ID: ALA3806205

Max Phase: Preclinical

Molecular Formula: C22H36NO4P

Molecular Weight: 409.51

Molecule Type: Small molecule

Representations

Canonical SMILES:  CCCCCC[C@@H]1CCc2cc([C@H]3CC[C@](N)(COP(=O)(O)O)C3)ccc2C1

Standard InChI:  InChI=1S/C22H36NO4P/c1-2-3-4-5-6-17-7-8-19-14-20(10-9-18(19)13-17)21-11-12-22(23,15-21)16-27-28(24,25)26/h9-10,14,17,21H,2-8,11-13,15-16,23H2,1H3,(H2,24,25,26)/t17-,21+,22-/m1/s1

Standard InChI Key:  BWKSEIHXZRSETR-VOQZNFBZSA-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: No

Availability: No

Prodrug: No

Properties

Molecular Weight: 409.51

Molecular Weight (Monoisotopic): 409.2382

AlogP: 4.84

#Rotatable Bonds: 9

Polar Surface Area: 92.78

Molecular Species: ZWITTERION

HBA: 3

HBD: 3

#RO5 Violations: 0

HBA (Lipinski): 5

HBD (Lipinski): 4

#RO5 Violations (Lipinski): 0

CX Acidic pKa: 1.68

CX Basic pKa: 10.42

CX LogP: 4.21

CX LogD: 3.45

Aromatic Rings: 1

Heavy Atoms: 28

QED Weighted: 0.40

Np Likeness Score: 1.11

References

1. Dhar TG, Xiao HY, Xie J, Lehman-McKeeman LD, Wu DR, Dabros M, Yang X, Taylor TL, Zhou XD, Heimrich EM, Thomas R, McIntyre KW, Warrack B, Shi H, Levesque PC, Zhu JL, Hennan J, Balimane P, Yang Z, Marino AM, Cornelius G, D'Arienzo CJ, Mathur A, Shen DR, Cvijic ME, Salter-Cid L, Barrish JC, Carter PH, Dyckman AJ..  (2016)  Identification and Preclinical Pharmacology of BMS-986104: A Differentiated S1P1 Receptor Modulator in Clinical Trials.,  7  (3): [PMID:26985316] [10.1021/acsmedchemlett.5b00448]

2. Xiao Z, Yang MG, Dhar TGM, Xiao HY, Gilmore JL, Marcoux D, McIntyre KW, Taylor TL, Shi H, Levesque PC, Marino AM, Cornelius G, Mathur A, Shen DR, Cvijic ME, Lehman-McKeeman LD, Sun H, Xie JH, Carter PH, Dyckman AJ..  (2020)  Aryl Ether-Derived Sphingosine-1-Phosphate Receptor (S1P₁) Modulators: Optimization of the PK, PD, and Safety Profiles.,  11  (9): [PMID:32944145] [10.1021/acsmedchemlett.0c00333]

3. Yang MG,Xiao Z,Dhar TG,Xiao HY,Gilmore JL,Marcoux D,Xie JH,McIntyre KW,Taylor TL,Borowski V,Heimrich E,Li YW,Feng J,Fernandes A,Yang Z,Balimane P,Marino AM,Cornelius G,Warrack BM,Mathur A,Wu DR,Li P,Gupta A,Pragalathan B,Shen DR,Cvijic ME,Lehman-McKeeman LD,Salter-Cid L,Barrish JC,Carter PH,Dyckman AJ.  (2016)  Asymmetric Hydroboration Approach to the Scalable Synthesis of ((1R,3S)-1-Amino-3-((R)-6-hexyl-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol (BMS-986104) as a Potent S1P Receptor Modulator.,  59  (24.0): [PMID:28002964] [10.1021/acs.jmedchem.6b01433]

4. Gilmore JL,Xiao HY,Dhar TGM,Yang M,Xiao Z,Yang X,Taylor TL,McIntyre KW,Warrack BM,Shi H,Levesque PC,Marino AM,Cornelius G,Mathur A,Shen DR,Pang J,Cvijic ME,Lehman-McKeeman LD,Sun H,Xie J,Salter-Cid L,Carter PH,Dyckman AJ.  (2021)  Bicyclic Ligand-Biased Agonists of S1P: Exploring Side Chain Modifications to Modulate the PK, PD, and Safety Profiles.,  64  (3.0): [PMID:33492963] [10.1021/acs.jmedchem.0c01109]

5. Gilmore JL,Xiao HY,Dhar TGM,Yang MG,Xiao Z,Xie J,Lehman-McKeeman LD,Gong L,Sun H,Lecureux L,Chen C,Wu DR,Dabros M,Yang X,Taylor TL,Zhou XD,Heimrich EM,Thomas R,McIntyre KW,Borowski V,Warrack BM,Li Y,Shi H,Levesque PC,Yang Z,Marino AM,Cornelius G,D'Arienzo CJ,Mathur A,Rampulla R,Gupta A,Pragalathan B,Shen DR,Cvijic ME,Salter-Cid LM,Carter PH,Dyckman AJ.  (2019)  Identification and Preclinical Pharmacology of ((1 R,3 S)-1-Amino-3-(( S)-6-(2-methoxyphenethyl)-5,6,7,8-tetrahydronaphthalen-2-yl)cyclopentyl)methanol (BMS-986166): A Differentiated Sphingosine-1-phosphate Receptor 1 (S1P) Modulator Advanced into Clinical Trials.,  62  (5.0): [PMID:30785748] [10.1021/acs.jmedchem.8b01695]

Source

Source(1):

• Scientific Literature