ID: ALA365307

Max Phase: Preclinical

Molecular Formula: C22H25N5O6

Molecular Weight: 455.47

Molecule Type: Small molecule

Representations

Canonical SMILES:  Nc1nc2[nH]c(CCCCc3ccc(C(=O)N[C@@H](CCC(=O)O)C(=O)O)cc3)cc2c(=O)[nH]1

Standard InChI:  InChI=1S/C22H25N5O6/c23-22-26-18-15(20(31)27-22)11-14(24-18)4-2-1-3-12-5-7-13(8-6-12)19(30)25-16(21(32)33)9-10-17(28)29/h5-8,11,16H,1-4,9-10H2,(H,25,30)(H,28,29)(H,32,33)(H4,23,24,26,27,31)/t16-/m0/s1

Standard InChI Key:  CEPQCJFDTGQKDN-INIZCTEOSA-N

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Properties

Molecular Weight: 455.47

Molecular Weight (Monoisotopic): 455.1805

AlogP: 1.45

#Rotatable Bonds: 11

Polar Surface Area: 191.26

Molecular Species: ACID

HBA: 6

HBD: 6

#RO5 Violations: 1

HBA (Lipinski): 11

HBD (Lipinski): 7

#RO5 Violations (Lipinski): 2

CX Acidic pKa: 3.33

CX Basic pKa: 4.88

CX LogP: 0.50

CX LogD: -4.62

Aromatic Rings: 3

Heavy Atoms: 33

QED Weighted: 0.23

Np Likeness Score: 0.06

References

1. Gangjee A, Zeng Y, McGuire JJ, Kisliuk RL..  (2005)  Synthesis of classical, four-carbon bridged 5-substituted furo[2,3-d]pyrimidine and 6-substituted pyrrolo[2,3-d]pyrimidine analogues as antifolates.,  48  (16): [PMID:16078850] [10.1021/jm058213s]

2. Deng Y, Wang Y, Cherian C, Hou Z, Buck SA, Matherly LH, Gangjee A..  (2008)  Synthesis and discovery of high affinity folate receptor-specific glycinamide ribonucleotide formyltransferase inhibitors with antitumor activity.,  51  (16): [PMID:18680275] [10.1021/jm8003366]

3. Wang L, Cherian C, Desmoulin SK, Polin L, Deng Y, Wu J, Hou Z, White K, Kushner J, Matherly LH, Gangjee A..  (2010)  Synthesis and antitumor activity of a novel series of 6-substituted pyrrolo[2,3-d]pyrimidine thienoyl antifolate inhibitors of purine biosynthesis with selectivity for high affinity folate receptors and the proton-coupled folate transporter over the reduced folate carrier for cellular entry.,  53  (3): [PMID:20085328] [10.1021/jm9015729]

4. Wang Y, Cherian C, Orr S, Mitchell-Ryan S, Hou Z, Raghavan S, Matherly LH, Gangjee A..  (2013)  Tumor-targeting with novel non-benzoyl 6-substituted straight chain pyrrolo[2,3-d]pyrimidine antifolates via cellular uptake by folate receptor α and inhibition of de novo purine nucleotide biosynthesis.,  56  (21): [PMID:24111942] [10.1021/jm401139z]

5. Mitchell-Ryan S, Wang Y, Raghavan S, Ravindra MP, Hales E, Orr S, Cherian C, Hou Z, Matherly LH, Gangjee A..  (2013)  Discovery of 5-substituted pyrrolo[2,3-d]pyrimidine antifolates as dual-acting inhibitors of glycinamide ribonucleotide formyltransferase and 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase in de novo purine nucleotide biosynthesis: implications of inhibiting 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase to ampk activation and antitumor activity.,  56  (24): [PMID:24256410] [10.1021/jm401328u]

6. Ravindra M, Wallace-Povirk A, Karim MA, Wilson MR, O'Connor C, White K, Kushner J, Polin L, George C, Hou Z, Matherly LH, Gangjee A..  (2018)  Tumor Targeting with Novel Pyridyl 6-Substituted Pyrrolo[2,3- d]Pyrimidine Antifolates via Cellular Uptake by Folate Receptor α and the Proton-Coupled Folate Transporter and Inhibition of De Novo Purine Nucleotide Biosynthesis.,  61  (5): [PMID:29425443] [10.1021/acs.jmedchem.7b01708]

7. 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]

8. Golani LK, Islam F, O'Connor C, Dekhne AS, Hou Z, Matherly LH, Gangjee A..  (2020)  Design, synthesis and biological evaluation of novel pyrrolo[2,3-d]pyrimidine as tumor-targeting agents with selectivity for tumor uptake by high affinity folate receptors over the reduced folate carrier.,  28  (12): [PMID:32503687] [10.1016/j.bmc.2020.115544]

Source

Source(1):

• Scientific Literature