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
- Weight
- Average: 419.39
Monoisotopic: 419.010899327 - Chemical Formula
- C16H12F3NO5S2
- Synonyms
- Not Available
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
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- 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
- 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]
- 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]
- External Links
- PubChem Compound
- 9844981
- PubChem Substance
- 310264857
- ChemSpider
- 8020695
- ChEMBL
- CHEMBL289288
- ZINC
- ZINC000001546374
Clinical Trials
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
Property Value Source Water Solubility 0.0795 mg/mL ALOGPS logP 2.66 ALOGPS logP 2.76 Chemaxon logS -3.7 ALOGPS pKa (Strongest Acidic) 9.45 Chemaxon pKa (Strongest Basic) -5.2 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 100.54 Å2 Chemaxon Rotatable Bond Count 3 Chemaxon Refractivity 92.47 m3·mol-1 Chemaxon Polarizability 35.76 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS splash10-00ea-4891100000-008dc78eadecff68c2ee Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-0000900000-9a4467b53734fdb3d7d4 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-0100900000-4b51424270e3eff26d7f Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-0000900000-cb984fa33e46bd6a50fa Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-03xr-0920600000-fade626e397ae0347a66 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-03di-1190000000-d7f734b44efb427ecc96 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0a4r-1392100000-d9ad78b435800f308006 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 183.77571 predictedDeepCCS 1.0 (2019) [M+H]+ 186.13373 predictedDeepCCS 1.0 (2019) [M+Na]+ 192.6471 predictedDeepCCS 1.0 (2019)
Drug created at November 18, 2007 18:25 / Updated at June 12, 2020 16:52