SK55998A3 - Use of pipecolic acid derivative - Google Patents

Use of pipecolic acid derivative Download PDF

Info

Publication number: SK55998A3
Authority: SK; Slovakia
Prior art keywords: acid derivative; pipecolic acid; branched; alkenyl; straight
Prior art date: 1995-10-31

Application number

SK559-98A

Other languages

English (en)

Slovak (sk)

Inventor

Joseph P Steiner

Gregory S Hamilton

Original Assignee

Guilford Pharm Inc

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.)

1995-10-31

Filing date

1996-08-26

Publication date

1999-02-11

1995-10-31 Priority claimed from US08/551,026 external-priority patent/US20020013344A1/en

1996-08-26 Application filed by Guilford Pharm Inc filed Critical Guilford Pharm Inc

1999-02-11 Publication of SK55998A3 publication Critical patent/SK55998A3/sk

Links

HXEACLLIILLPRG-YFKPBYRVSA-N L-pipecolic acid Chemical class [O-]C(=O)[C@@H]1CCCC[NH2+]1 HXEACLLIILLPRG-YFKPBYRVSA-N 0.000 title claims description 60
-1 pipecolic acid derivative compounds Chemical class 0.000 claims abstract description 56
102000000521 Immunophilins Human genes 0.000 claims abstract description 47
108010016648 Immunophilins Proteins 0.000 claims abstract description 47
230000000694 effects Effects 0.000 claims abstract description 38
230000000508 neurotrophic effect Effects 0.000 claims abstract description 33
101710103508 FK506-binding protein Proteins 0.000 claims abstract description 30
101710104425 FK506-binding protein 2 Proteins 0.000 claims abstract description 30
101710104423 FK506-binding protein 3 Proteins 0.000 claims abstract description 30
101710104333 FK506-binding protein 4 Proteins 0.000 claims abstract description 30
101710104342 FK506-binding protein 5 Proteins 0.000 claims abstract description 30
101710149710 FKBP-type 16 kDa peptidyl-prolyl cis-trans isomerase Proteins 0.000 claims abstract description 30
101710121306 FKBP-type 22 kDa peptidyl-prolyl cis-trans isomerase Proteins 0.000 claims abstract description 30
101710180800 FKBP-type peptidyl-prolyl cis-trans isomerase FkpA Proteins 0.000 claims abstract description 30
101710104030 Long-type peptidyl-prolyl cis-trans isomerase Proteins 0.000 claims abstract description 30
101710114693 Outer membrane protein MIP Proteins 0.000 claims abstract description 30
101710116692 Peptidyl-prolyl cis-trans isomerase Proteins 0.000 claims abstract description 30
101710111764 Peptidyl-prolyl cis-trans isomerase FKBP10 Proteins 0.000 claims abstract description 30
101710111749 Peptidyl-prolyl cis-trans isomerase FKBP11 Proteins 0.000 claims abstract description 30
101710111747 Peptidyl-prolyl cis-trans isomerase FKBP12 Proteins 0.000 claims abstract description 30
101710111757 Peptidyl-prolyl cis-trans isomerase FKBP14 Proteins 0.000 claims abstract description 30
101710111682 Peptidyl-prolyl cis-trans isomerase FKBP1A Proteins 0.000 claims abstract description 30
101710111689 Peptidyl-prolyl cis-trans isomerase FKBP1B Proteins 0.000 claims abstract description 30
101710147154 Peptidyl-prolyl cis-trans isomerase FKBP2 Proteins 0.000 claims abstract description 30
101710147149 Peptidyl-prolyl cis-trans isomerase FKBP3 Proteins 0.000 claims abstract description 30
101710147152 Peptidyl-prolyl cis-trans isomerase FKBP4 Proteins 0.000 claims abstract description 30
101710147150 Peptidyl-prolyl cis-trans isomerase FKBP5 Proteins 0.000 claims abstract description 30
101710147138 Peptidyl-prolyl cis-trans isomerase FKBP7 Proteins 0.000 claims abstract description 30
101710147137 Peptidyl-prolyl cis-trans isomerase FKBP8 Proteins 0.000 claims abstract description 30
101710147136 Peptidyl-prolyl cis-trans isomerase FKBP9 Proteins 0.000 claims abstract description 30
101710174853 Peptidyl-prolyl cis-trans isomerase Mip Proteins 0.000 claims abstract description 30
101710200991 Peptidyl-prolyl cis-trans isomerase, rhodopsin-specific isozyme Proteins 0.000 claims abstract description 30
101710092145 Peptidyl-prolyl cis-trans isomerase-like 1 Proteins 0.000 claims abstract description 30
101710092146 Peptidyl-prolyl cis-trans isomerase-like 2 Proteins 0.000 claims abstract description 30
101710092148 Peptidyl-prolyl cis-trans isomerase-like 3 Proteins 0.000 claims abstract description 30
101710092149 Peptidyl-prolyl cis-trans isomerase-like 4 Proteins 0.000 claims abstract description 30
101710113444 Probable parvulin-type peptidyl-prolyl cis-trans isomerase Proteins 0.000 claims abstract description 30
101710090737 Probable peptidyl-prolyl cis-trans isomerase Proteins 0.000 claims abstract description 30
101710133309 Putative peptidyl-prolyl cis-trans isomerase Proteins 0.000 claims abstract description 30
101710124237 Short-type peptidyl-prolyl cis-trans isomerase Proteins 0.000 claims abstract description 30
238000000034 method Methods 0.000 claims abstract description 14
230000009689 neuronal regeneration Effects 0.000 claims abstract description 13
230000007514 neuronal growth Effects 0.000 claims abstract description 4
102100038809 Peptidyl-prolyl cis-trans isomerase FKBP9 Human genes 0.000 claims abstract 8
125000000217 alkyl group Chemical group 0.000 claims description 62
125000003342 alkenyl group Chemical group 0.000 claims description 61
239000001257 hydrogen Substances 0.000 claims description 45
229910052739 hydrogen Inorganic materials 0.000 claims description 45
229910052760 oxygen Inorganic materials 0.000 claims description 30
239000003018 immunosuppressive agent Substances 0.000 claims description 28
108010025020 Nerve Growth Factor Proteins 0.000 claims description 26
150000002431 hydrogen Chemical class 0.000 claims description 25
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 24
239000001301 oxygen Substances 0.000 claims description 24
239000003102 growth factor Substances 0.000 claims description 23
229960003444 immunosuppressant agent Drugs 0.000 claims description 23
208000012902 Nervous system disease Diseases 0.000 claims description 21
230000001861 immunosuppressant effect Effects 0.000 claims description 20
230000004770 neurodegeneration Effects 0.000 claims description 20
208000025966 Neurological disease Diseases 0.000 claims description 16
238000002360 preparation method Methods 0.000 claims description 14
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 13
102000007072 Nerve Growth Factors Human genes 0.000 claims description 13
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 13
210000000578 peripheral nerve Anatomy 0.000 claims description 13
125000006709 (C5-C7) cycloalkenyl group Chemical group 0.000 claims description 12
125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 12
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
230000012010 growth Effects 0.000 claims description 12
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
239000000203 mixture Substances 0.000 claims description 12
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
125000001424 substituent group Chemical group 0.000 claims description 12
229910052717 sulfur Inorganic materials 0.000 claims description 12
239000011593 sulfur Chemical group 0.000 claims description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
108010046910 brain-derived growth factor Proteins 0.000 claims description 11
210000002569 neuron Anatomy 0.000 claims description 11
230000001737 promoting effect Effects 0.000 claims description 11
239000003900 neurotrophic factor Substances 0.000 claims description 10
230000006931 brain damage Effects 0.000 claims description 9
231100000874 brain damage Toxicity 0.000 claims description 9
208000029028 brain injury Diseases 0.000 claims description 9
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 9
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
150000003839 salts Chemical class 0.000 claims description 9
230000004936 stimulating effect Effects 0.000 claims description 9
230000006378 damage Effects 0.000 claims description 8
230000002518 glial effect Effects 0.000 claims description 8
208000024827 Alzheimer disease Diseases 0.000 claims description 7
108010005939 Ciliary Neurotrophic Factor Proteins 0.000 claims description 7
102100031614 Ciliary neurotrophic factor Human genes 0.000 claims description 7
102000004230 Neurotrophin 3 Human genes 0.000 claims description 7
108090000742 Neurotrophin 3 Proteins 0.000 claims description 7
208000018737 Parkinson disease Diseases 0.000 claims description 7
201000010099 disease Diseases 0.000 claims description 7
125000005842 heteroatom Chemical group 0.000 claims description 7
229940032018 neurotrophin 3 Drugs 0.000 claims description 7
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 6
125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 6
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical group 0.000 claims description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
208000027232 peripheral nervous system disease Diseases 0.000 claims description 6
208000033808 peripheral neuropathy Diseases 0.000 claims description 6
210000000278 spinal cord Anatomy 0.000 claims description 6
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 5
208000014674 injury Diseases 0.000 claims description 5
230000000926 neurological effect Effects 0.000 claims description 5
125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 4
241001465754 Metazoa Species 0.000 claims description 4
125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 3
208000027418 Wounds and injury Diseases 0.000 claims description 3
230000009471 action Effects 0.000 claims description 3
125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 3
125000004432 carbon atom Chemical group C* 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 3
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
125000002950 monocyclic group Chemical group 0.000 claims description 3
229910052757 nitrogen Inorganic materials 0.000 claims description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
208000020431 spinal cord injury Diseases 0.000 claims description 3
238000006467 substitution reaction Methods 0.000 claims description 3
125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
102000005755 Intercellular Signaling Peptides and Proteins Human genes 0.000 claims description 2
230000001886 ciliary effect Effects 0.000 claims description 2
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
230000008733 trauma Effects 0.000 claims description 2
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
125000004122 cyclic group Chemical group 0.000 claims 1
239000003112 inhibitor Substances 0.000 abstract description 7
102000009658 Peptidylprolyl Isomerase Human genes 0.000 abstract description 4
108010020062 Peptidylprolyl Isomerase Proteins 0.000 abstract description 4
238000011069 regeneration method Methods 0.000 abstract description 3
102000004190 Enzymes Human genes 0.000 abstract 2
108090000790 Enzymes Proteins 0.000 abstract 2
150000001875 compounds Chemical class 0.000 description 24
102100020739 Peptidyl-prolyl cis-trans isomerase FKBP4 Human genes 0.000 description 22
230000014511 neuron projection development Effects 0.000 description 16
239000000126 substance Substances 0.000 description 15
102000015336 Nerve Growth Factor Human genes 0.000 description 13
102000018679 Tacrolimus Binding Proteins Human genes 0.000 description 13
229940053128 nerve growth factor Drugs 0.000 description 13
108010027179 Tacrolimus Binding Proteins Proteins 0.000 description 12
QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 11
239000003795 chemical substances by application Substances 0.000 description 11
QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 11
230000005764 inhibitory process Effects 0.000 description 10
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
210000000609 ganglia Anatomy 0.000 description 8
230000001537 neural effect Effects 0.000 description 8
210000001044 sensory neuron Anatomy 0.000 description 8
PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 7
229930105110 Cyclosporin A Natural products 0.000 description 7
108010036949 Cyclosporine Proteins 0.000 description 7
210000004027 cell Anatomy 0.000 description 7
210000003169 central nervous system Anatomy 0.000 description 7
229960001265 ciclosporin Drugs 0.000 description 7
231100000673 dose–response relationship Toxicity 0.000 description 7
239000000243 solution Substances 0.000 description 7
102100027913 Peptidyl-prolyl cis-trans isomerase FKBP1A Human genes 0.000 description 6
108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 description 6
235000018102 proteins Nutrition 0.000 description 6
102000004169 proteins and genes Human genes 0.000 description 6
108090000623 proteins and genes Proteins 0.000 description 6
241000287828 Gallus gallus Species 0.000 description 5
208000003098 Ganglion Cysts Diseases 0.000 description 5
208000005400 Synovial Cyst Diseases 0.000 description 5
235000013330 chicken meat Nutrition 0.000 description 5
239000002552 dosage form Substances 0.000 description 5
229940079593 drug Drugs 0.000 description 5
239000003814 drug Substances 0.000 description 5
230000001506 immunosuppresive effect Effects 0.000 description 5
230000002401 inhibitory effect Effects 0.000 description 5
230000008569 process Effects 0.000 description 5
ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 5
QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 5
229960002930 sirolimus Drugs 0.000 description 5
210000003594 spinal ganglia Anatomy 0.000 description 5
239000000725 suspension Substances 0.000 description 5
102000003922 Calcium Channels Human genes 0.000 description 4
108090000312 Calcium Channels Proteins 0.000 description 4
239000004480 active ingredient Substances 0.000 description 4
239000003446 ligand Substances 0.000 description 4
210000002241 neurite Anatomy 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
239000000758 substrate Substances 0.000 description 4
230000001228 trophic effect Effects 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
102000001493 Cyclophilins Human genes 0.000 description 3
108010068682 Cyclophilins Proteins 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
102000019027 Ryanodine Receptor Calcium Release Channel Human genes 0.000 description 3
239000003085 diluting agent Substances 0.000 description 3
230000002255 enzymatic effect Effects 0.000 description 3
229940124589 immunosuppressive drug Drugs 0.000 description 3
210000005036 nerve Anatomy 0.000 description 3
210000000653 nervous system Anatomy 0.000 description 3
235000019271 petrolatum Nutrition 0.000 description 3
108091052345 ryanodine receptor (TC 1.A.3.1) family Proteins 0.000 description 3
239000002904 solvent Substances 0.000 description 3
230000000638 stimulation Effects 0.000 description 3
PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
108090000317 Chymotrypsin Proteins 0.000 description 2
229920002261 Corn starch Polymers 0.000 description 2
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
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 2
MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
102100023085 Serine/threonine-protein kinase mTOR Human genes 0.000 description 2
238000002835 absorbance Methods 0.000 description 2
AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 2
239000007900 aqueous suspension Substances 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
230000008499 blood brain barrier function Effects 0.000 description 2
210000001218 blood-brain barrier Anatomy 0.000 description 2
239000002775 capsule Substances 0.000 description 2
238000006243 chemical reaction Methods 0.000 description 2
229960002376 chymotrypsin Drugs 0.000 description 2
239000008120 corn starch Substances 0.000 description 2
208000035475 disorder Diseases 0.000 description 2
239000002270 dispersing agent Substances 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 2
210000000987 immune system Anatomy 0.000 description 2
229940125721 immunosuppressive agent Drugs 0.000 description 2
230000003993 interaction Effects 0.000 description 2
238000007914 intraventricular administration Methods 0.000 description 2
HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 2
239000008101 lactose Substances 0.000 description 2
239000007788 liquid Substances 0.000 description 2
KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
208000004296 neuralgia Diseases 0.000 description 2
210000004498 neuroglial cell Anatomy 0.000 description 2
230000005015 neuronal process Effects 0.000 description 2
230000002981 neuropathic effect Effects 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
239000003921 oil Substances 0.000 description 2
235000019198 oils Nutrition 0.000 description 2
239000002674 ointment Substances 0.000 description 2
230000026731 phosphorylation Effects 0.000 description 2
238000006366 phosphorylation reaction Methods 0.000 description 2
230000003389 potentiating effect Effects 0.000 description 2
210000000664 rectum Anatomy 0.000 description 2
230000008929 regeneration Effects 0.000 description 2
229940121392 rotamase inhibitor Drugs 0.000 description 2
230000011664 signaling Effects 0.000 description 2
150000003384 small molecules Chemical class 0.000 description 2
AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 2
239000000375 suspending agent Substances 0.000 description 2
208000011580 syndromic disease Diseases 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
230000000699 topical effect Effects 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 1
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
VUQPJRPDRDVQMN-UHFFFAOYSA-N 1-chlorooctadecane Chemical compound CCCCCCCCCCCCCCCCCCCl VUQPJRPDRDVQMN-UHFFFAOYSA-N 0.000 description 1
LDMOEFOXLIZJOW-UHFFFAOYSA-N 1-dodecanesulfonic acid Chemical compound CCCCCCCCCCCCS(O)(=O)=O LDMOEFOXLIZJOW-UHFFFAOYSA-N 0.000 description 1
KWTSXDURSIMDCE-UHFFFAOYSA-N 1-phenylpropan-2-amine Chemical compound CC(N)CC1=CC=CC=C1 KWTSXDURSIMDCE-UHFFFAOYSA-N 0.000 description 1
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 1
229940080296 2-naphthalenesulfonate Drugs 0.000 description 1
LEACJMVNYZDSKR-UHFFFAOYSA-N 2-octyldodecan-1-ol Chemical compound CCCCCCCCCCC(CO)CCCCCCCC LEACJMVNYZDSKR-UHFFFAOYSA-N 0.000 description 1
WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical compound BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
LKDMKWNDBAVNQZ-WJNSRDFLSA-N 4-[[(2s)-1-[[(2s)-1-[(2s)-2-[[(2s)-1-(4-nitroanilino)-1-oxo-3-phenylpropan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxopropan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-oxobutanoic acid Chemical compound OC(=O)CCC(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)NC=1C=CC(=CC=1)[N+]([O-])=O)CC1=CC=CC=C1 LKDMKWNDBAVNQZ-WJNSRDFLSA-N 0.000 description 1
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
241000238876 Acari Species 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical group CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
206010002383 Angina Pectoris Diseases 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
102000004631 Calcineurin Human genes 0.000 description 1
108010042955 Calcineurin Proteins 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
102000014914 Carrier Proteins Human genes 0.000 description 1
102000003813 Cis-trans-isomerases Human genes 0.000 description 1
108090000175 Cis-trans-isomerases Proteins 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
206010010356 Congenital anomaly Diseases 0.000 description 1
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
MQJKPEGWNLWLTK-UHFFFAOYSA-N Dapsone Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 MQJKPEGWNLWLTK-UHFFFAOYSA-N 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
XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
241000792859 Enema Species 0.000 description 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
108091011114 FK506 binding proteins Proteins 0.000 description 1
206010016654 Fibrosis Diseases 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
108700042658 GAP-43 Proteins 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
208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
206010019233 Headaches Diseases 0.000 description 1
206010019909 Hernia Diseases 0.000 description 1
101000979249 Homo sapiens Neuromodulin Proteins 0.000 description 1
101000623857 Homo sapiens Serine/threonine-protein kinase mTOR Proteins 0.000 description 1
206010020772 Hypertension Diseases 0.000 description 1
108091008585 IP3 receptors Proteins 0.000 description 1
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 1
206010062016 Immunosuppression Diseases 0.000 description 1
102000010789 Interleukin-2 Receptors Human genes 0.000 description 1
108010038453 Interleukin-2 Receptors Proteins 0.000 description 1
102000004195 Isomerases Human genes 0.000 description 1
108090000769 Isomerases Proteins 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
239000004472 Lysine Substances 0.000 description 1
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
206010049567 Miller Fisher syndrome Diseases 0.000 description 1
MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
206010029155 Nephropathy toxic Diseases 0.000 description 1
206010029301 Neurological disorders of the eye Diseases 0.000 description 1
102100023206 Neuromodulin Human genes 0.000 description 1
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
240000007817 Olea europaea Species 0.000 description 1
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
239000005642 Oleic acid Substances 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
206010033799 Paralysis Diseases 0.000 description 1
239000004264 Petrolatum Substances 0.000 description 1
229920001214 Polysorbate 60 Polymers 0.000 description 1
241000097929 Porphyria Species 0.000 description 1
208000010642 Porphyrias Diseases 0.000 description 1
208000012287 Prolapse Diseases 0.000 description 1
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
206010039966 Senile dementia Diseases 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
206010041591 Spinal osteoarthritis Diseases 0.000 description 1
230000006052 T cell proliferation Effects 0.000 description 1
108091008874 T cell receptors Proteins 0.000 description 1
102000016266 T-Cell Antigen Receptors Human genes 0.000 description 1
ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
206010044565 Tremor Diseases 0.000 description 1
RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 1
239000002671 adjuvant Substances 0.000 description 1
239000003513 alkali Substances 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001447 alkali salts Chemical class 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
238000003556 assay Methods 0.000 description 1
239000002585 base Substances 0.000 description 1
235000013871 bee wax Nutrition 0.000 description 1
239000012166 beeswax Substances 0.000 description 1
229960000686 benzalkonium chloride Drugs 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
229940077388 benzenesulfonate Drugs 0.000 description 1
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
108091008324 binding proteins Proteins 0.000 description 1
230000037396 body weight Effects 0.000 description 1
210000004556 brain Anatomy 0.000 description 1
239000007853 buffer solution Substances 0.000 description 1
FUSVYSIRZDZAGP-UHFFFAOYSA-N butanoic acid;sulfuric acid Chemical compound OS(O)(=O)=O.CCCC(O)=O FUSVYSIRZDZAGP-UHFFFAOYSA-N 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
230000003185 calcium uptake Effects 0.000 description 1
MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
239000004359 castor oil Substances 0.000 description 1
235000019438 castor oil Nutrition 0.000 description 1
230000002490 cerebral effect Effects 0.000 description 1
208000036319 cervical spondylosis Diseases 0.000 description 1
229940081733 cetearyl alcohol Drugs 0.000 description 1
230000008859 change Effects 0.000 description 1
238000007697 cis-trans-isomerization reaction Methods 0.000 description 1
229940110456 cocoa butter Drugs 0.000 description 1
235000019868 cocoa butter Nutrition 0.000 description 1
229920001436 collagen Polymers 0.000 description 1
239000003086 colorant Substances 0.000 description 1
239000006071 cream Substances 0.000 description 1
229930182912 cyclosporin Natural products 0.000 description 1
229960000684 cytarabine Drugs 0.000 description 1
229960000860 dapsone Drugs 0.000 description 1
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
206010012601 diabetes mellitus Diseases 0.000 description 1
150000008050 dialkyl sulfates Chemical class 0.000 description 1
LMEDOLJKVASKTP-UHFFFAOYSA-N dibutyl sulfate Chemical group CCCCOS(=O)(=O)OCCCC LMEDOLJKVASKTP-UHFFFAOYSA-N 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
235000014113 dietary fatty acids Nutrition 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
GAFRWLVTHPVQGK-UHFFFAOYSA-N dipentyl sulfate Chemical compound CCCCCOS(=O)(=O)OCCCCC GAFRWLVTHPVQGK-UHFFFAOYSA-N 0.000 description 1
CZZYITDELCSZES-UHFFFAOYSA-N diphenylmethane Chemical group C=1C=CC=CC=1CC1=CC=CC=C1 CZZYITDELCSZES-UHFFFAOYSA-N 0.000 description 1
238000010494 dissociation reaction Methods 0.000 description 1
230000005593 dissociations Effects 0.000 description 1
VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
210000002257 embryonic structure Anatomy 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
239000007920 enema Substances 0.000 description 1
229940095399 enema Drugs 0.000 description 1
CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
230000029142 excretion Effects 0.000 description 1
210000000256 facial nerve Anatomy 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
150000004665 fatty acids Chemical class 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
230000004761 fibrosis Effects 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000003599 food sweetener Nutrition 0.000 description 1
210000001035 gastrointestinal tract Anatomy 0.000 description 1
FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 description 1
230000024924 glomerular filtration Effects 0.000 description 1
239000008103 glucose Substances 0.000 description 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
125000005456 glyceride group Chemical group 0.000 description 1
ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
231100000869 headache Toxicity 0.000 description 1
230000036541 health Effects 0.000 description 1
ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
238000002513 implantation Methods 0.000 description 1
238000001802 infusion Methods 0.000 description 1
229940102223 injectable solution Drugs 0.000 description 1
229940102213 injectable suspension Drugs 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
230000003834 intracellular effect Effects 0.000 description 1
230000031146 intracellular signal transduction Effects 0.000 description 1
238000007917 intracranial administration Methods 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000007913 intrathecal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
230000002427 irreversible effect Effects 0.000 description 1
SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 1
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
239000006210 lotion Substances 0.000 description 1
210000003750 lower gastrointestinal tract Anatomy 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
159000000003 magnesium salts Chemical class 0.000 description 1
239000000463 material Substances 0.000 description 1
230000010534 mechanism of action Effects 0.000 description 1
239000000155 melt Substances 0.000 description 1
238000001000 micrograph Methods 0.000 description 1
229940042472 mineral oil Drugs 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
201000000585 muscular atrophy Diseases 0.000 description 1
201000006938 muscular dystrophy Diseases 0.000 description 1
206010028417 myasthenia gravis Diseases 0.000 description 1
125000001421 myristyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
230000025020 negative regulation of T cell proliferation Effects 0.000 description 1
230000007694 nephrotoxicity Effects 0.000 description 1
231100000417 nephrotoxicity Toxicity 0.000 description 1
208000015122 neurodegenerative disease Diseases 0.000 description 1
230000003957 neurotransmitter release Effects 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
231100000344 non-irritating Toxicity 0.000 description 1
239000000346 nonvolatile oil Substances 0.000 description 1
GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
230000036961 partial effect Effects 0.000 description 1
230000002093 peripheral effect Effects 0.000 description 1
229940066842 petrolatum Drugs 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
229940127557 pharmaceutical product Drugs 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
229920000642 polymer Polymers 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
159000000001 potassium salts Chemical class 0.000 description 1
230000035935 pregnancy Effects 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
230000000750 progressive effect Effects 0.000 description 1
201000008752 progressive muscular atrophy Diseases 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
108010043671 prostatic acid phosphatase Proteins 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
229940100618 rectal suppository Drugs 0.000 description 1
239000006215 rectal suppository Substances 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
230000008439 repair process Effects 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000007787 solid Substances 0.000 description 1
239000001587 sorbitan monostearate Substances 0.000 description 1
229940035048 sorbitan monostearate Drugs 0.000 description 1
235000011076 sorbitan monostearate Nutrition 0.000 description 1
208000002320 spinal muscular atrophy Diseases 0.000 description 1
208000005801 spondylosis Diseases 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
238000012360 testing method Methods 0.000 description 1
210000000115 thoracic cavity Anatomy 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
210000003901 trigeminal nerve Anatomy 0.000 description 1
ZDPHROOEEOARMN-UHFFFAOYSA-N undecanoic acid Chemical compound CCCCCCCCCCC(O)=O ZDPHROOEEOARMN-UHFFFAOYSA-N 0.000 description 1
230000002792 vascular Effects 0.000 description 1
239000001993 wax Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1
239000003871 white petrolatum Substances 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- 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
- A61P25/14—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

Landscapes

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

SK559-98A 1995-10-31 1996-08-26 Use of pipecolic acid derivative SK55998A3 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US08/551,026 US20020013344A1 (en)	1995-10-31	1995-10-31	Rotamas enzyme activity inhibitors
US08/645,149 US5801197A (en)	1995-10-31	1996-05-13	Rotamase enzyme activity inhibitors
PCT/US1996/013624 WO1997016190A1 (fr)	1995-10-31	1996-08-26	Inhibiteurs de l'activite de l'enzyme rotamase

Publications (1)

Publication Number	Publication Date
SK55998A3 true SK55998A3 (en)	1999-02-11

Family

ID=27069634

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK559-98A SK55998A3 (en)	1995-10-31	1996-08-26	Use of pipecolic acid derivative

Country Status (17)

Country	Link
US (1)	US5801197A (fr)
EP (1)	EP0859614A4 (fr)
JP (1)	JPH11514643A (fr)
KR (1)	KR19990067257A (fr)
BG (1)	BG62596B1 (fr)
BR (1)	BRPI9611271A2 (fr)
CA (1)	CA2236328A1 (fr)
CZ (1)	CZ125198A3 (fr)
EA (1)	EA001481B1 (fr)
EE (1)	EE9800125A (fr)
HU (1)	HUP9901752A3 (fr)
LV (1)	LV12102B (fr)
NO (1)	NO981903L (fr)
NZ (1)	NZ316361A (fr)
PL (1)	PL326420A1 (fr)
SK (1)	SK55998A3 (fr)
WO (1)	WO1997016190A1 (fr)

Families Citing this family (60)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5898029A (en) *	1994-04-12	1999-04-27	The John Hopkins University	Direct influences on nerve growth of agents that interact with immunophilins in combination with neurotrophic factors
US6509477B1 (en)	1998-11-12	2003-01-21	Guilford Pharmaceuticals Inc.	Small molecule inhibitors of rotamase enzyme activity
US5859031A (en)	1995-06-07	1999-01-12	Gpi Nil Holdings, Inc.	Small molecule inhibitors of rotamase enzyme activity
AT500193B1 (de) *	1995-06-07	2007-11-15	Guilford Pharm Inc	Neurotrophe verbindung und verfahren zu ihrer herstellung
US6291510B1 (en)	1995-06-07	2001-09-18	Gpi Nil Holdings, Inc.	Small molecule inhibitors of rotamase enzyme activity
AT500192B1 (de) *	1995-06-07	2008-05-15	Guilford Pharm Inc	Neurotrophe verbindung, diese enthaltende pharmazeutische masse, verwendung der verbindung und verfahren zu ihrer herstellung
US7056935B2 (en) *	1995-06-07	2006-06-06	Gpi Nil Holdings, Inc.	Rotamase enzyme activity inhibitors
US6037370A (en) *	1995-06-08	2000-03-14	Vertex Pharmaceuticals Incorporated	Methods and compositions for stimulating neurite growth
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
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
US5780484A (en) *	1996-11-13	1998-07-14	Vertex Pharmaceuticals Incorporated	Methods for stimulating neurite growth with piperidine compounds
US5935989A (en)	1996-12-31	1999-08-10	Gpi Nil Holdings Inc.	N-linked ureas and carbamates of heterocyclic thioesters
EP0959882A4 (fr)	1996-12-31	2001-12-05		Urees et carbamates a liaison n de thioesters heterocycliques
US5721256A (en) *	1997-02-12	1998-02-24	Gpi Nil Holdings, Inc.	Method of using neurotrophic sulfonamide compounds
US5846979A (en)	1997-02-28	1998-12-08	Gpi Nil Holdings, Inc.	N-oxides of heterocyclic esters, amides, thioesters, and ketones
US5945441A (en) *	1997-06-04	1999-08-31	Gpi Nil Holdings, Inc.	Pyrrolidine carboxylate hair revitalizing agents
US20010049381A1 (en) *	1997-06-04	2001-12-06	Gpl Nil Holdings, Inc.,	Pyrrolidine derivative hair growth compositions and uses
US6852496B1 (en) *	1997-08-12	2005-02-08	Oregon Health And Science University	Methods of screening for agents that promote nerve cell growth
US6268384B1 (en)	1997-08-29	2001-07-31	Vertex Pharmaceuticals Incorporated	Compounds possessing neuronal activity
US6121280A (en) *	1998-03-24	2000-09-19	Pfizer Inc.	Azabicyclic rotomase inhibitors
AU743199B2 (en)	1998-06-02	2002-01-24	Bristol-Myers Squibb Company	Neurotrophic difluoroamide agents
US6331537B1 (en)	1998-06-03	2001-12-18	Gpi Nil Holdings, Inc.	Carboxylic acids and carboxylic acid isosteres of N-heterocyclic compounds
WO1999062880A1 (fr)	1998-06-03	1999-12-09	Gpi Nil Holdings, Inc.	Sulfonamides a liaison n d'acides carboxyliques n-heterocycliques ou d'isosteres d'acide carboxylique
EP1085853A1 (fr) *	1998-06-03	2001-03-28	GPI NIL Holdings, Inc.	Compositions pour la croissance des cheveux a base d'amides et d'esters heterocycliques et utilisation de ces compositions
IL140676A0 (en) *	1998-07-17	2002-02-10	Agouron Pharma	Compounds, compositions, and methods for stimulating neuronal growth and elongation
GB9815880D0 (en) *	1998-07-21	1998-09-16	Pfizer Ltd	Heterocycles
CA2335815A1 (fr) *	1998-08-14	2000-02-24	Hansjorg Sauer	Compositions destinees a des troubles de la vision et de la memoire, et leurs utilisations
US7265150B1 (en) *	1998-08-14	2007-09-04	Gpi Nil Holdings Inc.	Carboxylic acids and carboxylic acid isosteres of N-heterocyclic compounds for vision and memory disorders
US6376517B1 (en) *	1998-08-14	2002-04-23	Gpi Nil Holdings, Inc.	Pipecolic acid derivatives for vision and memory disorders
US6335348B1 (en) *	1998-08-14	2002-01-01	Gpi Nil Holdings, Inc.	Nitrogen-containing linear and azepinyl/ compositions and uses for vision and memory disorders
US7338976B1 (en) *	1998-08-14	2008-03-04	Gpi Nil Holdings, Inc.	Heterocyclic esters or amides for vision and memory disorders
US6462072B1 (en)	1998-09-21	2002-10-08	Gpi Nil Holdings, Inc.	Cyclic ester or amide derivatives
US6307049B1 (en)	1998-09-30	2001-10-23	The Procter & Gamble Co.	Heterocyclic 2-substituted ketoamides
US6300341B1 (en)	1998-09-30	2001-10-09	The Procter & Gamble Co.	2-substituted heterocyclic sulfonamides
US6228872B1 (en)	1998-11-12	2001-05-08	Bristol-Myers Squibb Company	Neurotrophic diamide and carbamate agents
AU3221300A (en) *	1999-02-03	2000-08-25	Schering Aktiengesellschaft	Carboxylic acid derivatives, process for their preparation and their use as rotamase enzyme activity inhibitors
US6284779B1 (en)	1999-02-03	2001-09-04	Schering Aktiiengesellschaft	Heteroaromatic compounds
AU5914200A (en) *	1999-07-06	2001-01-22	Vertex Pharmaceuticals Incorporated	Amino-alkyl derivatives
WO2001002372A1 (fr) *	1999-07-06	2001-01-11	Vertex Pharmaceuticals Incorporated	Derives d'acides amines cyclises
JP2003503479A (ja)	1999-07-06	2003-01-28	バーテックスファーマシューティカルズインコーポレイテッド	Ｎ置換化グリシン誘導体
RU2241709C2 (ru)	1999-07-09	2004-12-10	Орто-Макнейл Фармасьютикал, Инк.	Производные азотсодержащих гетероциклических соединений и способ лечения расстройств, характеризующихся поражением нейронов
WO2001004090A2 (fr)	1999-07-09	2001-01-18	Ortho-Mcneil Pharmaceutical, Inc.	Tetrahydro-isoquinolines et tetrahydrothienopyridines neurotrophiques, compositions et procedes associes
US6544976B1 (en)	1999-07-09	2003-04-08	Ortho-Mcneil Pharmaceutical, Inc.	Neurotrophic 2-azetidinecarboxylic acid derivatives, and related compositions and methods
AU7353300A (en) *	1999-09-08	2001-04-10	Guilford Pharmaceuticals Inc.	Non-peptidic cyclophilin binding compounds and their use
US7253169B2 (en)	1999-11-12	2007-08-07	Gliamed, Inc.	Aza compounds, pharmaceutical compositions and methods of use
US6417189B1 (en)	1999-11-12	2002-07-09	Gpi Nil Holdings, Inc.	AZA compounds, pharmaceutical compositions and methods of use
DOP2000000107A (es) *	1999-12-01	2002-09-16	Agouron Pharmaceutical Inc	Compuestos, composiciones y metodos para estimular el crecimiento y alongamiento de las neuronas
US6818643B1 (en)	1999-12-08	2004-11-16	Bristol-Myers Squibb Company	Neurotrophic bicyclic diamides
EP1244670B1 (fr)	1999-12-21	2006-03-08	MGI GP, Inc.	Composes a base de derives d'hydanto ne, compositions pharmaceutiques, et modes d'utilisation
US6821731B2 (en) *	2000-11-28	2004-11-23	Wyeth	Expression analysis of FKBP nucleic acids and polypeptides useful in the diagnosis of prostate cancer
MXPA03006666A (es)	2001-01-25	2004-05-31	Guilford Pharm Inc	Compuestos de union de ciclofilina carbociclicos trisubstituidos y su uso.
US6593362B2 (en)	2001-05-21	2003-07-15	Guilford Pharmaceuticals Inc.	Non-peptidic cyclophilin binding compounds and their use
KR20050071510A (ko) *	2002-10-15	2005-07-07	후지사와 야꾸힝 고교 가부시키가이샤	신경영양인자 생산 촉진제
ATE546430T1 (de) *	2004-06-29	2012-03-15	Aventis Pharma Inc	Fkbp bindende zusammensetzung und deren pharmazeutische verwendung
US20060189551A1 (en) *	2004-10-04	2006-08-24	Duke University	Combination therapies for fungal pathogens
DE102008060549A1 (de)	2008-12-04	2010-06-10	MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V.	Wirkstoff-Peptid-Konstrukt zur extrazellulären Anreicherung
US20100317711A1 (en) *	2008-12-17	2010-12-16	Gliamed, Inc.	Stem-like cells and method for reprogramming adult mammalian somatic cells
EP2705856A1 (fr)	2012-09-07	2014-03-12	Deutsches Zentrum für Neurodegenerative Erkrankungen e.V.	Composés pour le traitement de troubles neurodégénératifs

Family Cites Families (68)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL58849A (en) *	1978-12-11	1983-03-31	Merck & Co Inc	Carboxyalkyl dipeptides and derivatives thereof,their preparation and pharmaceutical compositions containing them
US4390695A (en) *	1980-06-23	1983-06-28	E. R. Squibb & Sons, Inc.	Imido, amido and amino derivatives of mercaptoacyl prolines and pipecolic acids
US4310461A (en) *	1980-06-23	1982-01-12	E. R. Squibb & Sons, Inc.	Imido, amido and amino derivatives of mercaptoacyl prolines and pipecolic acids
US4578474A (en) *	1980-06-23	1986-03-25	E. R. Squibb & Sons, Inc.	Imido, amido and amino derivatives of mercaptoacyl prolines and pipecolic acids
US4950649A (en) *	1980-09-12	1990-08-21	University Of Illinois	Didemnins and nordidemnins
EP0048159A3 (fr) *	1980-09-17	1982-05-12	University Of Miami	Peptides carboxyalcoyliques, thioéthers et éthers de peptides comme agents antihypertensifs
ZA817261B (en) *	1980-10-23	1982-09-29	Schering Corp	Carboxyalkyl dipeptides,processes for their production and pharmaceutical compositions containing them
EP0050800B2 (fr) *	1980-10-23	1995-06-07	Schering Corporation	Dipeptides carboxyalcoyliques, procédés pour les préparer et compositions pharmaceutiques les contenant
ZA826022B (en) *	1981-08-21	1983-08-31	Univ Miami	Novel complex amido and imido derivatives of carboxyalkyl peptides and thioethers and ethers of peptides
US4535167A (en) *	1981-12-14	1985-08-13	Merck & Co. Inc.	Chiral, N-protected, N-substituted α-amino acids
DE3360065D1 (en) *	1982-03-08	1985-03-28	Schering Corp	Carboxyalkyl dipeptides, processes for their production and pharmaceutical compositions containing them
US4531964A (en) *	1982-09-13	1985-07-30	Nippon Kayaku Kabushiki Kaisha	Heterocyclic compound and a herbicidal composition containing said compound
US4574079A (en) *	1983-05-27	1986-03-04	Gavras Haralambos P	Radiolabeled angiotensin converting enzyme inhibitors for radiolabeling mammalian organ sites
US4593102A (en) *	1984-04-10	1986-06-03	A. H. Robins Company, Inc.	N-[(amino)alkyl]-1-pyrrolidine, 1-piperidine and 1-homopiperidinecarboxamides (and thiocarboxamides) with sulfur linked substitution in the 2, 3 or 4-position
DE3508251A1 (de) *	1985-03-08	1986-09-11	Merck Patent Gmbh, 6100 Darmstadt	Dipeptide
CN86101850A (zh) *	1985-03-22	1987-02-04	森得克斯(美国)有限公司	N，n′-二烷基胍基二肽的制造方法与用途
ATE70048T1 (de) *	1986-09-10	1991-12-15	Syntex Inc	Selektive amidinierung von diaminen.
IT1206078B (it) *	1987-06-03	1989-04-14	Polifarma Spa	Procedimento per la produzione di acido 3-indolpiruvico e suoi derivati loro uso farmaceutico
US5187156A (en) *	1988-03-16	1993-02-16	Fujisawa Pharmaceutical Co., Ltd.	Peptide compounds, processes for preparation thereof and pharmaceutical composition comprising the same
US5156797A (en) *	1988-06-30	1992-10-20	Idemitsu Kosan Co., Ltd.	Nonwoven fabrics
IL90872A0 (en) *	1988-07-08	1990-02-09	Smithkline Beckman Corp	Retroviral protease binding peptides
DE3931051A1 (de) *	1988-09-22	1990-03-29	Hoechst Ag	Salze von herbizid-saeuren mit langkettigen stickstoffbasen
EP0378318A1 (fr) *	1989-01-11	1990-07-18	Merck & Co. Inc.	Procédé pour la préparation de FK-506 ainsi que produits intermédiaires tricarbonyliques
US5359138A (en) *	1989-04-15	1994-10-25	Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai	Poststatin and related compounds or salts thereof
US5162500A (en) *	1989-04-15	1992-11-10	Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai	Poststatin and related compounds or salts thereof
US5164525A (en) *	1989-06-30	1992-11-17	Merck & Co., Inc.	Synthetic process for fk-506 type macrolide intermediates
NZ234883A (en) *	1989-08-22	1995-01-27	Merck Frosst Canada Inc	Quinolin-2-ylmethoxy indole derivatives, preparation and pharmaceutical compositions thereof
GB8922026D0 (en) *	1989-09-29	1989-11-15	Pharma Mar Sa	Novel anti-viral and cytotoxic agent
US5115098A (en) *	1990-02-28	1992-05-19	President And Fellows Of Harvard College	End-blocked peptides inhibiting binding capacity of gp120
JPH04211648A (ja) *	1990-07-27	1992-08-03	Nippon Kayaku Co Ltd	ケト酸アミド誘導体
DE4015255A1 (de) *	1990-05-12	1991-11-14	Hoechst Ag	Oxalyl-aminosaeurederivate, verfahren zu ihrer herstellung und ihrer verwendung als arzneimittel zur inhibierung der prolyl-hydroxylase
US5192773A (en) *	1990-07-02	1993-03-09	Vertex Pharmaceuticals, Inc.	Immunosuppressive compounds
AU8740991A (en) *	1990-08-24	1992-03-17	Upjohn Company, The	Peptides containing amino-polyols as transition-state mimics
WO1992004370A1 (fr) *	1990-08-29	1992-03-19	Vertex Pharmaceuticals Incorporated	Composes immunosuppresseurs de di- et tripeptidyle modifies
GB2247456A (en) *	1990-09-03	1992-03-04	Fujisawa Pharmaceutical Co	Tetrahydropyrane compounds, a process for their production and a pharmaceutical composition containing the same
JPH04149166A (ja) *	1990-10-12	1992-05-22	Nippon Kayaku Co Ltd	新規ケト酸アミド誘導体
WO1992016501A1 (fr) *	1991-03-20	1992-10-01	Vertex Pharmaceuticals Incorporated	Derives de tetrahydroxyalcane utiles comme inhibiteurs de la protease d'aspartyle du vih
IT1245712B (it) *	1991-04-09	1994-10-14	Boehringer Mannheim Italia	Ammine eterocicliche utili terapia dell'asma e dell'infiammazione delle vie aeree
US5147877A (en) *	1991-04-18	1992-09-15	Merck & Co. Inc.	Semi-synthetic immunosuppressive macrolides
AU2007192A (en) *	1991-05-08	1992-12-21	Vertex Pharmaceuticals Incorporated	Rfkbp: a novel prolyl isomerase and rapamycin/fk506 binding protein
HU217621B (hu) *	1991-05-09	2000-03-28	Vertex Pharmaceuticals Inc.	Eljárás új glioxaloil-pipekolinsav-észterek, származékaik és az ezeket tartalmazó gyógyszerkészítmények előállítására
MX9202466A (es) *	1991-05-24	1994-06-30	Vertex Pharma	Compuestos inmunosupresores novedosos.
JPH05178824A (ja) *	1991-08-05	1993-07-20	Takeda Chem Ind Ltd	アスパラギン誘導体およびその用途
AU2803692A (en) *	1991-10-11	1993-05-03	Vertex Pharmaceuticals Incorporated	Isolation of an mr 52,000 fk506 binding protein and molecular cloning of a corresponding human cdna
IL103394A0 (en) *	1991-10-11	1993-03-15	Ciba Geigy	Pyrimidinyl and triazinyl ethers and thioethers,their preparation and their use as herbicides
WO1993013066A1 (fr) *	1991-12-20	1993-07-08	Syntex (U.S.A.) Inc.	Amides cycliques d'acides 3-amino-2-hydroxy-carboxyliques utilises comme inhibiteurs de la protease du vih
AU4388893A (en) *	1992-05-20	1993-12-13	Vertex Pharmaceuticals Incorporated	Method of detecting tissue-specific FK506 binding protein messenger RNAs and uses thereof
IT1254373B (it) *	1992-05-29	1995-09-14		Eteroprostanoidi, procedimento per la loro preparazione e loro impiegoterapeutico.
US5334719A (en) *	1992-06-17	1994-08-02	Merck Frosst Canada, Inc.	Bicyclic(azaaromatic)indoles as inhibitors of leukotriene bisynthesis
IS2334B (is) *	1992-09-08	2008-02-15	Vertex Pharmaceuticals Inc., (A Massachusetts Corporation)	Aspartyl próteasi hemjari af nýjum flokki súlfonamíða
NZ314207A (en) *	1992-09-28	2000-12-22	Vertex Pharma	1-(2-Oxoacetyl)-piperidine-2-carboxylic acid derivatives as multi drug resistant cancer cell sensitizers
WO1994013629A1 (fr) *	1992-12-11	1994-06-23	Vertex Pharmaceuticals Incorporated	Derives de mannitol et leur utilisation comme inhibiteurs de l'aspartyle-protease
DE4302860A1 (de) *	1993-01-22	1994-08-04	Chemie Linz Deutschland	N-Cyclische und N,N'dicyclische Harnstoffe
US5252579A (en) *	1993-02-16	1993-10-12	American Home Products Corporation	Macrocyclic immunomodulators
US5319098A (en) *	1993-05-18	1994-06-07	Celgene Corporation	Process for the stereoselective preparation of L-alanyl-L-proline
IT1270882B (it) *	1993-10-05	1997-05-13	Isagro Srl	Oligopeptidi ad attivita' fungicida
DE69417012T2 (de) *	1993-11-04	1999-10-07	Abbott Laboratories, Abbott Park	Cyclobutan-derivate als inhibitoren der squalen-synthetase und der protein-farnesyltransferase
ES2139195T3 (es) *	1994-03-07	2000-02-01	Vertex Pharma	Derivados de sulfonamidas como inhibidores de la aspartil-proteasa.
US5744485A (en) *	1994-03-25	1998-04-28	Vertex Pharmaceuticals Incorporated	Carbamates and ureas as modifiers of multi-drug resistance
US5856116A (en) *	1994-06-17	1999-01-05	Vertex Pharmaceuticals, Incorporated	Crystal structure and mutants of interleukin-1 beta converting enzyme
US5716929A (en) *	1994-06-17	1998-02-10	Vertex Pharmaceuticals, Inc.	Inhibitors of interleukin-1β converting enzyme
AU3367995A (en) *	1994-08-18	1996-03-14	Ariad Pharmaceuticals, Inc.	New multimerizing agents
IL115685A (en) *	1994-11-16	2000-08-31	Vertex Pharma	Amino acid derivatives pharmaceutical compositions containing the same and processes for the preparation thereof
US5543423A (en) *	1994-11-16	1996-08-06	Vertex Pharmaceuticals, Incorporated	Amino acid derivatives with improved multi-drug resistance activity
US5621108A (en) *	1994-12-05	1997-04-15	Trustees Of The University Of Pennsylvania	Processes and intermediates for preparing macrocycles
US5859031A (en) *	1995-06-07	1999-01-12	Gpi Nil Holdings, Inc.	Small molecule inhibitors of rotamase enzyme activity
US5696135A (en) *	1995-06-07	1997-12-09	Gpi Nil Holdings, Inc.	Inhibitors of rotamase enzyme activity effective at stimulating neuronal growth
US6037370A (en) *	1995-06-08	2000-03-14	Vertex Pharmaceuticals Incorporated	Methods and compositions for stimulating neurite growth

1996
- 1996-05-13 US US08/645,149 patent/US5801197A/en not_active Expired - Lifetime
- 1996-08-26 EP EP96929014A patent/EP0859614A4/fr not_active Withdrawn
- 1996-08-26 WO PCT/US1996/013624 patent/WO1997016190A1/fr not_active Ceased
- 1996-08-26 EA EA199800329A patent/EA001481B1/ru not_active IP Right Cessation
- 1996-08-26 CZ CZ981251A patent/CZ125198A3/cs unknown
- 1996-08-26 JP JP9517308A patent/JPH11514643A/ja active Pending
- 1996-08-26 SK SK559-98A patent/SK55998A3/sk unknown
- 1996-08-26 CA CA002236328A patent/CA2236328A1/fr not_active Abandoned
- 1996-08-26 NZ NZ316361A patent/NZ316361A/xx unknown
- 1996-08-26 KR KR1019980703218A patent/KR19990067257A/ko not_active Withdrawn
- 1996-08-26 BR BRPI9611271-9A patent/BRPI9611271A2/pt unknown
- 1996-08-26 HU HU9901752A patent/HUP9901752A3/hu unknown
- 1996-08-26 EE EE9800125A patent/EE9800125A/xx unknown
- 1996-08-26 PL PL96326420A patent/PL326420A1/xx unknown
1998
- 1998-04-27 NO NO981903A patent/NO981903L/no not_active Application Discontinuation
- 1998-04-28 BG BG102410A patent/BG62596B1/bg unknown
- 1998-06-25 LV LVP-98-85A patent/LV12102B/en unknown

Also Published As

Publication number	Publication date
US5801197A (en)	1998-09-01
EA199800329A1 (ru)	1998-12-24
NO981903D0 (no)	1998-04-27
LV12102B (en)	1998-10-20
BRPI9611271A2 (pt)	2019-04-30
EP0859614A1 (fr)	1998-08-26
WO1997016190A1 (fr)	1997-05-09
CZ125198A3 (cs)	1998-12-16
BG62596B1 (bg)	2000-03-31
BG102410A (en)	1998-12-30
EA001481B1 (ru)	2001-04-23
AU6857396A (en)	1997-05-22
NO981903L (no)	1998-06-30
PL326420A1 (en)	1998-09-14
LV12102A (lv)	1998-08-20
AU713302B2 (en)	1999-11-25
EE9800125A (et)	1998-10-15
HUP9901752A2 (hu)	1999-10-28
CA2236328A1 (fr)	1997-05-09
NZ316361A (en)	1999-08-30
HUP9901752A3 (en)	2001-04-28
KR19990067257A (ko)	1999-08-16
JPH11514643A (ja)	1999-12-14
EP0859614A4 (fr)	2000-04-26
MX9803356A (es)	1998-09-30

Publication	Publication Date	Title
US5801197A (en)	1998-09-01	Rotamase enzyme activity inhibitors
US6245783B1 (en)	2001-06-12	Method of using neurotrophic sulfonamide compounds
US6200972B1 (en)	2001-03-13	Heterocyclic esters and amides
EP0934263B1 (fr)	2005-11-23	Inhibiteurs non-immunosuppresseurs de la fkbp rotamase
CN1331853C (zh)	2007-08-15	旋转异构酶活性的小分子抑制剂
KR20000075502A (ko)	2000-12-15	헤테로고리형 에스테르, 아미드, 티오에스테르 및 케톤의 ｎ－옥사이드
CZ154599A3 (cs)	1999-11-17	N-vázané sulfonamidy heterocyklických thioesterů
CA2281096A1 (fr)	1998-09-03	Methode d'utilisation de carbamates et d'urees neurotrophiques
EP1404325A2 (fr)	2004-04-07	Procede de traitement d'accidents nerveux entraines par une operation
US6242468B1 (en)	2001-06-05	Carbamate and urea compositions and neurotrophic uses
US20020013344A1 (en)	2002-01-31	Rotamas enzyme activity inhibitors
AU713302C (en)	2000-06-22	Rotamase enzyme activity inhibitors
MXPA98003356A (en)	1998-11-16	Inhibitors of the activity of enzima rotam
MXPA99007384A (en)	2000-07-01	Method of using neutrophic sulfonamide compounds
MXPA99007938A (en)	2000-09-04	Method of using neurotrophic carbamates and ureas
HK1018006A (en)	1999-12-10	Rotamase enzyme activity inhibitors
CN1205635A (zh)	1999-01-20	旋转异构酶活性抑制剂