ID: ALA23541

Max Phase: Preclinical

Molecular Formula: C26H27NO3

Molecular Weight: 401.51

Molecule Type: Small molecule

Representations

Synonyms (2): SCH-47949 | SCH-48461
Synonyms from Alternative Forms(2):

Canonical SMILES:  COc1ccc([C@@H]2[C@@H](CCCc3ccccc3)C(=O)N2c2ccc(OC)cc2)cc1

Standard InChI:  InChI=1S/C26H27NO3/c1-29-22-15-11-20(12-16-22)25-24(10-6-9-19-7-4-3-5-8-19)26(28)27(25)21-13-17-23(30-2)18-14-21/h3-5,7-8,11-18,24-25H,6,9-10H2,1-2H3/t24-,25-/m1/s1

Standard InChI Key:  IMNTVVOUWFPRSB-JWQCQUIFSA-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: 401.51

Molecular Weight (Monoisotopic): 401.1991

AlogP: 5.43

#Rotatable Bonds: 8

Polar Surface Area: 38.77

Molecular Species: NEUTRAL

HBA: 3

HBD: 0

#RO5 Violations: 1

HBA (Lipinski): 4

HBD (Lipinski): 0

#RO5 Violations (Lipinski): 1

CX Acidic pKa:

CX Basic pKa:

CX LogP: 5.49

CX LogD: 5.49

Aromatic Rings: 3

Heavy Atoms: 30

QED Weighted: 0.47

Np Likeness Score: -0.02

References

1. Dugar S, Yumibe N, Clader JW, Vizziano M, Huie K, Van Heek M, Compton DS, Davis HR.  (1996)  Metabolism and structure activity data based drug design: discovery of () SCH 53079 an analog of the potent cholesterol absorption inhibitor () SCH 48461,  6  (11): [10.1016/0960-894X(96)00214-4]

2. Dugar S, Yumibe N, Clader JW, Vizziano M, Huie K, Van Heek M, Compton DS, Davis HR.  (1996)  Metabolism and structure activity data based drug design: discovery of () SCH 53079 an analog of the potent cholesterol absorption inhibitor () SCH 48461,  6  (11): [10.1016/0960-894X(96)00214-4]

3. Burnett DA, Caplen MA, Davis HR, Burrier RE, Clader JW..  (1994)  2-Azetidinones as inhibitors of cholesterol absorption.,  37  (12): [PMID:8021912] [10.1021/jm00038a001]

4. Burnett DA, Caplen MA, Davis HR, Burrier RE, Clader JW..  (1994)  2-Azetidinones as inhibitors of cholesterol absorption.,  37  (12): [PMID:8021912] [10.1021/jm00038a001]

5. Burnett DA, Caplen MA, Davis HR, Burrier RE, Clader JW..  (1994)  2-Azetidinones as inhibitors of cholesterol absorption.,  37  (12): [PMID:8021912] [10.1021/jm00038a001]

6. McKittrick BA, Ma K, Dugar S, Clader JW, Davis H, Czarniecki M, McPhail AT.  (1996)  Stereoselective synthesis and biological activity of cis azetidinones as cholesterol absorption inhibitors,  6  (16): [10.1016/0960-894X(96)00347-2]

7. Dugar S, Kirkup MP, Clader JW, Lin S, Rizvi R, Snow ME, Davis HR, McCombie SW.  (1995)  Gamma-lactams and related compounds as cholesterol absorption inhibitors: homologs of the beta-lactam cholesterol absorption inhibitor SCH 484611,  5  (24): [10.1016/0960-894X(95)00516-6]

8. Dugar S, Kirkup MP, Clader JW, Lin S, Rizvi R, Snow ME, Davis HR, McCombie SW.  (1995)  Gamma-lactams and related compounds as cholesterol absorption inhibitors: homologs of the beta-lactam cholesterol absorption inhibitor SCH 484611,  5  (24): [10.1016/0960-894X(95)00516-6]

9. Burnett DA, Caplen MA, Domalski MS, Browne ME, Davis HR, Clader JW..  (2002)  Synthesis of iodinated biochemical tools related to the 2-azetidinone class of cholesterol absorption inhibitors.,  12  (3): [PMID:11814785] [10.1016/s0960-894x(01)00750-8]

10. Vaccaro WD, Davis HR..  (1998)  Sugar-substituted 2-azetidinone cholesterol absorption inhibitors: enhanced potency by modification of the sugar.,  8  (3): [PMID:9871676] [10.1016/s0960-894x(98)00008-0]

11. Burnett DA, Caplen MA, Browne ME, Zhau H, Altmann SW, Davis HR, Clader JW..  (2002)  Synthesis of fluorescent biochemical tools related to the 2-azetidinone class of cholesterol absorption inhibitors.,  12  (3): [PMID:11814786] [10.1016/s0960-894x(01)00752-1]

12. Vaccaro WD, Sher R, Davis HR..  (1998)  Carboxy-substituted 2-azetidinones as cholesterol absorption inhibitors.,  8  (3): [PMID:9871677] [10.1016/s0960-894x(98)00009-2]

13. Vaccaro WD, Sher R, Davis HR..  (1998)  Carboxy-substituted 2-azetidinones as cholesterol absorption inhibitors.,  8  (3): [PMID:9871677] [10.1016/s0960-894x(98)00009-2]

14. Clader JW, Burnett DA, Caplen MA, Domalski MS, Dugar S, Vaccaro W, Sher R, Browne ME, Zhao H, Burrier RE, Salisbury B, Davis HR..  (1996)  2-Azetidinone cholesterol absorption inhibitors: structure-activity relationships on the heterocyclic nucleus.,  39  (19): [PMID:8809157] [10.1021/jm960405n]

15. Vaccaro WD, Sher R, Davis HR..  (1998)  Sugar-substituted 2-azetidinones as cholesterol absorption inhibitors.,  8  (1): [PMID:9871624] [10.1016/s0960-894x(97)10185-8]

16. Dugar S, Clader JW, Chan TM, Davis H..  (1995)  Substituted 2-azaspiro[5.3]nonan-1-ones as potent cholesterol absorption inhibitors: defining a binding conformation for SCH 48461.,  38  (25): [PMID:8523398] [10.1021/jm00025a002]

17. Dugar S, Clader JW, Chan TM, Davis H..  (1995)  Substituted 2-azaspiro[5.3]nonan-1-ones as potent cholesterol absorption inhibitors: defining a binding conformation for SCH 48461.,  38  (25): [PMID:8523398] [10.1021/jm00025a002]

18. McKittrick BA, Ma K, Huie K, Yumibe N, Davis H, Clader JW, Czarniecki M, McPhail AT..  (1998)  Synthesis of C3 heteroatom-substituted azetidinones that display potent cholesterol absorption inhibitory activity.,  41  (5): [PMID:9513603] [10.1021/jm970676d]

19. Rosenblum SB, Huynh T, Afonso A, Davis HR, Yumibe N, Clader JW, Burnett DA..  (1998)  Discovery of 1-(4-fluorophenyl)-(3R)-[3-(4-fluorophenyl)-(3S)-hydroxypropyl]-(4S)-(4 -hydroxyphenyl)-2-azetidinone (SCH 58235): a designed, potent, orally active inhibitor of cholesterol absorption.,  41  (6): [PMID:9526571] [10.1021/jm970701f]

20. Itzhak Y, Kalir A, Weissman BA, Cohen S..  (1981)  New analgesic drugs derived from phencyclidine.,  24  (5): [PMID:7241506] [10.1021/jm00137a004]

21. Itzhak Y, Kalir A, Weissman BA, Cohen S..  (1981)  New analgesic drugs derived from phencyclidine.,  24  (5): [PMID:7241506] [10.1021/jm00137a004]

22. Kvaernø L, Werder M, Hauser H, Carreira EM..  (2005)  Synthesis and in vitro evaluation of inhibitors of intestinal cholesterol absorption.,  48  (19): [PMID:16162006] [10.1021/jm050422p]

23. Mehta PD, Sengar NP, Pathak AK..  (2010)  2-Azetidinone--a new profile of various pharmacological activities.,  45  (12): [PMID:20970895] [10.1016/j.ejmech.2010.09.035]

Source

Source(1):

• Scientific Literature