{"id":1010,"date":"2014-08-22T10:11:00","date_gmt":"2014-08-22T09:11:00","guid":{"rendered":"http:\/\/nextmovesoftware.com\/blog\/?p=1010"},"modified":"2015-06-22T16:41:01","modified_gmt":"2015-06-22T15:41:01","slug":"what-is-a-med-chemists-favourite-phenyl-substituent","status":"publish","type":"post","link":"https:\/\/nextmovesoftware.com\/blog\/2014\/08\/22\/what-is-a-med-chemists-favourite-phenyl-substituent\/","title":{"rendered":"What is a med chemist’s favourite phenyl substituent?"},"content":{"rendered":"

In the course of preparing a talk for the recent ACS meeting (more on this later<\/a>), I thought it would be interesting to give an overview of the ChEMBL data on substituted phenyls. What I did was take all those matched series* with associated IC50<\/sub> data containing 4 or more phenyl substituents, and then count the frequency of each particular phenyl.<\/p>\n

In other words, when a medicinal chemist was trying to optimize the substituents around a phenyl ring, which were the most frequent groups tested?<\/p>\n

\"The<\/a>
The most popular substituted phenyls<\/figcaption><\/figure>\n

The order of popularity at the 4 position is OMe > Cl > F > Me, while at the 2 and 3 positions it’s Cl > OMe > F > Me. For these groups, in general the corresponding frequencies are in the order 4 >> 3 > 2. It would be interesting to know whether this corresponds to the ease of synthesis of these groups (in the general case) or whether other factors are at play.<\/p>\n

In response to a query about whether the preferences have changed over time, I’ve generated the following image (click for bigger) that provides this information for the period 1990-2013 (the x-axis). The y-axis shows frequencies divided by the total number of substituted phenyls that year.

\"Changes<\/a>
Changes in frequencies over time<\/figcaption><\/figure>It’s a bit hard to draw any conclusions, but possibly 4-nitrile is becoming more popular, along with 3-F, while 2-NO2 and 2,3,4-OMe are going down.<\/p>\n

*A matched (molecular) series is a series of analogs with same scaffold but different R groups (all at the same position). In this context, each matched series contains only molecules from the same assay and paper.<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

In the course of preparing a talk for the recent ACS meeting (more on this later), I thought it would be interesting to give an overview of the ChEMBL data on substituted phenyls. What I did was take all those matched series* with associated IC50 data containing 4 or more phenyl substituents, and then count … Continue reading What is a med chemist’s favourite phenyl substituent?<\/span><\/a><\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[],"_links":{"self":[{"href":"https:\/\/nextmovesoftware.com\/blog\/wp-json\/wp\/v2\/posts\/1010"}],"collection":[{"href":"https:\/\/nextmovesoftware.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/nextmovesoftware.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/nextmovesoftware.com\/blog\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/nextmovesoftware.com\/blog\/wp-json\/wp\/v2\/comments?post=1010"}],"version-history":[{"count":12,"href":"https:\/\/nextmovesoftware.com\/blog\/wp-json\/wp\/v2\/posts\/1010\/revisions"}],"predecessor-version":[{"id":1430,"href":"https:\/\/nextmovesoftware.com\/blog\/wp-json\/wp\/v2\/posts\/1010\/revisions\/1430"}],"wp:attachment":[{"href":"https:\/\/nextmovesoftware.com\/blog\/wp-json\/wp\/v2\/media?parent=1010"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nextmovesoftware.com\/blog\/wp-json\/wp\/v2\/categories?post=1010"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nextmovesoftware.com\/blog\/wp-json\/wp\/v2\/tags?post=1010"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}