OA11585A - Heterocyclic compounds as inhibitors of rotamase enzymes. - Google Patents

Heterocyclic compounds as inhibitors of rotamase enzymes. Download PDF

Info

Publication number: OA11585A
Authority: OA; OAPI
Prior art keywords: compound; alkyl; formula; benzoxazol; aryl
Prior art date: 1998-07-21

Application number

OA1200100023A

Other languages

English (en)

Inventor

Mark Ian Kemp

Michael John Palmer

Mark Allen Sanner

Martin James Wythes

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.)

1998-07-21

Filing date

1999-06-28

Publication date

2004-07-26

1999-06-28 Application filed by Pfizer filed Critical Pfizer

2004-07-26 Publication of OA11585A publication Critical patent/OA11585A/en

Links

101710147152 Peptidyl-prolyl cis-trans isomerase FKBP4 Proteins 0.000 title abstract description 11
102000004190 Enzymes Human genes 0.000 title abstract description 10
108090000790 Enzymes Proteins 0.000 title abstract description 10
239000003112 inhibitor Substances 0.000 title abstract description 7
101710111747 Peptidyl-prolyl cis-trans isomerase FKBP12 Proteins 0.000 title abstract description 6
101710111682 Peptidyl-prolyl cis-trans isomerase FKBP1A Proteins 0.000 title abstract description 6
101710103508 FK506-binding protein Proteins 0.000 title abstract description 5
101710104425 FK506-binding protein 2 Proteins 0.000 title abstract description 5
101710104423 FK506-binding protein 3 Proteins 0.000 title abstract description 5
101710104333 FK506-binding protein 4 Proteins 0.000 title abstract description 5
101710104342 FK506-binding protein 5 Proteins 0.000 title abstract description 5
101710149710 FKBP-type 16 kDa peptidyl-prolyl cis-trans isomerase Proteins 0.000 title abstract description 5
101710121306 FKBP-type 22 kDa peptidyl-prolyl cis-trans isomerase Proteins 0.000 title abstract description 5
101710180800 FKBP-type peptidyl-prolyl cis-trans isomerase FkpA Proteins 0.000 title abstract description 5
101710104030 Long-type peptidyl-prolyl cis-trans isomerase Proteins 0.000 title abstract description 5
101710114693 Outer membrane protein MIP Proteins 0.000 title abstract description 5
101710116692 Peptidyl-prolyl cis-trans isomerase Proteins 0.000 title abstract description 5
101710111764 Peptidyl-prolyl cis-trans isomerase FKBP10 Proteins 0.000 title abstract description 5
101710111749 Peptidyl-prolyl cis-trans isomerase FKBP11 Proteins 0.000 title abstract description 5
101710111757 Peptidyl-prolyl cis-trans isomerase FKBP14 Proteins 0.000 title abstract description 5
101710111689 Peptidyl-prolyl cis-trans isomerase FKBP1B Proteins 0.000 title abstract description 5
101710147154 Peptidyl-prolyl cis-trans isomerase FKBP2 Proteins 0.000 title abstract description 5
101710147149 Peptidyl-prolyl cis-trans isomerase FKBP3 Proteins 0.000 title abstract description 5
101710147150 Peptidyl-prolyl cis-trans isomerase FKBP5 Proteins 0.000 title abstract description 5
101710147138 Peptidyl-prolyl cis-trans isomerase FKBP7 Proteins 0.000 title abstract description 5
101710147137 Peptidyl-prolyl cis-trans isomerase FKBP8 Proteins 0.000 title abstract description 5
101710147136 Peptidyl-prolyl cis-trans isomerase FKBP9 Proteins 0.000 title abstract description 5
101710174853 Peptidyl-prolyl cis-trans isomerase Mip Proteins 0.000 title abstract description 5
101710200991 Peptidyl-prolyl cis-trans isomerase, rhodopsin-specific isozyme Proteins 0.000 title abstract description 5
101710092145 Peptidyl-prolyl cis-trans isomerase-like 1 Proteins 0.000 title abstract description 5
101710092146 Peptidyl-prolyl cis-trans isomerase-like 2 Proteins 0.000 title abstract description 5
101710092148 Peptidyl-prolyl cis-trans isomerase-like 3 Proteins 0.000 title abstract description 5
101710092149 Peptidyl-prolyl cis-trans isomerase-like 4 Proteins 0.000 title abstract description 5
101710113444 Probable parvulin-type peptidyl-prolyl cis-trans isomerase Proteins 0.000 title abstract description 5
101710090737 Probable peptidyl-prolyl cis-trans isomerase Proteins 0.000 title abstract description 5
101710133309 Putative peptidyl-prolyl cis-trans isomerase Proteins 0.000 title abstract description 5
101710124237 Short-type peptidyl-prolyl cis-trans isomerase Proteins 0.000 title abstract description 5
102100038809 Peptidyl-prolyl cis-trans isomerase FKBP9 Human genes 0.000 title 1
150000002391 heterocyclic compounds Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 204
125000003118 aryl group Chemical group 0.000 claims abstract description 47
208000012902 Nervous system disease Diseases 0.000 claims abstract description 28
125000001424 substituent group Chemical group 0.000 claims abstract description 28
125000000217 alkyl group Chemical group 0.000 claims abstract description 26
229910052760 oxygen Inorganic materials 0.000 claims abstract description 24
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 20
229910052717 sulfur Inorganic materials 0.000 claims abstract description 19
208000025966 Neurological disease Diseases 0.000 claims abstract description 18
125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 17
125000002947 alkylene group Chemical group 0.000 claims abstract description 14
230000004770 neurodegeneration Effects 0.000 claims abstract description 13
208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 12
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 8
125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 5
125000003342 alkenyl group Chemical group 0.000 claims abstract description 5
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 4
229910052757 nitrogen Inorganic materials 0.000 claims abstract 7
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 6
-1 1,4-butylene Chemical group 0.000 claims description 119
238000000034 method Methods 0.000 claims description 70
239000000203 mixture Substances 0.000 claims description 53
125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 35
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 34
125000005843 halogen group Chemical group 0.000 claims description 24
208000024827 Alzheimer disease Diseases 0.000 claims description 22
206010012601 diabetes mellitus Diseases 0.000 claims description 22
210000001428 peripheral nervous system Anatomy 0.000 claims description 20
230000006378 damage Effects 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 17
210000003169 central nervous system Anatomy 0.000 claims description 17
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 17
238000006243 chemical reaction Methods 0.000 claims description 16
238000011282 treatment Methods 0.000 claims description 15
125000003545 alkoxy group Chemical group 0.000 claims description 14
208000011580 syndromic disease Diseases 0.000 claims description 14
206010002027 Amyotrophy Diseases 0.000 claims description 12
206010012289 Dementia Diseases 0.000 claims description 12
208000026072 Motor neurone disease Diseases 0.000 claims description 12
208000018737 Parkinson disease Diseases 0.000 claims description 12
208000009205 Tinnitus Diseases 0.000 claims description 12
238000004519 manufacturing process Methods 0.000 claims description 12
208000005264 motor neuron disease Diseases 0.000 claims description 12
208000033808 peripheral neuropathy Diseases 0.000 claims description 12
210000000278 spinal cord Anatomy 0.000 claims description 12
231100000886 tinnitus Toxicity 0.000 claims description 12
206010039966 Senile dementia Diseases 0.000 claims description 11
201000006417 multiple sclerosis Diseases 0.000 claims description 11
230000000750 progressive effect Effects 0.000 claims description 11
208000016621 Hearing disease Diseases 0.000 claims description 10
201000010099 disease Diseases 0.000 claims description 10
210000000653 nervous system Anatomy 0.000 claims description 10
230000000926 neurological effect Effects 0.000 claims description 10
230000000472 traumatic effect Effects 0.000 claims description 10
208000023105 Huntington disease Diseases 0.000 claims description 9
208000035475 disorder Diseases 0.000 claims description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
206010003694 Atrophy Diseases 0.000 claims description 8
208000034189 Sclerosis Diseases 0.000 claims description 8
230000037444 atrophy Effects 0.000 claims description 8
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 8
125000001309 chloro group Chemical group Cl* 0.000 claims description 8
230000008569 process Effects 0.000 claims description 7
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
241000238876 Acari Species 0.000 claims description 6
208000006373 Bell palsy Diseases 0.000 claims description 6
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 6
206010041591 Spinal osteoarthritis Diseases 0.000 claims description 6
208000036826 VIIth nerve paralysis Diseases 0.000 claims description 6
230000001363 autoimmune Effects 0.000 claims description 6
208000036319 cervical spondylosis Diseases 0.000 claims description 6
229960000860 dapsone Drugs 0.000 claims description 6
206010028417 myasthenia gravis Diseases 0.000 claims description 6
210000001328 optic nerve Anatomy 0.000 claims description 6
125000003386 piperidinyl group Chemical group 0.000 claims description 6
208000002320 spinal muscular atrophy Diseases 0.000 claims description 6
208000005801 spondylosis Diseases 0.000 claims description 6
206010048627 thoracic outlet syndrome Diseases 0.000 claims description 6
206010044652 trigeminal neuralgia Diseases 0.000 claims description 6
208000037859 AIDS-related disorder Diseases 0.000 claims description 5
206010003591 Ataxia Diseases 0.000 claims description 5
208000024777 Prion disease Diseases 0.000 claims description 5
239000000546 pharmaceutical excipient Substances 0.000 claims description 5
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 5
125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 claims description 5
125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 5
125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 4
208000021965 Glossopharyngeal Nerve disease Diseases 0.000 claims description 4
208000035895 Guillain-Barré syndrome Diseases 0.000 claims description 4
206010049567 Miller Fisher syndrome Diseases 0.000 claims description 4
DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 4
125000001246 bromo group Chemical group Br* 0.000 claims description 4
230000008878 coupling Effects 0.000 claims description 4
238000010168 coupling process Methods 0.000 claims description 4
238000005859 coupling reaction Methods 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
125000001153 fluoro group Chemical group F* 0.000 claims description 4
201000005442 glossopharyngeal neuralgia Diseases 0.000 claims description 4
HRDXJKGNWSUIBT-UHFFFAOYSA-N methoxybenzene Chemical group [CH2]OC1=CC=CC=C1 HRDXJKGNWSUIBT-UHFFFAOYSA-N 0.000 claims description 4
201000000585 muscular atrophy Diseases 0.000 claims description 4
201000006938 muscular dystrophy Diseases 0.000 claims description 4
125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 4
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 4
125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 claims description 4
238000006467 substitution reaction Methods 0.000 claims description 4
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 claims description 3
125000002883 imidazolyl group Chemical group 0.000 claims description 3
125000002950 monocyclic group Chemical group 0.000 claims description 3
239000008194 pharmaceutical composition Substances 0.000 claims description 3
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
125000001425 triazolyl group Chemical group 0.000 claims description 3
125000004227 1,3-benzoxazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)OC2=C1[H] 0.000 claims description 2
206010029240 Neuritis Diseases 0.000 claims description 2
101100258328 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) crc-2 gene Proteins 0.000 claims description 2
SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical class [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 3
125000000000 cycloalkoxy group Chemical group 0.000 claims 2
238000007259 addition reaction Methods 0.000 claims 1
238000005904 alkaline hydrolysis reaction Methods 0.000 claims 1
125000004599 benzpyrazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 1
238000007257 deesterification reaction Methods 0.000 claims 1
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 abstract description 11
102100027913 Peptidyl-prolyl cis-trans isomerase FKBP1A Human genes 0.000 abstract description 10
102100020739 Peptidyl-prolyl cis-trans isomerase FKBP4 Human genes 0.000 abstract description 10
208000028389 Nerve injury Diseases 0.000 abstract description 2
230000008764 nerve damage Effects 0.000 abstract description 2
230000009689 neuronal regeneration Effects 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 195
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 117
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
239000002904 solvent Substances 0.000 description 75
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 72
238000005160 1H NMR spectroscopy Methods 0.000 description 69
239000000243 solution Substances 0.000 description 56
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 54
229940093499 ethyl acetate Drugs 0.000 description 39
235000019439 ethyl acetate Nutrition 0.000 description 39
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
239000012043 crude product Substances 0.000 description 32
239000000741 silica gel Substances 0.000 description 32
229910002027 silica gel Inorganic materials 0.000 description 32
229960001866 silicon dioxide Drugs 0.000 description 32
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
238000004440 column chromatography Methods 0.000 description 30
239000011541 reaction mixture Substances 0.000 description 24
239000007787 solid Substances 0.000 description 23
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 17
238000004458 analytical method Methods 0.000 description 17
229910021653 sulphate ion Inorganic materials 0.000 description 17
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 16
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 16
239000012044 organic layer Substances 0.000 description 16
239000000047 product Substances 0.000 description 16
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 14
239000002253 acid Substances 0.000 description 14
235000011114 ammonium hydroxide Nutrition 0.000 description 14
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
238000002360 preparation method Methods 0.000 description 13
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 11
230000000508 neurotrophic effect Effects 0.000 description 11
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
239000006260 foam Substances 0.000 description 9
150000003839 salts Chemical class 0.000 description 9
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
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 9
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
229940088598 enzyme Drugs 0.000 description 8
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 7
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 7
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 6
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
238000005481 NMR spectroscopy Methods 0.000 description 6
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
239000002585 base Substances 0.000 description 6
229910002092 carbon dioxide Inorganic materials 0.000 description 6
210000000609 ganglia Anatomy 0.000 description 6
239000007789 gas Substances 0.000 description 6
230000005764 inhibitory process Effects 0.000 description 6
239000000543 intermediate Substances 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
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 5
238000003556 assay Methods 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
239000010410 layer Substances 0.000 description 5
230000001537 neural effect Effects 0.000 description 5
JSPCTNUQYWIIOT-UHFFFAOYSA-N piperidine-1-carboxamide Chemical compound NC(=O)N1CCCCC1 JSPCTNUQYWIIOT-UHFFFAOYSA-N 0.000 description 5
239000000843 powder Substances 0.000 description 5
238000010992 reflux Methods 0.000 description 5
HBVNLKQGRZPGRP-NSHDSACASA-N (3s)-1-benzylpyrrolidin-3-amine Chemical compound C1[C@@H](N)CCN1CC1=CC=CC=C1 HBVNLKQGRZPGRP-NSHDSACASA-N 0.000 description 4
208000003435 Optic Neuritis Diseases 0.000 description 4
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
201000011101 acute retrobulbar neuritis Diseases 0.000 description 4
210000004027 cell Anatomy 0.000 description 4
230000000694 effects Effects 0.000 description 4
239000012458 free base Substances 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
230000014511 neuron projection development Effects 0.000 description 4
NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 4
208000022670 retrobulbar neuritis Diseases 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
235000011121 sodium hydroxide Nutrition 0.000 description 4
229940083608 sodium hydroxide Drugs 0.000 description 4
239000000725 suspension Substances 0.000 description 4
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 4
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
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 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
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 3
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 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
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
229920002472 Starch Polymers 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
239000012131 assay buffer Substances 0.000 description 3
125000002393 azetidinyl group Chemical group 0.000 description 3
239000000872 buffer Substances 0.000 description 3
239000002775 capsule 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
239000000499 gel Substances 0.000 description 3
239000003102 growth factor Substances 0.000 description 3
238000010438 heat treatment Methods 0.000 description 3
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 3
235000011167 hydrochloric acid Nutrition 0.000 description 3
229960000443 hydrochloric acid Drugs 0.000 description 3
239000008101 lactose Substances 0.000 description 3
239000007788 liquid Substances 0.000 description 3
CWFCFEKUVPYMAB-NSHDSACASA-N methyl (2s)-1-(1,3-benzoxazol-2-yl)piperidine-2-carboxylate Chemical compound COC(=O)[C@@H]1CCCCN1C1=NC2=CC=CC=C2O1 CWFCFEKUVPYMAB-NSHDSACASA-N 0.000 description 3
210000002569 neuron Anatomy 0.000 description 3
239000002674 ointment Substances 0.000 description 3
235000019271 petrolatum Nutrition 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
235000009518 sodium iodide Nutrition 0.000 description 3
239000008107 starch Substances 0.000 description 3
235000019698 starch Nutrition 0.000 description 3
239000000758 substrate Substances 0.000 description 3
239000008096 xylene Substances 0.000 description 3
WVQBCPKMRCVDJD-JTQLQIEISA-N (2s)-1-(1,3-benzothiazol-2-yl)piperidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCCN1C1=NC2=CC=CC=C2S1 WVQBCPKMRCVDJD-JTQLQIEISA-N 0.000 description 2
GSYYAQYEJQVYOY-JTQLQIEISA-N (2s)-1-(6-chloro-1,3-benzothiazol-2-yl)piperidine-2-carboxylic acid Chemical compound OC(=O)[C@@H]1CCCCN1C1=NC2=CC=C(Cl)C=C2S1 GSYYAQYEJQVYOY-JTQLQIEISA-N 0.000 description 2
IILGAEIUCGHFMZ-JTQLQIEISA-N (3s)-1-(pyridin-3-ylmethyl)pyrrolidin-3-amine Chemical compound C1[C@@H](N)CCN1CC1=CC=CN=C1 IILGAEIUCGHFMZ-JTQLQIEISA-N 0.000 description 2
NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-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
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 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
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
239000006144 Dulbecco’s modiﬁed Eagle's medium Substances 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
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 2
108010016648 Immunophilins Proteins 0.000 description 2
102000000521 Immunophilins Human genes 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
108010020062 Peptidylprolyl Isomerase Proteins 0.000 description 2
102000009658 Peptidylprolyl Isomerase Human genes 0.000 description 2
239000004264 Petrolatum Substances 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
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-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
150000001408 amides Chemical class 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
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 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
239000012267 brine Substances 0.000 description 2
125000004432 carbon atom Chemical group C* 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
239000003795 chemical substances by application Substances 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
239000006071 cream Substances 0.000 description 2
230000007812 deficiency Effects 0.000 description 2
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 2
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
SZIKRGHFZTYTIT-ZETCQYMHSA-N ethyl (2s)-piperidine-2-carboxylate Chemical compound CCOC(=O)[C@@H]1CCCCN1 SZIKRGHFZTYTIT-ZETCQYMHSA-N 0.000 description 2
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
239000000796 flavoring agent Substances 0.000 description 2
238000009472 formulation Methods 0.000 description 2
238000001640 fractional crystallisation Methods 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
238000010191 image analysis Methods 0.000 description 2
125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 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
238000000338 in vitro Methods 0.000 description 2
230000003993 interaction Effects 0.000 description 2
239000006210 lotion Substances 0.000 description 2
239000000314 lubricant Substances 0.000 description 2
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 2
ODKLEQPZOCJQMT-UHFFFAOYSA-N n,n-diethylpyridin-4-amine Chemical compound CCN(CC)C1=CC=NC=C1 ODKLEQPZOCJQMT-UHFFFAOYSA-N 0.000 description 2
229940066842 petrolatum Drugs 0.000 description 2
RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 2
DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 description 2
229920001223 polyethylene glycol Polymers 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
230000001737 promoting effect Effects 0.000 description 2
239000003380 propellant Substances 0.000 description 2
125000006513 pyridinyl methyl group Chemical group 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
210000003497 sciatic nerve Anatomy 0.000 description 2
239000000377 silicon dioxide Substances 0.000 description 2
239000011734 sodium Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
210000003594 spinal ganglia Anatomy 0.000 description 2
239000007858 starting material Substances 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
150000003456 sulfonamides Chemical class 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
238000001665 trituration Methods 0.000 description 2
VBQYGIBFRXFIII-PPHPATTJSA-N (2S)-1-(1,3-benzoxazol-2-yl)piperidine-2-carboxylic acid hydrochloride Chemical compound Cl.OC(=O)[C@@H]1CCCCN1C1=NC2=CC=CC=C2O1 VBQYGIBFRXFIII-PPHPATTJSA-N 0.000 description 1
QQKVZQKLHLDEKU-HNNXBMFYSA-N (2s)-1-(1,3-benzoxazol-2-yl)-n-(1-ethylazetidin-3-yl)piperidine-2-carboxamide Chemical compound C1N(CC)CC1NC(=O)[C@H]1N(C=2OC3=CC=CC=C3N=2)CCCC1 QQKVZQKLHLDEKU-HNNXBMFYSA-N 0.000 description 1
MZCSZOLSCYJVOU-JSGCOSHPSA-N (2s)-1-(1,3-benzoxazol-2-yl)-n-[(3s)-pyrrolidin-3-yl]piperidine-2-carboxamide Chemical compound O=C([C@H]1N(CCCC1)C=1OC2=CC=CC=C2N=1)N[C@H]1CCNC1 MZCSZOLSCYJVOU-JSGCOSHPSA-N 0.000 description 1
VLECDMDGMKPUSK-NUBCRITNSA-N (3r)-piperidin-3-ol;hydrochloride Chemical compound Cl.O[C@@H]1CCCNC1 VLECDMDGMKPUSK-NUBCRITNSA-N 0.000 description 1
QIVUCLWGARAQIO-OLIXTKCUSA-N (3s)-n-[(3s,5s,6r)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl]-2-oxospiro[1h-pyrrolo[2,3-b]pyridine-3,6'-5,7-dihydrocyclopenta[b]pyridine]-3'-carboxamide Chemical compound C1([C@H]2[C@H](N(C(=O)[C@@H](NC(=O)C=3C=C4C[C@]5(CC4=NC=3)C3=CC=CN=C3NC5=O)C2)CC(F)(F)F)C)=C(F)C=CC(F)=C1F QIVUCLWGARAQIO-OLIXTKCUSA-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
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-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
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-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
LYTNNHXGUOKXFI-UHFFFAOYSA-N 1-benzhydrylazetidin-3-amine Chemical compound C1C(N)CN1C(C=1C=CC=CC=1)C1=CC=CC=C1 LYTNNHXGUOKXFI-UHFFFAOYSA-N 0.000 description 1
HARWNWOLWMTQCC-UHFFFAOYSA-N 1-benzylpiperidin-3-amine Chemical compound C1C(N)CCCN1CC1=CC=CC=C1 HARWNWOLWMTQCC-UHFFFAOYSA-N 0.000 description 1
PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
XBNGYFFABRKICK-UHFFFAOYSA-N 2,3,4,5,6-pentafluorophenol Chemical compound OC1=C(F)C(F)=C(F)C(F)=C1F XBNGYFFABRKICK-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
JPMRGPPMXHGKRO-UHFFFAOYSA-N 2-(chloromethyl)pyridine hydrochloride Chemical compound Cl.ClCC1=CC=CC=N1 JPMRGPPMXHGKRO-UHFFFAOYSA-N 0.000 description 1
WCURBUJUIMRCCJ-UHFFFAOYSA-N 2-amino-1-(2,5-dimethoxy-4-methylphenyl)ethanol Chemical compound COC1=CC(C(O)CN)=C(OC)C=C1C WCURBUJUIMRCCJ-UHFFFAOYSA-N 0.000 description 1
JUIKUQOUMZUFQT-UHFFFAOYSA-N 2-bromoacetamide Chemical compound NC(=O)CBr JUIKUQOUMZUFQT-UHFFFAOYSA-N 0.000 description 1
IMRWILPUOVGIMU-UHFFFAOYSA-N 2-bromopyridine Chemical compound BrC1=CC=CC=N1 IMRWILPUOVGIMU-UHFFFAOYSA-N 0.000 description 1
BSQLQMLFTHJVKS-UHFFFAOYSA-N 2-chloro-1,3-benzothiazole Chemical compound C1=CC=C2SC(Cl)=NC2=C1 BSQLQMLFTHJVKS-UHFFFAOYSA-N 0.000 description 1
BBVQDWDBTWSGHQ-UHFFFAOYSA-N 2-chloro-1,3-benzoxazole Chemical compound C1=CC=C2OC(Cl)=NC2=C1 BBVQDWDBTWSGHQ-UHFFFAOYSA-N 0.000 description 1
AYPSHJCKSDNETA-UHFFFAOYSA-N 2-chloro-1h-benzimidazole Chemical compound C1=CC=C2NC(Cl)=NC2=C1 AYPSHJCKSDNETA-UHFFFAOYSA-N 0.000 description 1
SDKQWXCBSNMYBN-UHFFFAOYSA-N 2-chloroquinoline-3-carbaldehyde Chemical compound C1=CC=C2C=C(C=O)C(Cl)=NC2=C1 SDKQWXCBSNMYBN-UHFFFAOYSA-N 0.000 description 1
CSDSSGBPEUDDEE-UHFFFAOYSA-N 2-formylpyridine Chemical compound O=CC1=CC=CC=N1 CSDSSGBPEUDDEE-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
LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical compound C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-UHFFFAOYSA-N 0.000 description 1
OOYATKQQGVPYQR-UHFFFAOYSA-N 3-(chloromethyl)benzamide Chemical compound NC(=O)C1=CC=CC(CCl)=C1 OOYATKQQGVPYQR-UHFFFAOYSA-N 0.000 description 1
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
QVTCEZINLKFYJJ-UHFFFAOYSA-N 4-(bromomethyl)-2-fluoropyridine Chemical compound FC1=CC(CBr)=CC=N1 QVTCEZINLKFYJJ-UHFFFAOYSA-N 0.000 description 1
WZIYCIBURCPKAR-UHFFFAOYSA-N 4-(chloromethyl)pyridine Chemical compound ClCC1=CC=NC=C1 WZIYCIBURCPKAR-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
208000030507 AIDS Diseases 0.000 description 1
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 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
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
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
235000019739 Dicalciumphosphate Nutrition 0.000 description 1
239000004338 Dichlorodifluoromethane Substances 0.000 description 1
239000004150 EU approved colour Substances 0.000 description 1
244000166102 Eucalyptus leucoxylon Species 0.000 description 1
235000004694 Eucalyptus leucoxylon Nutrition 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
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 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
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 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
VTJUNIYRYIAIHF-IUCAKERBSA-N Leu-Pro Chemical compound CC(C)C[C@H](N)C(=O)N1CCC[C@H]1C(O)=O VTJUNIYRYIAIHF-IUCAKERBSA-N 0.000 description 1
240000007472 Leucaena leucocephala Species 0.000 description 1
235000010643 Leucaena leucocephala Nutrition 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
229910002651 NO3 Inorganic materials 0.000 description 1
108010025020 Nerve Growth Factor Proteins 0.000 description 1
102000015336 Nerve Growth Factor Human genes 0.000 description 1
206010029260 Neuroblastoma Diseases 0.000 description 1
206010029301 Neurological disorders of the eye Diseases 0.000 description 1
108090000742 Neurotrophin 3 Proteins 0.000 description 1
102100029268 Neurotrophin-3 Human genes 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
229930182555 Penicillin Natural products 0.000 description 1
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 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
102000029797 Prion Human genes 0.000 description 1
108091000054 Prion Proteins 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
RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
PQODJDRAIZUTJL-FPOVZHCZSA-N [(3s)-1-(pyridin-2-ylmethyl)piperidin-3-yl] (2s)-1-(1,3-benzoxazol-2-yl)piperidine-2-carboxylate Chemical compound C([C@@H](C1)OC(=O)[C@H]2N(CCCC2)C=2OC3=CC=CC=C3N=2)CCN1CC1=CC=CC=N1 PQODJDRAIZUTJL-FPOVZHCZSA-N 0.000 description 1
BLFKPWSRRGIALQ-BYPYZUCNSA-N [(3s)-pyrrolidin-3-yl] carbamate Chemical compound NC(=O)O[C@H]1CCNC1 BLFKPWSRRGIALQ-BYPYZUCNSA-N 0.000 description 1
229960000583 acetic acid Drugs 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
125000004450 alkenylene group Chemical group 0.000 description 1
239000004411 aluminium Substances 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 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
239000007900 aqueous suspension Substances 0.000 description 1
210000003050 axon Anatomy 0.000 description 1
125000005604 azodicarboxylate group Chemical group 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
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
210000002779 brain fornix Anatomy 0.000 description 1
210000000133 brain stem Anatomy 0.000 description 1
108010046910 brain-derived growth factor Proteins 0.000 description 1
AEILLAXRDHDKDY-UHFFFAOYSA-N bromomethylcyclopropane Chemical compound BrCC1CC1 AEILLAXRDHDKDY-UHFFFAOYSA-N 0.000 description 1
230000005587 bubbling Effects 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
239000001506 calcium phosphate Substances 0.000 description 1
244000309466 calf Species 0.000 description 1
239000001569 carbon dioxide Substances 0.000 description 1
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
229940081733 cetearyl alcohol Drugs 0.000 description 1
239000003153 chemical reaction reagent Substances 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
229940125898 compound 5 Drugs 0.000 description 1
238000013270 controlled release Methods 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
239000013078 crystal Substances 0.000 description 1
238000012258 culturing Methods 0.000 description 1
XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 description 1
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
230000003412 degenerative effect Effects 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
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
235000019404 dichlorodifluoromethane Nutrition 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
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
229910001873 dinitrogen Inorganic materials 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
229960003638 dopamine Drugs 0.000 description 1
210000005064 dopaminergic neuron Anatomy 0.000 description 1
231100000673 dose–response relationship Toxicity 0.000 description 1
229940079593 drug Drugs 0.000 description 1
239000003814 drug Substances 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
DXSGYVFSLRMGNM-LBPRGKRZSA-N ethyl (2s)-1-(1,3-benzothiazol-2-yl)piperidine-2-carboxylate Chemical compound CCOC(=O)[C@@H]1CCCCN1C1=NC2=CC=CC=C2S1 DXSGYVFSLRMGNM-LBPRGKRZSA-N 0.000 description 1
DAOHYNCMMIRAGH-LBPRGKRZSA-N ethyl (2s)-1-(6-chloro-1,3-benzothiazol-2-yl)piperidine-2-carboxylate Chemical compound CCOC(=O)[C@@H]1CCCCN1C1=NC2=CC=C(Cl)C=C2S1 DAOHYNCMMIRAGH-LBPRGKRZSA-N 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
235000013355 food flavoring agent Nutrition 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
239000012362 glacial acetic acid 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
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
125000005842 heteroatom Chemical group 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000005828 hydrofluoroalkanes Chemical class 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
VEIWYFRREFUNRC-UHFFFAOYSA-N hydron;piperidine;chloride Chemical compound [Cl-].C1CC[NH2+]CC1 VEIWYFRREFUNRC-UHFFFAOYSA-N 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 1
JBFYUZGYRGXSFL-UHFFFAOYSA-N imidazolide Chemical compound C1=C[N-]C=N1 JBFYUZGYRGXSFL-UHFFFAOYSA-N 0.000 description 1
230000001506 immunosuppresive effect Effects 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
238000001802 infusion Methods 0.000 description 1
230000030214 innervation Effects 0.000 description 1
JHKJQWFHNIOUKY-UHFFFAOYSA-N iodomethylcyclopropane Chemical compound ICC1CC1 JHKJQWFHNIOUKY-UHFFFAOYSA-N 0.000 description 1
JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
229940011051 isopropyl acetate Drugs 0.000 description 1
GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
108010057821 leucylproline Proteins 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
230000001404 mediated effect Effects 0.000 description 1
239000002609 medium Substances 0.000 description 1
FSOMWDZZTOBGPC-NSHDSACASA-N methyl (2s)-1-(6-bromo-1,3-benzoxazol-2-yl)piperidine-2-carboxylate Chemical compound COC(=O)[C@@H]1CCCCN1C1=NC2=CC=C(Br)C=C2O1 FSOMWDZZTOBGPC-NSHDSACASA-N 0.000 description 1
VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-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
LKPFBGKZCCBZDK-UHFFFAOYSA-N n-hydroxypiperidine Chemical compound ON1CCCCC1 LKPFBGKZCCBZDK-UHFFFAOYSA-N 0.000 description 1
229940053128 nerve growth factor Drugs 0.000 description 1
229940000041 nervous system drug Drugs 0.000 description 1
208000004296 neuralgia Diseases 0.000 description 1
210000002241 neurite Anatomy 0.000 description 1
201000001119 neuropathy Diseases 0.000 description 1
230000007823 neuropathy Effects 0.000 description 1
229940032018 neurotrophin 3 Drugs 0.000 description 1
231100000252 nontoxic Toxicity 0.000 description 1
230000003000 nontoxic effect Effects 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
239000012074 organic phase Substances 0.000 description 1
238000012261 overproduction Methods 0.000 description 1
DIVDFFZHCJEHGG-UHFFFAOYSA-N oxidopamine Chemical compound NCCC1=CC(O)=C(O)C=C1O DIVDFFZHCJEHGG-UHFFFAOYSA-N 0.000 description 1
238000002638 palliative care Methods 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
IZUPBVBPLAPZRR-UHFFFAOYSA-N pentachloro-phenol Natural products OC1=C(Cl)C(Cl)=C(Cl)C(Cl)=C1Cl IZUPBVBPLAPZRR-UHFFFAOYSA-N 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
HXEACLLIILLPRG-UHFFFAOYSA-M pipecolate Chemical compound [O-]C(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-M 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
235000020004 porter Nutrition 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
QJZUKDFHGGYHMC-UHFFFAOYSA-N pyridine-3-carbaldehyde Chemical compound O=CC1=CC=CN=C1 QJZUKDFHGGYHMC-UHFFFAOYSA-N 0.000 description 1
NGXSWUFDCSEIOO-UHFFFAOYSA-N pyrrolidin-3-amine Chemical compound NC1CCNC1 NGXSWUFDCSEIOO-UHFFFAOYSA-N 0.000 description 1
230000004044 response Effects 0.000 description 1
238000012552 review Methods 0.000 description 1
230000007017 scission Effects 0.000 description 1
150000004760 silicates Chemical class 0.000 description 1
239000001509 sodium citrate Substances 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
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
239000008247 solid mixture Substances 0.000 description 1
238000000638 solvent extraction Methods 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
241000894007 species Species 0.000 description 1
210000000273 spinal nerve root Anatomy 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
229960005322 streptomycin Drugs 0.000 description 1
239000000126 substance Substances 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
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
XBXCNNQPRYLIDE-UHFFFAOYSA-N tert-butylcarbamic acid Chemical compound CC(C)(C)NC(O)=O XBXCNNQPRYLIDE-UHFFFAOYSA-N 0.000 description 1
MHXBHWLGRWOABW-UHFFFAOYSA-N tetradecyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCC MHXBHWLGRWOABW-UHFFFAOYSA-N 0.000 description 1
NQRYJNQNLNOLGT-UHFFFAOYSA-N tetrahydropyridine hydrochloride Natural products C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 1
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 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
125000003944 tolyl group Chemical group 0.000 description 1
239000003053 toxin Substances 0.000 description 1
231100000765 toxin Toxicity 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
239000003871 white petrolatum Substances 0.000 description 1
239000011701 zinc Substances 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- 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
- 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
- A61P25/14—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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- 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
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Landscapes

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

OA1200100023A 1998-07-21 1999-06-28 Heterocyclic compounds as inhibitors of rotamase enzymes. OA11585A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GBGB9815880.1A GB9815880D0 (en)	1998-07-21	1998-07-21	Heterocycles

Publications (1)

Publication Number	Publication Date
OA11585A true OA11585A (en)	2004-07-26

Family

ID=10835920

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
OA1200100023A OA11585A (en)	1998-07-21	1999-06-28	Heterocyclic compounds as inhibitors of rotamase enzymes.

Country Status (45)

Country	Link
US (2)	US6372736B1 (is)
EP (1)	EP1100797B1 (is)
JP (2)	JP3795329B2 (is)
KR (2)	KR100450008B1 (is)
CN (3)	CN1611499A (is)
AP (1)	AP2001002046A0 (is)
AR (1)	AR019427A1 (is)
AT (1)	ATE233261T1 (is)
AU (1)	AU765925B2 (is)
BG (1)	BG105254A (is)
BR (1)	BR9912330A (is)
CA (1)	CA2338214C (is)
CO (1)	CO5080782A1 (is)
CR (1)	CR6073A (is)
DE (1)	DE69905582T2 (is)
DK (1)	DK1100797T3 (is)
DZ (1)	DZ2851A1 (is)
EA (1)	EA003513B1 (is)
EE (1)	EE200100044A (is)
ES (1)	ES2191484T3 (is)
GB (1)	GB9815880D0 (is)
GE (1)	GEP20033028B (is)
GT (1)	GT199900115A (is)
HK (1)	HK1039779A1 (is)
HN (1)	HN1999000106A (is)
HR (1)	HRP20010052A2 (is)
HU (1)	HUP0103413A3 (is)
ID (1)	ID26991A (is)
IL (1)	IL140244A0 (is)
IS (1)	IS5790A (is)
MA (1)	MA24936A1 (is)
MY (1)	MY118222A (is)
NO (1)	NO20010322L (is)
NZ (2)	NZ522270A (is)
OA (1)	OA11585A (is)
PA (1)	PA8478501A1 (is)
PE (1)	PE20001037A1 (is)
PL (1)	PL345734A1 (is)
SI (1)	SI1100797T1 (is)
SK (1)	SK772001A3 (is)
SV (1)	SV1999000102A (is)
TN (1)	TNSN99147A1 (is)
TR (1)	TR200100135T2 (is)
TW (1)	TWI229672B (is)
WO (1)	WO2000005232A1 (is)

Families Citing this family (32)

* 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
TR200101239T2 (tr)	1998-11-03	2001-11-21	Basf Aktiengesellschaft	İkameli-2-fenilbenzimidazoller, üretimleri ve kullanımları
GT200000203A (es)	1999-12-01	2002-05-24		Compuestos, composiciones y metodos para estimular el crecimiento y elongacion de neuronas.
FR2805818B1 (fr) *	2000-03-03	2002-04-26	Aventis Pharma Sa	Derives d'azetidine, leur preparation et les compositions pharmaceutiques les contenant
DE10124953A1 (de) *	2001-05-21	2002-12-12	Marlies Knipper	Substanz für die therapeutische Behandlung von Tinnitus
JP4812758B2 (ja) *	2004-06-29	2011-11-09	アベンティス・ファーマスーティカルズ・インコーポレイテツド	Ｆｋｂｐ結合組成物及びその医薬上の使用
US7728026B2 (en) *	2005-04-11	2010-06-01	Abbott Laboratories, Inc.	2-substituted-1 h-benzimidazile-4-carboxamides are PARP inhibitors
TWI375673B (en) *	2005-04-11	2012-11-01	Abbott Lab	1h-benzimidazole-4-carboxamides substituted with a quaternary carbon at the 2-position are potent parp inhibitors
CN101316834A (zh) *	2005-09-29	2008-12-03	艾博特公司	在2位取代有苯基的1h-苯并咪唑-4-甲酰胺是强效parp抑制剂
JP5162465B2 (ja) *	2005-11-15	2013-03-13	アボット・ラボラトリーズ	置換１ｈ−ベンズイミダゾール−４−カルボキサミド類は強力なｐａｒｐ阻害薬である
EP3205644A1 (en)	2005-12-29	2017-08-16	Celtaxsys Inc.	Diamine derivatives as inhibitors of leukotriene a4 hydrolase
BRPI0707719A2 (pt)	2006-02-10	2011-05-10	Summit Corp Plc	uso de um composto ou de um sal farmaceuticamente aceitÁvel do mesmo
RU2462458C2 (ru) *	2006-02-10	2012-09-27	Байомарин Ига Лимитед	Лечение миодистрофии дюшена
GB0602768D0 (en) *	2006-02-10	2006-03-22	Vastox Plc	Treatment of muscular dystrophy
MX2008014004A (es) *	2006-05-02	2008-11-12	Abbott Lab	1h-benzimidazol-4-carboxamidas sustituidas son inhibidores de parp potentes.
MX2009006543A (es) *	2006-12-20	2009-06-26	Amgen Inc	Compuestos heterociclicos y su uso en el tratamiento de la inflamacion, angiogenesis y cancer.
CL2008000666A1 (es) *	2007-03-07	2008-06-13	Xenon Pharmaceuticals Inc	Compuestos derivados de triciclos sustituidos, inhibidores del transportador de metales divalentes-1; y uso para tratar una enfermedad asociada con un trastorno del hierro.
US8067613B2 (en) *	2007-07-16	2011-11-29	Abbott Laboratories	Benzimidazole poly(ADP ribose)polymerase inhibitors
AU2008285289A1 (en) *	2007-08-03	2009-02-12	Biomarin Iga Limited	Drug combinations for the treatment of Duchenne muscular dystrophy
GB0715937D0 (en) *	2007-08-15	2007-09-26	Vastox Plc	Method of treatment og duchenne muscular dystrophy
GB0715939D0 (en) *	2007-08-15	2007-09-26	Vastox Plc	Method of treatment of duchenne muscular dystrophy
DE102008060549A1 (de)	2008-12-04	2010-06-10	MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V.	Wirkstoff-Peptid-Konstrukt zur extrazellulären Anreicherung
WO2010083199A1 (en) *	2009-01-19	2010-07-22	Abbott Laboratories	Benzthiazole inhibitors of poly(adp-ribose)polymerase
GB0905664D0 (en) *	2009-04-02	2009-05-13	Summit Corp Plc	Compounds for treatment of duchenne muscular dystrophy
AU2014249168B2 (en)	2013-03-12	2018-07-12	Celltaxis, Llc	Methods of inhibiting leukotriene A4 hydrolase
MX2015011678A (es)	2013-03-14	2016-07-08	Celtaxsys Inc	Inhibidores de leucotrieno a4 hidrolasa.
AU2014240042C1 (en)	2013-03-14	2019-09-05	Celltaxis, Llc	Inhibitors of leukotriene A4 hydrolase
EP2968265A4 (en)	2013-03-14	2016-12-28	Celtaxsys Inc	INHIBITORS OF THE LEUKOTRIEN A4 HYDROLASE
NZ726874A (en) *	2014-05-19	2018-03-23	Merial Inc	Anthelmintic compounds
EP3801559B1 (en)	2018-05-31	2025-01-01	Celltaxis, LLC	Method of reducing pulmonary exacerbations in respiratory disease patients
CN109111376B (zh) *	2018-09-18	2021-09-14	四川医立特生物医药有限公司	一种2,5-双脱氧链霉胺衍生物及其应用

Family Cites Families (16)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5612332A (en) *	1984-03-19	1997-03-18	Alteon Inc.	Di- and triaminoguanidines, and methods of use
JPS6428245A (en)	1987-07-22	1989-01-30	Sumitomo Electric Industries	Production of fluoride glass
MX9202466A (es)	1991-05-24	1994-06-30	Vertex Pharma	Compuestos inmunosupresores novedosos.
CO4520280A1 (es) *	1993-10-26	1997-10-15	Boehringer Ingelheim Pharma	Derivados de pirrolidina, inhibidores de la bioscientesis de leucotrienos
DE19514313A1 (de)	1994-08-03	1996-02-08	Bayer Ag	Benzoxazolyl- und Benzothiazolyloxazolidinone
US5696135A (en) *	1995-06-07	1997-12-09	Gpi Nil Holdings, Inc.	Inhibitors of rotamase enzyme activity effective at stimulating neuronal growth
US5859031A (en)	1995-06-07	1999-01-12	Gpi Nil Holdings, Inc.	Small molecule inhibitors of rotamase enzyme activity
US5801197A (en) *	1995-10-31	1998-09-01	Gpi Nil Holdings, Inc.	Rotamase enzyme activity inhibitors
US5786378A (en) *	1996-09-25	1998-07-28	Gpi Nil Holdings, Inc.	Heterocyclic thioesters
US5801187A (en) *	1996-09-25	1998-09-01	Gpi-Nil Holdings, Inc.	Heterocyclic esters and amides
US5780484A (en)	1996-11-13	1998-07-14	Vertex Pharmaceuticals Incorporated	Methods for stimulating neurite growth with piperidine compounds
US5840736A (en)	1996-11-13	1998-11-24	Vertex Pharmaceuticals Incorporated	Methods and compositions for stimulating neurite growth
US5811434A (en)	1996-11-13	1998-09-22	Vertex Pharmacueticals Incorporated	Methods and compositions for stimulating neurite growth
US5721256A (en)	1997-02-12	1998-02-24	Gpi Nil Holdings, Inc.	Method of using neurotrophic sulfonamide compounds
GB9815696D0 (en) *	1998-07-20	1998-09-16	Pfizer Ltd	Heterocyclics
GB9815880D0 (en) *	1998-07-21	1998-09-16	Pfizer Ltd	Heterocycles

1998
- 1998-07-21 GB GBGB9815880.1A patent/GB9815880D0/en not_active Ceased
1999
- 1999-06-28 OA OA1200100023A patent/OA11585A/en unknown
- 1999-06-28 CA CA002338214A patent/CA2338214C/en not_active Expired - Fee Related
- 1999-06-28 HK HK02100933.8A patent/HK1039779A1/zh unknown
- 1999-06-28 CN CNA2004100399747A patent/CN1611499A/zh active Pending
- 1999-06-28 AT AT99963123T patent/ATE233261T1/de not_active IP Right Cessation
- 1999-06-28 IL IL14024499A patent/IL140244A0/xx unknown
- 1999-06-28 HR HR20010052A patent/HRP20010052A2/hr not_active Application Discontinuation
- 1999-06-28 TR TR2001/00135T patent/TR200100135T2/xx unknown
- 1999-06-28 EE EEP200100044A patent/EE200100044A/xx unknown
- 1999-06-28 NZ NZ522270A patent/NZ522270A/en unknown
- 1999-06-28 BR BR9912330-4A patent/BR9912330A/pt not_active Application Discontinuation
- 1999-06-28 HU HU0103413A patent/HUP0103413A3/hu unknown
- 1999-06-28 SI SI9930246T patent/SI1100797T1/xx unknown
- 1999-06-28 EA EA200100052A patent/EA003513B1/ru not_active IP Right Cessation
- 1999-06-28 ES ES99963123T patent/ES2191484T3/es not_active Expired - Lifetime
- 1999-06-28 DK DK99963123T patent/DK1100797T3/da active
- 1999-06-28 AU AU42858/99A patent/AU765925B2/en not_active Ceased
- 1999-06-28 PL PL99345734A patent/PL345734A1/xx not_active Application Discontinuation
- 1999-06-28 ID IDW20010155A patent/ID26991A/id unknown
- 1999-06-28 WO PCT/IB1999/001211 patent/WO2000005232A1/en not_active Ceased
- 1999-06-28 GE GEAP19995715A patent/GEP20033028B/en unknown
- 1999-06-28 AP APAP/P/2001/002046A patent/AP2001002046A0/en unknown
- 1999-06-28 NZ NZ508838A patent/NZ508838A/xx unknown
- 1999-06-28 KR KR10-2001-7000927A patent/KR100450008B1/ko not_active Expired - Fee Related
- 1999-06-28 EP EP99963123A patent/EP1100797B1/en not_active Expired - Lifetime
- 1999-06-28 DE DE69905582T patent/DE69905582T2/de not_active Expired - Fee Related
- 1999-06-28 CN CNB998089974A patent/CN1174978C/zh not_active Expired - Fee Related
- 1999-06-28 CN CNA2003101239079A patent/CN1511837A/zh active Pending
- 1999-06-28 KR KR10-2004-7007852A patent/KR100468185B1/ko not_active Expired - Fee Related
- 1999-06-28 SK SK77-2001A patent/SK772001A3/sk unknown
- 1999-06-28 JP JP2000561188A patent/JP3795329B2/ja not_active Expired - Fee Related
- 1999-07-07 HN HN1999000106A patent/HN1999000106A/es unknown
- 1999-07-13 TW TW088111868A patent/TWI229672B/zh not_active IP Right Cessation
- 1999-07-19 CO CO99045677A patent/CO5080782A1/es unknown
- 1999-07-19 AR ARP990103544A patent/AR019427A1/es unknown
- 1999-07-20 DZ DZ990151A patent/DZ2851A1/xx active
- 1999-07-20 SV SV1999000102A patent/SV1999000102A/es not_active Application Discontinuation
- 1999-07-20 PE PE1999000727A patent/PE20001037A1/es not_active Application Discontinuation
- 1999-07-20 GT GT199900115A patent/GT199900115A/es unknown
- 1999-07-20 MA MA25691A patent/MA24936A1/fr unknown
- 1999-07-20 MY MYPI99003048A patent/MY118222A/en unknown
- 1999-07-20 TN TNTNSN99147A patent/TNSN99147A1/fr unknown
- 1999-07-20 PA PA19998478501A patent/PA8478501A1/es unknown
- 1999-07-20 CR CR6073A patent/CR6073A/es not_active Application Discontinuation
- 1999-07-21 US US09/358,107 patent/US6372736B1/en not_active Expired - Fee Related
2000
- 2000-12-22 IS IS5790A patent/IS5790A/is unknown
2001
- 2001-01-19 NO NO20010322A patent/NO20010322L/no not_active Application Discontinuation
- 2001-02-14 BG BG105254A patent/BG105254A/xx unknown
2002
- 2002-01-23 US US10/056,901 patent/US6562964B1/en not_active Expired - Fee Related
2003
- 2003-04-09 JP JP2003105099A patent/JP2004002374A/ja active Pending

Also Published As

Publication number	Publication date
TNSN99147A1 (fr)	2005-11-10
IS5790A (is)	2000-12-22
BR9912330A (pt)	2001-04-17
TR200100135T2 (tr)	2001-06-21
ID26991A (id)	2001-02-22
CO5080782A1 (es)	2001-09-25
NZ522270A (en)	2004-03-26
TWI229672B (en)	2005-03-21
CN1174978C (zh)	2004-11-10
CR6073A (es)	2004-04-29
HUP0103413A2 (hu)	2002-05-29
JP2002521382A (ja)	2002-07-16
MY118222A (en)	2004-09-30
GEP20033028B (en)	2003-07-25
DK1100797T3 (da)	2003-04-22
DE69905582D1 (de)	2003-04-03
KR20010071013A (ko)	2001-07-28
NZ508838A (en)	2002-12-20
GB9815880D0 (en)	1998-09-16
EE200100044A (et)	2002-06-17
DZ2851A1 (fr)	2004-02-04
SK772001A3 (en)	2001-12-03
HRP20010052A2 (en)	2001-12-31
WO2000005232A1 (en)	2000-02-03
EP1100797A1 (en)	2001-05-23
KR20040062640A (ko)	2004-07-07
EA200100052A1 (ru)	2001-06-25
KR100450008B1 (ko)	2004-09-24
SV1999000102A (es)	2000-07-06
CA2338214A1 (en)	2000-02-03
HK1039779A1 (zh)	2002-05-10
SI1100797T1 (en)	2003-06-30
ATE233261T1 (de)	2003-03-15
PL345734A1 (en)	2002-01-02
JP3795329B2 (ja)	2006-07-12
HUP0103413A3 (en)	2002-10-28
NO20010322D0 (no)	2001-01-19
EP1100797B1 (en)	2003-02-26
AP2001002046A0 (en)	2001-03-31
EA003513B1 (ru)	2003-06-26
KR100468185B1 (ko)	2005-01-26
DE69905582T2 (de)	2003-09-04
CN1310718A (zh)	2001-08-29
GT199900115A (es)	2001-01-10
IL140244A0 (en)	2002-02-10
CN1611499A (zh)	2005-05-04
PE20001037A1 (es)	2000-10-11
PA8478501A1 (es)	2000-05-24
US6562964B1 (en)	2003-05-13
HN1999000106A (es)	1999-11-11
JP2004002374A (ja)	2004-01-08
NO20010322L (no)	2001-03-15
CA2338214C (en)	2006-08-01
AR019427A1 (es)	2002-02-20
AU765925B2 (en)	2003-10-02
MA24936A1 (fr)	2000-04-01
ES2191484T3 (es)	2003-09-01
BG105254A (en)	2001-10-31
CN1511837A (zh)	2004-07-14
AU4285899A (en)	2000-02-14
US6372736B1 (en)	2002-04-16

Publication	Publication Date	Title
US6372736B1 (en)	2002-04-16	Heterocyclic compounds as inhibitors of rotamase enzymes
EP0783500B1 (en)	1998-07-22	Aminoheterocyclic derivatives as antithrombotic or anticoagulant agents
EP0976732B1 (en)	2004-11-24	1,4-substituted cyclic amine derivatives
CA2873850C (en)	2016-10-04	Sulfonyl piperidine derivatives and their use for treating prokineticin mediated diseases
US5914328A (en)	1999-06-22	Heterocyclic ether compounds useful in controlling neurotransmitter release
KR20070052693A (ko)	2007-05-22	폴리헤테로시클릭 화합물 및 대사성 글루타메이트 수용체길항제로서 이들의 용도
WO2002006234A1 (en)	2002-01-24	Sulfone derivatives, process for their production and use thereof
AU5355794A (en)	1994-05-09	Heterocyclic ether compounds that enhance cognitive function
JPWO2004069824A1 (ja)	2006-05-25	ピラゾール誘導体
CA2338276C (en)	2007-01-09	Fkbp inhibitors
US6509464B1 (en)	2003-01-21	FKBP inhibitors
CZ2001236A3 (cs)	2001-06-13	Heterocyklické sloučeniny jako inhibitory rotamasy
WO2025245351A1 (en)	2025-11-27	Substituted aryl sulfonamides and compositions and uses thereof
MXPA99008986A (en)	2000-02-02	1,4-substituted cyclic amine derivatives