Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: MathewConnors1999 on February 04, 2021, 10:48:40 AM
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I've working with Alzeihemers and more specifically its medicine treatments. I've been tasked with finding the functional groups of Sertindole (C24H26ClFN4O) and describe its build with perspective towards acting as a drug. If anyone could help me, I would really appreciate it, as I have no idea of where to even start.
Regards
Matthew Conner
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I assume that you have found the structure at some appropriate site, such as PubChem or elsewhere. Do you recognize any functional groups from your organic chemistry classes?
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Begin by drawing the structure of your chemical, then look for its mechanism of action. Draw a chemical compound with which the drug is competing for the receptor and compare the structural elements.
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Begin by drawing the structure of your chemical, then look for its mechanism of action. Draw a chemical compound with which the drug is competing for the receptor and compare the structural elements.
Thank you for your answer. The drug binds with the (along others) D2 dopamin receptor. I don't see any similarities between the two, except for there being a benzene ring and nitrogen present.
I assume that you have found the structure at some appropriate site, such as PubChem or elsewhere. Do you recognize any functional groups from your organic chemistry classes?
Thank you for your answer. I have found the structure on PubChem yes. I do recognise a huge number of benzene rings along with ethyl chains? Is that right? And I also think that there is something about hydrogen bonding.
The problem is, to my knowledge I am just not sure what seperates a group.
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And I can see fragments in the molecule similar to dopamine and serotonin.
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Let me just focus on the organic chemistry perspective (I am not sure it is even necessary to do so), inasmuch as AWK has nicely covered it from a medicinal angle. One of the functional groups present is an amine. What kind of amine is it, primary, secondary, or tertiary?
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Let me just focus on the organic chemistry perspective (I am not sure it is even necessary to do so), inasmuch as AWK has nicely covered it from a medicinal angle. One of the functional groups present is an amine. What kind of amine is it, primary, secondary, or tertiary?
Thank you for your time. If I am not mistaken I can see a secondary amine at the very "top" of the molecule and three tertiary aminegroups throughout.
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And I can see fragments in the molecule similar to dopamine and serotonin.
Thank you for your time. Yes I can see that as well. Could it be that when metabolished the drug could alter to apear more like dopamine or serotonin, or is the simple resemblance enough to attach?
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I was thinking of the one nitrogen in the six-membered ring as being a tertiary amine. Regarding the two nitrogen atoms that are in the five-membered ring, I would consider those two nitrogen atoms and the intervening carbonyl (C=O) to be a single functional group that is related to a common substance found in many biochemistry laboratories. One might consider the entirety of the lone nitrogen in the five-membered ring fused with a six-membered ring to be a single group also.
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I was thinking of the one nitrogen in the six-membered ring as being a tertiary amine. Regarding the two nitrogen atoms that are in the five-membered ring, I would consider those two nitrogen atoms and the intervening carbonyl (C=O) to be a single functional group that is related to a common substance found in many biochemistry laboratories. One might consider the entirety of the lone nitrogen in the five-membered ring fused with a six-membered ring to be a single group also.
Oh okay I think I see. Regarding naming these groups, would that be by solely looking at them as if they were an isolated molecule and naming them thereafter?
And lastly what about the fluorobenzene. Is that of importance?
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I would name them that way, but perhaps others would do it differently. I am not sure exactly what the reason for the fluorine is.
EDT
Obviously I agree with what AWK wrote about fluorine, and all that I can think to add is that one drug, flunitrazepam, has an aromatic fluorine in the ortho-position.
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Fluoride is very common in synthetic drugs but must be present in non-reactive groups as p-fluorophenyl or trifluoromethyl.
The radius of the van der Waals of fluorine is only about 20% greater than the radius of hydrogen, therefore enzymes and receptors do not notice a difference in size, but enzymes are unable to metabolize such a group, e.g. oxidize the phenolic group, especially in the para position or to a carboxyl group.
In addition, fluoride has a beneficial effect when drugs overcome lipid barriers, i.e. the drug gets to places where it would not reach due to the rapid metabolism of the unsubstituted compound.
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I would name them that way, but perhaps others would do it differently. I am not sure exactly what the reason for the fluorine is.
EDT
Obviously I agree with what AWK wrote about fluorine, and all that I can think to add is that one drug, flunitrazepam, has an aromatic fluorine in the ortho-position.
Thank you very much for your *delete me*
Fluoride is very common in synthetic drugs but must be present in non-reactive groups as p-fluorophenyl or trifluoromethyl.
The radius of the van der Waals of fluorine is only about 20% greater than the radius of hydrogen, therefore enzymes and receptors do not notice a difference in size, but enzymes are unable to metabolize such a group, e.g. oxidize the phenolic group, especially in the para position or to a carboxyl group.
In addition, fluoride has a beneficial effect when drugs overcome lipid barriers, i.e. the drug gets to places where it would not reach due to the rapid metabolism of the unsubstituted compound.
This is a very detailed answer. Thank you for that.
You would agree that this drug is competetive antagonistic, right? I am having a hard time getting how a drug as Sertindole, big and heavy and looks only a bit simmilar with dopamine can sit on the D2-dopamine receptors. I get that, as you mentioned the Van Der Waals radius of flourine is small and does not contribute to its size in the eyes of the receptors, but even if we don't consider the floruide, the drugs still seem rather unsimmilar to sit on the receptors. Could pH level have an effect?
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It is not uncommon that drugs are much bigger then the natural compound they mimic.
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If you look at the side chain of the amino acid tryptophan, you will see an heterocyclic aromatic structure that shows up in many drugs. The name of this functional group is included in the name of this compound. With respect to naming the other functional group, the one with two nitrogens and a carbonyl group, I would think about a major constituent of urine, the same compound often found in biochemistry labs to denature proteins.
EDT
In general the effect of pH can either be on the receptor or the drug itself, because either one might gain or lose a proton. Which functional group on this compound is capable of gaining or losing a proton?
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If you look at the side chain of the amino acid tryptophan, you will see an heterocyclic aromatic structure that shows up in many drugs. The name of this functional group is included in the name of this compound. With respect to naming the other functional group, the one with two nitrogens and a carbonyl group, I would think about a major constituent of urine, the same compound often found in biochemistry labs to denature proteins.
EDT
In general the effect of pH can either be on the receptor or the drug itself, because either one might gain or lose a proton. Which functional group on this compound is capable of gaining or losing a proton?
Thank you for your answer Babcock_Hall.
It does look like a pyrrole. It that right?
The major constituent of urine is urea, right?
With regards to which functional groups that is capable of gaining or losing a proton, I am not quite sure, I am afraid.
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When a six-membered ring is fused to a five-membered ring with a nitrogen, it is called indole. The name of the molecule of interest is Sertindole. Urea has a structure similar to a portion of your molecule, and it is a major component of urine. I am not sure how to give you a hint regarding protonation, off the top of my head. Maybe you can look at a table of pKa values to get an idea. Some functional groups can gain or lose a proton near physiological pH, but others cannot.
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The major constituent of urine is urea, right?
No, water.
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As far as I see sertindole is a neuroleptic?
https://en.wikipedia.org/wiki/Sertindole
Is that used against Alzheimers?
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Sorry for the late answers.
As far as I see sertindole is a neuroleptic?
https://en.wikipedia.org/wiki/Sertindole
Is that used against Alzheimers?
Oh my God I am an idiot. Indeed it is not used against Alzheimers but rather schizophrenia. I am terribly sorry for this. English is not my primiary language and I didn't capture it, as Alzheimers is spelled more like schizophrenia in my language.
When a six-membered ring is fused to a five-membered ring with a nitrogen, it is called indole. The name of the molecule of interest is Sertindole. Urea has a structure similar to a portion of your molecule, and it is a major component of urine. I am not sure how to give you a hint regarding protonation, off the top of my head. Maybe you can look at a table of pKa values to get an idea. Some functional groups can gain or lose a proton near physiological pH, but others cannot.
Serindole, indole. Of course. Thank you so much for pointing this out. I did wonder what its name was a derreviate of.
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Am I wrong or Sertindole is widely used to treat chizophrenia with placebo level extrapyramidal symptoms?
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I can see as uncommon adverse effect, "penis disorder" and "taste perversion" It does not sound good…
The drug was discontinued in the US in 2014 so its probably not so usefull.
https://en.m.wikipedia.org/wiki/Sertindole
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Yeah, that's why Sertindole isn't recommended to be used as first-line treatment for first-episode patients with schizophrenia because of the QTc prolongation. The 3 most common side effects usually are: weight gain, rhinitis, and a decreased ejaculation volume. Some studies also show that patients may have vision problems after using it. You can find more info (https://www.exploremedicalcareers.com/optician/) on specialized websites about the treatment of schizophrenia though.
It seems that it's not the best drug for the treatment of anything, so it's rarely used in US clinics.
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It should be said that all neuroleptics have very bad side-effects, weight-gain and/or extrapyramidal symptoms, also tardive dyskinesia when used long-term. And then we dont even start to mention CNS-depression and changes in brain-receptor density wich is really not a side-effect but rather the effect…