Home Cart Sign in  
Chemical Structure| 3189-13-7 Chemical Structure| 3189-13-7

Structure of 3189-13-7

Chemical Structure| 3189-13-7

*Storage: {[sel_prStorage]}

*Shipping: {[sel_prShipping]}

,{[proInfo.pro_purity]}

4.5 *For Research Use Only !

{[proInfo.pro_purity]}
Cat. No.: {[proInfo.prAm]} Purity: {[proInfo.pro_purity]}

Change View

Size Price VIP Price

US Stock

Global Stock

In Stock
{[ item.pr_size ]} Inquiry {[ getRatePrice(item.pr_usd,item.pr_rate,item.mem_rate,item.pr_is_large_size_no_price, item.vip_usd) ]}

US Stock: ship in 0-1 business day
Global Stock: ship in 5-7 days

  • {[ item.pr_size ]}

In Stock

- +

Please Login or Create an Account to: See VIP prices and availability

US Stock: ship in 0-1 business day
Global Stock: ship in 2 weeks

  • 1-2 Day Shipping
  • High Quality
  • Technical Support
Product Citations

Product Citations      Show More

Shriver, James A. ; Kaller, Kaylie S. ; Kinsey, Ally L. ; Wang, Katelyn R. ; Sterrenberg, Summer R. ; Van Vors, Madison K. , et al.

Abstract: The spontaneous conversion of 3-indoxyl to indigo was a well-established process used to produce indigo dyes. It was recently shown that some indoles, when reacted with molybdenum hexacarbonyl and cumyl peroxide, proceed through an indoxyl intermediate to produce significant amounts of indirubin through a competing mechanism. Modulation of this system to lower temperatures allows for careful tuning, leading to selective production of indirubins in a general process. A systematic assay of indoles show that electron deficient indoles work well when substituted at the 5 and 7 positions. In contrast, 6-substituted electron rich indoles give the best results whereas halogeno indoles work well in all cases. This process shows broad functional group tolerance for generally reactive carbonyl-containing compounds such as aldehydes and carboxylic acids.

Gardner, Eric ;

Abstract: The overall aim of my work was to expand the practical utility of prenyltransferase_x005f_x0002_based biocatalysis as a tool in organic synthesis, natural product diversification, and drug discovery efforts. Aromatic prenyltransferases (PTs) serve a key role in the biosynthesis of countless bioactive natural products (NPs), by catalyzing the transfer of a 5 carbon prenyl(dimethylallyl) moiety from an alkyl pyrophosphate “donor”onto an aromatic “acceptor”substrate via electrophilic aromatic substitution. Many PTs have been observed to have remarkably broad substrate scopes, capable of accepting allylic, benzylic, heterobenzylic, and diene containing alkyl donors and transferring them to a range of phenolic and indole_x005f_x0002_containing substrates. Having evolved to carry out highly regioselective and chemoselective alkylation in complex chemical environments, PTs represent a powerful untapped source of late-stage functionalization catalysts for both natural and synthetic drug diversification efforts. Chapter 1 introduces and highlights the significance of indole-containing NPs and the diverse spectrum of biological activity that arises from substituted indole scaffolds. A brief overview of known synthetic methods for indole functionalization is covered, focusing on the challenges associated with functionalizing the benzenoid portion of indole. Subsequently, indole-modifying enzymes are introduced, and the structure, function, and mechanism of indole PTs is described as a foundation to this dissertation work. Chapter 2 demonstrates the utility of PT-based natural product diversification, in which the cytotoxic prenylated tryptophan-containing cyclic dipeptide tryprostatin B (TPS_x005f_x0002_B) wassynthesized and chemoenzymatically alkylated using the promiscuous PT CdpNPT. Using a library of 66 synthetic alkyl-pyrophosphate donors, 24 unique donors were accepted by CdpNPT in the presence of TPS-B to generate novel NP analogs. 11 of these chemoenzymatically produced TPS-B analogs were isolated for structure elucidation via nuclear magnetic resonance (NMR) to reveal high selectivity for indole C6 alkylation. Cytotoxicity assays revealed that the TPS-B analogs produced in this work have a potency similar to their parent NPs. This work demonstrates that PT-based biocatalysts can be used for the late-stage diversification of NPs which provides direct access to NP analogs not accessible through current synthetic methods. Chapter 3 outlines the synthesis and utilization of a series of azaindole-substituted tryptophan analogs (Aza-Trp) to probe the compatibility of tryptophan-PTs with medicinally relevant indole isosteres. Synthetic tryptophan-mimetic substrates containing additional aromatic N atoms at the 2, 4, 5, 6, and 7 positions were prepared and screened as substrates for the indole C4-PT FgaPT2. These results identified 4-azatryprophan and 5-azatryptophan as previously unreported substrate classes for aromatic PTs. After structural elucidation of the prenylated products, we discovered FgaPT2 catalyzed N_x005f_x0002_prenylation of the 6-membered ring of these azaindole substrates to form a cationic N_x005f_x0002_prenylpyridinium products. Not only is this the first report of chemoenzymatic prenylation of azaindole substrates, but this work uncovered a previously undocumented PT-catalyzed reaction. Chapter 4 reports the synthesis and evaluation of azaindole-substituted tryptophan-proline cyclic dipeptides (Aza-CyWP) as substrates for aromatic PTs, with the goal of chemoenzymatically producing azaindole-containing analogs of this privileged NP core scaffold with enhanced aqueous solubility and altered bioactivity. We discovered that the indole-C2 PT which has the native function of TPS-B biosynthesis, FtmPT1, was capable of prenylating all 5 azaindole-containing substrates. However, these synthetic substrates were found to alter the regioselectivity of prenylation in an azaindole iso_x005f_x0002_dependent manner, resulting in a total of 7 fully characterized N1, C2, and C3 prenylated products. Additionally, the highly promiscuous PT utilized in Chapter 2, CdpNPT, was found to accept the 7-azaindole containing Aza-CyWP, to produce cyclized C3-reverse prenylated and N1 prenylated products. Using the common medicinal chemistry strategy of isosteric replacement, azaindole containing NP analogs were successfully generated using indole PTs. This work represents the first step toward the application of PT-based biocatalytic functionalization of synthetic heterocyclic scaffolds commonly utilized in structure-activity relationship studies.

Purchased from AmBeed: ;

Gardner, Eric D. ; Dimas, Dustin A. ; Finneran, Matthew C. ; Brown, Sara M. ; Burgett, Anthony W. ; Singh, Shanteri

Abstract: Tryprostatin A and B are prenylated, tryptophan-containing, diketopiperazine natural products, displaying cytotoxic activity through different mechanisms of action. The presence of the 6-methoxy substituent on the indole moiety of tryprostatin A was shown to be essential for the dual inhibition of topoisomerase II and tubulin polymerization However, the inability to perform late-stage modification of the indole ring has limited the structure-activity relationship studies of this class of natural products. Herein, we describe an efficient chemoenzymic approach for the late-stage modification of tryprostatin B using a cyclic dipeptide N-prenyltransferase (CdpNPT) from Aspergillus fumigatus, which generates novel analogs functionalized with allylic, benzylic, heterocyclic, and diene moieties. Notably, this biocatalytic functionalizational study revealed high selectivity for the indole C6 position. Seven of the 11 structurally characterized analogs were exclusively C6-alkylated, and the remaining four contained predominant C6-regioisomers. Of the 24 accepted substrates, 10 provided >50% conversion and eight provided 20-50% conversion, with the remaining six giving <20% conversion under standard conditions. This study demonstrates that prenyltransferase-based late-stage diversification enables direct access to previously inaccessible natural product analogs.

Keywords: biocatalysts ; chemoenzymatic synthesis ; late-stage functionalization ; prenyltransferase ; tryprostatin

Purchased from AmBeed: ; ; ; ;

Alternative Products

Product Details of [ 3189-13-7 ]

CAS No. :3189-13-7
Formula : C9H9NO
M.W : 147.17
SMILES Code : C1=C(C=C2C(=C1)C=C[NH]2)OC
MDL No. :MFCD00022780
InChI Key :QJRWYBIKLXNYLF-UHFFFAOYSA-N
Pubchem ID :76659

Safety of [ 3189-13-7 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Computational Chemistry of [ 3189-13-7 ] Show Less

Physicochemical Properties

Num. heavy atoms 11
Num. arom. heavy atoms 9
Fraction Csp3 0.11
Num. rotatable bonds 1
Num. H-bond acceptors 1.0
Num. H-bond donors 1.0
Molar Refractivity 44.79
TPSA ?

Topological Polar Surface Area: Calculated from
Ertl P. et al. 2000 J. Med. Chem.

25.02 Ų

Lipophilicity

Log Po/w (iLOGP)?

iLOGP: in-house physics-based method implemented from
Daina A et al. 2014 J. Chem. Inf. Model.

1.71
Log Po/w (XLOGP3)?

XLOGP3: Atomistic and knowledge-based method calculated by
XLOGP program, version 3.2.2, courtesy of CCBG, Shanghai Institute of Organic Chemistry

2.02
Log Po/w (WLOGP)?

WLOGP: Atomistic method implemented from
Wildman SA and Crippen GM. 1999 J. Chem. Inf. Model.

2.18
Log Po/w (MLOGP)?

MLOGP: Topological method implemented from
Moriguchi I. et al. 1992 Chem. Pharm. Bull.
Moriguchi I. et al. 1994 Chem. Pharm. Bull.
Lipinski PA. et al. 2001 Adv. Drug. Deliv. Rev.

1.23
Log Po/w (SILICOS-IT)?

SILICOS-IT: Hybrid fragmental/topological method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

2.53
Consensus Log Po/w?

Consensus Log Po/w: Average of all five predictions

1.93

Water Solubility

Log S (ESOL):?

ESOL: Topological method implemented from
Delaney JS. 2004 J. Chem. Inf. Model.

-2.56
Solubility 0.401 mg/ml ; 0.00273 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (Ali)?

Ali: Topological method implemented from
Ali J. et al. 2012 J. Chem. Inf. Model.

-2.17
Solubility 0.989 mg/ml ; 0.00672 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble
Log S (SILICOS-IT)?

SILICOS-IT: Fragmental method calculated by
FILTER-IT program, version 1.0.2, courtesy of SILICOS-IT, http://www.silicos-it.com

-3.39
Solubility 0.06 mg/ml ; 0.000407 mol/l
Class?

Solubility class: Log S scale
Insoluble < -10 < Poorly < -6 < Moderately < -4 < Soluble < -2 Very < 0 < Highly

Soluble

Pharmacokinetics

GI absorption?

Gatrointestinal absorption: according to the white of the BOILED-Egg

High
BBB permeant?

BBB permeation: according to the yolk of the BOILED-Egg

Yes
P-gp substrate?

P-glycoprotein substrate: SVM model built on 1033 molecules (training set)
and tested on 415 molecules (test set)
10-fold CV: ACC=0.72 / AUC=0.77
External: ACC=0.88 / AUC=0.94

No
CYP1A2 inhibitor?

Cytochrome P450 1A2 inhibitor: SVM model built on 9145 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.83 / AUC=0.90
External: ACC=0.84 / AUC=0.91

Yes
CYP2C19 inhibitor?

Cytochrome P450 2C19 inhibitor: SVM model built on 9272 molecules (training set)
and tested on 3000 molecules (test set)
10-fold CV: ACC=0.80 / AUC=0.86
External: ACC=0.80 / AUC=0.87

No
CYP2C9 inhibitor?

Cytochrome P450 2C9 inhibitor: SVM model built on 5940 molecules (training set)
and tested on 2075 molecules (test set)
10-fold CV: ACC=0.78 / AUC=0.85
External: ACC=0.71 / AUC=0.81

No
CYP2D6 inhibitor?

Cytochrome P450 2D6 inhibitor: SVM model built on 3664 molecules (training set)
and tested on 1068 molecules (test set)
10-fold CV: ACC=0.79 / AUC=0.85
External: ACC=0.81 / AUC=0.87

No
CYP3A4 inhibitor?

Cytochrome P450 3A4 inhibitor: SVM model built on 7518 molecules (training set)
and tested on 2579 molecules (test set)
10-fold CV: ACC=0.77 / AUC=0.85
External: ACC=0.78 / AUC=0.86

No
Log Kp (skin permeation)?

Skin permeation: QSPR model implemented from
Potts RO and Guy RH. 1992 Pharm. Res.

-5.76 cm/s

Druglikeness

Lipinski?

Lipinski (Pfizer) filter: implemented from
Lipinski CA. et al. 2001 Adv. Drug Deliv. Rev.
MW ≤ 500
MLOGP ≤ 4.15
N or O ≤ 10
NH or OH ≤ 5

0.0
Ghose?

Ghose filter: implemented from
Ghose AK. et al. 1999 J. Comb. Chem.
160 ≤ MW ≤ 480
-0.4 ≤ WLOGP ≤ 5.6
40 ≤ MR ≤ 130
20 ≤ atoms ≤ 70

None
Veber?

Veber (GSK) filter: implemented from
Veber DF. et al. 2002 J. Med. Chem.
Rotatable bonds ≤ 10
TPSA ≤ 140

0.0
Egan?

Egan (Pharmacia) filter: implemented from
Egan WJ. et al. 2000 J. Med. Chem.
WLOGP ≤ 5.88
TPSA ≤ 131.6

0.0
Muegge?

Muegge (Bayer) filter: implemented from
Muegge I. et al. 2001 J. Med. Chem.
200 ≤ MW ≤ 600
-2 ≤ XLOGP ≤ 5
TPSA ≤ 150
Num. rings ≤ 7
Num. carbon > 4
Num. heteroatoms > 1
Num. rotatable bonds ≤ 15
H-bond acc. ≤ 10
H-bond don. ≤ 5

1.0
Bioavailability Score?

Abbott Bioavailability Score: Probability of F > 10% in rat
implemented from
Martin YC. 2005 J. Med. Chem.

0.55

Medicinal Chemistry

PAINS?

Pan Assay Interference Structures: implemented from
Baell JB. & Holloway GA. 2010 J. Med. Chem.

0.0 alert
Brenk?

Structural Alert: implemented from
Brenk R. et al. 2008 ChemMedChem

0.0 alert: heavy_metal
Leadlikeness?

Leadlikeness: implemented from
Teague SJ. 1999 Angew. Chem. Int. Ed.
250 ≤ MW ≤ 350
XLOGP ≤ 3.5
Num. rotatable bonds ≤ 7

No; 1 violation:MW<1.0
Synthetic accessibility?

Synthetic accessibility score: from 1 (very easy) to 10 (very difficult)
based on 1024 fragmental contributions (FP2) modulated by size and complexity penaties,
trained on 12'782'590 molecules and tested on 40 external molecules (r2 = 0.94)

1.2

Application In Synthesis of [ 3189-13-7 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 3189-13-7 ]

[ 3189-13-7 ] Synthesis Path-Downstream   1~4

  • 1
  • [ 3189-13-7 ]
  • [ 26638-43-7 ]
  • 2-(6-methoxy-indole-1-sulfonyl)-benzoic acid methyl ester [ No CAS ]
  • 2
  • [ 52427-05-1 ]
  • [ 3189-13-7 ]
  • 3
  • [ 943835-77-6 ]
  • [ 3189-13-7 ]
  • [ 106-49-0 ]
  • [ 1207290-00-3 ]
  • 4
  • [ 3189-13-7 ]
  • [ 52351-75-4 ]
 

Historical Records

Technical Information

Categories

Related Functional Groups of
[ 3189-13-7 ]

Ethers

Chemical Structure| 37865-86-4

A194181 [37865-86-4]

6-Ethoxy-1H-indole

Similarity: 0.96

Chemical Structure| 3526-43-0

A207916 [3526-43-0]

N-(4-Methoxybenzyl)aniline

Similarity: 0.91

Chemical Structure| 21857-45-4

A101149 [21857-45-4]

5-Methoxyindoline

Similarity: 0.86

Chemical Structure| 887582-58-3

A112092 [887582-58-3]

(6-Methoxy-1H-indol-3-yl)methanamine

Similarity: 0.86

Chemical Structure| 4770-39-2

A375770 [4770-39-2]

5-Methoxyindoline hydrochloride

Similarity: 0.84

Related Parent Nucleus of
[ 3189-13-7 ]

Indoles

Chemical Structure| 37865-86-4

A194181 [37865-86-4]

6-Ethoxy-1H-indole

Similarity: 0.96

Chemical Structure| 887582-58-3

A112092 [887582-58-3]

(6-Methoxy-1H-indol-3-yl)methanamine

Similarity: 0.86

Chemical Structure| 1006-94-6

A105085 [1006-94-6]

5-Methoxyindole

Similarity: 0.84

Chemical Structure| 198479-63-9

A100829 [198479-63-9]

5-(Benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indole

Similarity: 0.82

Chemical Structure| 1076-74-0

A179099 [1076-74-0]

5-Methoxy-2-methyl-1H-indole

Similarity: 0.82