ID: ALA18861

Max Phase: Preclinical

Molecular Formula: C17H14F3NO3

Molecular Weight: 337.30

Molecule Type: Small molecule

Representations

Synonyms (1): ZD-6169
Synonyms from Alternative Forms(1):

Canonical SMILES:  C[C@](O)(C(=O)Nc1ccc(C(=O)c2ccccc2)cc1)C(F)(F)F

Standard InChI:  InChI=1S/C17H14F3NO3/c1-16(24,17(18,19)20)15(23)21-13-9-7-12(8-10-13)14(22)11-5-3-2-4-6-11/h2-10,24H,1H3,(H,21,23)/t16-/m0/s1

Standard InChI Key:  LVEDGSIMCSQNNX-INIZCTEOSA-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: 337.30

Molecular Weight (Monoisotopic): 337.0926

AlogP: 3.17

#Rotatable Bonds: 4

Polar Surface Area: 66.40

Molecular Species: NEUTRAL

HBA: 3

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 4

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 9.45

CX Basic pKa:

CX LogP: 3.45

CX LogD: 3.45

Aromatic Rings: 2

Heavy Atoms: 24

QED Weighted: 0.84

Np Likeness Score: -0.63

References

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2. Gilbert AM, Antane MM, Argentieri TM, Butera JA, Francisco GD, Freeden C, Gundersen EG, Graceffa RF, Herbst D, Hirth BH, Lennox JR, McFarlane G, Norton NW, Quagliato D, Sheldon JH, Warga D, Wojdan A, Woods M..  (2000)  Design and SAR of novel potassium channel openers targeted for urge urinary incontinence. 2. Selective and potent benzylamino cyclobutenediones.,  43  (6): [PMID:10737753] [10.1021/jm9905108]

3. Turner SC, Carroll WA, White TK, Brune ME, Buckner SA, Gopalakrishnan M, Fabiyi A, Coghlan MJ, Scott VE, Castle NA, Daza AV, Milicic I, Sullivan JP..  (2003)  Structure-activity relationship of a novel class of naphthyl amide KATP channel openers.,  13  (10): [PMID:12729655] [10.1016/s0960-894x(03)00205-1]

4. Aicher TD, Anderson RC, Bebernitz GR, Coppola GM, Jewell CF, Knorr DC, Liu C, Sperbeck DM, Brand LJ, Strohschein RJ, Gao J, Vinluan CC, Shetty SS, Dragland C, Kaplan EL, DelGrande D, Islam A, Liu X, Lozito RJ, Maniara WM, Walter RE, Mann WR..  (1999)  (R)-3,3,3-Trifluoro-2-hydroxy-2-methylpropionamides are orally active inhibitors of pyruvate dehydrogenase kinase.,  42  (15): [PMID:10425084] [10.1021/jm9902584]

5. Carroll WA, Altenbach RJ, Bai H, Brioni JD, Brune ME, Buckner SA, Cassidy C, Chen Y, Coghlan MJ, Daza AV, Drizin I, Fey TA, Fitzgerald M, Gopalakrishnan M, Gregg RJ, Henry RF, Holladay MW, King LL, Kort ME, Kym PR, Milicic I, Tang R, Turner SC, Whiteaker KL, Yi L, Zhang H, Sullivan JP..  (2004)  Synthesis and structure-activity relationships of a novel series of 2,3,5,6,7,9-hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide K(ATP) channel openers: discovery of (-)-(9S)-9-(3-bromo-4-fluorophenyl)-2,3,5,6,7,9- hexahydrothieno[3,2-b]quinolin-8(4H)-one 1,1-dioxide (A-278637), a potent K(ATP) opener that selectively inhibits spontaneous bladder contractions.,  47  (12): [PMID:15163196] [10.1021/jm030356w]

6. Perez-Medrano A, Buckner SA, Coghlan MJ, Gregg RJ, Gopalakrishnan M, Kort ME, Lynch JK, Scott VE, Sullivan JP, Whiteaker KL, Carroll WA..  (2004)  Design and synthesis of novel cyanoguanidine ATP-sensitive potassium channel openers for the treatment of overactive bladder.,  14  (2): [PMID:14698167] [10.1016/j.bmcl.2003.10.063]

7. Ohnmacht CJ, Russell K, Empfield JR, Frank CA, Gibson KH, Mayhugh DR, McLaren FM, Shapiro HS, Brown FJ, Trainor DA, Ceccarelli C, Lin MM, Masek BB, Forst JM, Harris RJ, Hulsizer JM, Lewis JJ, Silverman SM, Smith RW, Warwick PJ, Kau ST, Chun AL, Grant TL, Howe BB, Neilson KL..  (1996)  N-aryl-3,3,3-trifluoro-2-hydroxy-2-methylpropanamides: KATP potassium channel openers. Modifications on the western region.,  39  (23): [PMID:8917648] [10.1021/jm960365n]

8. Altenbach RJ, Brune ME, Buckner SA, Coghlan MJ, Daza AV, Fabiyi A, Gopalakrishnan M, Henry RF, Khilevich A, Kort ME, Milicic I, Scott VE, Smith JC, Whiteaker KL, Carroll WA..  (2006)  Effects of substitution on 9-(3-bromo-4-fluorophenyl)-5,9-dihydro-3H,4H-2,6-dioxa-4- azacyclopenta[b]naphthalene-1,8-dione, a dihydropyridine ATP-sensitive potassium channel opener.,  49  (23): [PMID:17154517] [10.1021/jm060549u]

9. Perez-Medrano A, Brune ME, Buckner SA, Coghlan MJ, Fey TA, Gopalakrishnan M, Gregg RJ, Kort ME, Scott VE, Sullivan JP, Whiteaker KL, Carroll WA..  (2007)  Structure-activity studies of novel cyanoguanidine ATP-sensitive potassium channel openers for the treatment of overactive bladder.,  50  (24): [PMID:17973362] [10.1021/jm7010194]

10. Warner DJ, Chen H, Cantin LD, Kenna JG, Stahl S, Walker CL, Noeske T..  (2012)  Mitigating the inhibition of human bile salt export pump by drugs: opportunities provided by physicochemical property modulation, in silico modeling, and structural modification.,  40  (12): [PMID:22961681] [10.1124/dmd.112.047068]

Source

Source(1):

• Scientific Literature