ID: ALA3262462

Max Phase: Preclinical

Molecular Formula: C16H13N3O4S2

Molecular Weight: 375.43

Molecule Type: Small molecule

Representations

Canonical SMILES:  CCOC(=O)NC(=O)c1ccsc1NC(=O)c1nc2ccccc2s1

Standard InChI:  InChI=1S/C16H13N3O4S2/c1-2-23-16(22)19-12(20)9-7-8-24-14(9)18-13(21)15-17-10-5-3-4-6-11(10)25-15/h3-8H,2H2,1H3,(H,18,21)(H,19,20,22)

Standard InChI Key:  ISNBJLXHBBZKSL-UHFFFAOYSA-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: 375.43

Molecular Weight (Monoisotopic): 375.0347

AlogP: 3.50

#Rotatable Bonds: 4

Polar Surface Area: 97.39

Molecular Species: ACID

HBA: 7

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 7

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 6.08

CX Basic pKa:

CX LogP: 3.99

CX LogD: 2.75

Aromatic Rings: 3

Heavy Atoms: 25

QED Weighted: 0.73

Np Likeness Score: -2.27

References

1. Panda M, Ramachandran S, Ramachandran V, Shirude PS, Humnabadkar V, Nagalapur K, Sharma S, Kaur P, Guptha S, Narayan A, Mahadevaswamy J, Ambady A, Hegde N, Rudrapatna SS, Hosagrahara VP, Sambandamurthy VK, Raichurkar A..  (2014)  Discovery of pyrazolopyridones as a novel class of noncovalent DprE1 inhibitor with potent anti-mycobacterial activity.,  57  (11): [PMID:24818517] [10.1021/jm5002937]

2. MMV Pathogen Box,  [10.6019/CHEMBL3637841]

3. Nathan group, Weill Cornell Medical College; Barry Lab, NIAID NIH; Winzeler lab, UCSD; Laboratory of Microbiology, Parasitology and Hygiene (LMPH), Univ. of Antwerp; London School of Hygiene and Tropical Medicine; Parasite Chemotherapy Unit at Swiss Tropical and Public Health Institute; Huston group at the University of Vermont; Castellanos group at UTMB, Galveston, Texas; Sakanari Lab, Univ. of Calif. San Francisco; Townson (Simon) Lab, Imperial College London; Fidelis Cho-Ngwa Lab, University of Buea, Buea, Cameroon; Laboratory of Molecular Parasitology at the New York Blood Center; Bickle Lab, London School of Hygiene and Tropical Medicine; Keiser Lab, Swiss Tropical and Public Health Institute; Caffrey group at the Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, UC San Diego; University of Cape Town; Shanmugam group at CSIR-National Chemical Laboratory, Pune (India); Novartis Institute for Tropical Disease-Singapore; Abbvie. MMV Pathogen Box Bioactivity Data,  [10.6019/CHEMBL3832761]

4. Anna Ehmann. The Australian National University Dept Of Immunology Pathogen Box Compounds Screened,  [10.6019/CHEMBL3987221]

5. Oh S, Park Y, Engelhart CA, Wallach JB, Schnappinger D, Arora K, Manikkam M, Gac B, Wang H, Murgolo N, Olsen DB, Goodwin M, Sutphin M, Weiner DM, Via LE, Boshoff HIM, Barry CE..  (2018)  Discovery and Structure-Activity-Relationship Study of N-Alkyl-5-hydroxypyrimidinone Carboxamides as Novel Antitubercular Agents Targeting Decaprenylphosphoryl-β-d-ribose 2'-Oxidase.,  61  (22): [PMID:30350998] [10.1021/acs.jmedchem.8b00883]

6. Chikhale RV, Barmade MA, Murumkar PR, Yadav MR..  (2018)  Overview of the Development of DprE1 Inhibitors for Combating the Menace of Tuberculosis.,  61  (19): [PMID:29851474] [10.1021/acs.jmedchem.8b00281]

7. Rogacki MK, Pitta E, Balabon O, Huss S, Lopez-Roman EM, Argyrou A, Blanco-Ruano D, Cacho M, Vande Velde CML, Augustyns K, Ballell L, Barros D, Bates RH, Cunningham F, Van der Veken P..  (2018)  Identification and Profiling of Hydantoins-A Novel Class of Potent Antimycobacterial DprE1 Inhibitors.,  61  (24): [PMID:30500189] [10.1021/acs.jmedchem.8b01356]

8. Balabon O, Pitta E, Rogacki MK, Meiler E, Casanueva R, Guijarro L, Huss S, Lopez-Roman EM, Santos-Villarejo Á, Augustyns K, Ballell L, Aguirre DB, Bates RH, Cunningham F, Cacho M, Van der Veken P..  (2020)  Optimization of Hydantoins as Potent Antimycobacterial Decaprenylphosphoryl-β-d-Ribose Oxidase (DprE1) Inhibitors.,  63  (10): [PMID:32342688] [10.1021/acs.jmedchem.0c00107]

9. Sarink, M; Mykytyn, A; Tielens, A; van Hellemond, J. Naegleria gruberi Pathogen Box compounds screening,  [10.6019/CHEMBL4513101]

10. Johannes Zuegg, Alysha Elliott, Maite Amado, Emma Cowie, Ali Hinton, Geraldine Kaeslin, Angela Kavanagh, Anne Kunert, Gabriell Lowe, Soumya Ramu, Janet Reid, Robin Trauer, Mathilde Desselle, Ruth Neale, Karl Hansford, Mark Blascovich, Matthew Cooper. CO-ADD screening of MMV (CH) - MMV compounds,  [10.6019/CHEMBL4513149]

11. Wang P, Batt SM, Wang B, Fu L, Qin R, Lu Y, Li G, Besra GS, Huang H..  (2021)  Discovery of Novel Thiophene-arylamide Derivatives as DprE1 Inhibitors with Potent Antimycobacterial Activities.,  64  (9.0): [PMID:33852302] [10.1021/acs.jmedchem.1c00263]

12. Radhakrishnan A, Brown CM, Guy CS, Cooper C, Pacheco-Gomez R, Stansfeld PJ, Fullam E..  (2022)  Interrogation of the Pathogen Box reveals small molecule ligands against the mycobacterial trehalose transporter LpqY-SugABC.,  13  (10.0): [PMID:36320433] [10.1039/d2md00104g]

13. Fernandes GFS, Thompson AM, Castagnolo D, Denny WA, Dos Santos JL..  (2022)  Tuberculosis Drug Discovery: Challenges and New Horizons.,  65  (11.0): [PMID:35612311] [10.1021/acs.jmedchem.2c00227]

14. Liu J, Dai H, Wang B, Liu H, Tian Z, Zhang Y..  (2022)  Exploring disordered loops in DprE1 provides a functional site to combat drug-resistance in Mycobacterium strains.,  227  [PMID:34700267] [10.1016/j.ejmech.2021.113932]

15. Campaniço A, Moreira R, Lopes F..  (2018)  Drug discovery in tuberculosis. New drug targets and antimycobacterial agents.,  150  [PMID:29549838] [10.1016/j.ejmech.2018.03.020]

16. Mishra SK, Tripathi G, Kishore N, Singh RK, Singh A, Tiwari VK..  (2017)  Drug development against tuberculosis: Impact of alkaloids.,  137  [PMID:28628823] [10.1016/j.ejmech.2017.06.005]

17. Kumar G, Kapoor S..  (2023)  Targeting mycobacterial membranes and membrane proteins: Progress and limitations.,  81  [PMID:36804747] [10.1016/j.bmc.2023.117212]

Source

Source(3):

• Scientific Literature
• MMV Pathogen Box
• CO-ADD antimicrobial screening data