ID: ALA59441

Max Phase: Preclinical

Molecular Formula: C10H12N2O3

Molecular Weight: 208.22

Molecule Type: Small molecule

Representations

Canonical SMILES:  O=[N+]([O-])c1ccc2c(c1)CNC(CO)C2

Standard InChI:  InChI=1S/C10H12N2O3/c13-6-9-3-7-1-2-10(12(14)15)4-8(7)5-11-9/h1-2,4,9,11,13H,3,5-6H2

Standard InChI Key:  RNUCRXHRBPLYTA-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: 208.22

Molecular Weight (Monoisotopic): 208.0848

AlogP: 0.60

#Rotatable Bonds: 2

Polar Surface Area: 75.40

Molecular Species: NEUTRAL

HBA: 4

HBD: 2

#RO5 Violations: 0

HBA (Lipinski): 5

HBD (Lipinski): 2

#RO5 Violations (Lipinski): 0

CX Acidic pKa:

CX Basic pKa: 8.04

CX LogP: 0.88

CX LogD: 0.15

Aromatic Rings: 1

Heavy Atoms: 15

QED Weighted: 0.55

Np Likeness Score: 0.04

References

1. Grunewald GL, Dahanukar VH, Teoh B, Criscione KR..  (1999)  3,7-Disubstituted-1,2,3,4-tetrahydroisoquinolines display remarkable potency and selectivity as inhibitors of phenylethanolamine N-methyltransferase versus the alpha2-adrenoceptor.,  42  (11): [PMID:10354406] [10.1021/jm9807252]

2. Grunewald GL, Caldwell TM, Li Q, Criscione KR..  (2001)  Synthesis and evaluation of 4-fluoro-8-substituted-2,3,4,5-tetrahydro-1H-2-benzazapines as selective inhibitors of phenylethanolamine N-methyltransferase versus the alpha(2)-adrenoceptor.,  44  (17): [PMID:11495596] [10.1021/jm010147g]

3. Grunewald GL, Caldwell TM, Li Q, Slavica M, Criscione KR, Borchardt RT, Wang W..  (1999)  Synthesis and biochemical evaluation of 3-fluoromethyl-1,2,3, 4-tetrahydroisoquinolines as selective inhibitors of phenylethanolamine N-methyltransferase versus the alpha(2)-adrenoceptor.,  42  (18): [PMID:10479290] [10.1021/jm990045e]

4. Grunewald GL, Romero FA, Seim MR, Criscione KR, Deupree JD, Spackman CC, Bylund DB..  (2005)  Exploring the active site of phenylethanolamine N-methyltransferase with 3-hydroxyethyl- and 3-hydroxypropyl-7-substituted-1,2,3,4-tetrahydroisoquinolines.,  15  (4): [PMID:15686930] [10.1016/j.bmcl.2004.12.013]

5. Gee CL, Drinkwater N, Tyndall JD, Grunewald GL, Wu Q, McLeish MJ, Martin JL..  (2007)  Enzyme adaptation to inhibitor binding: a cryptic binding site in phenylethanolamine N-methyltransferase.,  50  (20): [PMID:17845018] [10.1021/jm0703385]

6. Lu J,Bart AG,Wu Q,Criscione KR,McLeish MJ,Scott EE,Grunewald GL.  (2020)  Structure-Based Drug Design of Bisubstrate Inhibitors of Phenylethanolamine N-Methyltransferase Possessing Low Nanomolar Affinity at Both Substrate Binding Domains.,  63  (22): [PMID:33147410] [10.1021/acs.jmedchem.0c01475]

Source

Source(1):

• Scientific Literature