ID: ALA85059

Max Phase: Preclinical

Molecular Formula: C17H15ClN2O3S

Molecular Weight: 362.84

Molecule Type: Small molecule

Representations

Canonical SMILES:  Cc1cc(C)cc(S(=O)(=O)c2c(C(N)=O)[nH]c3ccc(Cl)cc23)c1

Standard InChI:  InChI=1S/C17H15ClN2O3S/c1-9-5-10(2)7-12(6-9)24(22,23)16-13-8-11(18)3-4-14(13)20-15(16)17(19)21/h3-8,20H,1-2H3,(H2,19,21)

Standard InChI Key:  GXWODWMYKXULHQ-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: 362.84

Molecular Weight (Monoisotopic): 362.0492

AlogP: 3.37

#Rotatable Bonds: 3

Polar Surface Area: 93.02

Molecular Species: NEUTRAL

HBA: 3

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 5

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 9.56

CX Basic pKa:

CX LogP: 3.43

CX LogD: 3.43

Aromatic Rings: 3

Heavy Atoms: 24

QED Weighted: 0.75

Np Likeness Score: -1.03

References

1. Silvestri R, De Martino G, La Regina G, Artico M, Massa S, Vargiu L, Mura M, Loi AG, Marceddu T, La Colla P..  (2003)  Novel indolyl aryl sulfones active against HIV-1 carrying NNRTI resistance mutations: synthesis and SAR studies.,  46  (12): [PMID:12773052] [10.1021/jm0211063]

2. Silvestri R, Artico M, De Martino G, La Regina G, Loddo R, La Colla M, Mura M, La Colla P..  (2004)  Simple, short peptide derivatives of a sulfonylindolecarboxamide (L-737,126) active in vitro against HIV-1 wild type and variants carrying non-nucleoside reverse transcriptase inhibitor resistance mutations.,  47  (15): [PMID:15239667] [10.1021/jm031147e]

3. Ragno R, Artico M, De Martino G, La Regina G, Coluccia A, Di Pasquali A, Silvestri R..  (2005)  Docking and 3-D QSAR studies on indolyl aryl sulfones. Binding mode exploration at the HIV-1 reverse transcriptase non-nucleoside binding site and design of highly active N-(2-hydroxyethyl)carboxamide and N-(2-hydroxyethyl)carbohydrazide derivatives.,  48  (1): [PMID:15634015] [10.1021/jm040854k]

4. Ragno R, Coluccia A, La Regina G, De Martino G, Piscitelli F, Lavecchia A, Novellino E, Bergamini A, Ciaprini C, Sinistro A, Maga G, Crespan E, Artico M, Silvestri R..  (2006)  Design, molecular modeling, synthesis, and anti-HIV-1 activity of new indolyl aryl sulfones. Novel derivatives of the indole-2-carboxamide.,  49  (11): [PMID:16722636] [10.1021/jm0512490]

5. Piscitelli F, Coluccia A, Brancale A, La Regina G, Sansone A, Giordano C, Balzarini J, Maga G, Zanoli S, Samuele A, Cirilli R, La Torre F, Lavecchia A, Novellino E, Silvestri R..  (2009)  Indolylarylsulfones bearing natural and unnatural amino acids. Discovery of potent inhibitors of HIV-1 non-nucleoside wild type and resistant mutant strains reverse transcriptase and coxsackie B4 virus.,  52  (7): [PMID:19281225] [10.1021/jm801470b]

6. Huang B, Wang X, Liu X, Chen Z, Li W, Sun S, Liu H, Daelemans D, De Clercq E, Pannecouque C, Zhan P, Liu X..  (2017)  Discovery of novel DAPY-IAS hybrid derivatives as potential HIV-1 inhibitors using molecular hybridization based on crystallographic overlays.,  25  (16): [PMID:28659246] [10.1016/j.bmc.2017.06.022]

7. Zhao T, Meng Q, Kang D, Ji J, De Clercq E, Pannecouque C, Liu X, Zhan P..  (2019)  Discovery of novel indolylarylsulfones as potent HIV-1 NNRTIs via structure-guided scaffold morphing.,  182  [PMID:31434039] [10.1016/j.ejmech.2019.111619]

8. Gao P,Song S,Frutos-Beltrán E,Li W,Sun B,Kang D,Zou J,Zhang J,Pannecouque C,De Clercq E,Menéndez-Arias L,Zhan P,Liu X.  (2021)  Novel indolylarylsulfone derivatives as covalent HIV-1 reverse transcriptase inhibitors specifically targeting the drug-resistant mutant Y181C.,  30  [PMID:33352387] [10.1016/j.bmc.2020.115927]

9. Nalli M,Armijos Rivera JI,Masci D,Coluccia A,Badia R,Riveira-Muñoz E,Brambilla A,Cinquina E,Turriziani O,Falasca F,Catalano M,Limatola C,Esté JA,Maga G,Silvestri R,Crespan E,La Regina G.  (2020)  New indolylarylsulfone non-nucleoside reverse transcriptase inhibitors show low nanomolar inhibition of single and double HIV-1 mutant strains.,  208  [PMID:32883642] [10.1016/j.ejmech.2020.112696]

10. Gao S, Cheng Y, Song S, Song L, Zhao F, Xu S, Kang D, Sun L, Gao P, De Clercq E, Pannecouque C, Liu X, Zhan P..  (2022)  Chemical space exploration around indolylarylsulfone scaffold led to a novel class of highly active HIV-1 NNRTIs with spiro structural features.,  238  [PMID:35640327] [10.1016/j.ejmech.2022.114471]

11. Xu S, Song S, Sun L, Gao P, Gao S, Ma Y, Kang D, Cheng Y, Zhang X, Cherukupalli S, De Clercq E, Pannecouque C, Liu X, Zhan P..  (2022)  Indolylarylsulfones bearing phenylboronic acid and phenylboronate ester functionalities as potent HIV‑1 non-nucleoside reverse transcriptase inhibitors.,  53  [PMID:34890994] [10.1016/j.bmc.2021.116531]

Source

Source(1):

• Scientific Literature