UA67725C2 - K-252a derivatives and a method for improvement of functioning and cell survival enhancement - Google Patents

K-252a derivatives and a method for improvement of functioning and cell survival enhancement Download PDF

Info

Publication number: UA67725C2
Authority: UA; Ukraine
Prior art keywords: compound; lower alkyl; same meaning; unsubstituted; substituted
Prior art date: 1996-06-03

Application number

UA98126949A

Other languages

English (en)

Ukrainian (uk)

Original Assignee

Cephalon Inc

Kyowa Hakko Kogyo Kk

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.)

1996-06-03

Filing date

1997-02-06

Publication date

2004-07-15

1997-02-06 Application filed by Cephalon Inc, Kyowa Hakko Kogyo Kk filed Critical Cephalon Inc

2004-07-15 Publication of UA67725C2 publication Critical patent/UA67725C2/uk

Links

230000004083 survival effect Effects 0.000 title claims abstract description 15
238000000034 method Methods 0.000 title claims description 180
KOZFSFOOLUUIGY-IYYJOCMQSA-N k-252a, nocardiopsis sp. Chemical compound C12=C3N4C5=CC=CC=C5C3=C3CNC(=O)C3=C2C2=CC=CC=C2N1[C@@H]1C[C@](C(=O)OC)(O)[C@@]4(C)O1 KOZFSFOOLUUIGY-IYYJOCMQSA-N 0.000 title description 25
230000006872 improvement Effects 0.000 title description 4
150000001875 compounds Chemical class 0.000 claims abstract description 477
230000001228 trophic effect Effects 0.000 claims abstract description 9
230000015572 biosynthetic process Effects 0.000 claims description 175
125000000217 alkyl group Chemical group 0.000 claims description 120
239000001257 hydrogen Substances 0.000 claims description 118
229910052739 hydrogen Inorganic materials 0.000 claims description 118
150000002431 hydrogen Chemical class 0.000 claims description 59
-1 amino, guanidino Chemical group 0.000 claims description 54
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 53
125000001072 heteroaryl group Chemical group 0.000 claims description 49
125000003118 aryl group Chemical group 0.000 claims description 34
210000004027 cell Anatomy 0.000 claims description 28
150000003839 salts Chemical class 0.000 claims description 28
125000003107 substituted aryl group Chemical group 0.000 claims description 27
229910052736 halogen Inorganic materials 0.000 claims description 25
150000002367 halogens Chemical class 0.000 claims description 25
125000002252 acyl group Chemical group 0.000 claims description 22
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
125000003710 aryl alkyl group Chemical group 0.000 claims description 20
210000002569 neuron Anatomy 0.000 claims description 18
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
125000003545 alkoxy group Chemical group 0.000 claims description 13
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 12
210000002932 cholinergic neuron Anatomy 0.000 claims description 11
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 10
125000004076 pyridyl group Chemical group 0.000 claims description 10
125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 9
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 9
125000000623 heterocyclic group Chemical group 0.000 claims description 9
229910052757 nitrogen Inorganic materials 0.000 claims description 9
125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
229910052740 iodine Inorganic materials 0.000 claims description 8
201000010099 disease Diseases 0.000 claims description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
230000034994 death Effects 0.000 claims description 6
229910052760 oxygen Inorganic materials 0.000 claims description 6
125000004423 acyloxy group Chemical group 0.000 claims description 5
125000005103 alkyl silyl group Chemical group 0.000 claims description 5
125000002102 aryl alkyloxo group Chemical group 0.000 claims description 5
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
125000002947 alkylene group Chemical group 0.000 claims description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
229910052796 boron Inorganic materials 0.000 claims description 4
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 4
150000003536 tetrazoles Chemical class 0.000 claims description 4
125000002769 thiazolinyl group Chemical group 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 3
125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
125000003831 tetrazolyl group Chemical group 0.000 claims description 3
208000023105 Huntington disease Diseases 0.000 claims description 2
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 2
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 2
208000014674 injury Diseases 0.000 claims description 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
125000000335 thiazolyl group Chemical group 0.000 claims description 2
125000005504 styryl group Chemical group 0.000 claims 2
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=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
WJXSXWBOZMVFPJ-NENRSDFPSA-N N-[(2R,3R,4R,5S,6R)-4,5-dihydroxy-6-methoxy-2,4-dimethyloxan-3-yl]-N-methylacetamide Chemical compound CO[C@@H]1O[C@H](C)[C@@H](N(C)C(C)=O)[C@@](C)(O)[C@@H]1O WJXSXWBOZMVFPJ-NENRSDFPSA-N 0.000 claims 1
241000718541 Tetragastris balsamifera Species 0.000 claims 1
230000032683 aging Effects 0.000 claims 1
230000003833 cell viability Effects 0.000 claims 1
210000004962 mammalian cell Anatomy 0.000 claims 1
238000012876 topography Methods 0.000 claims 1
230000008733 trauma Effects 0.000 claims 1
238000004519 manufacturing process Methods 0.000 abstract description 3
VVVPGLRKXQSQSZ-UHFFFAOYSA-N indolo[3,2-c]carbazole Chemical class C1=CC=CC2=NC3=C4C5=CC=CC=C5N=C4C=CC3=C21 VVVPGLRKXQSQSZ-UHFFFAOYSA-N 0.000 abstract description 2
230000002708 enhancing effect Effects 0.000 abstract 1
230000001506 immunosuppresive effect Effects 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 297
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 254
238000003786 synthesis reaction Methods 0.000 description 166
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 130
239000000243 solution Substances 0.000 description 94
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 90
239000000203 mixture Substances 0.000 description 85
239000002904 solvent Substances 0.000 description 76
230000002829 reductive effect Effects 0.000 description 72
238000005160 1H NMR spectroscopy Methods 0.000 description 60
239000011541 reaction mixture Substances 0.000 description 54
229920006395 saturated elastomer Polymers 0.000 description 53
239000007864 aqueous solution Substances 0.000 description 51
238000005481 NMR spectroscopy Methods 0.000 description 49
239000011780 sodium chloride Substances 0.000 description 46
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 43
229910052938 sodium sulfate Inorganic materials 0.000 description 43
235000011152 sodium sulphate Nutrition 0.000 description 43
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 42
239000000741 silica gel Substances 0.000 description 41
229910002027 silica gel Inorganic materials 0.000 description 41
238000004587 chromatography analysis Methods 0.000 description 40
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 39
238000001704 evaporation Methods 0.000 description 33
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
238000006243 chemical reaction Methods 0.000 description 26
230000000694 effects Effects 0.000 description 25
230000008020 evaporation Effects 0.000 description 20
229910000027 potassium carbonate Inorganic materials 0.000 description 19
239000000047 product Substances 0.000 description 19
XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 18
229940125961 compound 24 Drugs 0.000 description 18
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
238000001914 filtration Methods 0.000 description 15
238000003756 stirring Methods 0.000 description 15
239000002585 base Substances 0.000 description 14
238000010898 silica gel chromatography Methods 0.000 description 14
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 12
230000003993 interaction Effects 0.000 description 12
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 11
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
238000007792 addition Methods 0.000 description 10
239000000706 filtrate Substances 0.000 description 10
LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 10
125000001424 substituent group Chemical group 0.000 description 10
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 9
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
101000629622 Homo sapiens Serine-pyruvate aminotransferase Proteins 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
102100026842 Serine-pyruvate aminotransferase Human genes 0.000 description 8
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 8
239000003054 catalyst Substances 0.000 description 8
230000001537 neural effect Effects 0.000 description 8
239000000546 pharmaceutical excipient Substances 0.000 description 8
TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 7
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 7
229940125851 compound 27 Drugs 0.000 description 7
230000002401 inhibitory effect Effects 0.000 description 7
239000011630 iodine Substances 0.000 description 7
230000009467 reduction Effects 0.000 description 7
238000006722 reduction reaction Methods 0.000 description 7
OOKAZRDERJMRCJ-KOUAFAAESA-N (3r)-7-[(1s,2s,4ar,6s,8s)-2,6-dimethyl-8-[(2s)-2-methylbutanoyl]oxy-1,2,4a,5,6,7,8,8a-octahydronaphthalen-1-yl]-3-hydroxy-5-oxoheptanoic acid Chemical compound C1=C[C@H](C)[C@H](CCC(=O)C[C@@H](O)CC(O)=O)C2[C@@H](OC(=O)[C@@H](C)CC)C[C@@H](C)C[C@@H]21 OOKAZRDERJMRCJ-KOUAFAAESA-N 0.000 description 6
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
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 description 6
230000009471 action Effects 0.000 description 6
239000012298 atmosphere Substances 0.000 description 6
229940127271 compound 49 Drugs 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000012044 organic layer Substances 0.000 description 6
150000002941 palladium compounds Chemical class 0.000 description 6
150000004714 phosphonium salts Chemical group 0.000 description 6
229910052698 phosphorus Inorganic materials 0.000 description 6
239000011574 phosphorus Substances 0.000 description 6
GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 5
UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 5
PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 5
BGAJNPLDJJBRHK-UHFFFAOYSA-N 3-[2-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,3,4-thiadiazol-2-yl]-3-methyl-6,7-dihydro-4h-pyrazolo[4,3-c]pyridin-5-yl]propanoic acid Chemical compound C1=C(Cl)C(OC(C)C)=CC=C1C1=NN=C(N2C(=C3CN(CCC(O)=O)CCC3=N2)C)S1 BGAJNPLDJJBRHK-UHFFFAOYSA-N 0.000 description 5
MPMKMQHJHDHPBE-RUZDIDTESA-N 4-[[(2r)-1-(1-benzothiophene-3-carbonyl)-2-methylazetidine-2-carbonyl]-[(3-chlorophenyl)methyl]amino]butanoic acid Chemical compound O=C([C@@]1(N(CC1)C(=O)C=1C2=CC=CC=C2SC=1)C)N(CCCC(O)=O)CC1=CC=CC(Cl)=C1 MPMKMQHJHDHPBE-RUZDIDTESA-N 0.000 description 5
DQAZPZIYEOGZAF-UHFFFAOYSA-N 4-ethyl-n-[4-(3-ethynylanilino)-7-methoxyquinazolin-6-yl]piperazine-1-carboxamide Chemical compound C1CN(CC)CCN1C(=O)NC(C(=CC1=NC=N2)OC)=CC1=C2NC1=CC=CC(C#C)=C1 DQAZPZIYEOGZAF-UHFFFAOYSA-N 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 5
229910052786 argon Inorganic materials 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
229910052794 bromium Inorganic materials 0.000 description 5
239000003638 chemical reducing agent Substances 0.000 description 5
230000001713 cholinergic effect Effects 0.000 description 5
229940125758 compound 15 Drugs 0.000 description 5
229940125810 compound 20 Drugs 0.000 description 5
238000001816 cooling Methods 0.000 description 5
JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 description 5
239000008194 pharmaceutical composition Substances 0.000 description 5
239000011734 sodium Substances 0.000 description 5
210000000278 spinal cord Anatomy 0.000 description 5
239000007858 starting material Substances 0.000 description 5
238000006467 substitution reaction Methods 0.000 description 5
UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 4
AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 4
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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
DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical class CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
210000001103 thalamus Anatomy 0.000 description 1
CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
238000000844 transformation Methods 0.000 description 1
125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
UCECZWKGWRJAFG-UHFFFAOYSA-M triphenyl(pyridin-2-ylmethyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)CC1=CC=CC=N1 UCECZWKGWRJAFG-UHFFFAOYSA-M 0.000 description 1
UGDYRTOUNGDPDN-UHFFFAOYSA-M triphenyl(pyridin-4-ylmethyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)CC1=CC=NC=C1 UGDYRTOUNGDPDN-UHFFFAOYSA-M 0.000 description 1
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
238000001665 trituration Methods 0.000 description 1
125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
229910052720 vanadium Inorganic materials 0.000 description 1
230000002541 vasodepressive effect Effects 0.000 description 1
239000003071 vasodilator agent Substances 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
238000005406 washing Methods 0.000 description 1
150000003751 zinc Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

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Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Veterinary Medicine (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Chemical Kinetics & Catalysis (AREA)
Neurosurgery (AREA)
Biomedical Technology (AREA)
Neurology (AREA)
Psychology (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Pain & Pain Management (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Saccharide Compounds (AREA)

UA98126949A 1996-06-03 1997-02-06 K-252a derivatives and a method for improvement of functioning and cell survival enhancement UA67725C2 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US65736696A	1996-06-03	1996-06-03
PCT/US1997/009448 WO1997046565A1 (en)	1996-06-03	1997-06-02	SELECTED DERIVATIVES OF K-252a

Publications (1)

Publication Number	Publication Date
UA67725C2 true UA67725C2 (en)	2004-07-15

Family

ID=24636859

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
UA98126949A UA67725C2 (en)	1996-06-03	1997-02-06	K-252a derivatives and a method for improvement of functioning and cell survival enhancement

Country Status (17)

Country	Link
US (1)	US6306849B1 (de)
EP (1)	EP0918777B1 (de)
JP (1)	JP2000511902A (de)
CN (1)	CN1198827C (de)
AT (1)	ATE222912T1 (de)
AU (1)	AU716656B2 (de)
BR (1)	BR9711093A (de)
CA (1)	CA2256633C (de)
DE (1)	DE69715010T2 (de)
DK (1)	DK0918777T3 (de)
ES (1)	ES2183184T3 (de)
NO (1)	NO312464B1 (de)
NZ (2)	NZ333018A (de)
PT (1)	PT918777E (de)
RU (1)	RU2205184C2 (de)
UA (1)	UA67725C2 (de)
WO (1)	WO1997046565A1 (de)

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US7569364B2 (en)	2002-12-24	2009-08-04	Pfizer Inc.	Anti-NGF antibodies and methods using same
US9498530B2 (en)	2002-12-24	2016-11-22	Rinat Neuroscience Corp.	Methods for treating osteoarthritis pain by administering a nerve growth factor antagonist and compositions containing the same
DK2270048T3 (en)	2002-12-24	2016-01-18	Rinat Neuroscience Corp	Anti-NGF antibodies and methods for their use
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EP3372614B1 (de)	2004-04-07	2022-06-08	Rinat Neuroscience Corp.	Verfahren zur schmerzbehandlung in knochenkrebs durch verabreichung eines ngf-antagonististen
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1997
- 1997-02-06 UA UA98126949A patent/UA67725C2/uk unknown
- 1997-06-02 PT PT97927906T patent/PT918777E/pt unknown
- 1997-06-02 JP JP10500751A patent/JP2000511902A/ja active Pending
- 1997-06-02 ES ES97927906T patent/ES2183184T3/es not_active Expired - Lifetime
- 1997-06-02 DK DK97927906T patent/DK0918777T3/da active
- 1997-06-02 CN CNB97196985XA patent/CN1198827C/zh not_active Expired - Fee Related
- 1997-06-02 EP EP97927906A patent/EP0918777B1/de not_active Expired - Lifetime
- 1997-06-02 NZ NZ333018A patent/NZ333018A/xx not_active IP Right Cessation
- 1997-06-02 AU AU32253/97A patent/AU716656B2/en not_active Ceased
- 1997-06-02 CA CA002256633A patent/CA2256633C/en not_active Expired - Fee Related
- 1997-06-02 BR BR9711093A patent/BR9711093A/pt active Search and Examination
- 1997-06-02 RU RU99100050/04A patent/RU2205184C2/ru not_active IP Right Cessation
- 1997-06-02 DE DE69715010T patent/DE69715010T2/de not_active Expired - Lifetime
- 1997-06-02 US US08/867,084 patent/US6306849B1/en not_active Expired - Fee Related
- 1997-06-02 AT AT97927906T patent/ATE222912T1/de not_active IP Right Cessation
- 1997-06-02 WO PCT/US1997/009448 patent/WO1997046565A1/en not_active Ceased
1998
- 1998-12-02 NO NO19985622A patent/NO312464B1/no not_active IP Right Cessation
2000
- 2000-04-19 NZ NZ504097A patent/NZ504097A/en unknown

Also Published As

Publication number	Publication date
HK1018703A1 (en)	1999-12-30
NO985622L (no)	1999-02-02
JP2000511902A (ja)	2000-09-12
WO1997046565A1 (en)	1997-12-11
CN1226893A (zh)	1999-08-25
NZ504097A (en)	2005-06-24
ATE222912T1 (de)	2002-09-15
PT918777E (pt)	2003-01-31
CN1198827C (zh)	2005-04-27
AU3225397A (en)	1998-01-05
AU716656B2 (en)	2000-03-02
ES2183184T3 (es)	2003-03-16
RU2205184C2 (ru)	2003-05-27
NO985622D0 (no)	1998-12-02
DE69715010D1 (de)	2002-10-02
CA2256633A1 (en)	1997-12-11
US6306849B1 (en)	2001-10-23
DE69715010T2 (de)	2003-04-03
BR9711093A (pt)	1999-08-17
NZ333018A (en)	2000-05-26
EP0918777A1 (de)	1999-06-02
EP0918777B1 (de)	2002-08-28
CA2256633C (en)	2009-04-07
DK0918777T3 (da)	2002-12-30
NO312464B1 (no)	2002-05-13

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