10-Propargyl-5,8-Dideazafolic Acid

Identification

Name
10-Propargyl-5,8-Dideazafolic Acid
Accession Number
DB03541  (EXPT00839)
Type
Small Molecule
Groups
Experimental
Description
Not Available
Structure
Thumb
Synonyms
Not Available
Categories
Not Available
UNII
Not Available
CAS number
Not Available
Weight
Average: 477.4693
Monoisotopic: 477.164833493
Chemical Formula
C24H23N5O6
InChI Key
LTKHPMDRMUCUEB-IBGZPJMESA-N
InChI
InChI=1S/C24H23N5O6/c1-2-11-29(13-14-3-8-18-17(12-14)22(33)28-24(25)27-18)16-6-4-15(5-7-16)21(32)26-19(23(34)35)9-10-20(30)31/h1,3-8,12,19H,9-11,13H2,(H,26,32)(H,30,31)(H,34,35)(H3,25,27,28,33)/t19-/m0/s1
IUPAC Name
(2S)-2-[(4-{[(2-amino-4-oxo-1,4-dihydroquinazolin-6-yl)methyl](prop-2-yn-1-yl)amino}phenyl)formamido]pentanedioic acid
SMILES
[H][[email protected]@](CCC(O)=O)(NC(=O)C1=CC=C(C=C1)N(CC#C)CC1=CC=C2NC(N)=NC(=O)C2=C1)C(O)=O

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UThymidylate synthaseNot AvailableLactobacillus casei
UThymidylate synthaseNot AvailableEscherichia coli (strain K12)
UThymidylate synthaseNot AvailablePneumocystis carinii
URibosyldihydronicotinamide dehydrogenase [quinone]Not AvailableHuman
UThymidylate synthaseNot AvailableHuman
UPutative dehydrogenase/reductase SDR family member 4-like 2Not AvailableHuman
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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
KEGG Compound
C11737
PubChem Compound
443388
PubChem Substance
46508002
ChemSpider
391617
BindingDB
18771
ChEBI
3258
ChEMBL
CHEMBL389051
HET
CB3
PDB Entries
1aiq / 1an5 / 1bq1 / 1ci7 / 1ddu / 1dna / 1fwm / 1kce / 1kzj / 1lca
show 23 more

Clinical Trials

Clinical Trials
Not Available

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 Solubility0.0204 mg/mLALOGPS
logP1.22ALOGPS
logP1.02ChemAxon
logS-4.4ALOGPS
pKa (Strongest Acidic)3.24ChemAxon
pKa (Strongest Basic)1.02ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area174.42 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity127.72 m3·mol-1ChemAxon
Polarizability48.8 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption-0.7435
Blood Brain Barrier-0.7739
Caco-2 permeable-0.8286
P-glycoprotein substrateSubstrate0.7069
P-glycoprotein inhibitor INon-inhibitor0.9258
P-glycoprotein inhibitor IINon-inhibitor0.988
Renal organic cation transporterNon-inhibitor0.8386
CYP450 2C9 substrateNon-substrate0.8102
CYP450 2D6 substrateNon-substrate0.7874
CYP450 3A4 substrateNon-substrate0.5543
CYP450 1A2 substrateNon-inhibitor0.8885
CYP450 2C9 inhibitorNon-inhibitor0.887
CYP450 2D6 inhibitorNon-inhibitor0.9281
CYP450 2C19 inhibitorNon-inhibitor0.8511
CYP450 3A4 inhibitorNon-inhibitor0.8964
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9602
Ames testNon AMES toxic0.7139
CarcinogenicityNon-carcinogens0.949
BiodegradationNot ready biodegradable0.9783
Rat acute toxicity2.5900 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9225
hERG inhibition (predictor II)Non-inhibitor0.6978
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as glutamic acid and derivatives. These are compounds containing glutamic acid or a derivative thereof resulting from reaction of glutamic acid at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Glutamic acid and derivatives
Alternative Parents
N-acyl-alpha amino acids / Hippuric acids / Quinazolinamines / Aminobenzamides / Aniline and substituted anilines / Benzoyl derivatives / Dialkylarylamines / Aminopyrimidines and derivatives / Pyrimidones / Aralkylamines
show 13 more
Substituents
Glutamic acid or derivatives / N-acyl-alpha-amino acid / Hippuric acid or derivatives / Hippuric acid / N-acyl-alpha amino acid or derivatives / Quinazolinamine / Diazanaphthalene / Aminobenzamide / Aminobenzoic acid or derivatives / Quinazoline
show 34 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
N-acyl-L-glutamic acid (CHEBI:3258)

Targets

Kind
Protein
Organism
Lactobacillus casei
Pharmacological action
Unknown
General Function
Thymidylate synthase activity
Specific Function
Provides the sole de novo source of dTMP for DNA biosynthesis.
Gene Name
thyA
Uniprot ID
P00469
Uniprot Name
Thymidylate synthase
Molecular Weight
36579.235 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Unknown
General Function
Thymidylate synthase activity
Specific Function
Provides the sole de novo source of dTMP for DNA biosynthesis. This protein also binds to its mRNA thus repressing its own translation.
Gene Name
thyA
Uniprot ID
P0A884
Uniprot Name
Thymidylate synthase
Molecular Weight
30479.475 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Pneumocystis carinii
Pharmacological action
Unknown
General Function
Thymidylate synthase activity
Specific Function
Not Available
Gene Name
THYA
Uniprot ID
P13100
Uniprot Name
Thymidylate synthase
Molecular Weight
34361.99 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Nadph dehydrogenase (quinone) activity
Specific Function
The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vi...
Gene Name
NQO2
Uniprot ID
P16083
Uniprot Name
Ribosyldihydronicotinamide dehydrogenase [quinone]
Molecular Weight
25918.4 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Details
5. Thymidylate synthase
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Thymidylate synthase activity
Specific Function
Contributes to the de novo mitochondrial thymidylate biosynthesis pathway.
Gene Name
TYMS
Uniprot ID
P04818
Uniprot Name
Thymidylate synthase
Molecular Weight
35715.65 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Oxidoreductase activity
Specific Function
Putative oxidoreductase.
Gene Name
DHRS4L1
Uniprot ID
P0CG22
Uniprot Name
Putative dehydrogenase/reductase SDR family member 4-like 1
Molecular Weight
30607.35 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Drug created on June 13, 2005 07:24 / Updated on December 01, 2017 15:15