Query Query
N
Results
Date
2 substances in Reaxys
2018-06-06 17h:14m:35s (UTC)
O
NH
N
1. Query N
Search as: As drawn ))
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Reaxys ID 19344173 View in Reaxys
1/2
N
Chemical Name: (4-benzylpiperazin-1-yl)-[2-(3-methylbutylamino) pyridin-3-yl]methanone Linear Structure Formula: C22H30N4O Molecular Formula: C22H30N4O Molecular Weight: 366.506 InChI Key: DYTOQURYRYYNOR-UHFFFAOYSA-N Note:
O
NH
N
N
Substance Label (2) Label References NSI-189
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys; Patent; Neuralstem, Inc.; JOHE, Karl K.; (6 pag.); US2018/71267; (2018); (A1) English, View in Reaxys
1E
Patent; NEURALSTEM, INC.; Venkatraman, Sripathy; Mahmood, Syed; Mobele, Bingidimi I.; Lapina, Olga; Vercoe, Kellie; Li, Ying; Salsbury, Jonathan; McLaws, Mark; (14 pag.); US9278933; (2016); (B2) English, View in Reaxys
Patent-Specific Data (2) Prophetic ComLocation in Patent pound prophetic product
Paragraph 0050
References Patent; Neuralstem, Inc.; JOHE, Karl K.; (6 pag.); US2018/71267; (2018); (A1) English, View in Reaxys Patent; NEURALSTEM, INC.; Venkatraman, Sripathy; Mahmood, Syed; Mobele, Bingidimi I.; Lapina, Olga; Vercoe, Kellie; Li, Ying; Salsbury, Jonathan; McLaws, Mark; (14 pag.); US9278933; (2016); (B2) English, View in Reaxys
Crystal Property Description (1) Colour & Other Location Properties brown
Use (12) Use Pattern
Page/Page column 13
References Patent; NEURALSTEM, INC.; Venkatraman, Sripathy; Mahmood, Syed; Mobele, Bingidimi I.; Lapina, Olga; Vercoe, Kellie; Li, Ying; Salsbury, Jonathan; McLaws, Mark; (14 pag.); US9278933; (2016); (B2) English, View in Reaxys
References
Neurodegenerative disorders
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys
Neuropsychiatric disorders
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys
Stroke
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys
Alzheimer's disease Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys Parkinson's disease
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys
Depression
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys
Mild cognitive impairment (MCI)
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys
Traumatic brain injury
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys
Neurogenic agent
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys
Aging
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys
Promotion of cognitive enhancement to counteract loss of neurons due to
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys
Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.
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disease, injury or age Promotion of cognitive enhancement beneficial for military purposes
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys
Medchem (12) 1 of 12
Substance Effect
Neurogenic
Bioassay Category
In Vivo (Animal models)
Bioassay Name
In vivo Measurement
Bioassay Details
Effect : neurogenicSpecies : C57B16In Vivo Neurogenic Effects of NSI CompoundsIn one embodiment, fifteen of the compounds from Table I above are administered orally to mice at 10 mg/kg for ten days and co-administered bromodeoxyuridine (BrdU) by intraperitoneal injection for the first six days. One class of compounds caused a significant
Biological Species/NCBI ID
mouse
Substance RN
19344173View in Reaxys
Substance Name
NSI-189
Substance Route of Adm.
oral administration
Qualitative Results
title compound was effective in promoting neurogenesis in the dentate gyrus
Measurement Parameter
qualitative
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys 2 of 12
Substance Effect
Antineurodegenerative
Bioassay Category
In Vitro (Efficacy)
Bioassay Name
In Vitro (others)
Bioassay Details
Effect : neurodegeneration; inhibition ofBioassay : hippocampal stem cell-derived neuronsMethod for Measuring Caspase-3 Activity as a Measure of ApoptosisAnother assay used to determine the ability of a compound to provide neuroprotection is an apoptosis assay. Apoptosis is measured using the activity of an early marker of the programmed cell death pathway, caspase-3. Following 24 hours
Biological Species/NCBI ID
human
Substance RN
19344173View in Reaxys
Substance Name
NSI-189
Qualitative Results
neuron nuclear fragmentation was inhibited by 121 %; intracellular level of activated caspase -3/-7 was inhibited by 182%
Measurement Parameter
qualitative
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys 3 of 12
Substance Effect
Neurogenic
Bioassay Category
In Vitro (Efficacy)
Bioassay Name
In Vitro (others)
Bioassay Details
Effect : neurogenicBioassay : undifferentiated hippocampal stem cellsDetection of NeurogenesisThe final neuron number is detected by immunostaining of the culture with antibodies against neurons and is quantified by counting of the immunopositive neurons and/or by measuring the staining intensity. Therefore, after seven days of compound treatment, the cells are stained
Biological Species/NCBI ID
human
Substance RN
19344173View in Reaxys
Substance Name
NSI-189
Substance Route of Adm.
oral administration
Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.
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Qualitative Results
relative neuron number was 102% relative to control; relative neuron ratio was 130% relative to control
Measurement Parameter
qualitative
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys 4 of 12
Substance Effect
Neurogenic
Bioassay Category
In Vitro (Efficacy)
Bioassay Name
In Vitro (others)
Bioassay Details
Effect : neurogenicBioassay : differentiating hippocampal stem cellsDose-Response ProfilesIn another in vitro assay, compounds are tested as above at varying concentrations to obtain a dose-response curve and EC50 values (effective concentration of the compound which produces 50% of the maximum possible response for that compound). Compounds with EC50 values below 10
Biological Species/NCBI ID
human
Substance RN
19344173View in Reaxys
Substance Name
NSI-189
Substance Route of Adm.
oral administration
Measurement Parameter
EC50
Unit
nM
Quantitative value
411
Measurement pX
6.39
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys 5 of 12
Substance Effect
Proliferative
Bioassay Category
In Vitro (Efficacy)
Bioassay Name
In Vitro (others)
Bioassay Details
Effect : proliferativeBioassay : differentiating hippocampal stem cellsFurther Studies of NSI-Compound Effects on the Stages of In Vitro NeurogenesisIn another in vitro assay, compounds of the fused imidazole, aminopyrimidine, nicotinamide, aminomethyl phenoxypiperidine and aryloxypiperidine types are evaluated for their effect on the differentiation of the culture-born
Biological Species/NCBI ID
human
Substance RN
19344173View in Reaxys
Substance Name
NSI-189
Substance Route of Adm.
oral administration
Qualitative Results
title compound induced proliferation and differentiation into neurons at ~120% of control; figure given
Measurement Parameter
qualitative
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys 6 of 12
Substance Effect
Proliferative
Bioassay Category
In Vitro (Efficacy)
Bioassay Name
In Vitro (others)
Bioassay Details
Effect : proliferativeBioassay : undifferentiated hippocampal stem cellsDetection of Cell ProliferationNeural stem cells and progenitor cells differentiate spontaneously in the absence of a mitogen; therefore, undifferentiated mitotic cells are harvested by enzyme treatment to remove residual mitogen, such as basic fibroblast growth factor (bFGF) used in expansion and proliferation
Biological Species/NCBI ID
human
Substance RN
19344173View in Reaxys
Substance Name
NSI-189
Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.
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Substance Route of Adm.
oral administration
Qualitative Results
title compound caused 70% proliferation relative to control
Measurement Parameter
qualitative
Patent; Neuralstem, Inc.; US7560553; (2009); (B1) English, View in Reaxys 7 of 12
Substance Effect
Neurogenic
Bioassay Category
In Vivo (Animal models)
Bioassay Name
In vivo Measurement
Bioassay Details
Effect : neurogenicSpecies : C57B16In Vivo Neurogenic Effects of NSI CompoundsIn one embodiment, fifteen of the compounds from Table I above are administered orally to mice at 10 mg/kg for ten days and co-administered bromodeoxyuridine (BrdU) by intraperitoneal injection for the first six days. One class of compounds caused a significant
Biological Species/NCBI ID
mouse
Substance RN
19344173View in Reaxys
Substance Name
NSI-189
Substance Route of Adm.
oral administration
Qualitative Results
title compound was effective in promoting neurogenesis in the dentate gyrus
Measurement Parameter
qualitative
Patent; Kelleher-Andersson; Johe; (36 pag.); US7560553; (B1); (2009), View in Reaxys 8 of 12
Substance Effect
Antineurodegenerative
Bioassay Category
In Vitro (Efficacy)
Bioassay Name
In Vitro (others)
Bioassay Details
Effect : neurodegeneration; inhibition ofBioassay : hippocampal stem cell-derived neuronsMethod for Measuring Caspase-3 Activity as a Measure of ApoptosisAnother assay used to determine the ability of a compound to provide neuroprotection is an apoptosis assay. Apoptosis is measured using the activity of an early marker of the programmed cell death pathway, caspase-3. Following 24 hours
Biological Species/NCBI ID
human
Substance RN
19344173View in Reaxys
Substance Name
NSI-189
Qualitative Results
neuron nuclear fragmentation was inhibited by 121 %; intracellular level of activated caspase -3/-7 was inhibited by 182%
Measurement Parameter
qualitative
Patent; Kelleher-Andersson; Johe; (36 pag.); US7560553; (B1); (2009), View in Reaxys 9 of 12
Substance Effect
Neurogenic
Bioassay Category
In Vitro (Efficacy)
Bioassay Name
In Vitro (others)
Bioassay Details
Effect : neurogenicBioassay : undifferentiated hippocampal stem cellsDetection of NeurogenesisThe final neuron number is detected by immunostaining of the culture with antibodies against neurons and is quantified by counting of the immunopositive neurons and/or by measuring the staining intensity. Therefore, after seven days of compound treatment, the cells are stained
Biological Species/NCBI ID
human
Substance RN
19344173View in Reaxys
Substance Name
NSI-189
Substance Route of Adm.
oral administration
Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.
5/7
2018-06-06 17:16:54
Qualitative Results
relative neuron number was 102% relative to control; relative neuron ratio was 130% relative to control
Measurement Parameter
qualitative
Patent; Kelleher-Andersson; Johe; (36 pag.); US7560553; (B1); (2009), View in Reaxys 10 of 12
Substance Effect
Neurogenic
Bioassay Category
In Vitro (Efficacy)
Bioassay Name
In Vitro (others)
Bioassay Details
Effect : neurogenicBioassay : differentiating hippocampal stem cellsDose-Response ProfilesIn another in vitro assay, compounds are tested as above at varying concentrations to obtain a dose-response curve and EC50 values (effective concentration of the compound which produces 50% of the maximum possible response for that compound). Compounds with EC50 values below 10
Biological Species/NCBI ID
human
Substance RN
19344173View in Reaxys
Substance Name
NSI-189
Substance Route of Adm.
oral administration
Measurement Parameter
EC50
Unit
nM
Quantitative value
411
Measurement pX
6.39
Patent; Kelleher-Andersson; Johe; (36 pag.); US7560553; (B1); (2009), View in Reaxys 11 of 12
Substance Effect
Proliferative
Bioassay Category
In Vitro (Efficacy)
Bioassay Name
In Vitro (others)
Bioassay Details
Effect : proliferativeBioassay : differentiating hippocampal stem cellsFurther Studies of NSI-Compound Effects on the Stages of In Vitro NeurogenesisIn another in vitro assay, compounds of the fused imidazole, aminopyrimidine, nicotinamide, aminomethyl phenoxypiperidine and aryloxypiperidine types are evaluated for their effect on the differentiation of the culture-born
Biological Species/NCBI ID
human
Substance RN
19344173View in Reaxys
Substance Name
NSI-189
Substance Route of Adm.
oral administration
Qualitative Results
title compound induced proliferation and differentiation into neurons at ~120% of control; figure given
Measurement Parameter
qualitative
Patent; Kelleher-Andersson; Johe; (36 pag.); US7560553; (B1); (2009), View in Reaxys 12 of 12
Substance Effect
Proliferative
Bioassay Category
In Vitro (Efficacy)
Bioassay Name
In Vitro (others)
Bioassay Details
Effect : proliferativeBioassay : undifferentiated hippocampal stem cellsDetection of Cell ProliferationNeural stem cells and progenitor cells differentiate spontaneously in the absence of a mitogen; therefore, undifferentiated mitotic cells are harvested by enzyme treatment to remove residual mitogen, such as basic fibroblast growth factor (bFGF) used in expansion and proliferation
Biological Species/NCBI ID
human
Substance RN
19344173View in Reaxys
Substance Name
NSI-189
Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.
6/7
2018-06-06 17:16:54
Substance Route of Adm.
oral administration
Qualitative Results
title compound caused 70% proliferation relative to control
Measurement Parameter
qualitative
Patent; Kelleher-Andersson; Johe; (36 pag.); US7560553; (B1); (2009), View in Reaxys
Reaxys ID 29313942 View in Reaxys
2/2 Linear Structure Formula: xH3O4P*C22H30N4O Molecular Formula: C22H30N4O*(x)H3O4P InChI Key: LWHMGALTTIYPJU-UHFFFAOYSA-N Note:
N
HN O O
N -1
P HO
N
OH HO
Substance Label (1) Label References 1E*H3PO4
Patent; NEURALSTEM, INC.; Venkatraman, Sripathy; Mahmood, Syed; Mobele, Bingidimi I.; Lapina, Olga; Vercoe, Kellie; Li, Ying; Salsbury, Jonathan; McLaws, Mark; (14 pag.); US9278933; (2016); (B2) English, View in Reaxys
Patent-Specific Data (1) References Patent; NEURALSTEM, INC.; Venkatraman, Sripathy; Mahmood, Syed; Mobele, Bingidimi I.; Lapina, Olga; Vercoe, Kellie; Li, Ying; Salsbury, Jonathan; McLaws, Mark; (14 pag.); US9278933; (2016); (B2) English, View in Reaxys Druglikeness (1) 1 of 1
H Bond Donors
4
H Bond Acceptors
9
Rotatable Bonds
8
TPSA
136.04
Lipinski Number
3
Veber Number
2
Crystal Property Description (1) Colour & Other Location Properties white
Page/Page column 15
References Patent; NEURALSTEM, INC.; Venkatraman, Sripathy; Mahmood, Syed; Mobele, Bingidimi I.; Lapina, Olga; Vercoe, Kellie; Li, Ying; Salsbury, Jonathan; McLaws, Mark; (14 pag.); US9278933; (2016); (B2) English, View in Reaxys
Copyright © 2018 Reed Elsevier Properties SA. All rights reserved. Authorized use only. Reaxys® and the Reaxys® trademark are owned and protected by Reed Elsevier Properties SA and used under license.
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