OA11586A - FKBP inhibotors. - Google Patents

FKBP inhibotors. Download PDF

Info

Publication number: OA11586A
Authority: OA; OAPI
Prior art keywords: alkyl; substance according; halo; optionally substituted; formula
Prior art date: 1998-07-20

Application number

OA1200100024A

Other languages

English (en)

Inventor

James Francis Blake Jr

Mark Ian Kemp

Malcolm Christian Mackenny

Robert John Maguire

Michael John Palmer

Wythes Martin James

Original Assignee

Pfizer

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.)

1998-07-20

Filing date

1999-07-01

Publication date

2004-07-26

1999-07-01 Application filed by Pfizer filed Critical Pfizer

2004-07-26 Publication of OA11586A publication Critical patent/OA11586A/en

Links

102000018679 Tacrolimus Binding Proteins Human genes 0.000 title abstract description 4
108010027179 Tacrolimus Binding Proteins Proteins 0.000 title abstract description 4
150000001875 compounds Chemical class 0.000 claims abstract description 142
150000003839 salts Chemical class 0.000 claims abstract description 15
238000000034 method Methods 0.000 claims description 78
125000000217 alkyl group Chemical group 0.000 claims description 76
239000000126 substance Substances 0.000 claims description 65
125000005843 halogen group Chemical group 0.000 claims description 55
239000000203 mixture Substances 0.000 claims description 40
125000000753 cycloalkyl group Chemical group 0.000 claims description 38
125000003342 alkenyl group Chemical group 0.000 claims description 32
238000006243 chemical reaction Methods 0.000 claims description 32
125000003545 alkoxy group Chemical group 0.000 claims description 31
125000001424 substituent group Chemical group 0.000 claims description 30
229910052760 oxygen Inorganic materials 0.000 claims description 23
229910052757 nitrogen Inorganic materials 0.000 claims description 21
-1 phenyloxy, benzyloxy Chemical group 0.000 claims description 21
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 18
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
229910052717 sulfur Inorganic materials 0.000 claims description 17
208000024827 Alzheimer disease Diseases 0.000 claims description 16
208000012902 Nervous system disease Diseases 0.000 claims description 16
206010012601 diabetes mellitus Diseases 0.000 claims description 15
210000001428 peripheral nervous system Anatomy 0.000 claims description 14
230000000508 neurotrophic effect Effects 0.000 claims description 13
125000003118 aryl group Chemical group 0.000 claims description 12
210000003169 central nervous system Anatomy 0.000 claims description 11
208000011580 syndromic disease Diseases 0.000 claims description 10
238000011282 treatment Methods 0.000 claims description 10
208000025966 Neurological disease Diseases 0.000 claims description 9
229910052799 carbon Inorganic materials 0.000 claims description 9
208000035475 disorder Diseases 0.000 claims description 9
206010002027 Amyotrophy Diseases 0.000 claims description 8
206010012289 Dementia Diseases 0.000 claims description 8
208000026072 Motor neurone disease Diseases 0.000 claims description 8
208000034189 Sclerosis Diseases 0.000 claims description 8
206010039966 Senile dementia Diseases 0.000 claims description 8
208000009205 Tinnitus Diseases 0.000 claims description 8
125000003302 alkenyloxy group Chemical group 0.000 claims description 8
201000010099 disease Diseases 0.000 claims description 8
201000006417 multiple sclerosis Diseases 0.000 claims description 8
230000004770 neurodegeneration Effects 0.000 claims description 8
208000015122 neurodegenerative disease Diseases 0.000 claims description 8
230000000926 neurological effect Effects 0.000 claims description 8
208000033808 peripheral neuropathy Diseases 0.000 claims description 8
230000000750 progressive effect Effects 0.000 claims description 8
210000000278 spinal cord Anatomy 0.000 claims description 8
231100000886 tinnitus Toxicity 0.000 claims description 8
230000000472 traumatic effect Effects 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
208000018737 Parkinson disease Diseases 0.000 claims description 7
125000001153 fluoro group Chemical group F* 0.000 claims description 7
125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
230000008569 process Effects 0.000 claims description 7
208000016621 Hearing disease Diseases 0.000 claims description 6
125000002947 alkylene group Chemical group 0.000 claims description 6
125000000000 cycloalkoxy group Chemical group 0.000 claims description 6
208000005264 motor neuron disease Diseases 0.000 claims description 6
210000000653 nervous system Anatomy 0.000 claims description 6
206010003694 Atrophy Diseases 0.000 claims description 5
208000023105 Huntington disease Diseases 0.000 claims description 5
230000037444 atrophy Effects 0.000 claims description 5
239000003795 chemical substances by application Substances 0.000 claims description 5
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
239000000546 pharmaceutical excipient Substances 0.000 claims description 5
125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 4
241000238876 Acari Species 0.000 claims description 4
206010003591 Ataxia Diseases 0.000 claims description 4
208000006373 Bell palsy Diseases 0.000 claims description 4
MQJKPEGWNLWLTK-UHFFFAOYSA-N Dapsone Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 MQJKPEGWNLWLTK-UHFFFAOYSA-N 0.000 claims description 4
101100134927 Gallus gallus COR8 gene Proteins 0.000 claims description 4
208000003435 Optic Neuritis Diseases 0.000 claims description 4
208000024777 Prion disease Diseases 0.000 claims description 4
206010041591 Spinal osteoarthritis Diseases 0.000 claims description 4
208000036826 VIIth nerve paralysis Diseases 0.000 claims description 4
201000011101 acute retrobulbar neuritis Diseases 0.000 claims description 4
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 4
230000001363 autoimmune Effects 0.000 claims description 4
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
229960000860 dapsone 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
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
JYQQWQJCEUMXQZ-UHFFFAOYSA-N methyl cyanate Chemical compound COC#N JYQQWQJCEUMXQZ-UHFFFAOYSA-N 0.000 claims description 4
206010028417 myasthenia gravis Diseases 0.000 claims description 4
125000001624 naphthyl group Chemical group 0.000 claims description 4
210000001328 optic nerve Anatomy 0.000 claims description 4
208000022670 retrobulbar neuritis Diseases 0.000 claims description 4
241000894007 species Species 0.000 claims description 4
208000002320 spinal muscular atrophy Diseases 0.000 claims description 4
208000005801 spondylosis Diseases 0.000 claims description 4
206010044652 trigeminal neuralgia Diseases 0.000 claims description 4
208000037859 AIDS-related disorder Diseases 0.000 claims description 3
101100328886 Caenorhabditis elegans col-2 gene Proteins 0.000 claims description 3
208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 3
206010049567 Miller Fisher syndrome Diseases 0.000 claims description 3
JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 3
150000001540 azides Chemical class 0.000 claims description 3
208000036319 cervical spondylosis Diseases 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
150000002148 esters Chemical class 0.000 claims description 3
QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 claims description 3
201000000585 muscular atrophy Diseases 0.000 claims description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
125000006413 ring segment Chemical group 0.000 claims description 3
206010048627 thoracic outlet syndrome Diseases 0.000 claims description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 claims description 2
125000002619 bicyclic group Chemical group 0.000 claims description 2
125000005842 heteroatom Chemical group 0.000 claims description 2
125000002950 monocyclic group Chemical group 0.000 claims description 2
230000003387 muscular Effects 0.000 claims description 2
125000002524 organometallic group Chemical group 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims description 2
229910052739 hydrogen Inorganic materials 0.000 claims 8
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 7
WXMNXZYSBAJBKT-ZDUSSCGKSA-N (2s)-1-(5-chloro-1,3-benzoxazol-2-yl)-2-methylpyrrolidine-2-carboxylic acid Chemical compound OC(=O)[C@]1(C)CCCN1C1=NC2=CC(Cl)=CC=C2O1 WXMNXZYSBAJBKT-ZDUSSCGKSA-N 0.000 claims 1
125000004429 atom Chemical group 0.000 claims 1
208000004296 neuralgia Diseases 0.000 claims 1
239000003112 inhibitor Substances 0.000 abstract description 6
239000012453 solvate Substances 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 186
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 93
239000002904 solvent Substances 0.000 description 80
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 71
239000000243 solution Substances 0.000 description 49
238000005160 1H NMR spectroscopy Methods 0.000 description 46
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 43
230000002829 reductive effect Effects 0.000 description 41
239000012043 crude product Substances 0.000 description 38
101150041968 CDC13 gene Proteins 0.000 description 36
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 36
239000000741 silica gel Substances 0.000 description 36
229910002027 silica gel Inorganic materials 0.000 description 36
229940093499 ethyl acetate Drugs 0.000 description 35
235000019439 ethyl acetate Nutrition 0.000 description 35
238000004440 column chromatography Methods 0.000 description 34
239000011541 reaction mixture Substances 0.000 description 31
239000007787 solid Substances 0.000 description 31
238000005481 NMR spectroscopy Methods 0.000 description 29
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 23
238000004458 analytical method Methods 0.000 description 22
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 20
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 18
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 17
235000011114 ammonium hydroxide Nutrition 0.000 description 17
229910021653 sulphate ion Inorganic materials 0.000 description 17
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 16
239000012044 organic layer Substances 0.000 description 16
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 12
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
239000002253 acid Substances 0.000 description 11
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 9
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 8
239000003153 chemical reaction reagent Substances 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 8
108010025020 Nerve Growth Factor Proteins 0.000 description 7
102000015336 Nerve Growth Factor Human genes 0.000 description 7
102100020739 Peptidyl-prolyl cis-trans isomerase FKBP4 Human genes 0.000 description 7
101710147152 Peptidyl-prolyl cis-trans isomerase FKBP4 Proteins 0.000 description 7
239000006260 foam Substances 0.000 description 7
229940053128 nerve growth factor Drugs 0.000 description 7
239000000047 product Substances 0.000 description 7
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
102100027913 Peptidyl-prolyl cis-trans isomerase FKBP1A Human genes 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
229960000583 acetic acid Drugs 0.000 description 6
238000010992 reflux Methods 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
238000003556 assay Methods 0.000 description 5
239000012131 assay buffer Substances 0.000 description 5
229910002092 carbon dioxide Inorganic materials 0.000 description 5
210000004027 cell Anatomy 0.000 description 5
239000012362 glacial acetic acid Substances 0.000 description 5
VEIWYFRREFUNRC-UHFFFAOYSA-N hydron;piperidine;chloride Chemical compound [Cl-].C1CC[NH2+]CC1 VEIWYFRREFUNRC-UHFFFAOYSA-N 0.000 description 5
239000010410 layer Substances 0.000 description 5
230000014511 neuron projection development Effects 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
235000011181 potassium carbonates Nutrition 0.000 description 5
239000000843 powder Substances 0.000 description 5
DQQHMRVHTMHDGE-DTORHVGOSA-N 2-[(2r,6s)-2,6-dimethylpiperidin-1-yl]ethanamine Chemical compound C[C@H]1CCC[C@@H](C)N1CCN DQQHMRVHTMHDGE-DTORHVGOSA-N 0.000 description 4
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
230000006978 adaptation Effects 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
238000007796 conventional method Methods 0.000 description 4
210000000609 ganglia Anatomy 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
239000011734 sodium Substances 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
239000007858 starting material Substances 0.000 description 4
239000000725 suspension Substances 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
239000008096 xylene Substances 0.000 description 4
WXTUPZCUXANAJB-JTQLQIEISA-N (2s)-1-(1,3-benzoxazol-2-yl)piperidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCCN1C1=NC2=CC=CC=C2O1 WXTUPZCUXANAJB-JTQLQIEISA-N 0.000 description 3
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
AYPSHJCKSDNETA-UHFFFAOYSA-N 2-chloro-1h-benzimidazole Chemical compound C1=CC=C2NC(Cl)=NC2=C1 AYPSHJCKSDNETA-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
208000021965 Glossopharyngeal Nerve disease Diseases 0.000 description 3
108010016648 Immunophilins Proteins 0.000 description 3
102000000521 Immunophilins Human genes 0.000 description 3
FEWJPZIEWOKRBE-JCYAYHJZSA-L L-tartrate(2-) Chemical compound [O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-L 0.000 description 3
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
108010020062 Peptidylprolyl Isomerase Proteins 0.000 description 3
102000009658 Peptidylprolyl Isomerase Human genes 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000003054 catalyst Substances 0.000 description 3
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 3
201000005442 glossopharyngeal neuralgia Diseases 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
201000006938 muscular dystrophy Diseases 0.000 description 3
210000002569 neuron Anatomy 0.000 description 3
239000002674 ointment Substances 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
235000019271 petrolatum Nutrition 0.000 description 3
239000002244 precipitate Substances 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
239000000377 silicon dioxide Substances 0.000 description 3
235000011121 sodium hydroxide Nutrition 0.000 description 3
229940083608 sodium hydroxide Drugs 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
239000008107 starch Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
PLRACCBDVIHHLZ-UHFFFAOYSA-N 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Chemical compound C1N(C)CCC(C=2C=CC=CC=2)=C1 PLRACCBDVIHHLZ-UHFFFAOYSA-N 0.000 description 2
CHZXTOCAICMPQR-UHFFFAOYSA-N 2-(2-bromoethyl)isoindole-1,3-dione Chemical compound C1=CC=C2C(=O)N(CCBr)C(=O)C2=C1 CHZXTOCAICMPQR-UHFFFAOYSA-N 0.000 description 2
SKPZIOZINPDRCY-UHFFFAOYSA-N 2-(3,5-dimethylmorpholin-4-yl)ethanamine Chemical compound CC1COCC(C)N1CCN SKPZIOZINPDRCY-UHFFFAOYSA-N 0.000 description 2
JMTMSDXUXJISAY-UHFFFAOYSA-N 2H-benzotriazol-4-ol Chemical compound OC1=CC=CC2=C1N=NN2 JMTMSDXUXJISAY-UHFFFAOYSA-N 0.000 description 2
ZJSQZQMVXKZAGW-UHFFFAOYSA-N 2H-benzotriazol-4-ol hydrate Chemical compound O.OC1=CC=CC2=C1N=NN2 ZJSQZQMVXKZAGW-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
102000004631 Calcineurin Human genes 0.000 description 2
108010042955 Calcineurin Proteins 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
101710103508 FK506-binding protein Proteins 0.000 description 2
101710104425 FK506-binding protein 2 Proteins 0.000 description 2
101710104423 FK506-binding protein 3 Proteins 0.000 description 2
101710104333 FK506-binding protein 4 Proteins 0.000 description 2
101710104342 FK506-binding protein 5 Proteins 0.000 description 2
101710149710 FKBP-type 16 kDa peptidyl-prolyl cis-trans isomerase Proteins 0.000 description 2
101710121306 FKBP-type 22 kDa peptidyl-prolyl cis-trans isomerase Proteins 0.000 description 2
101710180800 FKBP-type peptidyl-prolyl cis-trans isomerase FkpA Proteins 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
239000007995 HEPES buffer Substances 0.000 description 2
101710104030 Long-type peptidyl-prolyl cis-trans isomerase Proteins 0.000 description 2
101001135571 Mus musculus Tyrosine-protein phosphatase non-receptor type 2 Proteins 0.000 description 2
101710114693 Outer membrane protein MIP Proteins 0.000 description 2
101710116692 Peptidyl-prolyl cis-trans isomerase Proteins 0.000 description 2
101710111764 Peptidyl-prolyl cis-trans isomerase FKBP10 Proteins 0.000 description 2
101710111749 Peptidyl-prolyl cis-trans isomerase FKBP11 Proteins 0.000 description 2
101710111747 Peptidyl-prolyl cis-trans isomerase FKBP12 Proteins 0.000 description 2
101710111757 Peptidyl-prolyl cis-trans isomerase FKBP14 Proteins 0.000 description 2
101710111682 Peptidyl-prolyl cis-trans isomerase FKBP1A Proteins 0.000 description 2
101710111689 Peptidyl-prolyl cis-trans isomerase FKBP1B Proteins 0.000 description 2
101710147154 Peptidyl-prolyl cis-trans isomerase FKBP2 Proteins 0.000 description 2
101710147149 Peptidyl-prolyl cis-trans isomerase FKBP3 Proteins 0.000 description 2
101710147150 Peptidyl-prolyl cis-trans isomerase FKBP5 Proteins 0.000 description 2
101710147138 Peptidyl-prolyl cis-trans isomerase FKBP7 Proteins 0.000 description 2
101710147137 Peptidyl-prolyl cis-trans isomerase FKBP8 Proteins 0.000 description 2
101710147136 Peptidyl-prolyl cis-trans isomerase FKBP9 Proteins 0.000 description 2
101710174853 Peptidyl-prolyl cis-trans isomerase Mip Proteins 0.000 description 2
101710200991 Peptidyl-prolyl cis-trans isomerase, rhodopsin-specific isozyme Proteins 0.000 description 2
101710092145 Peptidyl-prolyl cis-trans isomerase-like 1 Proteins 0.000 description 2
101710092146 Peptidyl-prolyl cis-trans isomerase-like 2 Proteins 0.000 description 2
101710092148 Peptidyl-prolyl cis-trans isomerase-like 3 Proteins 0.000 description 2
101710092149 Peptidyl-prolyl cis-trans isomerase-like 4 Proteins 0.000 description 2
239000004264 Petrolatum Substances 0.000 description 2
101710113444 Probable parvulin-type peptidyl-prolyl cis-trans isomerase Proteins 0.000 description 2
101710090737 Probable peptidyl-prolyl cis-trans isomerase Proteins 0.000 description 2
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
101710133309 Putative peptidyl-prolyl cis-trans isomerase Proteins 0.000 description 2
101710124237 Short-type peptidyl-prolyl cis-trans isomerase Proteins 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
238000002835 absorbance Methods 0.000 description 2
108010027597 alpha-chymotrypsin Proteins 0.000 description 2
VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 2
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 2
230000000694 effects Effects 0.000 description 2
229940088598 enzyme Drugs 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
238000001640 fractional crystallisation Methods 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
239000000499 gel Substances 0.000 description 2
239000008273 gelatin Substances 0.000 description 2
229920000159 gelatin Polymers 0.000 description 2
235000019322 gelatine Nutrition 0.000 description 2
235000011852 gelatine desserts Nutrition 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
XLSMFKSTNGKWQX-UHFFFAOYSA-N hydroxyacetone Chemical compound CC(=O)CO XLSMFKSTNGKWQX-UHFFFAOYSA-N 0.000 description 2
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 2
238000010191 image analysis Methods 0.000 description 2
230000001506 immunosuppresive effect Effects 0.000 description 2
229960003444 immunosuppressant agent Drugs 0.000 description 2
230000001861 immunosuppressant effect Effects 0.000 description 2
239000003018 immunosuppressive agent Substances 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
FMKOJHQHASLBPH-UHFFFAOYSA-N isopropyl iodide Chemical compound CC(C)I FMKOJHQHASLBPH-UHFFFAOYSA-N 0.000 description 2
239000008101 lactose Substances 0.000 description 2
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
239000006210 lotion Substances 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
238000001819 mass spectrum Methods 0.000 description 2
238000005259 measurement Methods 0.000 description 2
239000002609 medium Substances 0.000 description 2
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
230000001537 neural effect Effects 0.000 description 2
210000002241 neurite Anatomy 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 2
229940066842 petrolatum Drugs 0.000 description 2
RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical class [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
230000001737 promoting effect Effects 0.000 description 2
229960005335 propanol Drugs 0.000 description 2
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 2
125000006239 protecting group Chemical group 0.000 description 2
238000012552 review Methods 0.000 description 2
210000003497 sciatic nerve Anatomy 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
210000003594 spinal ganglia Anatomy 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
238000003756 stirring Methods 0.000 description 2
UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
239000000758 substrate Substances 0.000 description 2
229940095064 tartrate Drugs 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
BIHRPYMMVOCREW-MJBXVCDLSA-N (2s)-n-[2-[(2r,6s)-2,6-dimethylpiperidin-1-yl]ethyl]piperidine-2-carboxamide Chemical compound C[C@H]1CCC[C@@H](C)N1CCNC(=O)[C@H]1NCCCC1 BIHRPYMMVOCREW-MJBXVCDLSA-N 0.000 description 1
IFNWESYYDINUHV-OLQVQODUSA-N (2s,6r)-2,6-dimethylpiperazine Chemical compound C[C@H]1CNC[C@@H](C)N1 IFNWESYYDINUHV-OLQVQODUSA-N 0.000 description 1
YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 1
LVGUZGTVOIAKKC-UHFFFAOYSA-N 1,1,1,2-tetrafluoroethane Chemical compound FCC(F)(F)F LVGUZGTVOIAKKC-UHFFFAOYSA-N 0.000 description 1
DDMOUSALMHHKOS-UHFFFAOYSA-N 1,2-dichloro-1,1,2,2-tetrafluoroethane Chemical compound FC(F)(Cl)C(F)(F)Cl DDMOUSALMHHKOS-UHFFFAOYSA-N 0.000 description 1
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
YQXCUYGIEMLUTR-FUNVUKJBSA-N 1-[2-[(2s,6r)-2,6-dimethylpiperazin-1-yl]ethyl]piperidine-2-carboxamide Chemical compound C[C@H]1CNC[C@@H](C)N1CCN1C(C(N)=O)CCCC1 YQXCUYGIEMLUTR-FUNVUKJBSA-N 0.000 description 1
FTLRWLFEIHMRFK-UHFFFAOYSA-N 1-ethylpiperidine-2-carboxamide Chemical compound CCN1CCCCC1C(N)=O FTLRWLFEIHMRFK-UHFFFAOYSA-N 0.000 description 1
HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
NJQJGRGGIUNVAB-UHFFFAOYSA-N 2,4,4,6-tetrabromocyclohexa-2,5-dien-1-one Chemical compound BrC1=CC(Br)(Br)C=C(Br)C1=O NJQJGRGGIUNVAB-UHFFFAOYSA-N 0.000 description 1
WCYGORCMAJDYJN-UHFFFAOYSA-N 2-(1-hydroxypropan-2-ylamino)propan-1-ol Chemical compound OCC(C)NC(C)CO WCYGORCMAJDYJN-UHFFFAOYSA-N 0.000 description 1
BKMMTJMQCTUHRP-UHFFFAOYSA-N 2-aminopropan-1-ol Chemical compound CC(N)CO BKMMTJMQCTUHRP-UHFFFAOYSA-N 0.000 description 1
GSLTVFIVJMCNBH-UHFFFAOYSA-N 2-isocyanatopropane Chemical compound CC(C)N=C=O GSLTVFIVJMCNBH-UHFFFAOYSA-N 0.000 description 1
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 1
ZAZPDOYUCVFPOI-UHFFFAOYSA-N 2-methylpropylboronic acid Chemical compound CC(C)CB(O)O ZAZPDOYUCVFPOI-UHFFFAOYSA-N 0.000 description 1
LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
CJNRGSHEMCMUOE-UHFFFAOYSA-N 2-piperidin-1-ylethanamine Chemical compound NCCN1CCCCC1 CJNRGSHEMCMUOE-UHFFFAOYSA-N 0.000 description 1
KLDLRDSRCMJKGM-UHFFFAOYSA-N 3-[chloro-(2-oxo-1,3-oxazolidin-3-yl)phosphoryl]-1,3-oxazolidin-2-one Chemical compound C1COC(=O)N1P(=O)(Cl)N1CCOC1=O KLDLRDSRCMJKGM-UHFFFAOYSA-N 0.000 description 1
QFVHZQCOUORWEI-UHFFFAOYSA-N 4-[(4-anilino-5-sulfonaphthalen-1-yl)diazenyl]-5-hydroxynaphthalene-2,7-disulfonic acid Chemical compound C=12C(O)=CC(S(O)(=O)=O)=CC2=CC(S(O)(=O)=O)=CC=1N=NC(C1=CC=CC(=C11)S(O)(=O)=O)=CC=C1NC1=CC=CC=C1 QFVHZQCOUORWEI-UHFFFAOYSA-N 0.000 description 1
MGGVALXERJRIRO-UHFFFAOYSA-N 4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-2-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-1H-pyrazol-5-one Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)O MGGVALXERJRIRO-UHFFFAOYSA-N 0.000 description 1
LLJMPRKYLLJAEB-UHFFFAOYSA-N 4-aminobenzene-1,3-diol;hydron;chloride Chemical compound Cl.NC1=CC=C(O)C=C1O LLJMPRKYLLJAEB-UHFFFAOYSA-N 0.000 description 1
FUOSRKZBOIVBOS-UHFFFAOYSA-N 4-iodobenzene-1,2-diamine Chemical compound NC1=CC=C(I)C=C1N FUOSRKZBOIVBOS-UHFFFAOYSA-N 0.000 description 1
GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 1
ZCUFTCUMEDALHC-UHFFFAOYSA-N CC[K] Chemical compound CC[K] ZCUFTCUMEDALHC-UHFFFAOYSA-N 0.000 description 1
PCBZRNYXXCIELG-WYFCWLEVSA-N COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 Chemical compound COC1=CC=C(C[C@H](NC(=O)OC2CCCC3(C2)OOC2(O3)C3CC4CC(C3)CC2C4)C(=O)N[C@@H]2[C@@H](CO)O[C@H]([C@@H]2O)N2C=NC3=C2N=CN=C3N(C)C)C=C1 PCBZRNYXXCIELG-WYFCWLEVSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 1
108090000317 Chymotrypsin Proteins 0.000 description 1
108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
102000008186 Collagen Human genes 0.000 description 1
108010035532 Collagen Proteins 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
DSLZVSRJTYRBFB-LLEIAEIESA-N D-glucaric acid Chemical compound OC(=O)[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O DSLZVSRJTYRBFB-LLEIAEIESA-N 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
239000004338 Dichlorodifluoromethane Substances 0.000 description 1
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 0.000 description 1
239000004150 EU approved colour Substances 0.000 description 1
241000400611 Eucalyptus deanei Species 0.000 description 1
102000021523 FK506 binding proteins Human genes 0.000 description 1
108091011114 FK506 binding proteins Proteins 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
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 1
239000004471 Glycine Substances 0.000 description 1
239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
206010053317 Hydrophobia Diseases 0.000 description 1
HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical compound [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
240000003183 Manihot esculenta Species 0.000 description 1
235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
208000028389 Nerve injury Diseases 0.000 description 1
206010029301 Neurological disorders of the eye Diseases 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
229920001214 Polysorbate 60 Polymers 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
244000061456 Solanum tuberosum Species 0.000 description 1
235000002595 Solanum tuberosum Nutrition 0.000 description 1
HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 description 1
239000004147 Sorbitan trioleate Substances 0.000 description 1
PRXRUNOAOLTIEF-ADSICKODSA-N Sorbitan trioleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCC\C=C/CCCCCCCC)[C@H]1OC[C@H](O)[C@H]1OC(=O)CCCCCCC\C=C/CCCCCCCC PRXRUNOAOLTIEF-ADSICKODSA-N 0.000 description 1
229930006000 Sucrose Natural products 0.000 description 1
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 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
239000005864 Sulphur Substances 0.000 description 1
241000746181 Therates Species 0.000 description 1
RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
JQLJYRIBRUXPSB-UHFFFAOYSA-N [Cl-].O=C(OCc1ccccc1)[NH+]1CCCCC1 Chemical compound [Cl-].O=C(OCc1ccccc1)[NH+]1CCCCC1 JQLJYRIBRUXPSB-UHFFFAOYSA-N 0.000 description 1
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
239000000783 alginic acid Substances 0.000 description 1
235000010443 alginic acid Nutrition 0.000 description 1
229920000615 alginic acid Polymers 0.000 description 1
229960001126 alginic acid Drugs 0.000 description 1
150000004781 alginic acids Chemical class 0.000 description 1
125000004450 alkenylene group Chemical group 0.000 description 1
239000004411 aluminium Substances 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
NOFOAYPPHIUXJR-APNQCZIXSA-N aphidicolin Chemical compound C1[C@@]23[C@@]4(C)CC[C@@H](O)[C@@](C)(CO)[C@@H]4CC[C@H]3C[C@H]1[C@](CO)(O)CC2 NOFOAYPPHIUXJR-APNQCZIXSA-N 0.000 description 1
SEKZNWAQALMJNH-YZUCACDQSA-N aphidicolin Natural products C[C@]1(CO)CC[C@]23C[C@H]1C[C@@H]2CC[C@H]4[C@](C)(CO)[C@H](O)CC[C@]34C SEKZNWAQALMJNH-YZUCACDQSA-N 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000007900 aqueous suspension Substances 0.000 description 1
210000003050 axon Anatomy 0.000 description 1
ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 description 1
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
RSEPHCRIRACQML-LBPRGKRZSA-N benzyl (2s)-piperidine-2-carboxylate Chemical compound O=C([C@H]1NCCCC1)OCC1=CC=CC=C1 RSEPHCRIRACQML-LBPRGKRZSA-N 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
FMTDOYKIDNUJOX-IBGZPJMESA-N benzyl n-[2-[[(2s)-1-(1,3-benzoxazol-2-yl)piperidine-2-carbonyl]amino]ethyl]carbamate Chemical compound O=C([C@H]1N(CCCC1)C=1OC2=CC=CC=C2N=1)NCCNC(=O)OCC1=CC=CC=C1 FMTDOYKIDNUJOX-IBGZPJMESA-N 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
108010046910 brain-derived growth factor Proteins 0.000 description 1
239000012267 brine Substances 0.000 description 1
125000001246 bromo group Chemical group Br* 0.000 description 1
239000000872 buffer Substances 0.000 description 1
244000309464 bull Species 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
229910000019 calcium carbonate Inorganic materials 0.000 description 1
229960003563 calcium carbonate Drugs 0.000 description 1
235000010216 calcium carbonate Nutrition 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
244000309466 calf Species 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
229940081733 cetearyl alcohol Drugs 0.000 description 1
238000004296 chiral HPLC Methods 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
229960002376 chymotrypsin Drugs 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
238000004040 coloring Methods 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
239000010949 copper Substances 0.000 description 1
OPHUWKNKFYBPDR-UHFFFAOYSA-N copper lithium Chemical group [Li].[Cu] OPHUWKNKFYBPDR-UHFFFAOYSA-N 0.000 description 1
239000006071 cream Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000012258 culturing Methods 0.000 description 1
238000010511 deprotection reaction Methods 0.000 description 1
239000007933 dermal patch Substances 0.000 description 1
238000013461 design Methods 0.000 description 1
NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
229940038472 dicalcium phosphate Drugs 0.000 description 1
229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
229940042935 dichlorodifluoromethane Drugs 0.000 description 1
229940087091 dichlorotetrafluoroethane Drugs 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
238000004821 distillation Methods 0.000 description 1
210000005064 dopaminergic neuron Anatomy 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 0.000 description 1
229940112141 dry powder inhaler Drugs 0.000 description 1
238000010410 dusting Methods 0.000 description 1
239000000975 dye Substances 0.000 description 1
239000003995 emulsifying agent Substances 0.000 description 1
230000001804 emulsifying effect Effects 0.000 description 1
239000008387 emulsifying waxe Substances 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
210000000256 facial nerve Anatomy 0.000 description 1
239000000945 filler Substances 0.000 description 1
238000001914 filtration Methods 0.000 description 1
238000003818 flash chromatography Methods 0.000 description 1
235000013355 food flavoring agent Nutrition 0.000 description 1
238000009472 formulation Methods 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
230000002518 glial effect Effects 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
239000008103 glucose Substances 0.000 description 1
235000011187 glycerol Nutrition 0.000 description 1
229960002449 glycine Drugs 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 1
150000005828 hydrofluoroalkanes Chemical class 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
238000001802 infusion Methods 0.000 description 1
230000003993 interaction Effects 0.000 description 1
125000002346 iodo group Chemical group I* 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
230000000155 isotopic effect Effects 0.000 description 1
HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 1
229960001375 lactose Drugs 0.000 description 1
CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
150000002617 leukotrienes Chemical class 0.000 description 1
239000003446 ligand Substances 0.000 description 1
125000005647 linker group Chemical group 0.000 description 1
229940057995 liquid paraffin Drugs 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
230000007246 mechanism Effects 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
229910052751 metal Inorganic materials 0.000 description 1
239000002184 metal Substances 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
APCHKWZTSCBBJX-RGMNGODLSA-N methyl (2s)-piperidine-2-carboxylate;hydrochloride Chemical compound [Cl-].COC(=O)[C@@H]1CCCC[NH2+]1 APCHKWZTSCBBJX-RGMNGODLSA-N 0.000 description 1
OMWQHVRUXLRZRC-UHFFFAOYSA-N methyl 3-amino-2-hydroxybenzoate Chemical compound COC(=O)C1=CC=CC(N)=C1O OMWQHVRUXLRZRC-UHFFFAOYSA-N 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
238000002156 mixing Methods 0.000 description 1
238000012986 modification Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
239000002808 molecular sieve Substances 0.000 description 1
230000008764 nerve damage Effects 0.000 description 1
239000012038 nucleophile Substances 0.000 description 1
GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
125000003431 oxalo group Chemical group 0.000 description 1
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
210000000578 peripheral nerve Anatomy 0.000 description 1
229940124531 pharmaceutical excipient Drugs 0.000 description 1
RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
XIMBESZRBTVIOD-UHFFFAOYSA-N piperidine-2-carboxamide Chemical compound NC(=O)C1CCCCN1 XIMBESZRBTVIOD-UHFFFAOYSA-N 0.000 description 1
239000001818 polyoxyethylene sorbitan monostearate Substances 0.000 description 1
235000010989 polyoxyethylene sorbitan monostearate Nutrition 0.000 description 1
229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 1
229940113124 polysorbate 60 Drugs 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
229960003975 potassium Drugs 0.000 description 1
239000011591 potassium Substances 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
JCBJVAJGLKENNC-UHFFFAOYSA-M potassium ethyl xanthate Chemical compound [K+].CCOC([S-])=S JCBJVAJGLKENNC-UHFFFAOYSA-M 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
239000003380 propellant Substances 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000004044 response Effects 0.000 description 1
102220082674 rs538303703 Human genes 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
230000007017 scission Effects 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
229960001790 sodium citrate Drugs 0.000 description 1
235000011083 sodium citrates Nutrition 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000001587 sorbitan monostearate Substances 0.000 description 1
235000011076 sorbitan monostearate Nutrition 0.000 description 1
229940035048 sorbitan monostearate Drugs 0.000 description 1
235000019337 sorbitan trioleate Nutrition 0.000 description 1
229960000391 sorbitan trioleate Drugs 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000001117 sulphuric acid Substances 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
NUZXPHIQZUYMOR-DTORHVGOSA-N tert-butyl (3s,5r)-3,5-dimethylpiperazine-1-carboxylate Chemical compound C[C@H]1CN(C(=O)OC(C)(C)C)C[C@@H](C)N1 NUZXPHIQZUYMOR-DTORHVGOSA-N 0.000 description 1
BBERTFNNOJFDPY-UHFFFAOYSA-N tert-butyl 2-chloro-5-methylbenzimidazole-1-carboxylate Chemical compound CC1=CC=C2N(C(=O)OC(C)(C)C)C(Cl)=NC2=C1 BBERTFNNOJFDPY-UHFFFAOYSA-N 0.000 description 1
238000012360 testing method Methods 0.000 description 1
MHXBHWLGRWOABW-UHFFFAOYSA-N tetradecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC MHXBHWLGRWOABW-UHFFFAOYSA-N 0.000 description 1
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
210000000115 thoracic cavity Anatomy 0.000 description 1
230000036964 tight binding Effects 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
230000009466 transformation Effects 0.000 description 1
CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 description 1
229940029284 trichlorofluoromethane Drugs 0.000 description 1
125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 1
238000003828 vacuum filtration Methods 0.000 description 1
KMIOJWCYOHBUJS-HAKPAVFJSA-N vorolanib Chemical compound C1N(C(=O)N(C)C)CC[C@@H]1NC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C KMIOJWCYOHBUJS-HAKPAVFJSA-N 0.000 description 1
239000003871 white petrolatum Substances 0.000 description 1
239000012991 xanthate Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/423—Oxazoles condensed with carbocyclic rings
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/428—Thiazoles condensed with carbocyclic rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Neurology (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Epidemiology (AREA)
Biomedical Technology (AREA)
Neurosurgery (AREA)
Physical Education & Sports Medicine (AREA)
Orthopedic Medicine & Surgery (AREA)
Psychology (AREA)
Psychiatry (AREA)
Hospice & Palliative Care (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Hydrogenated Pyridines (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Glass Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

OA1200100024A 1998-07-20 1999-07-01 FKBP inhibotors. OA11586A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GBGB9815696.1A GB9815696D0 (en)	1998-07-20	1998-07-20	Heterocyclics

Publications (1)

Publication Number	Publication Date
OA11586A true OA11586A (en)	2004-07-26

Family

ID=10835773

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA1200100024A OA11586A (en)	1998-07-20	1999-07-01	FKBP inhibotors.

Country Status (45)

Country	Link
US (2)	US6166011A (de)
EP (1)	EP1098894B1 (de)
JP (1)	JP3545341B2 (de)
KR (1)	KR20010083130A (de)
CN (1)	CN1315951A (de)
AP (1)	AP2001002045A0 (de)
AR (1)	AR016501A1 (de)
AT (1)	ATE225346T1 (de)
AU (1)	AU756769B2 (de)
BG (1)	BG105249A (de)
BR (1)	BR9912307A (de)
CA (1)	CA2338276C (de)
CO (1)	CO5080761A1 (de)
CZ (1)	CZ2001224A3 (de)
DE (1)	DE69903319T2 (de)
DK (1)	DK1098894T3 (de)
DZ (1)	DZ2848A1 (de)
EA (1)	EA200100051A1 (de)
EE (1)	EE200100043A (de)
ES (1)	ES2183567T3 (de)
GB (1)	GB9815696D0 (de)
GT (1)	GT199900113A (de)
HK (1)	HK1040706A1 (de)
HN (1)	HN1999000101A (de)
HR (1)	HRP20010053A2 (de)
HU (1)	HUP0103020A3 (de)
ID (1)	ID27022A (de)
IL (1)	IL140243A0 (de)
IS (1)	IS5799A (de)
MA (1)	MA26661A1 (de)
NO (1)	NO20010299L (de)
NZ (1)	NZ508839A (de)
OA (1)	OA11586A (de)
PA (1)	PA8477601A1 (de)
PE (1)	PE20000867A1 (de)
PL (1)	PL345705A1 (de)
PT (1)	PT1098894E (de)
SI (1)	SI1098894T1 (de)
SK (1)	SK702001A3 (de)
TN (1)	TNSN99146A1 (de)
TR (1)	TR200100133T2 (de)
UA (1)	UA60368C2 (de)
WO (1)	WO2000005231A1 (de)
YU (1)	YU83100A (de)
ZA (1)	ZA200100229B (de)

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9815696D0 (en) *	1998-07-20	1998-09-16	Pfizer Ltd	Heterocyclics
GB9815880D0 (en) *	1998-07-21	1998-09-16	Pfizer Ltd	Heterocycles
GB0008939D0 (en) *	2000-04-11	2000-05-31	Glaxo Group Ltd	Process for preparing substituted benzimidazole compounds
CA2429722A1 (en)	2000-11-28	2002-06-06	Wyeth	Expression analysis of fkbp nucleic acids and polypeptides useful in the diagnosis and treatment of prostate cancer
US7186518B2 (en) *	2003-11-21	2007-03-06	Dade Behring Inc.	Method and composition useful for determining FK 506
US8354557B2 (en)	2008-06-17	2013-01-15	Concert Pharmaceuticals, Inc.	Synthesis of deuterated morpholine derivatives
DE102008060549A1 (de)	2008-12-04	2010-06-10	MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V.	Wirkstoff-Peptid-Konstrukt zur extrazellulären Anreicherung
TWI534142B (zh)	2011-03-15	2016-05-21	大正製藥股份有限公司	Azole derivatives
EP2705856A1 (de)	2012-09-07	2014-03-12	Deutsches Zentrum für Neurodegenerative Erkrankungen e.V.	Verbindungen zur Behandlung von neurodegenerativen Erkrankungen
CN106138044B (zh) *	2016-07-15	2017-05-03	鲁俊东	一种治疗腰椎间盘突出症的药物

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
FI91859C (fi) *	1987-06-17	1994-08-25	Eisai Co Ltd	Analogiamenetelmä antiallergisena aineena aktiivisen bentsotiatsolijohdannaisen valmistamiseksi
FR2696176B1 (fr) *	1992-09-28	1994-11-10	Synthelabo	Dérivés de pipéridine, leur préparation et leur application en thérapeutique.
CO4520280A1 (es) *	1993-10-26	1997-10-15	Boehringer Ingelheim Pharma	Derivados de pirrolidina, inhibidores de la bioscientesis de leucotrienos
US5801187A (en) *	1996-09-25	1998-09-01	Gpi-Nil Holdings, Inc.	Heterocyclic esters and amides
GB9700597D0 (en) *	1997-01-14	1997-03-05	Sandoz Pharma Uk	Organic compounds
US5721256A (en) *	1997-02-12	1998-02-24	Gpi Nil Holdings, Inc.	Method of using neurotrophic sulfonamide compounds
US6686357B1 (en) *	1999-07-15	2004-02-03	Pfizer, Inc.	FKBP inhibitors
GB9815696D0 (en) *	1998-07-20	1998-09-16	Pfizer Ltd	Heterocyclics
GB9815880D0 (en) *	1998-07-21	1998-09-16	Pfizer Ltd	Heterocycles

1998
- 1998-07-20 GB GBGB9815696.1A patent/GB9815696D0/en not_active Ceased
1999
- 1999-01-07 UA UA2001010434A patent/UA60368C2/uk unknown
- 1999-06-30 HN HN1999000101A patent/HN1999000101A/es unknown
- 1999-07-01 SI SI9930120T patent/SI1098894T1/xx unknown
- 1999-07-01 EP EP99926683A patent/EP1098894B1/de not_active Expired - Lifetime
- 1999-07-01 NZ NZ508839A patent/NZ508839A/xx unknown
- 1999-07-01 AP APAP/P/2001/002045A patent/AP2001002045A0/en unknown
- 1999-07-01 DK DK99926683T patent/DK1098894T3/da active
- 1999-07-01 ID IDW20010154A patent/ID27022A/id unknown
- 1999-07-01 EE EEP200100043A patent/EE200100043A/xx unknown
- 1999-07-01 HU HU0103020A patent/HUP0103020A3/hu unknown
- 1999-07-01 HK HK02102302.7A patent/HK1040706A1/zh unknown
- 1999-07-01 YU YU83100A patent/YU83100A/sh unknown
- 1999-07-01 JP JP2000561187A patent/JP3545341B2/ja not_active Expired - Fee Related
- 1999-07-01 DE DE69903319T patent/DE69903319T2/de not_active Expired - Fee Related
- 1999-07-01 OA OA1200100024A patent/OA11586A/en unknown
- 1999-07-01 SK SK70-2001A patent/SK702001A3/sk unknown
- 1999-07-01 KR KR1020017000834A patent/KR20010083130A/ko not_active Ceased
- 1999-07-01 CZ CZ2001224A patent/CZ2001224A3/cs unknown
- 1999-07-01 AT AT99926683T patent/ATE225346T1/de not_active IP Right Cessation
- 1999-07-01 PL PL99345705A patent/PL345705A1/xx not_active Application Discontinuation
- 1999-07-01 BR BR9912307-0A patent/BR9912307A/pt not_active Application Discontinuation
- 1999-07-01 ES ES99926683T patent/ES2183567T3/es not_active Expired - Lifetime
- 1999-07-01 IL IL14024399A patent/IL140243A0/xx unknown
- 1999-07-01 HR HR20010053A patent/HRP20010053A2/hr not_active Application Discontinuation
- 1999-07-01 CA CA002338276A patent/CA2338276C/en not_active Expired - Fee Related
- 1999-07-01 WO PCT/IB1999/001227 patent/WO2000005231A1/en not_active Ceased
- 1999-07-01 TR TR2001/00133T patent/TR200100133T2/xx unknown
- 1999-07-01 EA EA200100051A patent/EA200100051A1/ru unknown
- 1999-07-01 PT PT99926683T patent/PT1098894E/pt unknown
- 1999-07-01 CN CN99810385A patent/CN1315951A/zh active Pending
- 1999-07-01 AU AU43855/99A patent/AU756769B2/en not_active Ceased
- 1999-07-12 PA PA19998477601A patent/PA8477601A1/es unknown
- 1999-07-15 US US09/354,193 patent/US6166011A/en not_active Expired - Fee Related
- 1999-07-16 PE PE1999000722A patent/PE20000867A1/es not_active Application Discontinuation
- 1999-07-19 DZ DZ990148A patent/DZ2848A1/xx active
- 1999-07-19 MA MA25689A patent/MA26661A1/fr unknown
- 1999-07-19 GT GT199900113A patent/GT199900113A/es unknown
- 1999-07-19 CO CO99045678A patent/CO5080761A1/es unknown
- 1999-07-19 TN TNTNSN99146A patent/TNSN99146A1/fr unknown
- 1999-07-19 AR ARP990103543A patent/AR016501A1/es not_active Application Discontinuation
2000
- 2000-12-29 IS IS5799A patent/IS5799A/is unknown
2001
- 2001-01-09 ZA ZA200100229A patent/ZA200100229B/en unknown
- 2001-01-18 NO NO20010299A patent/NO20010299L/no not_active Application Discontinuation
- 2001-02-14 BG BG105249A patent/BG105249A/xx unknown
2003
- 2003-04-01 US US10/404,524 patent/US20040058905A1/en not_active Abandoned

Also Published As

Publication number	Publication date
NO20010299L (no)	2001-03-15
GB9815696D0 (en)	1998-09-16
JP3545341B2 (ja)	2004-07-21
KR20010083130A (ko)	2001-08-31
AP2001002045A0 (en)	2001-03-31
HUP0103020A2 (hu)	2002-05-29
DK1098894T3 (da)	2002-10-28
ATE225346T1 (de)	2002-10-15
IL140243A0 (en)	2002-02-10
JP2002521381A (ja)	2002-07-16
EA200100051A1 (ru)	2001-08-27
ZA200100229B (en)	2002-04-09
US20040058905A1 (en)	2004-03-25
DE69903319D1 (de)	2002-11-07
PT1098894E (pt)	2003-02-28
ES2183567T3 (es)	2003-03-16
NZ508839A (en)	2003-01-31
BG105249A (en)	2001-11-30
HN1999000101A (es)	2000-11-11
HK1040706A1 (zh)	2002-06-21
MA26661A1 (fr)	2004-12-20
CA2338276C (en)	2007-01-09
UA60368C2 (uk)	2003-10-15
AU756769B2 (en)	2003-01-23
DE69903319T2 (de)	2003-01-30
AU4385599A (en)	2000-02-14
YU83100A (sh)	2003-04-30
DZ2848A1 (fr)	2003-12-01
IS5799A (is)	2000-12-29
CN1315951A (zh)	2001-10-03
US6166011A (en)	2000-12-26
EE200100043A (et)	2002-06-17
CO5080761A1 (es)	2001-09-25
HRP20010053A2 (en)	2001-12-31
HUP0103020A3 (en)	2002-10-28
SK702001A3 (en)	2001-12-03
GT199900113A (es)	2001-01-09
PA8477601A1 (es)	2000-09-29
ID27022A (id)	2001-02-22
EP1098894A1 (de)	2001-05-16
TR200100133T2 (tr)	2001-06-21
CZ2001224A3 (cs)	2001-08-15
BR9912307A (pt)	2001-05-02
PE20000867A1 (es)	2000-08-31
EP1098894B1 (de)	2002-10-02
NO20010299D0 (no)	2001-01-18
PL345705A1 (en)	2002-01-02
AR016501A1 (es)	2001-07-04
SI1098894T1 (en)	2002-12-31
CA2338276A1 (en)	2000-02-03
TNSN99146A1 (fr)	2005-11-10
WO2000005231A1 (en)	2000-02-03

Publication	Publication Date	Title
US6610707B1 (en)	2003-08-26	Heterocyclic compounds as inhibitors of rotomase enzymes
AU2004309164B2 (en)	2007-11-15	Triazole derivatives as vasopressin antagonists
CA2997382C (en)	2024-01-02	Substituted amino triazoles useful as human chitinase inhibitors
US7960377B2 (en)	2011-06-14	Substituted pyridoxazines
JP7187575B2 (ja)	2022-12-12	Ｒｈｏキナーゼ阻害剤としてのベンゾピラゾール系化合物
JP6908536B2 (ja)	2021-07-28	ムスカリンｍ２受容体の正のアロステリックモジュレーター
JPH09501439A (ja)	1997-02-10	ニューロキニンアンタゴニストとして有用な複素環
WO2000005232A1 (en)	2000-02-03	Heterocyclic compounds as inhibitors of rotamase enzymes
BR112020005174A2 (pt)	2020-11-10	composto que possui estrutura cíclica
JP2006506380A (ja)	2006-02-23	月経困難症の治療用トリアゾール化合物
EP0790248B1 (de)	2003-05-28	3-Aza-piperidon- (Tetrahydropyrimidin-2-on) und 3-Oxa-piperidon (1,3-Oxazin-2-on) Derivate, deren Herstellung und deren Verwendung als Tachykinin/Neurokinin Antagonisten
CN101268068B (zh)	2015-12-02	β-内酰胺基苯丙氨酸、半胱氨酸和丝氨酸血管加压素拮抗剂
OA11586A (en)	2004-07-26	FKBP inhibotors.
MXPA04003358A (es)	2004-07-08	Antagonistas de vasopresina v1a de ?-lactamilo.
US5444074A (en)	1995-08-22	Piperidine tachykinin receptor antagonists
US6495549B1 (en)	2002-12-17	FKBP inhibitors
CN1898244B (zh)	2011-06-22	作为血管升压素拮抗剂的三唑衍生物
CA3207069A1 (en)	2022-07-07	Compounds and methods for modulating fxr
JPH0971564A (ja)	1997-03-18	ベンズアミドオキシム誘導体及びその医薬用途
HK1095822B (en)	2011-11-18	Triazole derivatives as vasopressin antagonists
MXPA06006155A (es)	2006-10-17	Derivados de triazol como antagonistas de vasopresina