N-(4-fluorobenzyl)-5,6-dihydroxy-2-thien-2-ylpyrimidine-4-carboxamide

ID: ALA216874

Chembl Id: CHEMBL216874

PubChem CID: 135520683

Max Phase: Preclinical

Molecular Formula: C16H12FN3O3S

Molecular Weight: 345.36

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  O=C(NCc1ccc(F)cc1)c1nc(-c2cccs2)nc(O)c1O

Standard InChI:  InChI=1S/C16H12FN3O3S/c17-10-5-3-9(4-6-10)8-18-15(22)12-13(21)16(23)20-14(19-12)11-2-1-7-24-11/h1-7,21H,8H2,(H,18,22)(H,19,20,23)

Standard InChI Key:  OKLYWXAJDGCACQ-UHFFFAOYSA-N

Alternative Forms

1. Parent:

   

   ALA216874

   ---

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

Calculated Properties

Molecular Weight: 345.36

Molecular Weight (Monoisotopic): 345.0583

AlogP: 2.69

#Rotatable Bonds: 4

Polar Surface Area: 95.34

Molecular Species: NEUTRAL

HBA: 6

HBD: 3

#RO5 Violations: ┄

HBA (Lipinski): 6

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 7.40

CX Basic pKa: ┄

CX LogP: 4.03

CX LogD: 3.74

Aromatic Rings: 3

Heavy Atoms: 24

QED Weighted: 0.68

Np Likeness Score: -1.88

References

1. Summa V, Petrocchi A, Matassa VG, Gardelli C, Muraglia E, Rowley M, Paz OG, Laufer R, Monteagudo E, Pace P..  (2006)  4,5-dihydroxypyrimidine carboxamides and N-alkyl-5-hydroxypyrimidinone carboxamides are potent, selective HIV integrase inhibitors with good pharmacokinetic profiles in preclinical species.,  49  (23): [PMID:17154493] [10.1021/jm060854f]

2. Pace P, Di Francesco ME, Gardelli C, Harper S, Muraglia E, Nizi E, Orvieto F, Petrocchi A, Poma M, Rowley M, Scarpelli R, Laufer R, Gonzalez Paz O, Monteagudo E, Bonelli F, Hazuda D, Stillmock KA, Summa V..  (2007)  Dihydroxypyrimidine-4-carboxamides as novel potent and selective HIV integrase inhibitors.,  50  (9): [PMID:17428043] [10.1021/jm070027u]

3. Petrocchi A, Koch U, Matassa VG, Pacini B, Stillmock KA, Summa V..  (2007)  From dihydroxypyrimidine carboxylic acids to carboxamide HIV-1 integrase inhibitors: SAR around the amide moiety.,  17  (2): [PMID:17107799] [10.1016/j.bmcl.2006.10.054]

4. Gardelli C, Nizi E, Muraglia E, Crescenzi B, Ferrara M, Orvieto F, Pace P, Pescatore G, Poma M, Ferreira Mdel R, Scarpelli R, Homnick CF, Ikemoto N, Alfieri A, Verdirame M, Bonelli F, Paz OG, Taliani M, Monteagudo E, Pesci S, Laufer R, Felock P, Stillmock KA, Hazuda D, Rowley M, Summa V..  (2007)  Discovery and synthesis of HIV integrase inhibitors: development of potent and orally bioavailable N-methyl pyrimidones.,  50  (20): [PMID:17824681] [10.1021/jm0704705]

5. Di Francesco ME, Pace P, Fiore F, Naimo F, Bonelli F, Rowley M, Summa V..  (2008)  Development of 2-t butyl-N-methyl pyrimidones as potent inhibitors of HIV integrase.,  18  (8): [PMID:18362069] [10.1016/j.bmcl.2008.03.017]

6. de Melo EB, Ferreira MM..  (2009)  Multivariate QSAR study of 4,5-dihydroxypyrimidine carboxamides as HIV-1 integrase inhibitors.,  44  (9): [PMID:19327872] [10.1016/j.ejmech.2009.03.001]

7. Chapman TM, Wallace C, Gillen KJ, Bakrania P, Khurana P, Coombs PJ, Fox S, Bureau EA, Brownlees J, Melton DW, Saxty B..  (2015)  N-Hydroxyimides and hydroxypyrimidinones as inhibitors of the DNA repair complex ERCC1-XPF.,  25  (19): [PMID:26321360] [10.1016/j.bmcl.2015.08.024]

8. He T, Edwards TC, Xie J, Aihara H, Geraghty RJ, Wang Z..  (2022)  4,5-Dihydroxypyrimidine Methyl Carboxylates, Carboxylic Acids, and Carboxamides as Inhibitors of Human Cytomegalovirus pUL89 Endonuclease.,  65  (7.0): [PMID:35377638] [10.1021/acs.jmedchem.2c00203]

Source

Source(1):

• Scientific Literature