1-(((5S,7S)-2-oxo-3-o-tolyl-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile

ID: ALA4571300

PubChem CID: 155562973

Max Phase: Preclinical

Molecular Formula: C24H24N4O2

Molecular Weight: 400.48

Molecule Type: Unknown

This compound is available for customization.

Associated Items:

Bioactivity Summary Target Summary Assay Summary

Names and Identifiers

Canonical SMILES: Cc1ccccc1N1C[C@@]2(CCC[C@H](Cn3cnc4ccc(C#N)cc43)C2)OC1=O

Standard InChI: InChI=1S/C24H24N4O2/c1-17-5-2-3-7-21(17)28-15-24(30-23(28)29)10-4-6-19(12-24)14-27-16-26-20-9-8-18(13-25)11-22(20)27/h2-3,5,7-9,11,16,19H,4,6,10,12,14-15H2,1H3/t19-,24-/m0/s1

Standard InChI Key: INCFOJCEVMZAIC-CYFREDJKSA-N

Molfile:

 
     RDKit          2D

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   14.1814  -24.8118    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.2209  -23.9957    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   13.4570  -23.7059    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.9454  -24.3429    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   11.7983  -28.0486    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.7972  -28.8681    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.5052  -29.2771    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.5034  -27.6397    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.2121  -28.0450    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.2169  -28.8636    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.9969  -29.1121    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.4742  -28.4469    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.9891  -27.7876    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   11.0911  -27.6407    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.3833  -27.2322    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   14.2371  -27.0089    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.6867  -26.4048    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.9367  -25.6292    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.5907  -25.1970    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.3406  -25.9760    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   12.8900  -26.5844    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.2423  -22.9174    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   14.9015  -23.5492    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.6315  -23.9190    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.3146  -23.4719    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.2690  -22.6551    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.5344  -22.2874    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   14.8544  -22.7367    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   15.6766  -24.7349    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  1  0
  4  5  1  0
  1  5  1  6
  6  7  2  0
  7  8  1  0
  8 11  2  0
 10  9  2  0
  9  6  1  0
 10 11  1  0
 11 12  1  0
 12 13  2  0
 13 14  1  0
 14 10  1  0
 15 16  3  0
  6 15  1  0
 14 17  1  0
 18 17  1  1
 18 19  1  0
 18 22  1  0
 19  1  1  0
  1 20  1  0
 20 21  1  0
 21 22  1  0
  4 23  2  0
 24 25  2  0
 25 26  1  0
 26 27  2  0
 27 28  1  0
 28 29  2  0
 29 24  1  0
  3 24  1  0
 25 30  1  0
M  END

Natural Product: No	Oral: No	Chemical Probe: No	Parenteral: No
Molecule Type: Unknown	Topical: No	First In Class: No	Black Box: No
Chirality: No	Availability: No	Prodrug: No

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Unknown

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 400.48	Molecular Weight (Monoisotopic): 400.1899	AlogP: 4.80	#Rotatable Bonds: 3
Polar Surface Area: 71.15	Molecular Species: NEUTRAL	HBA: 5	HBD: ┄
#RO5 Violations: ┄	HBA (Lipinski): 6	HBD (Lipinski): ┄	#RO5 Violations (Lipinski): ┄
CX Acidic pKa: ┄	CX Basic pKa: 5.17	CX LogP: 4.55	CX LogD: 4.54
Aromatic Rings: 3	Heavy Atoms: 30	QED Weighted: 0.63	Np Likeness Score: -0.94

References

1. Brooks CA, Barton LS, Behm DJ, Eidam HS, Fox RM, Hammond M, Hoang TH, Holt DA, Hilfiker MA, Lawhorn BG, Patterson JR, Stoy P, Roethke TJ, Ye G, Zhao S, Thorneloe KS, Goodman KB, Cheung M.. (2019) Discovery of GSK2798745: A Clinical Candidate for Inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4)., 10 (8): [PMID:31413810] [10.1021/acsmedchemlett.9b00274]
2. Watanabe, Hiroyuki H and 13 more authors. 2002-04-19 Activation of TRPV4 channels (hVRL-2/mTRP12) by phorbol derivatives. [PMID:11827975]
3. Suzuki, Makoto M, Mizuno, Atsuko A, Kodaira, Kunihiko K and Imai, Masashi M. 2003-06-20 Impaired pressure sensation in mice lacking TRPV4. [PMID:12692122]
4. Xu, Feng F, Satoh, Eisaku E and Iijima, Toshihiko T. 2003-09 Protein kinase C-mediated Ca2+ entry in HEK 293 cells transiently expressing human TRPV4. [PMID:12970074]
5. Everaerts, Wouter W and 17 more authors. 2010-11-02 Inhibition of the cation channel TRPV4 improves bladder function in mice and rats with cyclophosphamide-induced cystitis. [PMID:20956320]
6. Thorneloe, Kevin S KS and 35 more authors. 2012-11-07 An orally active TRPV4 channel blocker prevents and resolves pulmonary edema induced by heart failure. [PMID:23136043]
7. Washburn, David G DG and 22 more authors. 2013-09-01 The discovery of potent blockers of the canonical transient receptor channels, TRPC3 and TRPC6, based on an anilino-thiazole pharmacophore. [PMID:23886683]
8. Hilfiker, Mark A MA and 8 more authors. 2013-02-14 Optimization of a Novel Series of TRPV4 Antagonists with In Vivo Activity in a Model of Pulmonary Edema. [PMID:24900661]
9. Cheung, Mui M and 15 more authors. 2017-05-11 Discovery of GSK2193874: An Orally Active, Potent, and Selective Blocker of Transient Receptor Potential Vanilloid 4. [PMID:28523109]
10. Brnardic, Edward J EJ and 17 more authors. 2018-11-08 Discovery of Pyrrolidine Sulfonamides as Selective and Orally Bioavailable Antagonists of Transient Receptor Potential Vanilloid-4 (TRPV4). [PMID:30335378]
11. Pero, Joseph E JE and 27 more authors. 2018-12-27 Design and Optimization of Sulfone Pyrrolidine Sulfonamide Antagonists of Transient Receptor Potential Vanilloid-4 with in Vivo Activity in a Pulmonary Edema Model. [PMID:30500190]
12. Atobe, Masakazu M and 8 more authors. 2019-02-14 Discovery of Novel Transient Receptor Potential Vanilloid 4 (TRPV4) Agonists as Regulators of Chondrogenic Differentiation: Identification of Quinazolin-4(3 H)-ones and in Vivo Studies on a Surgically Induced Rat Model of Osteoarthritis. [PMID:30629441]
13. Sami, Yuichi Y and 5 more authors. 2019-09-01 Discovery of a novel orally active TRPV4 inhibitor: Part 1. Optimization from an HTS hit. [PMID:31327678]
14. Brooks, Carl A CA and 17 more authors. 2019-08-08 Discovery of GSK2798745: A Clinical Candidate for Inhibition of Transient Receptor Potential Vanilloid 4 (TRPV4). [PMID:31413810]
15. Lawhorn, Brian G; Brnardic, Edward J and Behm, David J. 2020-04-15 Recent advances in TRPV4 agonists and antagonists. [PMID:32063431]
16. Liu, Na; Yan, Fang; Ma, Qingjie and Zhao, Jianhua. 2020-08-15 Modulation of TRPV4 and BKCa for treatment of brain diseases. [PMID:32690264]
17. Patterson, Jaclyn R and 11 more authors. 2020-12-10 Design and Optimization of an Acyclic Amine Series of TRPV4 Antagonists by Electronic Modulation of Hydrogen Bond Interactions. [PMID:33201708]

1-(((5S,7S)-2-oxo-3-o-tolyl-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile

Names and Identifiers

Alternative Forms

Associated Targets(Human)

Molecule Features

Drug Indications

Mechanisms of Action

Biocomponents

Calculated Properties

References

Source