2-Bromo-3-((1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazol-4-yl)-methoxy)-benzaldehyde
, Yuhan Xie 3, Jerome P. L. Ng 1,2, Betty Yuen Kwan Law 1,2, Vincent Kam Wai Wong 1,2,* and Paolo Coghi 3,*Round 1
Reviewer 1 Report
Paolo Coghi and coworkers presented the synthesis of 2-Bromo-4-((1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazol-4-yl)-methoxy)-benzaldehyde. Authors did preliminary studies attempted to evaluate its interaction with Delta RBD of spike protein of SARS-CoV- 2.
I would suggest to do following changes:
Page 4 lines 135 and 136: change "DMSO-d6" to DMSO-d6
Page 5 line 168: change "30 C" to 30 °C
Page 5 line 170: change "then diluted with 50 ml water" to was diluted with water (50 mL)
Page 5 line 194: change "C19H12BrClN4O2" to C19H12BrClN4O2
Page 5 line 203: please use a uniform style of citations
Page 6 lines 216-227: please use a uniform style of the text
In the experimental part check 600 MHz, 150 MHz in the text, please use a uniform style
Page 5 lines 187 and 191: For compound 5 it is stated that 1H and 13C NMR was measured in CDCl3. In the supporting information, the provided spectra were measured in DMSO. What is true?
Author Response
Reviewer 1
Paolo Coghi and coworkers presented the synthesis of 2-Bromo-4-((1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazol-4-yl)-methoxy)-benzaldehyde. Authors did preliminary studies attempted to evaluate its interaction with Delta RBD of spike protein of SARS-CoV- 2.
We would like to thank reviewer to read and improve our paper.
I would suggest to do following changes:
Page 4 lines 135 and 136: change "DMSO-d6" to DMSO-d6
correct
Page 5 line 168: change "30 C" to 30 °C
correct
Page 5 line 170: change "then diluted with 50 ml water" to was diluted with water (50 mL)
correct
Page 5 line 194: change "C19H12BrClN4O2" to C19H12BrClN4O2
correct
Page 5 line 203: please use a uniform style of citations
correct
Page 6 lines 216-227: please use a uniform style of the text
correct
In the experimental part check 600 MHz, 150 MHz in the text, please use a uniform style
correct
Page 5 lines 187 and 191: For compound 5 it is stated that 1H and 13C NMR was measured in CDCl3. In the supporting information, the provided spectra were measured in DMSO. What is true?
DMSO
Correct in experimentals details.
Reviewer 2 Report
In this manuscript, the authors demonstrated the synthesis of a new 7‐chloroquinoline – 1,2,3‐triazole hybrid starting from 4,7-dichloroquinoline and 2-bromo-3-hydroxybenzaldehyde in a three-step sequence. The reactions were performed in good yields. The structures of the synthesized compounds have been adequately characterized by NMR spectroscopy, although the characterization of the novel compounds needs to be completed. The aimed hybrid showed low cytotoxic effect on the two cell lines examined. In addition, the authors found that the product has favorable pharmacokinetic properties, however, bio-layer interferometry showed that it has poor affinity with the RBD spike of SARS-CoV. In summary, I think that this manuscript may be suitable for publication in the Molbank after some modifications.
General remarks:
In connection with the title: the name given by the authors does not include that the substituted methoxy group is in the 3-position (meta) of the aromatic ring. Therefore, I suggest using the name generated by the ChemDraw: „2-Bromo-3-((1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazol-4-yl)methoxy)benzaldehyde”. The same is true for lines 83 and 178.
In describing the purpose, there is no explanation as to why an aromatic aldehyde containing a bromine atom was chosen as the substituent of the 1,2,3-triazole ring.
Of the compounds synthesized, HRMS was reported only for compound 5, although compound 4 was not previously described either in the literature, so HRMS should be replaced here. Besides, the melting points and retention factor (Rf) values of all three compounds (3-5) should be given.
References are not unified (eg. author names, abbreviations, full stops, commas, page number ranges, doi) and often do not follow molbank rules. As read in the instructions for authors, references should be described as follows:
- Author 1, A.B.; Author 2, C.D. Title of the article. Abbreviated Journal Name Year, Volume, page range.
The manuscript needs a revision:
L44: Molecular hybridization … combines instead of Molecular hybridization … combine
L50: triazole hybrids exhibit instead of triazole hybrids exhibits
L57: and evaluated instead of and evaluate
In Figure 1, in the square: the substituents R, R1 and R2 are confused. R must not be attached to the middle nitrogen atom and R2 must be attached to a carbon atom. R1 instead of R1
In Figure 1 and Scheme 1, no dot is required after compound numbers and letters. So a-g instead of a.-g. and 1-5 instead of 1.-5.
In the case of compounds f and g in Scheme 1, the bond between the aromatic ring and the chlorine atom should also be red.
L61: 1a-g instead of 1a-g
L62: 1,2,3-triazoles instead of 1,2,3 triazoles
L67: Reference [12] (Souza et al.) is missing from the text.
L72: 2-bromo-3 hydroxybenzaldehyde instead of 2-bromo-3 hydroxy-benzaldehyde
L93: recognize instead of recognzie
L104: What types of cell lines are LO2 and BEAS-2B?
L149: 4-azido-7-chloroquinoline instead of 4-azido-7-chloro-quinoline
L151 and 165: Compound numbers are missing. (4,7-dichloroquinoline: 1; 2-bromo-3-hydroxybenzaldehyde: 3)
L153: completion of the reaction instead of completion of reaction
L163: 2-bromo-3-(prop-2-yn-1-yloxy)benzaldehyde instead of 2-bromo-3-(prop-2-yn-1-yloxy) benzaldehyde
L165: 2-Bromo-3-hydroxybenzaldehyde instead of 2-bromo-3-hydroxybenzaldehyde
L168: at 30 oC instead of at 30 C
L174: 8.24 Hz, HAr instead of 8.24 Hz ,HAr (comma)
L175: (CHO, s) ppm instead of (CHO, s)ppm (space)
L175, 187 and 191: 150 MHz and 600 MHz instead of 150MHz and 600MHz (spaces)
L176: 77.4, 117.8 instead of 77.4,117.8 (space) and 135.0 instead of 135
L181: It is not specified how many moles of azide (2) were used. 1 mmol?
Related to this, recipes should not only provide the amount of substance, but also the mass (2-bromo-3-hydroxybenzaldehyde in line 165, furthermore 2 and 4 in line 181). Similarly, when describing yields, the mass should be given, not just the percentage.
L194: C19H12BrClN4O2 instead of C19H12BrClN4O2
L201: Compound 5 was dissolved instead of Compound 5 were dissolved
L211: Atreated / Acontrol instead of Atreated/ Acontrol (space)
L203: described [18]. instead of described.18
Congratulations to all the authors on their successful work!
Author Response
Reviewer 2
We would like to thank reviewer to read and improve our paper.
General remarks:
In connection with the title: the name given by the authors does not include that the substituted methoxy group is in the 3-position (meta) of the aromatic ring. Therefore, I suggest using the name generated by the ChemDraw: „2-Bromo-3-((1-(7-chloroquinolin-4-yl)-1H-1,2,3-triazol-4-yl)methoxy)benzaldehyde”. The same is true for lines 83 and 178.
correct
In describing the purpose, there is no explanation as to why an aromatic aldehyde containing a bromine atom was chosen as the substituent of the 1,2,3-triazole ring.
We added sentence (line 55-57) and some new reference
Of the compounds synthesized, HRMS was reported only for compound 5, although compound 4 was not previously described either in the literature, so HRMS should be replaced here. Besides, the melting points and retention factor (Rf) values of all three compounds (3-5) should be given.
We added HRMS for compound 4 and melting point and Rf for compounds cited.
References are not unified (eg. author names, abbreviations, full stops, commas, page number ranges, doi) and often do not follow molbank rules. As read in the instructions for authors, references should be described as follows:
- Author 1, A.B.; Author 2, C.D. Title of the article. Abbreviated Journal Name Year, Volume, page range.
References were correct
The manuscript needs a revision:
L44: Molecular hybridization … combines instead of Molecular hybridization … combine
correct
L50: triazole hybrids exhibit instead of triazole hybrids exhibits
correct
L57: and evaluated instead of and evaluate
correct
In Figure 1, in the square: the substituents R, R1 and R2 are confused. R must not be attached to the middle nitrogen atom and R2 must be attached to a carbon atom. R1 instead of R1
correct
In Figure 1 and Scheme 1, no dot is required after compound numbers and letters. So a-g instead of a.-g. and 1-5 instead of 1.-5.
correct
In the case of compounds f and g in Scheme 1, the bond between the aromatic ring and the chlorine atom should also be red.
correct
L61: 1a-g instead of 1a-g
correct
L62: 1,2,3-triazoles instead of 1,2,3 triazoles
correct
L67: Reference [12] (Souza et al.) is missing from the text.
correct
L72: 2-bromo-3 hydroxybenzaldehyde instead of 2-bromo-3 hydroxy-benzaldehyde
correct
L93: recognize instead of recognize
correct
L104: What types of cell lines are LO2 and BEAS-2B?
Add in text correctly.
L149: 4-azido-7-chloroquinoline instead of 4-azido-7-chloro-quinoline
correct
L151 and 165: Compound numbers are missing. (4,7-dichloroquinoline: 1; 2-bromo-3-hydroxybenzaldehyde: 3)
correct
L153: completion of the reaction instead of completion of reaction
correct
L163: 2-bromo-3-(prop-2-yn-1-yloxy)benzaldehyde instead of 2-bromo-3-(prop-2-yn-1-yloxy) benzaldehyde
correct
L165: 2-Bromo-3-hydroxybenzaldehyde instead of 2-bromo-3-hydroxybenzaldehyde
correct
L168: at 30 oC instead of at 30 C
correct
L174: 8.24 Hz, HAr instead of 8.24 Hz ,HAr (comma)
correct
L175: (CHO, s) ppm instead of (CHO, s)ppm (space)
correct
L175, 187 and 191: 150 MHz and 600 MHz instead of 150MHz and 600MHz (spaces)
correct
L176: 77.4, 117.8 instead of 77.4,117.8 (space) and 135.0 instead of 135
correct
L181: It is not specified how many moles of azide (2) were used. 1 mmol?
correct
Related to this, recipes should not only provide the amount of substance, but also the mass (2-bromo-3-hydroxybenzaldehyde in line 165, furthermore 2 and 4 in line 181). Similarly, when describing yields, the mass should be given, not just the percentage
correct.
L194: C19H12BrClN4O2 instead of C19H12BrClN4O2
correct
L201: Compound 5 was dissolved instead of Compound 5 were dissolved
Correct
L211: Atreated / Acontrol instead of Atreated/ Acontrol (space)
correct
L203: described [18]. instead of described.18
correct
