NAV

KW-7158

Identification

Generic Name
KW-7158
DrugBank Accession Number
DB05498
Background

KW-7158 is a tricyclic compound with a non-cholingergic mechanism of action for the treatment of "urinary urgency," "frequent urination" and "urinary incontinence" associated with bladder overactivity (involuntary abnormal contraction of the bladder). The therapeutic effects of KW-7158 in overactive bladder may be due to the activation of A-type K(+) channels which regulate afferent neuron excitability and firing properties in the dorsal root ganglion neurons.

Type
Small Molecule
Groups
Investigational
Structure
3D
Similar Structures
Weight
Average: 419.39
Monoisotopic: 419.010899327
Chemical Formula
C16H12F3NO5S2
Synonyms
Not Available
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Pharmacology

Indication

Investigated for use/treatment in urinary incontinence.

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Pharmacodynamics

KW-7158 is a tricyclic compound with a non-cholingergic mechanism of action for the treatment of "urinary urgency," "frequent urination" and "urinary incontinence" associated with bladder overactivity (involuntary abnormal contraction of the bladder). As the aging of population progresses, an increasing number of people are likely to suffer from urinary incontinence. Bladder overactivity, the indication for this compound, is estimated to affect around 2.4 million people in Japan and around 20 million in the US and Europe combined. We consider that the market for this therapeutic domain, which is characterised by the predominance of untreated patients, tends to grow. The current mainstay of treatment for bladder overactivity is anti-cholinergic agents, which, however, are associated with high incidences of adverse reactions such as thirst and urination disorder. The development of a new type of drugs, particularly those causing fewer side effects, is thus anticipated.

Mechanism of action

The therapeutic effects of KW-7158 in overactive bladder may be due to the activation of A-type K(+) channels which regulate afferent neuron excitability and firing properties in the dorsal root ganglion neurons. It is proposed that KW-7158 acts uniquely on the peripheral sensory nerves to control bladder activities by shortenining the action potential duration in DRG neurons.

Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism
Not Available
Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as benzothiepins. These are organic compounds containing a benzene fused to a thiepine ring (a seven-membered ring with six carbon atoms and one sulfur atom).
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzothiepins
Sub Class
Not Available
Direct Parent
Benzothiepins
Alternative Parents
N-arylamides / Aryl ketones / Benzenoids / Vinylogous amides / Thiophenes / Tertiary alcohols / Sulfones / Heteroaromatic compounds / Secondary carboxylic acid amides / Fluorohydrins
show 5 more
Substituents
Alcohol / Alkyl fluoride / Alkyl halide / Aromatic heteropolycyclic compound / Aryl ketone / Benzenoid / Benzothiepin / Carbonyl group / Carboxamide group / Carboxylic acid derivative
show 19 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
S2T07V1P1G
CAS number
Not Available
InChI Key
NAFSYPCVPLWHFY-HNNXBMFYSA-N
InChI
InChI=1S/C16H12F3NO5S2/c1-15(23,16(17,18)19)14(22)20-9-3-2-4-10-11(9)12(21)13-8(5-6-26-13)7-27(10,24)25/h2-6,23H,7H2,1H3,(H,20,22)/t15-/m0/s1
IUPAC Name
(2S)-3,3,3-trifluoro-2-hydroxy-2-methyl-N-{2,9,9-trioxo-4,9λ⁶-dithiatricyclo[8.4.0.0³,⁷]tetradeca-1(10),3(7),5,11,13-pentaen-14-yl}propanamide
SMILES
C[C@](O)(C(=O)NC1=CC=CC2=C1C(=O)C1=C(CS2(=O)=O)C=CS1)C(F)(F)F

References

General References
  1. Sculptoreanu A, Yoshimura N, de Groat WC: KW-7158 [(2S)-(+)-3,3,3-trifluoro-2-hydroxy-2-methyl-N-(5,5,10-trioxo-4,10-dihydrothieno[ 3,2-c][1]benzothiepin-9-yl)propanamide] enhances A-type K+ currents in neurons of the dorsal root ganglion of the adult rat. J Pharmacol Exp Ther. 2004 Jul;310(1):159-68. Epub 2004 Mar 9. [Article]
  2. Lu SH, Yamagata T, Atsuki K, Sun L, Smith CP, Yoshimura N, Chancellor MB, de Groat WC: Effect of KW-7158, a putative afferent nerve inhibitor, on bladder and vesico-vascular reflexes in rats. Brain Res. 2002 Aug 9;946(1):72-8. [Article]
PubChem Compound
9844981
PubChem Substance
310264857
ChemSpider
8020695
ChEMBL
CHEMBL289288
ZINC
ZINC000001546374

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0795 mg/mLALOGPS
logP2.66ALOGPS
logP2.76Chemaxon
logS-3.7ALOGPS
pKa (Strongest Acidic)9.45Chemaxon
pKa (Strongest Basic)-5.2Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area100.54 Å2Chemaxon
Rotatable Bond Count3Chemaxon
Refractivity92.47 m3·mol-1Chemaxon
Polarizability35.76 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-00ea-4891100000-008dc78eadecff68c2ee
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-0000900000-9a4467b53734fdb3d7d4
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0100900000-4b51424270e3eff26d7f
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-0000900000-cb984fa33e46bd6a50fa
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-03xr-0920600000-fade626e397ae0347a66
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-03di-1190000000-d7f734b44efb427ecc96
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0a4r-1392100000-d9ad78b435800f308006
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-183.77571
predicted
DeepCCS 1.0 (2019)
[M+H]+186.13373
predicted
DeepCCS 1.0 (2019)
[M+Na]+192.6471
predicted
DeepCCS 1.0 (2019)

Drug created at November 18, 2007 18:25 / Updated at June 12, 2020 16:52