-12-29 |
| DE50300710D1 (de) | 2005-08-04 |
| ES2242944T3 (es) | 2005-11-16 |
| EP1485352B1 (de) | 2005-06-29 |
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| Date | Code | Title | Description |
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| OP8 | Request for examination as to paragraph 44 patent law | ||
| 8131 | Rejection |