The Half Decent Pharmaceutical Chemistry Blog

First of all, The Half Decent Pharmaceutical Chemistry Blog has now a new, state-of-art, anti-spam, anti-trolls, anti-boring rubbish filter. You write your comment and I judge whether it'll be displayed or not. 
Will this prevent some people from annoying me? (I sincerely doubt it, but, at least, they won't annoy YOU any more).

Tomorrow, Frank S. Walsh, executive vice president of Wyeth Research, will visit our department of Pharmacology for a so-called "meeting with the students". Now, considering the organization of the said department/university, it's likely to be another bright example of how things must not be done. Bad omens surround the meeting: small room, odd scheduled time, lack of enthusiasm among the students, etc.
Now, you probably expect me to present Frank Walsh: talking about his articles I read or, given that I'm still an undergraduate student, mentioning where some of his researches have been quoted during lectures. Thing is I've never read  one of his articles because we don't have access to journals and I've recently noticed none of my lecturers/professors has ever quoted a single article (except one, sadly now retired, org chem professor, two years ago). This is an embarrassing thing to confess, but, as you can understand, it's not entirely my fault.
So, to sum up, I'll go to the meeting, take some pictures and write a report here tomorrow. Tonight, I'll maybe consider another research on the internet, but the odds that I'll ask him something (intelligent) are poor.
Should I ask him about this year's Nobel prize in Chemistry? (It doesn't sound like an intelligent question, does it? And, moreover, I am the last person who should say anything about this issue, considering what I'm going to do after the graduation).

Again on Walsh's visit. I'm wondering who is going to be there. Most of the students I know said something like: Who cares? I can't speak English! Why should I waste my time?
I guess most of the people there will be lecturers, professors, PhD students and other human beings working at the department, who, I hope, have read or know something that may deserve a question.
Am I wrong? And is this, at least, the only way who organized the whole thing has to avoid a long silence following a generally welcome phrase such as "who wants to ask Mr. Walsh a question"?

According to my prevision, there won't be any seat left by the time I'll be able to reach the place (I've lectures just until the very beginning of the debate...).
Will this make leave the few plucky students like me who SHOULD be the centre of the meeting quite soon? (I think so, especially if it's sunny).

You'll know the answers tomorrow.

This is not the most exciting synthesis ever, although what I describe here is a quick method to yield a very interesting drug: clonidine. A drug which, despite its age, hasn't lost its touch. Oh no, not at all.

Clonidine is an alpha-2 agonist used in the treatment of hypertension. Nowadays, however, this molecule is mainly used for a large spectrum of purposes: from helping former opiate consumers to cope with withdrawals, to the therapy against insomnia, ADHD (Attention-deficit hyperactivity disorders) and other neuropathologies. Some doctors prescribe clonidine for reducing hot flushes during menopause too.
Not to mention the many other clinical contexts where clonidine may find a place in the future, looking at the number of ongoing tests.

Going back to the chemical aspects, my favourite step is the intramolecular cyclization after the reaction with ethanediamine. I mean, it's the kind of thing that makes me think: "Well, in the end, organic synthesis is not that difficult: your adduct does everything." 

Ammonium thiocyanate provides, in the end, a good leaving group.
The two chlorine groups on the benzene guarantee a high activity, not only due to electronic effects, but, thanks to steric hindrance, because they perfectly block the aromatic ring orthogonally to the imidazoline: this is the active conformation, so, in terms of activity, Cl>Br>CF3>>F.

Of course, if you don't live in Europe, the title will lose all its sense but, come on, use some imagination!
This is the first synthesis here, and I opted for an important drug, Prazosin, mainly used in the treatment of hypertension: an alpha-1-adrenergic antagonist.

This molecule is the lead for other quinazoline derivatives such as doxazosin and cyclazosin.

Here is the synthesis:

This is not totally synthetic, so, if you know a more sophisticated version of this synthesis, please, I'd love to know where I can find it. (I mean, I'm still an undergrad).

For what concerns this synthesis, it's certainly not a complicated one. The very first step involves sodium cyanate and yields a product which can remind of a ketene.
Phosphoroxidchloride is used as chlorinating agent.
I'd like to point out that it's due to thermodynamic reasons that we substitute one Cl only (how lucky, eh?)

The most interesting aspect is the way we yield the furanyl-piperazinyl-methanone. We set pH at 5.5, because the two NH groups in the piperazine have different basicity and this, plus the great reactivity of the furan-2-carbonyl chloride, would lead to double substituted products (hence, a mixture of three products). Thanks to this particular pH, you may say, we protect one of the NH functions and we increase selectivity.

Today it should have been the beginning of the discussion of pharmaceutical syntheses. I have already prepared the pictures and I'm looking forward to reading your opinions on them. However, there is something that needs to be discussed before.

Last Monday I was pleased to reveal the recognition this relatively young blog got from an important website such as Sciencebase.

Writing on the internet means exposing yourself to a huge audience: it can mean becoming more or less popular (Dylan's tenderbutton was, at least in my opinion, a beautiful example of what a chemical blog should be). There are certainly a few drawbacks, though: what you say is public, everyone can read it and know something about you. When it comes to blogs, moreover, there are comments: these are the best part of the story, providing a immediate feedback. Readers can show their appreciation, share their views, correct you when you are wrong and so on. 

In Italy we use to say the more the enemies, the greater the honour. In my case, I cannot say I have achieved many honours, but not everyone can be our friend, right?
Writing your own real name on your web-site is not the best way to protect your privacy, but I don't think a smart guy like Paul Docherty has ever had problems with it. Or has ever received comments on his fantastic blog dealing with his private life (spam is an issue we all have to cope with and something completely different). 

Now, yesterday, a boring person I know well (that's for you: I can see your email address, your IP and how you came here through Google. Next time, you'd better pluck up courage and sign your rubbish with your real name, eh?) posted very inappropriate comments, in the WHOIS part of the blog. It was very sad: I always hope people are intelligent and smart, or, at least, grown enough to have left their childhood by the time they go to  university. How naive, eh? 

My first reaction was to remove the WHOIS page. Now, with the benefit of hindsight, I wouldn't have made that page but, after yesterday, I can't draw back: it'll be on line, in a new version, quite soon again.
Then, I considered not allowing comments any more. It would be an easy way to solve that kind of problem. Yes, but it would be too easy. 

Finally I reached my conclusion: we go on, whether the people who don't like us like it or not. IPs can be banned, unfortunately there is no way to do the same with people's stupidity, but I don't want to damage a lot of nice people because of one or four boring ignorants. 

That's it, lads. Seeya!

Last night I drove after three months of cycling. I took some relatives to a small restaurant on the hills surrounding Bologna. I ate quite a lot, as usuall, and we had a nice time together.
By the way, the journey from home to the place wasn't that nice, since, although I like driving VERY much, a small, dark, hill road is not what you would call the easiest one for reviewing your driving skills. Nevertheless, I didn't have any trouble: I was just a little bit worried in the beginning.

It's hard to define what memory actually is: maybe the faculty of recalling facts or recognizing episodes of the past is the clearest.
Certainly, finding out all the cerebral pathaways that deal with this faculty is one of the toughest tasks of today's neuroscientists.
However, nowadays we know something.

First of all, we can define three (but there are different classifications) memories: short-term, long-term implicit and explicit memory.

Short-term memory can be called working memory as well. This second, more modern name is used to underline the functions of this kind of memory. A short-term memory, in fact, helps us every time a particular task needs a quick storage and manipulation of information/data (i.e. remembering addends for a sum and calculating the result).
Studies on monkeys and patients with brain injuries have revealed that some areas of the premotor cortex show an increases activity during processes which require the use of working memory.

When it comes to long-term memories, things get more complicated and unknown. There are five regions certainly involved: one is subcortical ( the amygdala) and the others are in the temporal cortex (namely, enthorinal, perirhinal and parahippocampal cortex, hippocampus).
Explicit memory is also called declarative memory: basically, it's when we are aware of knowing something (i.e. where we live).

Amygdala has a central role in linking memories and emotions together.

Hippocampus is nicknamed "teacher", because of its paramount importance for declarative memory. Its bidirectional connections with all the cortices explain why it plays a key role in explicit memory.
Interestingly, in the hippocampus there are staminal neurons.

Perirhinal cortex makes us remember, in a nutshell, objects, while parahippocampal cortex is linked to visuospatial memory. Both have the same bidirectional links to all the cortices we described for the hippocampus.
These two regions send information to the enthorinal cortex, which processes the inputs. Enthorinal cortex is linked to the hippocampus too and provides a huge number of inputs for it.

Implicit memory is also known as procedural memory: we know how to do something, but we are just not aware of it. And that's the link between yesterday's driving after a long time and memory. Implicit memory is what  helps us doing many things without, literally, thinking about what we are doing. For example, if we constantly had to think about how to move our legs while cycling, we would be probably fall down very quickly.
The scheme is quite simple: all cortices have connections with basal ganglia but not the way back. Hence, we can't be aware of the process.
Basal nuclei (another name for basal ganglia) receive stimuli also from the substantia nigra.
Inputs travels from basal nuclei to ventral thalmus and, finally, reach the premotor and motor cortex.