ID: ALA1822067

Max Phase: Preclinical

Molecular Formula: C17H17F2N5O4S

Molecular Weight: 425.42

Molecule Type: Small molecule

Representations

Canonical SMILES:  CCCS(=O)(=O)Nc1ccc(F)c(C(=O)Nc2cnc3[nH]nc(OC)c3c2)c1F

Standard InChI:  InChI=1S/C17H17F2N5O4S/c1-3-6-29(26,27)24-12-5-4-11(18)13(14(12)19)16(25)21-9-7-10-15(20-8-9)22-23-17(10)28-2/h4-5,7-8,24H,3,6H2,1-2H3,(H,21,25)(H,20,22,23)

Standard InChI Key:  PFHJLTOLXWXCJH-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: 425.42

Molecular Weight (Monoisotopic): 425.0969

AlogP: 2.65

#Rotatable Bonds: 7

Polar Surface Area: 126.07

Molecular Species: NEUTRAL

HBA: 6

HBD: 3

#RO5 Violations: 0

HBA (Lipinski): 9

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 8.77

CX Basic pKa: 0.84

CX LogP: 1.66

CX LogD: 1.65

Aromatic Rings: 3

Heavy Atoms: 29

QED Weighted: 0.53

Np Likeness Score: -2.15

References

1. Wenglowsky S, Ahrendt KA, Buckmelter AJ, Feng B, Gloor SL, Gradl S, Grina J, Hansen JD, Laird ER, Lunghofer P, Mathieu S, Moreno D, Newhouse B, Ren L, Risom T, Rudolph J, Seo J, Sturgis HL, Voegtli WC, Wen Z..  (2011)  Pyrazolopyridine inhibitors of B-RafV600E. Part 2: structure-activity relationships.,  21  (18): [PMID:21802293] [10.1016/j.bmcl.2011.06.097]

2. Wenglowsky S, Moreno D, Rudolph J, Ran Y, Ahrendt KA, Arrigo A, Colson B, Gloor SL, Hastings G..  (2012)  Pyrazolopyridine inhibitors of B-Raf(V600E). Part 3: an increase in aqueous solubility via the disruption of crystal packing.,  22  (2): [PMID:22209462] [10.1016/j.bmcl.2011.12.030]

3. Wenglowsky S, Ren L, Ahrendt KA, Laird ER, Aliagas I, Alicke B, Buckmelter AJ, Choo EF, Dinkel V, Feng B, Gloor SL, Gould SE, Gross S, Gunzner-Toste J, Hansen JD, Hatzivassiliou G, Liu B, Malesky K, Mathieu S, Newhouse B, Raddatz NJ, Ran Y, Rana S, Randolph N, Risom T, Rudolph J, Savage S, Selby LT, Shrag M, Song K, Sturgis HL, Voegtli WC, Wen Z, Willis BS, Woessner RD, Wu WI, Young WB, Grina J..  (2011)  Pyrazolopyridine Inhibitors of B-Raf(V600E). Part 1: The Development of Selective, Orally Bioavailable, and Efficacious Inhibitors.,  2  (5): [PMID:24900315] [10.1021/ml200025q]

4. Ren L, Laird ER, Buckmelter AJ, Dinkel V, Gloor SL, Grina J, Newhouse B, Rasor K, Hastings G, Gradl SN, Rudolph J..  (2012)  Potent and selective pyrazolo[1,5-a]pyrimidine based inhibitors of B-Raf(V600E) kinase with favorable physicochemical and pharmacokinetic properties.,  22  (2): [PMID:22196124] [10.1016/j.bmcl.2011.11.092]

5. Mathieu S, Gradl SN, Ren L, Wen Z, Aliagas I, Gunzner-Toste J, Lee W, Pulk R, Zhao G, Alicke B, Boggs JW, Buckmelter AJ, Choo EF, Dinkel V, Gloor SL, Gould SE, Hansen JD, Hastings G, Hatzivassiliou G, Laird ER, Moreno D, Ran Y, Voegtli WC, Wenglowsky S, Grina J, Rudolph J..  (2012)  Potent and selective aminopyrimidine-based B-Raf inhibitors with favorable physicochemical and pharmacokinetic properties.,  55  (6): [PMID:22335519] [10.1021/jm300016v]

6. Hu CQ, Li K, Yao TT, Hu YZ, Ying HZ, Dong XW..  (2017)  Integrating docking scores and key interaction profiles to improve the accuracy of molecular docking: towards novel B-Raf^V600E inhibitors.,  8  (9): [PMID:30108894] [10.1039/C7MD00229G]

Source

Source(1):

• Scientific Literature