| Activity Type | Relation | Activity value | Units | Action Type | Journal | PubMed Id | doi | Assay Aladdin ID |
|---|
ID: ALA112624
Max Phase: Preclinical
Molecular Formula: C27H28BrN5O5S
Molecular Weight: 614.52
Molecule Type: Small molecule
Associated Items:
Representations
Canonical SMILES: Cc1ccc(-c2c(NS(=O)(=O)c3ccc(C(C)(C)CO)cc3)ncnc2OCCOc2ncc(Br)cn2)cc1
Standard InChI: InChI=1S/C27H28BrN5O5S/c1-18-4-6-19(7-5-18)23-24(33-39(35,36)22-10-8-20(9-11-22)27(2,3)16-34)31-17-32-25(23)37-12-13-38-26-29-14-21(28)15-30-26/h4-11,14-15,17,34H,12-13,16H2,1-3H3,(H,31,32,33)
Standard InChI Key: YAWNVAQKVARTGQ-UHFFFAOYSA-N
Associated Targets(Human)
Endothelin receptor ET-B 1928 Activities
Endothelin receptor ET-A 5008 Activities
| Activity Type | Relation | Activity value | Units | Action Type | Journal | PubMed Id | doi | Assay Aladdin ID |
|---|
Associated Targets(non-human)
Endothelin receptor ET-A 411 Activities
| Activity Type | Relation | Activity value | Units | Action Type | Journal | PubMed Id | doi | Assay Aladdin ID |
|---|
Endothelin receptor ET-A 1158 Activities
| Activity Type | Relation | Activity value | Units | Action Type | Journal | PubMed Id | doi | Assay Aladdin ID |
|---|
Endothelin receptor ET-B 471 Activities
| Activity Type | Relation | Activity value | Units | Action Type | Journal | PubMed Id | doi | Assay Aladdin ID |
|---|
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 |
Drug Indications
| MESH ID | MESH Heading | EFO IDs | EFO Terms | Max Phase for Indication | References |
|---|
Mechanisms of Action
| Mechanism of Action | Action Type | target ID | Target Name | Target Type | Target Organism | Binding Site Name | References |
|---|
Properties
| Molecular Weight: 614.52 | Molecular Weight (Monoisotopic): 613.0995 | AlogP: 4.53 | #Rotatable Bonds: 11 |
| Polar Surface Area: 136.42 | Molecular Species: ACID | HBA: 9 | HBD: 2 |
| #RO5 Violations: 1 | HBA (Lipinski): 10 | HBD (Lipinski): 2 | #RO5 Violations (Lipinski): 1 |
| CX Acidic pKa: 6.27 | CX Basic pKa: 3.37 | CX LogP: 5.16 | CX LogD: 4.41 |
| Aromatic Rings: 4 | Heavy Atoms: 39 | QED Weighted: 0.23 | Np Likeness Score: -1.17 |
References
| 1. Morimoto H, Ohashi N, Shimadzu H, Kushiyama E, Kawanishi H, Hosaka T, Kawase Y, Yasuda K, Kikkawa K, Yamauchi-Kohno R, Yamada K.. (2001) Potent and selective ET-A antagonists. 2. Discovery and evaluation of potent and water soluble N-(6-(2-(aryloxy)ethoxy)-4-pyrimidinyl)sulfonamide derivatives., 44 (21): [PMID:11585442] [10.1021/jm000538f] |
| 2. Bolli MH, Boss C, Binkert C, Buchmann S, Bur D, Hess P, Iglarz M, Meyer S, Rein J, Rey M, Treiber A, Clozel M, Fischli W, Weller T.. (2012) The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N'-propylsulfamide (Macitentan), an orally active, potent dual endothelin receptor antagonist., 55 (17): [PMID:22862294] [10.1021/jm3009103] |
| 3. Boss C, Bolli MH, Gatfield J.. (2016) From bosentan (Tracleer®) to macitentan (Opsumit®): The medicinal chemistry perspective., 26 (15): [PMID:27321813] [10.1016/j.bmcl.2016.06.014] |
| 4. Aubert JD, Juillerat-Jeanneret L.. (2016) Endothelin-Receptor Antagonists beyond Pulmonary Arterial Hypertension: Cancer and Fibrosis., 59 (18): [PMID:27266371] [10.1021/acs.jmedchem.5b01781] |
Source
Source(1):