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(S)-N-((1S,2S)-1-{(1S,2S)-1-[(S)-1-Carboxy-2-(1H-indol-3-yl)-ethylcarbamoyl]-2-methyl-butylcarbamoyl}-2-methyl-butyl)-3-{(S)-2-[(S)-2-(cyclohexanecarbonyl-amino)-3,3-diphenyl-propionylamino]-4-methyl-pentanoylamino}-succinamic acid

ID: ALA414082

PubChem CID: 44327585

Max Phase: Preclinical

Molecular Formula: C55H73N7O10

Molecular Weight: 992.23

Molecule Type: Small molecule

This compound is available for customization.

Associated Items:

Names and Identifiers

Canonical SMILES:  CC[C@H](C)[C@H](NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)C1CCCCC1)C(c1ccccc1)c1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)O)[C@@H](C)CC

Standard InChI:  InChI=1S/C55H73N7O10/c1-7-33(5)46(52(68)59-43(55(71)72)29-38-31-56-40-27-19-18-26-39(38)40)61-53(69)47(34(6)8-2)60-51(67)42(30-44(63)64)57-50(66)41(28-32(3)4)58-54(70)48(62-49(65)37-24-16-11-17-25-37)45(35-20-12-9-13-21-35)36-22-14-10-15-23-36/h9-10,12-15,18-23,26-27,31-34,37,41-43,45-48,56H,7-8,11,16-17,24-25,28-30H2,1-6H3,(H,57,66)(H,58,70)(H,59,68)(H,60,67)(H,61,69)(H,62,65)(H,63,64)(H,71,72)/t33-,34-,41-,42-,43-,46-,47-,48-/m0/s1

Standard InChI Key:  AOHDSQGONFMAPD-AXCZMTTCSA-N

Molfile:  

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M  END

Associated Targets(Human)

EDNRA Tclin Endothelin receptor ET-A (5008 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Ednrb Endothelin receptor ET-B (454 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Molecule Features

Natural Product: NoOral: NoChemical Probe: NoParenteral: No
Molecule Type: Small moleculeTopical: NoFirst In Class: NoBlack Box: No
Chirality: NoAvailability: NoProdrug: No

Biocomponents

Calculated Properties

Molecular Weight: 992.23Molecular Weight (Monoisotopic): 991.5419AlogP: 5.73#Rotatable Bonds: 26
Polar Surface Area: 264.99Molecular Species: ACIDHBA: 8HBD: 9
#RO5 Violations: 3HBA (Lipinski): 17HBD (Lipinski): 9#RO5 Violations (Lipinski): 4
CX Acidic pKa: 3.78CX Basic pKa: CX LogP: 6.86CX LogD: 0.67
Aromatic Rings: 4Heavy Atoms: 72QED Weighted: 0.04Np Likeness Score: -0.03

References

1. Cody WL, He JX, DePue PL, Waite LA, Leonard DM, Sefler AM, Kaltenbronn JS, Haleen SJ, Walker DM, Flynn MA..  (1995)  Structure-activity relationships of the potent combined endothelin-A/endothelin-B receptor antagonist Ac-DDip16-Leu-Asp-Ile-Ile-Trp21: development of endothelin-B receptor selective antagonists.,  38  (15): [PMID:7636842] [10.1021/jm00015a003]
2. Patt, W C WC and 13 more authors.  1999-06-17  Butenolide endothelin antagonists with improved aqueous solubility.  [PMID:10377221]
3. Wu, C C and 12 more authors.  2001-04-12  Acyl substitution at the ortho position of anilides enhances oral bioavailability of thiophene sulfonamides: TBC3214, an ETA selective endothelin antagonist.  [PMID:11312921]
4. Wu, Chengde C and 11 more authors.  2004-04-08  Discovery, modeling, and human pharmacokinetics of N-(2-acetyl-4,6-dimethylphenyl)-3-(3,4-dimethylisoxazol-5-ylsulfamoyl)thiophene-2-carboxamide (TBC3711), a second generation, ETA selective, and orally bioavailable endothelin antagonist.  [PMID:15055997]
5. Bolli, Martin H MH and 14 more authors.  2004-05-20  Novel benzo[1,4]diazepin-2-one derivatives as endothelin receptor antagonists.  [PMID:15139756]
6. Morris, C D and 5 more authors.  2005-06-20  Specific inhibition of the endothelin A receptor with ZD4054: clinical and pre-clinical evidence.  [PMID:15956965]
7. Iglarz, Marc M and 13 more authors.  2008-12  Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist.  [PMID:18780830]
8. Aubert, John-David JD and Juillerat-Jeanneret, Lucienne L.  2016-09-22  Endothelin-Receptor Antagonists beyond Pulmonary Arterial Hypertension: Cancer and Fibrosis.  [PMID:27266371]
9. Lepri, Susan S, Goracci, Laura L, Valeri, Aurora A and Cruciani, Gabriele G.  2016-10-04  Metabolism study and biological evaluation of bosentan derivatives.  [PMID:27318985]
10. Boss, Christoph C, Bolli, Martin H MH and Gatfield, John J.  2016-08-01  From bosentan (Tracleer®) to macitentan (Opsumit®): The medicinal chemistry perspective.  [PMID:27321813]
11. Khadtare, Nikhil; Stephani, Ralph and Korlipara, Vijaya.  2017-06-01  Design, synthesis and evaluation of 1,3,6-trisubstituted-4-oxo-1,4-dihydroquinoline-2-carboxylic acid derivatives as ETA receptor selective antagonists using FRET assay.  [PMID:28462837]
12. Gege, Christian and 15 more authors.  2018-05-15  Identification and biological evaluation of thiazole-based inverse agonists of RORγt.  [PMID:29631962]

Source