BG106162A - Трициклени аналгетици - Google Patents

Трициклени аналгетици Download PDF

Info

Publication number: BG106162A
Authority: BG; Bulgaria
Prior art keywords: piperidine; dihydro; oxospiro; naphthalene; methoxy
Prior art date: 1999-06-07

Application number

BG106162A

Other languages

Bulgarian (bg)

English (en)

Inventor

Alain Calvet

Henri Jacobelli

Jocelyne Puaud

Francois Roman

Jacques Hamon

Agnes Grouhel

Original Assignee

Warner-Lambert Company Llc

Priority date (The priority date 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 date listed.)

1999-06-07

Filing date

2001-11-30

Publication date

2002-05-31

2001-11-30 Application filed by Warner-Lambert Company Llc filed Critical Warner-Lambert Company Llc

2002-05-31 Publication of BG106162A publication Critical patent/BG106162A/bg

Links

229940035676 analgesics Drugs 0.000 title description 2
239000000730 antalgic agent Substances 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 67
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
239000001257 hydrogen Substances 0.000 claims abstract description 24
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 19
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 13
125000000217 alkyl group Chemical group 0.000 claims abstract description 11
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 11
125000003342 alkenyl group Chemical group 0.000 claims abstract description 10
150000003839 salts Chemical class 0.000 claims abstract description 8
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 6
208000004296 neuralgia Diseases 0.000 claims abstract description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 5
208000021722 neuropathic pain Diseases 0.000 claims abstract description 5
239000001301 oxygen Substances 0.000 claims abstract description 5
229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 4
125000001475 halogen functional group Chemical group 0.000 claims abstract 6
125000004356 hydroxy functional group Chemical group O* 0.000 claims abstract 4
-1 3,3-diphenylpropyl Chemical group 0.000 claims description 45
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 44
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 34
238000000034 method Methods 0.000 claims description 25
208000002193 Pain Diseases 0.000 claims description 22
230000036407 pain Effects 0.000 claims description 14
238000011282 treatment Methods 0.000 claims description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
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 description 10
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 9
150000002431 hydrogen Chemical class 0.000 claims description 9
UFTZAIGLEUTKQH-UHFFFAOYSA-N spiro[3,4-dihydronaphthalene-2,4'-piperidine]-1-one Chemical compound O=C1C2=CC=CC=C2CCC11CCNCC1 UFTZAIGLEUTKQH-UHFFFAOYSA-N 0.000 claims description 8
241000124008 Mammalia Species 0.000 claims description 6
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
QMMOXUPEWRXHJS-HYXAFXHYSA-N (z)-pent-2-ene Chemical compound CC\C=C/C QMMOXUPEWRXHJS-HYXAFXHYSA-N 0.000 claims description 5
208000032131 Diabetic Neuropathies Diseases 0.000 claims description 5
201000010099 disease Diseases 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 4
ODLAPCNVGLBQPY-UHFFFAOYSA-N 1'-(cyclopropylmethyl)spiro[8,9-dihydro-7h-benzo[7]annulene-6,4'-piperidine]-5-one Chemical compound O=C1C2=CC=CC=C2CCCC1(CC1)CCN1CC1CC1 ODLAPCNVGLBQPY-UHFFFAOYSA-N 0.000 claims description 3
239000003937 drug carrier Substances 0.000 claims description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
BQTJMKIHKULPCZ-UHFFFAOYSA-N 2H-indene Chemical compound C1=CC=CC2=CCC=C21 BQTJMKIHKULPCZ-UHFFFAOYSA-N 0.000 claims 1
208000015114 central nervous system disease Diseases 0.000 abstract description 4
125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract description 3
125000004435 hydrogen atom Chemical group [H]* 0.000 abstract 5
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
101100134925 Gallus gallus COR6 gene Proteins 0.000 abstract 1
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 abstract 1
IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical compound C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 58
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 45
239000000243 solution Substances 0.000 description 34
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
239000011734 sodium Substances 0.000 description 30
239000000047 product Substances 0.000 description 29
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
239000000203 mixture Substances 0.000 description 24
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
238000006243 chemical reaction Methods 0.000 description 17
239000002904 solvent Substances 0.000 description 17
239000000843 powder Substances 0.000 description 15
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
108091006146 Channels Proteins 0.000 description 12
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
238000004458 analytical method Methods 0.000 description 12
239000012074 organic phase Substances 0.000 description 12
238000003756 stirring Methods 0.000 description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
208000000094 Chronic Pain Diseases 0.000 description 8
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 8
238000012360 testing method Methods 0.000 description 7
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
208000006011 Stroke Diseases 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
210000004027 cell Anatomy 0.000 description 6
238000004587 chromatography analysis Methods 0.000 description 6
230000001684 chronic effect Effects 0.000 description 6
238000001035 drying Methods 0.000 description 6
230000000694 effects Effects 0.000 description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
238000002425 crystallisation Methods 0.000 description 5
230000008025 crystallization Effects 0.000 description 5
125000005843 halogen group Chemical group 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
150000003053 piperidines Chemical class 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
238000010992 reflux Methods 0.000 description 5
239000000725 suspension Substances 0.000 description 5
206010001497 Agitation Diseases 0.000 description 4
208000004454 Hyperalgesia Diseases 0.000 description 4
208000035154 Hyperesthesia Diseases 0.000 description 4
208000028389 Nerve injury Diseases 0.000 description 4
230000001154 acute effect Effects 0.000 description 4
230000000202 analgesic effect Effects 0.000 description 4
238000003556 assay Methods 0.000 description 4
239000012298 atmosphere Substances 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
239000002808 molecular sieve Substances 0.000 description 4
230000008764 nerve damage Effects 0.000 description 4
239000008188 pellet Substances 0.000 description 4
210000001044 sensory neuron Anatomy 0.000 description 4
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 4
210000003594 spinal ganglia Anatomy 0.000 description 4
125000003003 spiro group Chemical group 0.000 description 4
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 3
239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 description 3
235000019743 Choline chloride Nutrition 0.000 description 3
241001465754 Metazoa Species 0.000 description 3
241000700159 Rattus Species 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
FVECELJHCSPHKY-UHFFFAOYSA-N Veratridine Natural products C1=C(OC)C(OC)=CC=C1C(=O)OC1C2(O)OC34CC5(O)C(CN6C(CCC(C)C6)C6(C)O)C6(O)C(O)CC5(O)C4CCC2C3(C)CC1 FVECELJHCSPHKY-UHFFFAOYSA-N 0.000 description 3
239000011230 binding agent Substances 0.000 description 3
AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 3
239000000872 buffer Substances 0.000 description 3
125000004432 carbon atom Chemical group C* 0.000 description 3
SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 description 3
229960003178 choline chloride Drugs 0.000 description 3
239000012043 crude product Substances 0.000 description 3
125000004122 cyclic group Chemical group 0.000 description 3
230000006378 damage Effects 0.000 description 3
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
206010015037 epilepsy Diseases 0.000 description 3
230000008020 evaporation Effects 0.000 description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
239000012071 phase Substances 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
FVECELJHCSPHKY-JLSHOZRYSA-N veratridine Chemical compound C1=C(OC)C(OC)=CC=C1C(=O)O[C@@H]1[C@@]2(O)O[C@]34C[C@@]5(O)[C@H](CN6[C@@H](CC[C@H](C)C6)[C@@]6(C)O)[C@]6(O)[C@@H](O)C[C@@]5(O)[C@@H]4CC[C@H]2[C@]3(C)CC1 FVECELJHCSPHKY-JLSHOZRYSA-N 0.000 description 3
XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 2
WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
206010010904 Convulsion Diseases 0.000 description 2
UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
208000019695 Migraine disease Diseases 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
206010029260 Neuroblastoma Diseases 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 description 2
229920002472 Starch Polymers 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
238000009825 accumulation Methods 0.000 description 2
239000008351 acetate buffer Substances 0.000 description 2
OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
230000002411 adverse Effects 0.000 description 2
125000006242 amine protecting group Chemical group 0.000 description 2
239000005557 antagonist Substances 0.000 description 2
239000012131 assay buffer Substances 0.000 description 2
BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 description 2
125000001246 bromo group Chemical group Br* 0.000 description 2
239000002775 capsule Substances 0.000 description 2
235000011089 carbon dioxide Nutrition 0.000 description 2
239000000969 carrier Substances 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
238000004821 distillation Methods 0.000 description 2
DLKPVDVPOKKOFU-UHFFFAOYSA-N ethyl 4-oxospiro[1,2-dihydronaphthalene-3,4'-piperidine]-1'-carboxylate Chemical compound C1CN(C(=O)OCC)CCC21C(=O)C1=CC=CC=C1CC2 DLKPVDVPOKKOFU-UHFFFAOYSA-N 0.000 description 2
238000000605 extraction Methods 0.000 description 2
238000001914 filtration Methods 0.000 description 2
239000008103 glucose Substances 0.000 description 2
229910052736 halogen Inorganic materials 0.000 description 2
238000011534 incubation Methods 0.000 description 2
208000014674 injury Diseases 0.000 description 2
229960004194 lidocaine Drugs 0.000 description 2
239000003446 ligand Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
230000001537 neural effect Effects 0.000 description 2
210000002569 neuron Anatomy 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
239000000546 pharmaceutical excipient Substances 0.000 description 2
229960002036 phenytoin Drugs 0.000 description 2
238000002360 preparation method Methods 0.000 description 2
238000000159 protein binding assay Methods 0.000 description 2
230000001105 regulatory effect Effects 0.000 description 2
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
239000008107 starch Substances 0.000 description 2
235000019698 starch Nutrition 0.000 description 2
239000007858 starting material Substances 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
125000001424 substituent group Chemical group 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
CFMYXEVWODSLAX-QOZOJKKESA-N tetrodotoxin Chemical compound O([C@@]([C@H]1O)(O)O[C@H]2[C@@]3(O)CO)[C@H]3[C@@H](O)[C@]11[C@H]2[C@@H](O)N=C(N)N1 CFMYXEVWODSLAX-QOZOJKKESA-N 0.000 description 2
229950010357 tetrodotoxin Drugs 0.000 description 2
CFMYXEVWODSLAX-UHFFFAOYSA-N tetrodotoxin Natural products C12C(O)NC(=N)NC2(C2O)C(O)C3C(CO)(O)C1OC2(O)O3 CFMYXEVWODSLAX-UHFFFAOYSA-N 0.000 description 2
238000012546 transfer Methods 0.000 description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
SLHSRCBFPHCSGL-UHFFFAOYSA-N (3-bromo-1-phenylpropyl)benzene Chemical compound C=1C=CC=CC=1C(CCBr)C1=CC=CC=C1 SLHSRCBFPHCSGL-UHFFFAOYSA-N 0.000 description 1
125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
YAFMYKFAUNCQPU-UHFFFAOYSA-N 1-(2-bromoethyl)-4-chlorobenzene Chemical compound ClC1=CC=C(CCBr)C=C1 YAFMYKFAUNCQPU-UHFFFAOYSA-N 0.000 description 1
125000006074 1-ethyl-2-butenyl group Chemical group 0.000 description 1
HIDYPDZZGNFUSP-UHFFFAOYSA-N 1-iodopropan-2-ylbenzene Chemical compound ICC(C)C1=CC=CC=C1 HIDYPDZZGNFUSP-UHFFFAOYSA-N 0.000 description 1
125000006052 1-methyl-3-pentenyl group Chemical group 0.000 description 1
YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 1
FYELSNVLZVIGTI-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-5-ethylpyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1CC)CC(=O)N1CC2=C(CC1)NN=N2 FYELSNVLZVIGTI-UHFFFAOYSA-N 0.000 description 1
YHHKEXPNBPDPOW-UHFFFAOYSA-N 2-bromo-n-(2-bromoethyl)ethanamine;hydrobromide Chemical compound Br.BrCCNCCBr YHHKEXPNBPDPOW-UHFFFAOYSA-N 0.000 description 1
JDTFHOGNNYGIBU-UHFFFAOYSA-N 2-bromoethyl carbamate Chemical compound NC(=O)OCCBr JDTFHOGNNYGIBU-UHFFFAOYSA-N 0.000 description 1
SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
RUROFEVDCUGKHD-UHFFFAOYSA-N 3-bromoprop-1-enylbenzene Chemical compound BrCC=CC1=CC=CC=C1 RUROFEVDCUGKHD-UHFFFAOYSA-N 0.000 description 1
125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 1
RGCKJSPKMTWLLX-UHFFFAOYSA-N 3-iodopropylbenzene Chemical compound ICCCC1=CC=CC=C1 RGCKJSPKMTWLLX-UHFFFAOYSA-N 0.000 description 1
125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
FNZDRXLIUWLYML-UHFFFAOYSA-N 4-[2-(4-chlorophenyl)ethyl]piperidine-1,4-dicarboxylic acid Chemical compound C1CN(C(=O)O)CCC1(C(O)=O)CCC1=CC=C(Cl)C=C1 FNZDRXLIUWLYML-UHFFFAOYSA-N 0.000 description 1
125000006043 5-hexenyl group Chemical group 0.000 description 1
MNALUTYMBUBKNX-UHFFFAOYSA-N 6-methoxy-3,4-dihydro-2h-naphthalen-1-one Chemical compound O=C1CCCC2=CC(OC)=CC=C21 MNALUTYMBUBKNX-UHFFFAOYSA-N 0.000 description 1
208000002381 Brain Hypoxia Diseases 0.000 description 1
201000006474 Brain Ischemia Diseases 0.000 description 1
239000002126 C01EB10 - Adenosine Substances 0.000 description 1
206010008120 Cerebral ischaemia Diseases 0.000 description 1
206010009192 Circulatory collapse Diseases 0.000 description 1
208000007342 Diabetic Nephropathies Diseases 0.000 description 1
206010015150 Erythema Diseases 0.000 description 1
208000010201 Exanthema Diseases 0.000 description 1
206010019280 Heart failures Diseases 0.000 description 1
229930194542 Keto Natural products 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
208000005890 Neuroma Diseases 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
208000001294 Nociceptive Pain Diseases 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
235000019502 Orange oil Nutrition 0.000 description 1
208000000114 Pain Threshold Diseases 0.000 description 1
206010038687 Respiratory distress Diseases 0.000 description 1
FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 description 1
206010058679 Skin oedema Diseases 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
108010052164 Sodium Channels Proteins 0.000 description 1
102000018674 Sodium Channels Human genes 0.000 description 1
229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
208000027418 Wounds and injury Diseases 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000036982 action potential Effects 0.000 description 1
229960005305 adenosine Drugs 0.000 description 1
150000001335 aliphatic alkanes Chemical class 0.000 description 1
230000002152 alkylating effect Effects 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
238000010171 animal model Methods 0.000 description 1
229940125681 anticonvulsant agent Drugs 0.000 description 1
239000001961 anticonvulsive agent Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
230000007844 axonal damage Effects 0.000 description 1
230000003376 axonal effect Effects 0.000 description 1
150000007514 bases Chemical class 0.000 description 1
229960005274 benzocaine Drugs 0.000 description 1
150000001559 benzoic acids Chemical class 0.000 description 1
230000027455 binding Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
FLHFTXCMKFVKRP-UHFFFAOYSA-N bromomethylcyclobutane Chemical compound BrCC1CCC1 FLHFTXCMKFVKRP-UHFFFAOYSA-N 0.000 description 1
UUWSLBWDFJMSFP-UHFFFAOYSA-N bromomethylcyclohexane Chemical compound BrCC1CCCCC1 UUWSLBWDFJMSFP-UHFFFAOYSA-N 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
239000001913 cellulose Substances 0.000 description 1
229920002678 cellulose Polymers 0.000 description 1
235000010980 cellulose Nutrition 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
235000013339 cereals Nutrition 0.000 description 1
210000003710 cerebral cortex Anatomy 0.000 description 1
206010008118 cerebral infarction Diseases 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
229960001231 choline Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
208000022371 chronic pain syndrome Diseases 0.000 description 1
239000000470 constituent Substances 0.000 description 1
230000001276 controlling effect Effects 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
239000010779 crude oil Substances 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 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
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
239000012024 dehydrating agents‎ Substances 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
208000033679 diabetic kidney disease Diseases 0.000 description 1
ZFTFAPZRGNKQPU-UHFFFAOYSA-N dicarbonic acid Chemical compound OC(=O)OC(O)=O ZFTFAPZRGNKQPU-UHFFFAOYSA-N 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
150000005332 diethylamines Chemical class 0.000 description 1
229940043279 diisopropylamine Drugs 0.000 description 1
150000004656 dimethylamines Chemical class 0.000 description 1
XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 1
ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
235000019797 dipotassium phosphate Nutrition 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
206010013663 drug dependence Diseases 0.000 description 1
239000003480 eluent Substances 0.000 description 1
231100000321 erythema Toxicity 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
201000005884 exanthem Diseases 0.000 description 1
239000012530 fluid Substances 0.000 description 1
125000001153 fluoro group Chemical group F* 0.000 description 1
238000005755 formation reaction Methods 0.000 description 1
238000009472 formulation Methods 0.000 description 1
229960002870 gabapentin Drugs 0.000 description 1
238000007429 general method Methods 0.000 description 1
125000001188 haloalkyl group Chemical group 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
201000001421 hyperglycemia Diseases 0.000 description 1
230000002102 hyperpolarization Effects 0.000 description 1
230000007954 hypoxia Effects 0.000 description 1
238000002513 implantation Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
230000006698 induction Effects 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
239000006207 intravenous dosage form Substances 0.000 description 1
238000010253 intravenous injection Methods 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
239000002555 ionophore Substances 0.000 description 1
230000000236 ionophoric effect Effects 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([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
125000000468 ketone group Chemical group 0.000 description 1
230000003902 lesion Effects 0.000 description 1
239000007788 liquid Substances 0.000 description 1
238000002690 local anesthesia Methods 0.000 description 1
239000003589 local anesthetic agent Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
238000005259 measurement Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
125000006431 methyl cyclopropyl group Chemical group 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
206010027599 migraine Diseases 0.000 description 1
239000011707 mineral Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
239000002480 mineral oil Substances 0.000 description 1
235000010446 mineral oil Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
125000001298 n-hexoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
230000002981 neuropathic effect Effects 0.000 description 1
230000004112 neuroprotection Effects 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
239000010502 orange oil Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
150000002913 oxalic acids Chemical class 0.000 description 1
230000037040 pain threshold Effects 0.000 description 1
208000035824 paresthesia Diseases 0.000 description 1
230000007310 pathophysiology Effects 0.000 description 1
210000000578 peripheral nerve Anatomy 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
125000003884 phenylalkyl group Chemical group 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
IIKFXOLJMNWWCH-UHFFFAOYSA-N piperidine-1,4-dicarboxylic acid Chemical compound OC(=O)C1CCN(C(O)=O)CC1 IIKFXOLJMNWWCH-UHFFFAOYSA-N 0.000 description 1
239000004033 plastic Substances 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
239000003223 protective agent Substances 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
238000000746 purification Methods 0.000 description 1
229940070891 pyridium Drugs 0.000 description 1
206010037844 rash Diseases 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
229960004181 riluzole Drugs 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
150000003870 salicylic acids Chemical class 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
208000007771 sciatic neuropathy Diseases 0.000 description 1
239000002795 scorpion venom Substances 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
230000035807 sensation Effects 0.000 description 1
229940076279 serotonin Drugs 0.000 description 1
238000004088 simulation Methods 0.000 description 1
231100000046 skin rash Toxicity 0.000 description 1
239000003195 sodium channel blocking agent Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
238000013222 sprague-dawley male rat Methods 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
238000012289 standard assay Methods 0.000 description 1
208000023516 stroke disease Diseases 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
208000011117 substance-related disease Diseases 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
238000013268 sustained release Methods 0.000 description 1
239000012730 sustained-release form Substances 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 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
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
229960002372 tetracaine Drugs 0.000 description 1
GKCBAIGFKIBETG-UHFFFAOYSA-N tetracaine Chemical compound CCCCNC1=CC=C(C(=O)OCCN(C)C)C=C1 GKCBAIGFKIBETG-UHFFFAOYSA-N 0.000 description 1
KKHJTSPUUIRIOP-UHFFFAOYSA-J tetrachlorostannane;hydrate Chemical compound O.Cl[Sn](Cl)(Cl)Cl KKHJTSPUUIRIOP-UHFFFAOYSA-J 0.000 description 1
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
239000010936 titanium Substances 0.000 description 1
230000008733 trauma Effects 0.000 description 1
206010044652 trigeminal neuralgia Diseases 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
ISNYUQWBWALXEY-OMIQOYQYSA-N tsg6xhx09r Chemical compound O([C@@H](C)C=1[C@@]23CN(C)CCO[C@]3(C3=CC[C@H]4[C@]5(C)CC[C@@](C4)(O)O[C@@]53[C@H](O)C2)CC=1)C(=O)C=1C(C)=CNC=1C ISNYUQWBWALXEY-OMIQOYQYSA-N 0.000 description 1
238000003828 vacuum filtration Methods 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
210000001835 viscera Anatomy 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/20—Spiro-condensed ring systems
- 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
- A61K31/438—The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
- 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
- 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]
- A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Medicinal Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Rheumatology (AREA)
Epidemiology (AREA)
Biomedical Technology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pain & Pain Management (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Other In-Based Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Hydrogenated Pyridines (AREA)

BG106162A 1999-06-07 2001-11-30 Трициклени аналгетици BG106162A (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US13786899P	1999-06-07	1999-06-07
PCT/EP2000/005783 WO2000075116A2 (en)	1999-06-07	2000-06-07	Tricyclic analgesics

Publications (1)

Publication Number	Publication Date
BG106162A true BG106162A (bg)	2002-05-31

Family

ID=22479397

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG106162A BG106162A (bg)	1999-06-07	2001-11-30	Трициклени аналгетици

Country Status (21)

Country	Link
EP (1)	EP1235808A2 (pl)
JP (1)	JP2003513006A (pl)
KR (1)	KR20020010923A (pl)
CN (1)	CN1635998A (pl)
AP (1)	AP2001002356A0 (pl)
AU (1)	AU6428400A (pl)
BG (1)	BG106162A (pl)
BR (1)	BR0011427A (pl)
CA (1)	CA2376076A1 (pl)
EA (1)	EA200101117A1 (pl)
HR (1)	HRP20010913A2 (pl)
HU (1)	HUP0203317A2 (pl)
IL (1)	IL146755A0 (pl)
IS (1)	IS6175A (pl)
MA (1)	MA26795A1 (pl)
MX (1)	MXPA01012694A (pl)
NO (1)	NO20015966D0 (pl)
PL (1)	PL357340A1 (pl)
SK (1)	SK17512001A3 (pl)
TR (1)	TR200103531T2 (pl)
WO (1)	WO2000075116A2 (pl)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20030045449A1 (en) *	2001-08-15	2003-03-06	Pfizer, Inc.	Pharmaceutical combinations for the treatment of neurodegenerative diseases
FR2915099B1 (fr) *	2007-04-19	2009-06-05	Sanofi Aventis Sa	Utilisation du 4-cyclopropylmethoxy-n-(3,5-dichloro-1-oxydo- pyridin-4-yl)-5-(methoxy)pyridine-2-carboxamide pour le traitement des traumatismes craniens
BR112013019211A2 (pt) *	2011-02-02	2021-07-06	Vertex Pharma	amidas de piperidina espirocíclicas de pirrolopirazina como moduladores de canais de íon
GB201416346D0 (en) *	2014-09-16	2014-10-29	Shire Internat Gmbh	Spirocyclic derivatives
CN115872873B (zh) *	2022-12-29	2024-11-29	上海泰坦科技股份有限公司	一种双(2-溴乙基)胺氢溴酸盐的重结晶纯化方法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB8917069D0 (en) *	1989-07-26	1989-09-13	Merck Sharp & Dohme	Therapeutic agents
IL96507A0 (en) *	1989-12-08	1991-08-16	Merck & Co Inc	Nitrogen-containing spirocycles and pharmaceutical compositions containing them
ATE169001T1 (de) *	1993-01-28	1998-08-15	Merck & Co Inc	Substituierte spiro-azaringen als tachykinine rezeptor antagonisten
US5439914A (en) *	1994-02-18	1995-08-08	Merck & Co., Inc.	Spirocycles
AU5604998A (en) *	1996-12-13	1998-07-03	Merck & Co., Inc.	Spiro-substituted azacycles as modulators of chemokine receptor activity
US6013644A (en) *	1997-12-12	2000-01-11	Merck & Co., Inc.	Spiro-substituted azacycles as modulators of chemokine receptor activity

2000
- 2000-06-07 SK SK1751-2001A patent/SK17512001A3/sk unknown
- 2000-06-07 TR TR2001/03531T patent/TR200103531T2/xx unknown
- 2000-06-07 WO PCT/EP2000/005783 patent/WO2000075116A2/en not_active Ceased
- 2000-06-07 AU AU64284/00A patent/AU6428400A/en not_active Abandoned
- 2000-06-07 KR KR1020017015730A patent/KR20020010923A/ko not_active Withdrawn
- 2000-06-07 HU HU0203317A patent/HUP0203317A2/hu unknown
- 2000-06-07 CN CNA008086427A patent/CN1635998A/zh active Pending
- 2000-06-07 IL IL14675500A patent/IL146755A0/xx unknown
- 2000-06-07 PL PL00357340A patent/PL357340A1/pl not_active Application Discontinuation
- 2000-06-07 EP EP00951290A patent/EP1235808A2/en not_active Withdrawn
- 2000-06-07 CA CA002376076A patent/CA2376076A1/en not_active Abandoned
- 2000-06-07 MX MXPA01012694A patent/MXPA01012694A/es unknown
- 2000-06-07 EA EA200101117A patent/EA200101117A1/ru unknown
- 2000-06-07 AP APAP/P/2001/002356A patent/AP2001002356A0/en unknown
- 2000-06-07 HR HR20010913A patent/HRP20010913A2/hr not_active Application Discontinuation
- 2000-06-07 BR BR0011427-8A patent/BR0011427A/pt not_active IP Right Cessation
- 2000-06-07 JP JP2001501597A patent/JP2003513006A/ja active Pending
2001
- 2001-11-23 IS IS6175A patent/IS6175A/is unknown
- 2001-11-30 BG BG106162A patent/BG106162A/bg unknown
- 2001-11-30 MA MA26431A patent/MA26795A1/fr unknown
- 2001-12-06 NO NO20015966A patent/NO20015966D0/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
BR0011427A (pt)	2002-03-26
KR20020010923A (ko)	2002-02-06
MA26795A1 (fr)	2004-12-20
TR200103531T2 (tr)	2002-06-21
CN1635998A (zh)	2005-07-06
AP2001002356A0 (en)	2001-12-31
IS6175A (is)	2001-11-23
CA2376076A1 (en)	2000-12-14
NO20015966L (no)	2001-12-06
NO20015966D0 (no)	2001-12-06
AU6428400A (en)	2000-12-28
JP2003513006A (ja)	2003-04-08
SK17512001A3 (sk)	2002-11-06
WO2000075116A2 (en)	2000-12-14
IL146755A0 (en)	2002-07-25
HUP0203317A2 (hu)	2003-02-28
WO2000075116A3 (en)	2002-07-04
EA200101117A1 (ru)	2002-06-27
EP1235808A2 (en)	2002-09-04
HRP20010913A2 (en)	2003-04-30
PL357340A1 (pl)	2004-07-26
MXPA01012694A (es)	2003-10-15

Publication	Publication Date	Title
DE69623306T2 (de)	2003-04-17	Pyrimidinderivate als 5ht2c-rezeptorantagonisten
FI96690C (fi)	1996-08-12	Menetelmä valmistaa terapeuttisesti aktiivista bentsopyridopiperidiini-, piperidylideeni- ja -piperatsiiniyhdistettä
US5302599A (en)	1994-04-12	Therapeutically useful heterocyclic indole compounds
RU2114848C1 (ru)	1998-07-10	Фторалкоксибензиламинные производные азотсодержащих гетероциклов, фармацевтическая композиция, способ ингибирования действия вещества р у млекопитающих
CA2111461C (en)	1996-12-17	3-aminopiperidine derivatives and related nitrogen containing heterocycles
DE69130120T2 (de)	1999-02-18	Derivate von zyklischen Amiden
PT862567E (pt)	2001-11-30	5-azabiciclo(3.1.0)hexilalquil-2-piperidonas e -glutarimidas como antagonistas do receptor de neurocinina
EP0675886A1 (en)	1995-10-11	Aminomethylene substituted non-aromatic heterocycles and use as substance p antagonists
HUT65831A (en)	1994-07-28	Process for producing substituted 3-amino-quinuclidine derivatives and pharmaceutically acceptable salts
EP1490361B1 (en)	2007-10-03	Polycyclic compounds as potent alpha2-adrenoceptor antagonists
JPH01190680A (ja)	1989-07-31	インドール誘導体およびその製造方法
EP0463810B1 (en)	1996-01-10	Heterocyclic compound and psychopharmaceutical composition containing same
JP3803268B2 (ja)	2006-08-02	アザビシクロアルカン誘導体とその治療的使用
JP2015143255A (ja)	2015-08-06	疼痛症候群および他の障害の治療法
US4937249A (en)	1990-06-26	Imide derivatives and their pharmaceutical use
FI106797B (fi)	2001-04-12	Menetelmä atsabisyklo [2.2.1] heptan-3-onioksiimien valmistamiseksi
JPH08511513A (ja)	1996-12-03	神経変性障害の治療において有用なベンズ（ｂ）アゼピン−２，５−ジオン
EP4463455B1 (en)	2026-04-29	Heteroalicyclic derivatives and their use in the treatment of cns disorders
JP2000505046A (ja)	2000-04-25	ドーパミン受容体リガンドとしての新規の融合イソキノリン類
US6313309B1 (en)	2001-11-06	4-thionaphthyl—1H—imidazoles which are usefulα22-adrenoceptoR agonists/ antagonists
US4612312A (en)	1986-09-16	Glutarimide antianxiety and antihypertensive agents
US20040266802A1 (en)	2004-12-30	Tricyclic analgesics
US5334594A (en)	1994-08-02	Amphoteric tricyclic compound
CA2376076A1 (en)	2000-12-14	Tricyclic analgesics
HK24194A (en)	1994-03-25	Pyrrolo[1,2-a][4,1]benzoxazepines, process for their preparation, pharmaceutical compositions containing these compounds and therapeutical use