ID: ALA174984

Max Phase: Preclinical

Molecular Formula: C19H23NO5

Molecular Weight: 345.40

Molecule Type: Small molecule

Representations

Canonical SMILES:  COc1cc(C[C@@H]2NCCc3cc(O)c(O)cc32)cc(OC)c1OC

Standard InChI:  InChI=1S/C19H23NO5/c1-23-17-7-11(8-18(24-2)19(17)25-3)6-14-13-10-16(22)15(21)9-12(13)4-5-20-14/h7-10,14,20-22H,4-6H2,1-3H3/t14-/m0/s1

Standard InChI Key:  RGVPOXRFEPSFGH-AWEZNQCLSA-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: 345.40

Molecular Weight (Monoisotopic): 345.1576

AlogP: 2.55

#Rotatable Bonds: 5

Polar Surface Area: 80.18

Molecular Species: BASE

HBA: 6

HBD: 3

#RO5 Violations: 0

HBA (Lipinski): 6

HBD (Lipinski): 3

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 9.53

CX Basic pKa: 8.52

CX LogP: 2.24

CX LogD: 1.31

Aromatic Rings: 2

Heavy Atoms: 25

QED Weighted: 0.72

Np Likeness Score: 1.18

References

1. Clark MT, Chang J, Navran SS, Huzoor-Akbar, Mukhopadhyay A, Amin H, Feller DR, Miller DD..  (1986)  Synthesis and investigation of the beta-adrenoceptor agonist and platelet antiaggregatory properties of 1,7,8-trisubstituted 2,3,4,5-tetrahydro-1H-2-benzazepine analogues of trimetoquinol.,  29  (2): [PMID:2869145] [10.1021/jm00152a003]

2. Parmee ER, Brockunier LL, He J, Singh SB, Candelore MR, Cascieri MA, Deng L, Liu Y, Tota L, Wyvratt MJ, Fisher MH, Weber AE..  (2000)  Tetrahydroisoquinoline derivatives containing a benzenesulfonamide moiety as potent, selective human beta3 adrenergic receptor agonists.,  10  (20): [PMID:11055339] [10.1016/s0960-894x(00)00459-5]

3. Zheng W, Nikulin VI, Konkar AA, Vansal SS, Shams G, Feller DR, Miller DD..  (1999)  2-Amino-4-benzyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridines: novel selective beta3-adrenoceptor agonists.,  42  (12): [PMID:10377236] [10.1021/jm990012z]

4. Kaiser C, Oh HJ, Garcia-Slanga BJ, Sulpizio AC, Hieble JP, Wawro JE, Kruse LI..  (1986)  6,7-Dichloro-1-(3,4,5-trimethoxybenzyl)-1,2,3,4-tetrahydroisoquinoline . A structurally novel beta-adrenergic receptor blocking agent.,  29  (11): [PMID:2878080] [10.1021/jm00161a039]

5. De Los Angeles JE, Nikulin VI, Shams G, Konkar AA, Mehta R, Feller DR, Miller DD..  (1996)  Iodinated analogs of trimetoquinol as highly potent and selective beta 2-adrenoceptor ligands.,  39  (19): [PMID:8809159] [10.1021/jm960208o]

6. Markovich KM, Tantishaiyakul V, Hamada A, Miller DD, Romstedt KJ, Shams G, Shin Y, Fraundorfer PF, Doyle K, Feller DR..  (1992)  Synthesis of halogenated trimetoquinol derivatives and evaluation of their beta-agonist and thromboxane A2 (TXA2) antagonist activities.,  35  (3): [PMID:1346651] [10.1021/jm00081a007]

7. He Y, Nikulin VI, Vansal SS, Feller DR, Miller DD..  (2000)  Synthesis and human beta-adrenoceptor activity of 1-(3,5-diiodo-4- methoxybenzyl)-1,2,3,4-tetrahydroisoquinolin-6-ol derivatives in vitro.,  43  (4): [PMID:10691685] [10.1021/jm990463j]

8. Brossi A, Rice KC, Mak CP, Reden J, Jacobson AE, Nimitkitpaisan Y, Skolnick P, Daly J..  (1980)  Mammalian alkaloids. 8. Synthesis and biological effects of tetrahydropapaveroline related 1-benzyltetrahydroisoquinolines.,  23  (6): [PMID:6248642] [10.1021/jm00180a013]

9. Christoff JJ, Bradley L, Miller DD, Lei L, Rodriguez F, Fraundorfer P, Romstedt K, Shams G, Feller DR..  (1997)  Synthesis and evaluation of trimetoquinol derivatives: novel thromboxane A2/prostaglandin H2 antagonists with diminished beta-adrenergic agonist activity.,  40  (1): [PMID:9016331] [10.1021/jm950896w]

10. Sober DJ, Chang J, Fowble JW, Mukhopadhyay A, Feller DR, Miller DD, Fairchild EH..  (1981)  Selective and potent beta 2-adrenoceptor agents within the tetrahydroisoquinoline class: effect of methyl substitution at the benzylic carbon of the 1-(3,4,5-trimethoxybenzyl) group of trimetoquinol.,  24  (8): [PMID:6120236] [10.1021/jm00140a011]

11. Mohler ML, Kang GS, Hong SS, Patil R, Kirichenko OV, Li W, Rakov IM, Geisert EE, Miller DD..  (2006)  Discovery of antiglioma activity of biaryl 1,2,3,4-tetrahydroisoquinoline derivatives and conformationally flexible analogues.,  49  (19): [PMID:16970409] [10.1021/jm060020x]

12. Osei-Gyimah P, Piascik MT, Fowble JW, Feller DR, Miller DD..  (1978)  Synthesis and beta-adrenoceptor activity of the erythro and threo isomers of substituted alpha-hydroxytrimetoquinol.,  21  (11): [PMID:31479] [10.1021/jm00209a019]

13. Miller DD, Kador PF, Venkatraman R, Feller DR..  (1976)  Synthesis and biological evaluation of fragmented derivatives of tetrahydroisoquinolines. 3. Trimetoquinol studies.,  19  (6): [PMID:950642] [10.1021/jm00228a005]

14. Bernhard Ellinger, Justus Dick, Vanessa Lage-Rupprecht, Bruce Schultz, Andrea Zaliani, Marcin Namysl, Stephan Gebel, Ole Pless, Jeanette Reinshagen, Christian Ebeling, Alexander Esser, Marc Jacobs, Carsten Claussen, and Martin Hofmann-Apitius.  (2021)  HDAC6 screening dataset using tau-based substrate in an enzymatic assay yields selective inhibitors and activators,  [10.6019/CHEMBL4808148]

15. Sutherland JJ, Yonchev D, Fekete A, Urban L..  (2023)  A preclinical secondary pharmacology resource illuminates target-adverse drug reaction associations of marketed drugs.,  14  (1): [PMID:37468498] [10.1038/s41467-023-40064-9]

Source

Source(2):

• Scientific Literature
• Fraunhofer HDAC6