ID: ALA336293

Max Phase: Preclinical

Molecular Formula: C21H19N3O3

Molecular Weight: 361.40

Molecule Type: Small molecule

Representations

Canonical SMILES:  O=C(C(=O)N1CCN(C(=O)c2ccccc2)CC1)c1c[nH]c2ccccc12

Standard InChI:  InChI=1S/C21H19N3O3/c25-19(17-14-22-18-9-5-4-8-16(17)18)21(27)24-12-10-23(11-13-24)20(26)15-6-2-1-3-7-15/h1-9,14,22H,10-13H2

Standard InChI Key:  GCCPYLCLTHXPRB-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: 361.40

Molecular Weight (Monoisotopic): 361.1426

AlogP: 2.34

#Rotatable Bonds: 3

Polar Surface Area: 73.48

Molecular Species: NEUTRAL

HBA: 3

HBD: 1

#RO5 Violations: 0

HBA (Lipinski): 6

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 12.31

CX Basic pKa:

CX LogP: 2.16

CX LogD: 2.16

Aromatic Rings: 3

Heavy Atoms: 27

QED Weighted: 0.57

Np Likeness Score: -0.94

References

1. Wang T, Zhang Z, Wallace OB, Deshpande M, Fang H, Yang Z, Zadjura LM, Tweedie DL, Huang S, Zhao F, Ranadive S, Robinson BS, Gong YF, Ricarrdi K, Spicer TP, Deminie C, Rose R, Wang HG, Blair WS, Shi PY, Lin PF, Colonno RJ, Meanwell NA..  (2003)  Discovery of 4-benzoyl-1-[(4-methoxy-1H- pyrrolo[2,3-b]pyridin-3-yl)oxoacetyl]-2- (R)-methylpiperazine (BMS-378806): a novel HIV-1 attachment inhibitor that interferes with CD4-gp120 interactions.,  46  (20): [PMID:13678401] [10.1021/jm034082o]

2. Meanwell NA, Wallace OB, Fang H, Wang H, Deshpande M, Wang T, Yin Z, Zhang Z, Pearce BC, James J, Yeung KS, Qiu Z, Kim Wright JJ, Yang Z, Zadjura L, Tweedie DL, Yeola S, Zhao F, Ranadive S, Robinson BA, Gong YF, Wang HG, Spicer TP, Blair WS, Shi PY, Colonno RJ, Lin PF..  (2009)  Inhibitors of HIV-1 attachment. Part 2: An initial survey of indole substitution patterns.,  19  (7): [PMID:19251416] [10.1016/j.bmcl.2009.02.040]

3. Meanwell NA, Wallace OB, Wang H, Deshpande M, Pearce BC, Trehan A, Yeung KS, Qiu Z, Wright JJ, Robinson BA, Gong YF, Wang HG, Spicer TP, Blair WS, Shi PY, Lin PF..  (2009)  Inhibitors of HIV-1 attachment. Part 3: A preliminary survey of the effect of structural variation of the benzamide moiety on antiviral activity.,  19  (17): [PMID:19632112] [10.1016/j.bmcl.2009.07.027]

4. Lu P, Wei X, Zhang R..  (2010)  CoMFA and CoMSIA studies on HIV-1 attachment inhibitors.,  45  (5): [PMID:20149491] [10.1016/j.ejmech.2010.01.011]

5. Yeung KS, Qiu Z, Yin Z, Trehan A, Fang H, Pearce B, Yang Z, Zadjura L, D'Arienzo CJ, Riccardi K, Shi PY, Spicer TP, Gong YF, Browning MR, Hansel S, Santone K, Barker J, Coulter T, Lin PF, Meanwell NA, Kadow JF..  (2013)  Inhibitors of HIV-1 attachment. Part 8: the effect of C7-heteroaryl substitution on the potency, and in vitro and in vivo profiles of indole-based inhibitors.,  23  (1): [PMID:23200249] [10.1016/j.bmcl.2012.10.117]

6. Patel RV, Park SW..  (2015)  Pyrroloaryls and pyrroloheteroaryls: Inhibitors of the HIV fusion/attachment, reverse transcriptase and integrase.,  23  (17): [PMID:26116177] [10.1016/j.bmc.2015.06.016]

7. Meanwell NA, Krystal MR, Nowicka-Sans B, Langley DR, Conlon DA, Eastgate MD, Grasela DM, Timmins P, Wang T, Kadow JF..  (2018)  Inhibitors of HIV-1 Attachment: The Discovery and Development of Temsavir and its Prodrug Fostemsavir.,  61  (1): [PMID:29271653] [10.1021/acs.jmedchem.7b01337]

8. Wang T, Ueda Y, Zhang Z, Yin Z, Matiskella J, Pearce BC, Yang Z, Zheng M, Parker DD, Yamanaka GA, Gong YF, Ho HT, Colonno RJ, Langley DR, Lin PF, Meanwell NA, Kadow JF..  (2018)  Discovery of the Human Immunodeficiency Virus Type 1 (HIV-1) Attachment Inhibitor Temsavir and Its Phosphonooxymethyl Prodrug Fostemsavir.,  61  (14): [PMID:29920093] [10.1021/acs.jmedchem.8b00759]

9. Wang T, Wallace OB, Zhang Z, Fang H, Yang Z, Robinson BA, Spicer TP, Gong YF, Blair WS, Shi PY, Lin PF, Deshpande M, Meanwell NA, Kadow JF..  (2019)  A survey of core replacements in indole-based HIV-1 attachment inhibitors.,  29  (11): [PMID:30940396] [10.1016/j.bmcl.2019.03.018]

Source

Source(1):

• Scientific Literature