(R)-3-((2S,3S)-2-Hydroxy-3-{(R)-2-[2-(isoquinolin-5-yloxy)-acetylamino]-3-methylsulfanyl-propionylamino}-4-phenyl-butyryl)-thiazolidine-4-carboxylic acid tert-butylamide

ID: ALA414640

Cas Number: 147318-81-8

PubChem CID: 60927

Max Phase: Preclinical

Molecular Formula: C33H41N5O6S2

Molecular Weight: 667.85

Molecule Type: Small molecule

Associated Items:

Bioactivity Summary Target Summary Assay Summary

This compound is not in our inventory system

Names and Identifiers

Synonyms: KNI-272 | kni-272|Kynostatin 272|147318-81-8|MUL0OE3YBF|CHEBI:80006|Kynostatin-272|NSC-651714|(4r)-n-tert-butyl-3-[(2s,3s)-2-hydroxy-3-({n-[(isoquinolin-5-yloxy)acetyl]-s-methyl-l-cysteinyl}amino)-4-phenylbutanoyl]-1,3-thiazolidine-4-carboxamide|4-Thiazolidinecarboxamide, N-(1,1-dimethylethyl)-3-(2-hydroxy-3-((2-(((5-isoquinolinyloxy)acetyl)amino)-3-(methylthio)-1-oxopropyl)amino)-1-oxo-4-phenylbutyl)-, (4R-(3(2S*,3S*(R*)),4R*))-|KNI|CCRIS 7458|UNII-MUL0OE3YBF|DRG-0219|NSC 651714|NSC651714|1hpx|Show More⌵

Canonical SMILES: CSC[C@H](NC(=O)COc1cccc2cnccc12)C(=O)N[C@@H](Cc1ccccc1)[C@H](O)C(=O)N1CSC[C@H]1C(=O)NC(C)(C)C

Standard InChI: InChI=1S/C33H41N5O6S2/c1-33(2,3)37-31(42)26-19-46-20-38(26)32(43)29(40)24(15-21-9-6-5-7-10-21)36-30(41)25(18-45-4)35-28(39)17-44-27-12-8-11-22-16-34-14-13-23(22)27/h5-14,16,24-26,29,40H,15,17-20H2,1-4H3,(H,35,39)(H,36,41)(H,37,42)/t24-,25-,26-,29-/m0/s1

Standard InChI Key: NJBBLOIWMSYVCQ-VZTVMPNDSA-N

Molfile:

     RDKit          2D

 46 49  0  0  0  0  0  0  0  0999 V2000
    6.0668    1.8497    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3523    1.4372    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3523    0.6122    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.0668    0.1997    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.7813    0.6122    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6379    0.1997    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.6379   -0.6253    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.3523   -1.0378    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.0668   -0.6253    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.2089    0.1997    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4945    0.6122    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0655    1.4372    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3511    0.1997    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0779    0.1997    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7924    0.6122    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0779   -0.6253    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5068    0.1997    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9750    0.2766    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.5270    0.8897    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.3075    1.4327    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.1465   -0.5303    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.1027   -1.5923    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.2742   -2.3992    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.2957   -1.7638    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.9096   -1.4207    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0655    0.6122    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.3511    2.6747    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7924   -1.0378    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7924   -1.8628    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5068   -2.2753    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2213   -1.8628    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2213   -1.0378    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.5068   -0.6253    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.7813    1.4372    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    1.7800    0.1997    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -0.3634    0.6122    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -3.2213    0.6122    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.9311   -0.7853    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.9234    0.6122    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.7924    1.4372    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    2.4945    1.4372    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -2.9918   -0.4678    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.5334   -1.0824    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.3511   -0.6253    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    0.3511    1.8497    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
   -4.1145    1.6042    0.0000 S   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  1 34  2  0
  2  3  2  0
  3  4  1  0
  3  6  1  0
  4  5  2  0
  4  9  1  0
  5 34  1  0
  6  7  2  0
  6 39  1  0
  7  8  1  0
  8  9  2  0
 10 11  1  0
 10 39  1  0
 11 35  1  0
 11 41  2  0
 12 26  1  0
 12 45  1  0
 13 26  1  0
 13 36  1  0
 13 44  2  0
 14 15  1  0
 14 16  1  0
 14 36  1  1
 15 17  1  0
 15 40  1  1
 16 28  1  0
 17 37  1  0
 17 42  2  0
 18 19  1  0
 18 21  1  6
 18 37  1  0
 19 46  1  0
 20 37  1  0
 20 46  1  0
 21 38  1  0
 21 43  2  0
 22 23  1  0
 22 24  1  0
 22 25  1  0
 22 38  1  0
 26 35  1  6
 27 45  1  0
 28 29  2  0
 28 33  1  0
 29 30  1  0
 30 31  2  0
 31 32  1  0
 32 33  2  0
M  END

Associated Targets(non-human)

pol Human immunodeficiency virus type 1 protease (9113 Activities)

Discover Target: pol

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

PMII Plasmepsin 2 (774 Activities)

Discover Target: PMII

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Human immunodeficiency virus 1 (70413 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

protease Protease (2551 Activities)

Discover Target: protease

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

SARS-CoV-2 (38078 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Natural Product: Yes	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

Natural Product: Yes

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: 667.85	Molecular Weight (Monoisotopic): 667.2498	AlogP: 2.37	#Rotatable Bonds: 13
Polar Surface Area: 149.96	Molecular Species: NEUTRAL	HBA: 9	HBD: 4
#RO5 Violations: 1	HBA (Lipinski): 11	HBD (Lipinski): 4	#RO5 Violations (Lipinski): 2
CX Acidic pKa: 11.87	CX Basic pKa: 4.55	CX LogP: 1.52	CX LogD: 1.52
Aromatic Rings: 3	Heavy Atoms: 46	QED Weighted: 0.22	Np Likeness Score: -0.57

References

1. Kimura T, Matsumoto H, Matsuda T, Hamawaki T, Akaji K, Kiso Y.. (1999) A new class of anti-HIV agents: synthesis and activity of conjugates of HIV protease inhibitors with a reverse transcriptase inhibitor., 9 (6): [PMID:10206539] [10.1016/s0960-894x(99)00089-x]
2. Hidaka K, Kimura T, Tsuchiya Y, Kamiya M, Ruben AJ, Freire E, Hayashi Y, Kiso Y.. (2007) Additional interaction of allophenylnorstatine-containing tripeptidomimetics with malarial aspartic protease plasmepsin II., 17 (11): [PMID:17400453] [10.1016/j.bmcl.2007.03.052]
3. Ami E, Nakahara K, Sato A, Nguyen JT, Hidaka K, Hamada Y, Nakatani S, Kimura T, Hayashi Y, Kiso Y.. (2007) Synthesis and antiviral property of allophenylnorstatine-based HIV protease inhibitors incorporating D-cysteine derivatives as P2/P3 moieties., 17 (15): [PMID:17537628] [10.1016/j.bmcl.2007.05.039]
4. Nakatani S, Hidaka K, Ami E, Nakahara K, Sato A, Nguyen JT, Hamada Y, Hori Y, Ohnishi N, Nagai A, Kimura T, Hayashi Y, Kiso Y.. (2008) Combination of non-natural D-amino acid derivatives and allophenylnorstatine-dimethylthioproline scaffold in HIV protease inhibitors have high efficacy in mutant HIV., 51 (10): [PMID:18426195] [10.1021/jm701555p]
5. Yang SS, Cragg GM, Newman DJ, Bader JP.. (2001) Natural product-based anti-HIV drug discovery and development facilitated by the NCI developmental therapeutics program., 64 (2): [PMID:11430019] [10.1021/np0003995]
6. Hidaka K, Kimura T, Sankaranarayanan R, Wang J, McDaniel KF, Kempf DJ, Kameoka M, Adachi M, Kuroki R, Nguyen JT, Hayashi Y, Kiso Y.. (2018) Identification of Highly Potent Human Immunodeficiency Virus Type-1 Protease Inhibitors against Lopinavir and Darunavir Resistant Viruses from Allophenylnorstatine-Based Peptidomimetics with P2 Tetrahydrofuranylglycine., 61 (12): [PMID:29852069] [10.1021/acs.jmedchem.7b01709]
7. Ellen Van Damme. (2021) Screening of ~5500 FDA-approved drugs and clinical candidates for anti-SARS-CoV-2 activity, [10.6019/CHEMBL4651402]
8. Kashif Khan R, Meanwell NA, Hager HH.. (2022) Pseudoprolines as stereoelectronically tunable proline isosteres., 75 [PMID:36096342] [10.1016/j.bmcl.2022.128983]

(R)-3-((2S,3S)-2-Hydroxy-3-{(R)-2-[2-(isoquinolin-5-yloxy)-acetylamino]-3-methylsulfanyl-propionylamino}-4-phenyl-butyryl)-thiazolidine-4-carboxylic acid tert-butylamide

Names and Identifiers

Alternative Forms

Associated Targets(Human)

Associated Targets(non-human)

Molecule Features

Drug Indications

Mechanisms of Action

Calculated Properties

References

Source