ICI-63197

Last updated
ICI-63197
ICI-63197.svg
Names
IUPAC name
2-Amino-6-methyl-4-propyl[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.043.970 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 248-383-5
PubChem CID
UNII
  • InChI=1S/C9H13N5O/c1-3-4-13-7(15)6(2)5-14-9(13)11-8(10)12-14/h5H,3-4H2,1-2H3,(H2,10,12)
    Key: UQDVRVNMIJAGRK-UHFFFAOYSA-N
  • InChI=1/C9H13N5O/c1-3-4-13-7(15)6(2)5-14-9(13)11-8(10)12-14/h5H,3-4H2,1-2H3,(H2,10,12)
    Key: UQDVRVNMIJAGRK-UHFFFAOYAG
  • CCCN1C(=O)C(=CN2C1=NC(=N2)N)C
Properties
C9H13N5O
Molar mass 207.237 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

ICI-63197 is a phosphodiesterase inhibitor. [1]

Related Research Articles

Phosphodiesterase inhibitor

A phosphodiesterase inhibitor is a drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), thereby preventing the inactivation of the intracellular second messengers cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) by the respective PDE subtype(s). The ubiquitous presence of this enzyme means that non-specific inhibitors have a wide range of actions, the actions in the heart, and lungs being some of the first to find a therapeutic use.

Phosphodiesterase

A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, phosphodiesterase refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many other families of phosphodiesterases, including phospholipases C and D, autotaxin, sphingomyelin phosphodiesterase, DNases, RNases, and restriction endonucleases, as well as numerous less-well-characterized small-molecule phosphodiesterases.

PDE5 inhibitor

A phosphodiesterase type 5 inhibitor is a vasodilating drug which works by blocking the degradative action of cGMP-specific phosphodiesterase type 5 (PDE5) on cyclic GMP in the smooth muscle cells lining the blood vessels supplying various tissues. These drugs dilate the corpora cavernosa of the penis, facilitating erection with sexual stimulation, and are used in the treatment of erectile dysfunction (ED). Sildenafil was the first effective oral treatment available for ED. Because PDE5 is also present in the smooth muscle of the walls of the arterioles within the lungs, sildenafil and tadalafil are FDA-approved for the treatment of pulmonary hypertension. As of 2019, the wider cardiovascular benefits of PDE5 inhibitors are being appreciated.

cGMP-specific phosphodiesterase type 5

cGMP-specific phosphodiesterase type 5 is an enzyme from the phosphodiesterase class. It is found in various tissues, most prominently the corpus cavernosum and the retina. It has also been recently discovered to play a vital role in the cardiovascular system.

Enoximone

Enoximone is an imidazole phosphodiesterase inhibitor. It is used in the treatment of congestive heart failure and is selective for phosphodiesterase 3.

EHNA

EHNA is a potent adenosine deaminase inhibitor, which also acts as a phosphodiesterase inhibitor that selectively inhibits phosphodiesterase type 2 (PDE2).

PDE1 is a phosphodiesterase enzyme also known as calcium- and calmodulin-dependent phosphodiesterase. It is one of the 11 families of phosphodiesterase (PDE1-PDE11). PDE1 has three subtypes, PDE1A, PDE1B and PDE1C which divide further into various isoforms. The various isoforms exhibit different affinities for cAMP and cGMP.

Phosphodiesterase 2

The PDE2 enzyme is one of 21 different phosphodiesterases (PDE) found in mammals. These different PDEs can be subdivided to 11 families. The different PDEs of the same family are functionally related despite the fact that their amino acid sequences show considerable divergence. The PDEs have different substrate specificities. Some are cAMP selective hydrolases, others are cGMP selective hydrolases and the rest can hydrolyse both cAMP and cGMP.

IBMX

IBMX (3-isobutyl-1-methylxanthine), like other methylated xanthine derivatives, is both a:

  1. competitive non-selective phosphodiesterase inhibitor which raises intracellular cAMP, activates PKA, inhibits TNFα and leukotriene synthesis, and reduces inflammation and innate immunity, and
  2. nonselective adenosine receptor antagonist.
PDE3 inhibitor

A PDE3 inhibitor is a drug which inhibits the action of the phosphodiesterase enzyme PDE3. They are used for the therapy of acute heart failure and cardiogenic shock.

Etazolate

Etazolate (SQ-20,009, EHT-0202) is an anxiolytic drug which is a pyrazolopyridine derivative and has unique pharmacological properties. It acts as a positive allosteric modulator of the GABAA receptor at the barbiturate binding site, as an adenosine antagonist of the A1 and A2 subtypes, and as a phosphodiesterase inhibitor selective for the PDE4 isoform. It is currently in clinical trials for the treatment of Alzheimer's disease.

Phosphodiesterase-4 inhibitor

A phosphodiesterase type 4 inhibitor, commonly referred to as a PDE4 inhibitor, is a drug used to block the degradative action of phosphodiesterase 4 (PDE4) on cyclic adenosine monophosphate (cAMP). It is a member of the larger family of PDE inhibitors. The PDE4 family of enzymes are the most prevalent PDE in immune cells. They are predominantly responsible for hydrolyzing cAMP within both immune cells and cells in the central nervous system.

Cartazolate

Cartazolate (SQ-65,396) is a drug of the pyrazolopyridine class. It acts as a GABAA receptor positive allosteric modulator at the barbiturate binding site of the complex and has anxiolytic effects in animals. It is also known to act as an adenosine antagonist at the A1 and A2 subtypes and as a phosphodiesterase inhibitor. Cartazolate was tested in human clinical trials and was found to be efficacious for anxiety but was never marketed. It was developed by a team at E.R. Squibb and Sons in the 1970s.

Zaprinast

Zaprinast was an unsuccessful clinical drug candidate that was a precursor to the chemically related PDE5 inhibitors, such as sildenafil (Viagra), which successfully reached the market. It is a phosphodiesterase inhibitor, selective for the subtypes PDE5, PDE6, PDE9 and PDE11. IC50 values are 0.76, 0.15, 29.0, and 12.0 μM, respectively.

Phosphodiesterases (PDEs) are a superfamily of enzymes. This superfamily is further classified into 11 families, PDE1 - PDE11, on the basis of regulatory properties, amino acid sequences, substrate specificities, pharmacological properties and tissue distribution. Their function is to degrade intracellular second messengers such as cyclic adenine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) which leads to several biological processes like effect on intracellular calcium level by the Ca2+ pathway.

Arofylline

Arofylline is a phosphodiesterase inhibitor.

Atizoram

Atizoram (CP-80633) is a phosphodiesterase 4 inhibitor.

SCH-51866

SCH-51866 is a phosphodiesterase inhibitor.

MY-5445

MY-5445 is a relatively specific phosphodiesterase 5 inhibitor.

Adibendan

Adibendan is an inhibitor of phosphodiesterase III.

References

  1. ↑ Davies, G.E.; Evans, D.P. (1973). "Studies with Two New Phosphodiesterase Inhibitors (ICI 58,301 and ICI 63,197) on Anaphylaxis in Guinea Pigs, Mice and Rats". Int Arch Allergy. 45 (3): 467–478. doi:10.1159/000231064. PMID   4355277.
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