Methyl (S)-2-((2-((3-(Trifluoromethoxy)phenyl)carbamoyl)-pyrrolidine-1-carboxamido)methyl)benzoate

ID: ALA4076148

PubChem CID: 122164799

Max Phase: Preclinical

Molecular Formula: C22H22F3N3O5

Molecular Weight: 465.43

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  COC(=O)c1ccccc1CNC(=O)N1CCC[C@H]1C(=O)Nc1cccc(OC(F)(F)F)c1

Standard InChI:  InChI=1S/C22H22F3N3O5/c1-32-20(30)17-9-3-2-6-14(17)13-26-21(31)28-11-5-10-18(28)19(29)27-15-7-4-8-16(12-15)33-22(23,24)25/h2-4,6-9,12,18H,5,10-11,13H2,1H3,(H,26,31)(H,27,29)/t18-/m0/s1

Standard InChI Key:  PFCVWXAGCYCOIQ-SFHVURJKSA-N

Molfile:  

     RDKit          2D

 33 35  0  0  0  0  0  0  0  0999 V2000
    7.2639  -16.1004    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.0811  -16.1004    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.3355  -15.3236    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.6725  -14.8415    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.0137  -15.3236    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.5606  -16.7620    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.2274  -17.5082    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    9.3735  -16.6776    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    9.8530  -17.3392    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5159  -18.0840    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.9948  -18.7453    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.8085  -18.6612    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.1411  -17.9101    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.6602  -17.2520    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   11.9536  -17.8227    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   12.4355  -18.4827    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   13.2480  -18.3954    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   12.1048  -19.2300    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
   12.8398  -19.1875    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    6.7827  -16.7608    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9701  -16.6744    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.1141  -17.5078    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    5.4889  -17.3349    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.8203  -18.0818    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3358  -18.7407    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6666  -19.4871    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.4800  -19.5741    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.9616  -18.9086    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6281  -18.1649    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5234  -18.6522    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.1938  -17.9044    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.0406  -19.3115    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.2282  -19.2230    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
  5  1  1  0
  2  6  1  1
  6  7  2  0
  6  8  1  0
  8  9  1  0
  9 10  2  0
 10 11  1  0
 11 12  2  0
 12 13  1  0
 13 14  2  0
 14  9  1  0
 13 15  1  0
 15 16  1  0
 16 17  1  0
 16 18  1  0
 16 19  1  0
  1 20  1  0
 20 21  1  0
 20 22  2  0
 21 23  1  0
 23 24  1  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
 25 30  1  0
 30 31  2  0
 30 32  1  0
 32 33  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4076148

   ---

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

Calculated Properties

Molecular Weight: 465.43

Molecular Weight (Monoisotopic): 465.1512

AlogP: 3.68

#Rotatable Bonds: 6

Polar Surface Area: 96.97

Molecular Species: NEUTRAL

HBA: 5

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 8

HBD (Lipinski): 2

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 12.93

CX Basic pKa: ┄

CX LogP: 4.00

CX LogD: 4.00

Aromatic Rings: 2

Heavy Atoms: 33

QED Weighted: 0.63

Np Likeness Score: -1.58

References

1. Vulpetti A, Randl S, Rüdisser S, Ostermann N, Erbel P, Mac Sweeney A, Zoller T, Salem B, Gerhartz B, Cumin F, Hommel U, Dalvit C, Lorthiois E, Maibaum J..  (2017)  Structure-Based Library Design and Fragment Screening for the Identification of Reversible Complement Factor D Protease Inhibitors.,  60  (5): [PMID:28157311] [10.1021/acs.jmedchem.6b01684]

2. Lorthiois E, Anderson K, Vulpetti A, Rogel O, Cumin F, Ostermann N, Steinbacher S, Mac Sweeney A, Delgado O, Liao SM, Randl S, Rüdisser S, Dussauge S, Fettis K, Kieffer L, de Erkenez A, Yang L, Hartwieg C, Argikar UA, La Bonte LR, Newton R, Kansara V, Flohr S, Hommel U, Jaffee B, Maibaum J..  (2017)  Discovery of Highly Potent and Selective Small-Molecule Reversible Factor D Inhibitors Demonstrating Alternative Complement Pathway Inhibition in Vivo.,  60  (13): [PMID:28621538] [10.1021/acs.jmedchem.7b00425]

3. Vulpetti A, Ostermann N, Randl S, Yoon T, Mac Sweeney A, Cumin F, Lorthiois E, Rüdisser S, Erbel P, Maibaum J..  (2018)  Discovery and Design of First Benzylamine-Based Ligands Binding to an Unlocked Conformation of the Complement Factor D.,  9  (5): [PMID:29795765] [10.1021/acsmedchemlett.8b00104]

4. Dalvit C, Vulpetti A..  (2019)  Ligand-Based Fluorine NMR Screening: Principles and Applications in Drug Discovery Projects.,  62  (5): [PMID:30295487] [10.1021/acs.jmedchem.8b01210]

5. Cheng KJ,Hsieh CM,Nepali K,Liou JP.  (2020)  Ocular Disease Therapeutics: Design and Delivery of Drugs for Diseases of the Eye.,  63  (19.0): [PMID:32482069] [10.1021/acs.jmedchem.9b01033]

6. Zhang W, Wu M, Vadlakonda S, Juarez L, Cheng X, Muppa S, Chintareddy V, Vogeti L, Kellogg-Yelder D, Williams J, Polach K, Chen X, Raman K, Babu YS, Kotian P..  (2022)  Scaffold hopping via ring opening enables identification of acyclic compounds as new complement Factor D inhibitors.,  74  [PMID:36272185] [10.1016/j.bmc.2022.117034]

Source

Source(1):

• Scientific Literature