ID: ALA3915620

Max Phase: Phase

Molecular Formula: C33H33NO3

Molecular Weight: 491.63

Molecule Type: Small molecule

Representations

Synonyms (3): Ly2881835 | LY-2881835 | LY2881835
Synonyms from Alternative Forms(3):

Canonical SMILES:  CC#C[C@@H](CC(=O)O)c1ccc(OCc2ccc(CN3CCC4(C=Cc5ccccc54)CC3)cc2)cc1

Standard InChI:  InChI=1S/C33H33NO3/c1-2-5-29(22-32(35)36)27-12-14-30(15-13-27)37-24-26-10-8-25(9-11-26)23-34-20-18-33(19-21-34)17-16-28-6-3-4-7-31(28)33/h3-4,6-17,29H,18-24H2,1H3,(H,35,36)/t29-/m0/s1

Standard InChI Key:  FHRWHNJJQGSCQC-LJAQVGFWSA-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: Yes

Availability: No

Prodrug: No

Properties

Molecular Weight: 491.63

Molecular Weight (Monoisotopic): 491.2460

AlogP: 6.41

#Rotatable Bonds: 8

Polar Surface Area: 49.77

Molecular Species: ZWITTERION

HBA: 3

HBD: 1

#RO5 Violations: 1

HBA (Lipinski): 4

HBD (Lipinski): 1

#RO5 Violations (Lipinski): 1

CX Acidic pKa: 3.80

CX Basic pKa: 9.27

CX LogP: 3.93

CX LogD: 3.93

Aromatic Rings: 3

Heavy Atoms: 37

QED Weighted: 0.37

Np Likeness Score: 0.02

References

1. Unpublished dataset, 

2. Krasavin M, Lukin A, Bagnyukova D, Zhurilo N, Zahanich I, Zozulya S, Ihalainen J, Forsberg MM, Lehtonen M, Rautio J, Moore D, Tikhonova IG..  (2016)  Free fatty acid receptor 1 (GPR40) agonists containing spirocyclic periphery inspired by LY2881835.,  24  (21): [PMID:27647366] [10.1016/j.bmc.2016.09.004]

3. Chen C, Li H, Long YQ..  (2016)  GPR40 agonists for the treatment of type 2 diabetes mellitus: The biological characteristics and the chemical space.,  26  (23): [PMID:27825762] [10.1016/j.bmcl.2016.10.074]

4. Hamdouchi C, Maiti P, Warshawsky AM, DeBaillie AC, Otto KA, Wilbur KL, Kahl SD, Patel Lewis A, Cardona GR, Zink RW, Chen K, Cr S, Lineswala JP, Neathery GL, Bouaichi C, Diseroad BA, Campbell AN, Sweetana SA, Adams LA, Cabrera O, Ma X, Yumibe NP, Montrose-Rafizadeh C, Chen Y, Miller AR..  (2018)  Discovery of LY3104607: A Potent and Selective G Protein-Coupled Receptor 40 (GPR40) Agonist with Optimized Pharmacokinetic Properties to Support Once Daily Oral Treatment in Patients with Type 2 Diabetes Mellitus.,  61  (3): [PMID:29236497] [10.1021/acs.jmedchem.7b01411]

5. Chen T, Ning M, Ye Y, Wang K, Leng Y, Shen J..  (2018)  Design, synthesis and structure-activity relationship studies of GPR40 agonists containing amide linker.,  152  [PMID:29705709] [10.1016/j.ejmech.2018.04.023]

6. Hamdouchi C,Kahl SD,Patel Lewis A,Cardona GR,Zink RW,Chen K,Eessalu TE,Ficorilli JV,Marcelo MC,Otto KA,Wilbur KL,Lineswala JP,Piper JL,Coffey DS,Sweetana SA,Haas JV,Brooks DA,Pratt EJ,Belin RM,Deeg MA,Ma X,Cannady EA,Johnson JT,Yumibe NP,Chen Q,Maiti P,Montrose-Rafizadeh C,Chen Y,Reifel Miller A.  (2016)  The Discovery, Preclinical, and Early Clinical Development of Potent and Selective GPR40 Agonists for the Treatment of Type 2 Diabetes Mellitus (LY2881835, LY2922083, and LY2922470).,  59  (24.0): [PMID:27749056] [10.1021/acs.jmedchem.6b00892]

Source

Source(2):

• Scientific Literature
• Clinical Candidates