3-((5-(5-chloro-1H-benzo[d]imidazol-2-yl)-2,3'-bipyridin-6'-yloxy)methyl)oxetane-3-carboxylic acid

ID: ALA4527223

PubChem CID: 155544326

Max Phase: Preclinical

Molecular Formula: C22H17ClN4O4

Molecular Weight: 436.86

Molecule Type: Unknown

Names and Identifiers

Canonical SMILES:  O=C(O)C1(COc2ccc(-c3ccc(-c4nc5cc(Cl)ccc5[nH]4)cn3)cn2)COC1

Standard InChI:  InChI=1S/C22H17ClN4O4/c23-15-3-5-17-18(7-15)27-20(26-17)14-1-4-16(24-9-14)13-2-6-19(25-8-13)31-12-22(21(28)29)10-30-11-22/h1-9H,10-12H2,(H,26,27)(H,28,29)

Standard InChI Key:  RFDLYPKRPJDMDM-UHFFFAOYSA-N

Molfile:  

 
     RDKit          2D

 31 35  0  0  0  0  0  0  0  0999 V2000
   27.0378  -20.9585    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.0337  -21.7757    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.8509  -21.7798    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   27.8550  -20.9626    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.4279  -21.3130    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   17.4267  -22.1325    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.1348  -22.5415    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.1330  -20.9041    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.8416  -21.3094    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   18.8464  -22.1280    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.6264  -22.3764    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   20.1038  -21.7113    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   19.6187  -21.0519    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   20.9190  -21.7060    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.3311  -22.4129    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.1476  -22.4084    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   22.5528  -21.6978    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   22.1356  -20.9902    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   21.3206  -20.9981    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.3657  -21.6905    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.7788  -22.3969    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.5952  -22.3914    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   24.9995  -21.6802    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   24.5814  -20.9731    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   23.7663  -20.9822    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   16.7201  -20.9045    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   25.8166  -21.6732    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   26.2192  -20.9620    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   27.4389  -20.2439    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   28.2560  -20.2369    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   27.0242  -19.5397    0.0000 O   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  1  1  0
  5  6  2  0
  6  7  1  0
  7 10  2  0
  9  8  2  0
  8  5  1  0
  9 10  1  0
 10 11  1  0
 11 12  1  0
 12 13  2  0
 13  9  1  0
 14 15  2  0
 15 16  1  0
 16 17  2  0
 17 18  1  0
 18 19  2  0
 19 14  1  0
 12 14  1  0
 20 21  2  0
 21 22  1  0
 22 23  2  0
 23 24  1  0
 24 25  2  0
 25 20  1  0
 17 20  1  0
  5 26  1  0
 23 27  1  0
 27 28  1  0
 28  1  1  0
  1 29  1  0
 29 30  1  0
 29 31  2  0
M  END

Alternative Forms

1. Parent:

   

   ALA4527223

   ---

Molecule Features

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: 436.86

Molecular Weight (Monoisotopic): 436.0938

AlogP: 3.82

#Rotatable Bonds: 6

Polar Surface Area: 110.22

Molecular Species: ACID

HBA: 6

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 3.59

CX Basic pKa: 4.76

CX LogP: 2.06

CX LogD: 0.00

Aromatic Rings: 4

Heavy Atoms: 31

QED Weighted: 0.47

Np Likeness Score: -1.07

References

1. Yu Y, Wu Z, Shi ZC, He S, Lai Z, Cernak TA, Vachal P, Liu M, Liu J, Hong Q, Jian T, Guiadeen D, Krikorian A, Sperbeck DM, Verras A, Sonatore LM, Murphy BA, Wiltsie J, Chung CC, Gorski JN, Liu J, Xiao J, Wolff M, Tong SX, Madeira M, Karanam BV, Shen DM, Balkovec JM, De Vita RJ, Pinto S, Nargund RP..  (2019)  Accelerating the discovery of DGAT1 inhibitors through the application of parallel medicinal chemistry (PMC).,  29  (11): [PMID:30952592] [10.1016/j.bmcl.2019.03.039]

2. Zhao, Gang G and 28 more authors.  2008-02-14  Validation of diacyl glycerolacyltransferase I as a novel target for the treatment of obesity and dyslipidemia using a potent and selective small molecule inhibitor.  [PMID:18183944]

3. Birch, Alan M AM and 7 more authors.  2009-03-26  Discovery of a potent, selective, and orally efficacious pyrimidinooxazinyl bicyclooctaneacetic acid diacylglycerol acyltransferase-1 inhibitor.  [PMID:19256504]

4. Nakada, Yoshihisa Y and 11 more authors.  2010-04-01  Novel acyl coenzyme A (CoA): diacylglycerol acyltransferase-1 inhibitors: synthesis and biological activities of diacylethylenediamine derivatives.  [PMID:20207151]

5. Qian, Yimin Y and 22 more authors.  2011-04-14  Discovery of orally active carboxylic acid derivatives of 2-phenyl-5-trifluoromethyloxazole-4-carboxamide as potent diacylglycerol acyltransferase-1 inhibitors for the potential treatment of obesity and diabetes.  [PMID:21413799]

6. Motiwala, Hashim H and 17 more authors.  2011-10-01  Exploration of pyridine containing heteroaryl analogs of biaryl ureas as DGAT1 inhibitors.  [PMID:21868220]

7. Yun, Weiya W and 11 more authors.  2011-12-01  Discovery and optimization of 2-phenyloxazole derivatives as diacylglycerol acyltransferase-1 inhibitors.  [PMID:22001092]

8. McCoull, William W and 28 more authors.  2012-06-15  Identification, optimisation and in vivo evaluation of oxadiazole DGAT-1 inhibitors for the treatment of obesity and diabetes.  [PMID:22608962]

9. Ting, Pauline C PC and 10 more authors.  2013-02-15  Lead optimization of a pyridine-carboxamide series as DGAT-1 inhibitors.  [PMID:23317570]

10. Kadam, Kishorkumar S KS and 14 more authors.  2013-07  Evaluation of thiazole containing biaryl analogs as diacylglycerol acyltransferase 1 (DGAT1) inhibitors.  [PMID:23735282]

11. Kwak, Hyun Jung HJ and 11 more authors.  2013-08-15  Synthesis and biological evaluation of aminobenzimidazole derivatives with a phenylcyclohexyl acetic acid group as anti-obesity and anti-diabetic agents.  [PMID:23810496]

12. Dow, Robert L RL and 13 more authors.  2013-09-01  Defining the key pharmacophore elements of PF-04620110: discovery of a potent, orally-active, neutral DGAT-1 inhibitor.  [PMID:23871442]

13. Kim, Hyunjin M HM and 8 more authors.  2013-12-01  Identification of 2-aminooxazole amides as acyl-CoA: diacylglycerol acyltransferase 1 (DGAT1) inhibitors through scaffold hopping strategy.  [PMID:24120540]

14. Fox, Brian M BM and 31 more authors.  2014-04-24  Discovery of 6-phenylpyrimido[4,5-b][1,4]oxazines as potent and selective acyl CoA:diacylglycerol acyltransferase 1 (DGAT1) inhibitors with in vivo efficacy in rodents.  [PMID:24670009]

15. Kandre, Shivaji S and 10 more authors.  2014-05-22  Synthesis and evaluation of cyclohexane carboxylic acid head group containing isoxazole and thiazole analogs as DGAT1 inhibitors.  [PMID:24735646]

16. Dow, Robert L RL and 15 more authors.  2011-05-12  Discovery of PF-04620110, a Potent, Selective, and Orally Bioavailable Inhibitor of DGAT-1.  [PMID:24900321]

17. Zhou, Gang G and 11 more authors.  2014-05-08  Development of novel benzomorpholine class of diacylglycerol acyltransferase I inhibitors.  [PMID:24900877]

18. Pagire, Suvarna H SH and 14 more authors.  2015-08-28  Discovery and optimization of adamantane carboxylic acid derivatives as potent diacylglycerol acyltransferase 1 inhibitors for the potential treatment of obesity and diabetes.  [PMID:26218650]

19. Yu, Tao T and 12 more authors.  2018-06-01  Discovery of dimethyl pent-4-ynoic acid derivatives, as potent and orally bioavailable DGAT1 inhibitors that suppress body weight in diet-induced mouse obesity model.  [PMID:29699923]

20. Harrison, Tyler J TJ and 16 more authors.  2019-08-08  Successful Strategies for Mitigation of a Preclinical Signal for Phototoxicity in a DGAT1 Inhibitor.  [PMID:31413796]

Source

Source(1):

• Scientific Literature