(3S,4R)-3-Hydroxy-2,2-dimethyl-4-(2-oxo-pyrrolidin-1-yl)-chroman-6-carbonitrile

ID: ALA11684

Chembl Id: CHEMBL11684

Cas Number: 94470-67-4

PubChem CID: 71191

Max Phase: Preclinical

Molecular Formula: C16H18N2O3

Molecular Weight: 286.33

Molecule Type: Small molecule

Associated Items:

Names and Identifiers

Canonical SMILES:  CC1(C)Oc2ccc(C#N)cc2[C@H](N2CCCC2=O)[C@H]1O

Standard InChI:  InChI=1S/C16H18N2O3/c1-16(2)15(20)14(18-7-3-4-13(18)19)11-8-10(9-17)5-6-12(11)21-16/h5-6,8,14-15,20H,3-4,7H2,1-2H3/t14-,15+/m0/s1

Standard InChI Key:  TVZCRIROJQEVOT-LSDHHAIUSA-N

Alternative Forms

  1. Parent:

Associated Targets(Human)

KCNJ11 Tclin Sulfonylurea receptors; K-ATP channels (596 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KCNJ11 Tclin Sulfonylurea receptor 2, Kir6.2 (426 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP2C19 Tchem Cytochrome P450 2C19 (29246 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP2D6 Tclin Cytochrome P450 2D6 (33882 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP2C9 Tchem Cytochrome P450 2C9 (32119 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP3A4 Tclin Cytochrome P450 3A4 (53859 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP1A2 Tchem Cytochrome P450 1A2 (26471 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Rattus norvegicus (775804 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Cavia porcellus (23802 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Sus scrofa (849 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
lef Anthrax lethal factor (7585 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Thoracic aorta (838 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Trachea (249 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Trachea/thoracic aorta (10 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Mus musculus (284745 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: YesOral: NoChemical Probe: NoParenteral: No
Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
Chirality: NoAvailability: NoProdrug: No

Drug Indications

MESH IDMESH Heading EFO IDsEFO TermsMax Phase for IndicationReferences

Mechanisms of Action

Mechanism of ActionAction Typetarget IDTarget NameTarget TypeTarget OrganismBinding Site NameReferences

Calculated Properties

Molecular Weight: 286.33Molecular Weight (Monoisotopic): 286.1317AlogP: 1.75#Rotatable Bonds: 1
Polar Surface Area: 73.56Molecular Species: NEUTRALHBA: 4HBD: 1
#RO5 Violations: HBA (Lipinski): 5HBD (Lipinski): 1#RO5 Violations (Lipinski):
CX Acidic pKa: 13.26CX Basic pKa: CX LogP: 1.02CX LogD: 1.02
Aromatic Rings: 1Heavy Atoms: 21QED Weighted: 0.85Np Likeness Score: 0.28

References

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2. Koga H, Sato H, Ishizawa T, Kuromaru K, Makino T, Taka N, Takahashi T, Sato T, Nabata H.  (1993)  Benzopyran-4-carboxamide K+ channel openers,  (6): [10.1016/S0960-894X(00)80298-X]
3. Coghlan MJ, Carroll WA, Gopalakrishnan M..  (2001)  Recent developments in the biology and medicinal chemistry of potassium channel modulators: update from a decade of progress.,  44  (11): [PMID:11356099] [10.1021/jm000484+]
4. Almansa C, Gomez LA, Cavalcanti FL, Rodriguez R, Garcia-Rafanell J, Forn J.  (1995)  4-(2-pyridyl)-2,2-dimethylnaphthalen-1-ones as new potassium channel activators with increased airways selectivity,  (16): [10.1016/0960-894X(95)00318-N]
5. Attwood MR, Brown BS, Dunsdon RM, Hurst DN, Jones PS, Kay PB.  (1992)  Synthesis of homochiral potassium channel openers: role of the benzopyranyl 3-hydroxyl group in cromakalim and pyridine N-oxides in determining the biological activities of enantiomers,  (3): [10.1016/S0960-894X(01)81070-2]
6. Attwood MR, Brown BS, Dunsdon RM, Hurst DN, Jones PS, Kay PB.  (1992)  Synthesis of homochiral potassium channel openers: role of the benzopyranyl 3-hydroxyl group in cromakalim and pyridine N-oxides in determining the biological activities of enantiomers,  (3): [10.1016/S0960-894X(01)81070-2]
7. Grant T, Frank C, Kau S, Li J, McLaren F, Ohnmacht C, Russell K, Shapiro H, Trivedi S.  (1993)  Anilide tertiary carbinols: A new structural class of potent potassium channel openers,  (12): [10.1016/S0960-894X(01)80750-2]
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9. Russell K, Brown F, Warwick P, Forst J, Grant T, Howe B, Kau S, Li J, McLaren F, Shapiro H, Trivedi S.  (1993)  A highly potent series of fluoroalkyl benzoxazine pyridine-N-oxide potassium channel openers,  (12): [10.1016/S0960-894X(01)80752-6]
10. Atwal KS, Grover GJ, Lodge NJ, Normandin DE, Traeger SC, Sleph PG, Cohen RB, Bryson CC, Dickinson KE..  (1998)  Binding of ATP-sensitive potassium channel (KATP) openers to cardiac membranes: correlation of binding affinities with cardioprotective and smooth muscle relaxing potencies.,  41  (3): [PMID:9464357] [10.1021/jm970762d]
11. Atwal KS, Grover GJ, Lodge NJ, Normandin DE, Traeger SC, Sleph PG, Cohen RB, Bryson CC, Dickinson KE..  (1998)  Binding of ATP-sensitive potassium channel (KATP) openers to cardiac membranes: correlation of binding affinities with cardioprotective and smooth muscle relaxing potencies.,  41  (3): [PMID:9464357] [10.1021/jm970762d]
12. 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]
13. Carroll WA, Agrios KA, Altenbach RJ, Buckner SA, Chen Y, Coghlan MJ, Daza AV, Drizin I, Gopalakrishnan M, Henry RF, Kort ME, Kym PR, Milicic I, Smith JC, Tang R, Turner SC, Whiteaker KL, Zhang H, Sullivan JP..  (2004)  Synthesis and structure-activity relationships of a novel series of tricyclic dihydropyridine-based KATP openers that potently inhibit bladder contractions in vitro.,  47  (12): [PMID:15163197] [10.1021/jm030357o]
14. Bergmann R, Gericke R..  (1990)  Synthesis and antihypertensive activity of 4-(1,2-dihydro-2-oxo-1-pyridyl)-2H-1-benzopyrans and related compounds, new potassium channel activators.,  33  (2): [PMID:2299619] [10.1021/jm00164a005]
15. Soll R, Dollings P, McCaully R, Argentieri T, Lodge N, Oshiro G, Colatsky T, Norton N, Zebick D, Havens C, Halaka N.  (1994)  N-sulfonamides of benzopyran-related potassium channel openers: Conversion of glyburide insensitive smooth muscle relaxants to potent smooth muscle contractors,  (5): [10.1016/S0960-894X(01)80198-0]
16. Empfield J, Mayhugh D, Ohnmacht C, Frank C, Grant T, Li J.  (1997)  4-Sulfonamidoanilide tertiary carbinols: A novel series of potassium channel openers,  (7): [10.1016/S0960-894X(97)00111-X]
17. 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]
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20. Bouhedja M, Peres B, Fhayli W, Ghandour Z, Boumendjel A, Faury G, Khelili S..  (2018)  Design, synthesis and biological evaluation of novel ring-opened cromakalim analogues with relaxant effects on vascular and respiratory smooth muscles and as stimulators of elastin synthesis.,  144  [PMID:29291445] [10.1016/j.ejmech.2017.12.071]
21. Roy Chowdhury U, Viker KB, Stoltz KL, Holman BH, Fautsch MP, Dosa PI..  (2016)  Analogs of the ATP-Sensitive Potassium (KATP) Channel Opener Cromakalim with in Vivo Ocular Hypotensive Activity.,  59  (13): [PMID:27367033] [10.1021/acs.jmedchem.6b00406]