l-791943 profile

L-791943: an phosphodiesterase iv inhibitor; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

ID Source	ID
PubMed CID	9808191
CHEMBL ID	286224
SCHEMBL ID	12013401
MeSH ID	M0441688

Synonym
l-791943
CHEMBL286224 ,
4-{2-(3,4-bis-difluoromethoxy-phenyl)-2-[4-(2,2,2-trifluoro-1-hydroxy-1-trifluoromethyl-ethyl)-phenyl]-ethyl}-pyridin-1-ol anion
bdbm50113425
2-{4-[1-(3,4-bis-difluoromethoxy-phenyl)-2-(1-oxy-pyridin-4-yl)-ethyl]-phenyl}-1,1,1,3,3,3-hexafluoro-propan-2-ol
SCHEMBL12013401
l791943
viowrsxfepszfi-uhfffaoysa-n
2-[4-[1-[3,4-bis(difluoromethoxy)phenyl]-2-(1-oxidopyridin-1-ium-4-yl)ethyl]phenyl]-1,1,1,3,3,3-hexafluoropropan-2-ol

Excerpt	Reference	Relevance
"A detailed SAR study directed toward the optimization of pharmacokinetic parameters for analogues of L-791,943 is reported."	( Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters. Blouin, M; Brideau, C; Chauret, N; Ducharme, Y; Frenette, R; Friesen, RW; Girard, Y; Hamel, P; Jones, TR; Laliberté, F; Li, C; Masson, P; McAuliffe, M, 2002)	0.31

Excerpt	Reference	Relevance
" The introduction of a soft metabolic site on this structure permitted the identification of L-826,141 as a potent phosphodiesterase type 4 (PDE4) inhibitor that is well absorbed and that presents a shorter half-life than L-791,943 in a variety of animal species."	( Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters. Blouin, M; Brideau, C; Chauret, N; Ducharme, Y; Frenette, R; Friesen, RW; Girard, Y; Hamel, P; Jones, TR; Laliberté, F; Li, C; Masson, P; McAuliffe, M, 2002)	0.31

Protein	Taxonomy	Measurement	Average	Min (ref.)	Avg (ref.)	Max (ref.)	Bioassay(s)
cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)	IC50 (µMol)	0.0042	0.0000	1.0680	10.0000	AID157776; AID157777; AID157778
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Process	via Protein(s)	Taxonomy
cAMP catabolic process	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
signal transduction	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
G protein-coupled receptor signaling pathway	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
sensory perception of smell	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
regulation of protein kinase A signaling	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
cellular response to xenobiotic stimulus	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
cAMP-mediated signaling	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
3',5'-cyclic-AMP phosphodiesterase activity	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
protein binding	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
cAMP binding	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
metal ion binding	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
3',5'-cyclic-GMP phosphodiesterase activity	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Process	via Protein(s)	Taxonomy
nucleoplasm	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
cytosol	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
plasma membrane	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
membrane	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
ruffle membrane	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
perinuclear region of cytoplasm	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
perinuclear region of cytoplasm	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
cytosol	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
nucleus	cAMP-specific 3',5'-cyclic phosphodiesterase 4A	Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (41)

Assay ID	Title	Year	Journal	Article
AID12697	Half-life in rat	2002	Bioorganic & medicinal chemistry letters, Oct-21, Volume: 12, Issue:20	Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters.
AID77555	Inhibition of the ovalbumin-induced bronchoconstriction in conscious guinea pigs after 0.5 hr pretreatment with 1 mg/kg administered intraperitoneally	2002	Bioorganic & medicinal chemistry letters, Oct-21, Volume: 12, Issue:20	Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters.
AID7751	Half life of compound was determined in squirrel monkey	2002	Bioorganic & medicinal chemistry letters, Jun-03, Volume: 12, Issue:11	Discovery of L-791,943: a potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor.
AID174377	In vitro metabolism of radiolabeled compound at 10 uM was performed in rat microsomal protein containing a NADPH-regenerating system for 1 hr at 37 degree C	2002	Bioorganic & medicinal chemistry letters, Aug-19, Volume: 12, Issue:16	Improving metabolic stability of phosphodiesterase-4 inhibitors containing a substituted catechol: prevention of reactive intermediate formation and covalent binding.
AID12308	Half life of compound was determined in rat	2002	Bioorganic & medicinal chemistry letters, Jun-03, Volume: 12, Issue:11	Discovery of L-791,943: a potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor.
AID363114	Half life in squirrel monkey	2008	Journal of medicinal chemistry, Sep-25, Volume: 51, Issue:18	Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease.
AID204426	Ascaris-induced early phase bronchoconstriction in conscious sheep administered intravenously at 2 mg/kg	2002	Bioorganic & medicinal chemistry letters, Jun-03, Volume: 12, Issue:11	Discovery of L-791,943: a potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor.
AID363115	Half life in dog	2008	Journal of medicinal chemistry, Sep-25, Volume: 51, Issue:18	Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease.
AID363108	Inhibition of ascaris-induced bronchoconstriction in sheep at 2 mg/kg, iv	2008	Journal of medicinal chemistry, Sep-25, Volume: 51, Issue:18	Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease.
AID7384	Emesis in ferrets at 30 mg/kg oral dose	2003	Bioorganic & medicinal chemistry letters, Feb-24, Volume: 13, Issue:4	Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors.
AID205154	Ascaris-induced bronchoconstriction in anesthetized squirrel monkey pretreated with 3 mg/kg peroral dose for 4 hr	2002	Bioorganic & medicinal chemistry letters, Jun-03, Volume: 12, Issue:11	Discovery of L-791,943: a potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor.
AID92877	Inhibition of LPS-induced TNF-alpha formation in human whole blood.	2002	Bioorganic & medicinal chemistry letters, Oct-21, Volume: 12, Issue:20	Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters.
AID204432	In vivo inhibition of ovalbumin-induced bronchoconstriction in sheep late phase at 2.0 mg/kg ip dose 2 hr prior to challenge	2003	Bioorganic & medicinal chemistry letters, Feb-24, Volume: 13, Issue:4	Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors.
AID92859	Inhibition of LPS-induced TNF-alpha production in human whole blood.	2003	Bioorganic & medicinal chemistry letters, Feb-24, Volume: 13, Issue:4	Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors.
AID363113	Half life in rat	2008	Journal of medicinal chemistry, Sep-25, Volume: 51, Issue:18	Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease.
AID77554	Ovalbumin induced bronchoconstriction in conscious guinea pig pretreated with 1 mg/kg intraperitoneal dose for 4 hr	2002	Bioorganic & medicinal chemistry letters, Jun-03, Volume: 12, Issue:11	Discovery of L-791,943: a potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor.
AID363110	Inhibition of ascaris-induced late bronchoconstriction in sheep at 0.5 mg/kg, iv	2008	Journal of medicinal chemistry, Sep-25, Volume: 51, Issue:18	Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease.
AID363107	Inhibition of ovalbumin-induced bronchoconstriction in guinea pig at 0.1 mg/kg, ip	2008	Journal of medicinal chemistry, Sep-25, Volume: 51, Issue:18	Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease.
AID204431	In vivo inhibition of ovalbumin-induced bronchoconstriction in sheep early phase at 2.0 mg/kg ip dose 4 hr prior to challenge	2003	Bioorganic & medicinal chemistry letters, Feb-24, Volume: 13, Issue:4	Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors.
AID204429	Inhibition of ascaris-induced bronchoconstriction in sheep after late treatment with 2 mg/kg intravenous dose	2002	Bioorganic & medicinal chemistry letters, Oct-21, Volume: 12, Issue:20	Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters.
AID363111	Inhibition of ascaris-induced bronchoconstriction in squirrel monkey at 3 mg/kg, po	2008	Journal of medicinal chemistry, Sep-25, Volume: 51, Issue:18	Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease.
AID71920	Cmax in ferrets after 30mg/kg oral dose	2002	Bioorganic & medicinal chemistry letters, Oct-21, Volume: 12, Issue:20	Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters.
AID77556	Inhibition of the ovalbumin-induced bronchoconstriction in conscious guinea pigs after 4 hr pretreatment with 1 mg/kg administered intraperitoneally	2002	Bioorganic & medicinal chemistry letters, Oct-21, Volume: 12, Issue:20	Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters.
AID71921	Emetic effect in ferrets	2002	Bioorganic & medicinal chemistry letters, Jun-03, Volume: 12, Issue:11	Discovery of L-791,943: a potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor.
AID7383	Cmax in ferrets after 30 mg/kg oral dose	2003	Bioorganic & medicinal chemistry letters, Feb-24, Volume: 13, Issue:4	Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors.
AID363106	Inhibition of ovalbumin-induced bronchoconstriction in guinea pig at 1 mg/kg, ip	2008	Journal of medicinal chemistry, Sep-25, Volume: 51, Issue:18	Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease.
AID157776	Inhibitory activity against human PDE4A expressed isoform using construct representing the common region of spliced variants as GST-fusion protein in Sf9 cells.	2003	Bioorganic & medicinal chemistry letters, Feb-24, Volume: 13, Issue:4	Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors.
AID10296	Half-life in Dog	2002	Bioorganic & medicinal chemistry letters, Oct-21, Volume: 12, Issue:20	Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters.
AID157778	Inhibition of human Phosphodiesterase 4A isoform using construct representing the common region of spliced variants expressed as GST-fusion proteins in Sf9 cells.	2002	Bioorganic & medicinal chemistry letters, Oct-21, Volume: 12, Issue:20	Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters.
AID12657	Half life period after intravenous administration at 5 mg/kg in rat	2003	Bioorganic & medicinal chemistry letters, Feb-24, Volume: 13, Issue:4	Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors.
AID77558	In vivo inhibition of ovalbumin-induced bronchoconstriction in conscious guinea pig at 1 mg/kg ip dose 4 hr prior 4 hr to challenge	2003	Bioorganic & medicinal chemistry letters, Feb-24, Volume: 13, Issue:4	Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors.
AID363109	Inhibition of ascaris-induced early bronchoconstriction in sheep at 0.5 mg/kg, iv	2008	Journal of medicinal chemistry, Sep-25, Volume: 51, Issue:18	Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease.
AID92871	Inhibitory concentration of compound against LPS- induced TNF-alpha production in whole human blood assay	2002	Bioorganic & medicinal chemistry letters, Jun-03, Volume: 12, Issue:11	Discovery of L-791,943: a potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor.
AID7764	Half-life in Squirrel monkey	2002	Bioorganic & medicinal chemistry letters, Oct-21, Volume: 12, Issue:20	Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters.
AID205153	Inhibition of ascaris-induced bronchoconstriction in Anaesthetized squirrel monkey after treatment with 3 mg/kg peroral dose	2002	Bioorganic & medicinal chemistry letters, Oct-21, Volume: 12, Issue:20	Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters.
AID157777	Inhibitory concentration against human PDE4A isoform using a construct representing the common region of spliced variants expressed as GST-fusion protein in Sf9 cells	2002	Bioorganic & medicinal chemistry letters, Jun-03, Volume: 12, Issue:11	Discovery of L-791,943: a potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor.
AID71919	Emetic effect in ferrets to maximum 30 mg/kg oral dose	2002	Bioorganic & medicinal chemistry letters, Oct-21, Volume: 12, Issue:20	Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters.
AID204427	Ascaris-induced late phase bronchoconstriction in conscious sheep administered intravenously at 2 mg/kg	2002	Bioorganic & medicinal chemistry letters, Jun-03, Volume: 12, Issue:11	Discovery of L-791,943: a potent, selective, non emetic and orally active phosphodiesterase-4 inhibitor.
AID13640	Oral bioavailability (dose 20 mg/kg p.o.)	2003	Bioorganic & medicinal chemistry letters, Feb-24, Volume: 13, Issue:4	Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors.
AID204428	Inhibition of ascaris-induced bronchoconstriction in sheep after early treatment with 2 mg/kg intravenous dose	2002	Bioorganic & medicinal chemistry letters, Oct-21, Volume: 12, Issue:20	Substituted 4-(2,2-diphenylethyl)pyridine-N-oxides as phosphodiesterase-4 inhibitors: SAR study directed toward the improvement of pharmacokinetic parameters.
AID11421	Cmax in rats after 20 mg/kg oral dose	2003	Bioorganic & medicinal chemistry letters, Feb-24, Volume: 13, Issue:4	Substituted aminopyridines as potent and selective phosphodiesterase-4 inhibitors.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Timeframe	Studies, This Drug (%)	All Drugs %
pre-1990	0 (0.00)	18.7374
1990's	0 (0.00)	18.2507
2000's	5 (100.00)	29.6817
2010's	0 (0.00)	24.3611
2020's	0 (0.00)	2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Publication Type	This drug (%)	All Drugs (%)
Trials	0 (0.00%)	5.53%
Reviews	1 (20.00%)	6.00%
Case Studies	0 (0.00%)	4.05%
Observational	0 (0.00%)	0.25%
Other	4 (80.00%)	84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Substance	Relationship Strength	Studies	Classes	Roles
theophylline [no description available]	3.14	1	dimethylxanthine	adenosine receptor antagonist; anti-asthmatic drug; anti-inflammatory agent; bronchodilator agent; drug metabolite; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; fungal metabolite; human blood serum metabolite; immunomodulator; muscle relaxant; vasodilator agent
ibudilast [no description available]	3.14	1	pyrazolopyridine
rolipram [no description available]	3.14	1	pyrrolidin-2-ones	antidepressant; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor
thalidomide Thalidomide: A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.. thalidomide : A racemate comprising equimolar amounts of R- and S-thalidomide.. 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione : A dicarboximide that is isoindole-1,3(2H)-dione in which the hydrogen attached to the nitrogen is substituted by a 2,6-dioxopiperidin-3-yl group.	3.14	1	phthalimides; piperidones
zardaverine zardaverine: structure given in first source. zardaverine : A pyridazinone derivative in which pyridazin-3(2H)-one is substituted at C-6 with a 4-(difluoromethoxy)-3-methoxyphenyl group. It is a phosphodiesterase inhibitor, selective for PDE3 and 4.	3.14	1	organofluorine compound; pyridazinone	anti-asthmatic drug; bronchodilator agent; EC 3.1.4.* (phosphoric diester hydrolase) inhibitor; peripheral nervous system drug
cdp 840 [no description available]	3.81	3
cilomilast [no description available]	3.81	3	methoxybenzenes
ovalbumin Ovalbumin: An albumin obtained from the white of eggs. It is a member of the serpin superfamily.	2.01	1
sch 351591 SCH 351591: a phosphodiesterase 4 inhibitor; structure in first source. SCH-351591 : An aromatic amide resulting from the formal condensation of the carboxy group of 8-methoxy-2-(trifluoromethyl)quinoline-5-carboxylic acid with the primary amino group of 3,5-dichloropyridin-4-amine 1-oxide. It is a potent inhibitor of phosphodiesterase IV (PDE4).	3.14	1
rs 14203 RS 14203: a type IV cyclic nucleotide phosphodiesterase inhibitor; structure in first source	3.14	1
ci 1044 CI 1044: inhibits PDE4; structure in first source	3.14	1
l-454,560 L-454,560: Phosphodiesterase Inhibitor; structure in first source	3.14	1
l-826,141 L-826,141: structure in first source	3.81	3

Condition	Relationship Strength	Studies
Emesis [description not available]	2.01	1
Vomiting The forcible expulsion of the contents of the STOMACH through the MOUTH.	2.01	1
Airflow Obstruction, Chronic [description not available]	2.96	1
Asthma, Bronchial [description not available]	2.96	1
Asthma A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).	2.96	1
Pulmonary Disease, Chronic Obstructive A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.	2.96	1

l-791943

Description

Cross-References

Synonyms (9)

Research Excerpts

Pharmacokinetics

Bioavailability

Protein Targets (1)

Inhibition Measurements

Biological Processes (8)

Molecular Functions (5)

Ceullar Components (7)

Bioassays (41)

Research

Studies (5)

Market Indicators

Research Demand Index: 12.56

Study Types

l-791943

Description

Cross-References

Synonyms (9)

Research Excerpts

Pharmacokinetics

Bioavailability

Protein Targets (1)

Inhibition Measurements

Biological Processes (8)

Molecular Functions (5)

Ceullar Components (7)

Bioassays (41)

Research

Studies (5)

Market Indicators

Research Demand Index: 12.56

Study Types

Related Drugs (13)

Related Conditions (6)