N-({5-[(2-Amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)propyl]thiophen-2-yl}carbonyl)-L-glutamic Acid

ID: ALA1834488

Chembl Id: CHEMBL1834488

PubChem CID: 135567029

Max Phase: Preclinical

Molecular Formula: C19H21N5O6S

Molecular Weight: 447.47

Molecule Type: Small molecule

Associated Items:

Names and Identifiers

Canonical SMILES:  Nc1nc2[nH]c(CCCc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)s3)cc2c(=O)[nH]1

Standard InChI:  InChI=1S/C19H21N5O6S/c20-19-23-15-11(16(27)24-19)8-9(21-15)2-1-3-10-4-6-13(31-10)17(28)22-12(18(29)30)5-7-14(25)26/h4,6,8,12H,1-3,5,7H2,(H,22,28)(H,25,26)(H,29,30)(H4,20,21,23,24,27)/t12-/m0/s1

Standard InChI Key:  WMBYSCVMFMNUQV-LBPRGKRZSA-N

Alternative Forms

  1. Parent:

    ALA1834488

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Associated Targets(Human)

IGROV-1 (47897 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
R2 (178 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KB (17409 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SLC46A1 Tchem Proton-coupled folate transporter (236 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SLC19A1 Tchem Folate transporter 1 (134 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FOLR2 Tchem Folate receptor beta (148 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
FOLR1 Tclin Folate receptor alpha (184 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
GART Tclin GAR transformylase (531 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SK-OV-3 (52876 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
A2780 (11979 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ATIC Tchem AICAR transformylase (241 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Mus musculus (284745 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: NoOral: NoChemical Probe: NoParenteral: No
Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
Chirality: NoAvailability: NoProdrug: No

Drug Indications

MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

Calculated Properties

Molecular Weight: 447.47Molecular Weight (Monoisotopic): 447.1213AlogP: 1.12#Rotatable Bonds: 10
Polar Surface Area: 191.26Molecular Species: ACIDHBA: 7HBD: 6
#RO5 Violations: 1HBA (Lipinski): 11HBD (Lipinski): 7#RO5 Violations (Lipinski): 2
CX Acidic pKa: 3.62CX Basic pKa: 4.83CX LogP: 0.26CX LogD: -4.84
Aromatic Rings: 3Heavy Atoms: 31QED Weighted: 0.27Np Likeness Score: -0.34

References

1. Wang L, Desmoulin SK, Cherian C, Polin L, White K, Kushner J, Fulterer A, Chang MH, Mitchell-Ryan S, Stout M, Romero MF, Hou Z, Matherly LH, Gangjee A..  (2011)  Synthesis, biological, and antitumor activity of a highly potent 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate inhibitor with proton-coupled folate transporter and folate receptor selectivity over the reduced folate carrier that inhibits β-glycinamide ribonucleotide formyltransferase.,  54  (20): [PMID:21879757] [10.1021/jm200739e]
2. Wang L, Cherian C, Kugel Desmoulin S, Mitchell-Ryan S, Hou Z, Matherly LH, Gangjee A..  (2012)  Synthesis and biological activity of 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl regioisomers as inhibitors of de novo purine biosynthesis with selectivity for cellular uptake by high affinity folate receptors and the proton-coupled folate transporter over the reduced folate carrier.,  55  (4): [PMID:22243528] [10.1021/jm201688n]
3. Golani LK, George C, Zhao S, Raghavan S, Orr S, Wallace A, Wilson MR, Hou Z, Matherly LH, Gangjee A..  (2014)  Structure-activity profiles of novel 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolates with modified amino acids for cellular uptake by folate receptors α and β and the proton-coupled folate transporter.,  57  (19): [PMID:25234128] [10.1021/jm501113m]
4. Wang L, Wallace A, Raghavan S, Deis SM, Wilson MR, Yang S, Polin L, White K, Kushner J, Orr S, George C, O'Connor C, Hou Z, Mitchell-Ryan S, Dann CE, Matherly LH, Gangjee A..  (2015)  6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Regioisomers as Targeted Antifolates for Folate Receptor α and the Proton-Coupled Folate Transporter in Human Tumors.,  58  (17): [PMID:26317331] [10.1021/acs.jmedchem.5b00801]
5. Ravindra M, Wilson MR, Tong N, O'Connor C, Karim M, Polin L, Wallace-Povirk A, White K, Kushner J, Hou Z, Matherly LH, Gangjee A..  (2018)  Fluorine-Substituted Pyrrolo[2,3- d]Pyrimidine Analogues with Tumor Targeting via Cellular Uptake by Folate Receptor α and the Proton-Coupled Folate Transporter and Inhibition of de Novo Purine Nucleotide Biosynthesis.,  61  (9): [PMID:29701475] [10.1021/acs.jmedchem.8b00408]
6. Xiang W, Dekhne A, Doshi A, O'Connor C, Hou Z, Matherly LH, Gangjee A..  (2019)  Discovery of amide-bridged pyrrolo[2,3-d]pyrimidines as tumor targeted classical antifolates with selective uptake by folate receptor α and inhibition of de novo purine nucleotide biosynthesis.,  27  (23): [PMID:31679978] [10.1016/j.bmc.2019.115125]
7. Golani LK, Wallace-Povirk A, Deis SM, Wong J, Ke J, Gu X, Raghavan S, Wilson MR, Li X, Polin L, de Waal PW, White K, Kushner J, O'Connor C, Hou Z, Xu HE, Melcher K, Dann CE, Matherly LH, Gangjee A..  (2016)  Tumor Targeting with Novel 6-Substituted Pyrrolo [2,3-d] Pyrimidine Antifolates with Heteroatom Bridge Substitutions via Cellular Uptake by Folate Receptor α and the Proton-Coupled Folate Transporter and Inhibition of de Novo Purine Nucleotide Biosynthesis.,  59  (17): [PMID:27458733] [10.1021/acs.jmedchem.6b00594]
8. Wallace-Povirk A,Tong N,Wong-Roushar J,O'Connor C,Zhou X,Hou Z,Bao X,Garcia GE,Li J,Kim S,Dann CE,Matherly LH,Gangjee A.  (2021)  Discovery of 6-substituted thieno[2,3-d]pyrimidine analogs as dual inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase in de novo purine nucleotide biosynthesis in folate receptor expressing human tumors.,  37  [PMID:33773393] [10.1016/j.bmc.2021.116093]

Source