Polyketides, Immunosuppressants, Chemotherapy Drugs and Lipinski's Rule of Five

From Wikipedia:

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In organic chemistry, polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (>C=O, or its reduced forms) and methylene (>CH2) groups: [−C(=O)−CH2−]n.[1] First studied in the early 20th century, discovery, biosynthesis, and application of polyketides has evolved. It is a large and diverse group of secondary metabolites caused by its complex biosynthesis which resembles that of fatty acid synthesis. Because of this diversity, polyketides can have various medicinal, agricultural, and industrial applications. Many polyketides are medicinal or exhibit acute toxicity. 

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Lipinski's rule of five, also known as Pfizer's rule of five or simply the rule of five (RO5), is a rule of thumb to evaluate druglikeness or determine if a chemical compound with a certain pharmacological or biological activity has chemical properties and physical properties that would likely make it an orally active drug in humans. The rule was formulated by Christopher A. Lipinski in 1997, based on the observation that most orally administered drugs are relatively small and moderately lipophilic molecules.

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Lipinski's rule states that, in general, an orally active drug has no more than one violation of the following criteria:

No more than 5 hydrogen bond donors (the total number of nitrogen–hydrogen and oxygen–hydrogen bonds)

No more than 10 hydrogen bond acceptors (all nitrogen or oxygen atoms)

A molecular mass less than 500 daltons

A calculated octanol-water partition coefficient (Clog P) that does not exceed 5

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In an attempt to improve the predictions of druglikeness, the rules have spawned many extensions, for example the Ghose filter:[10]

Partition coefficient log P in −0.4 to +5.6 range

Molar refractivity from 40 to 130

Molecular weight from 180 to 480

Number of atoms from 20 to 70 (includes H-bond donors [e.g. OHs and NHs] and H-bond acceptors [e.g. Ns and Os])

Veber's Rule further questions a 500 molecular weight cutoff. The polar surface area and the number of rotatable bonds has been found to better discriminate between compounds that are orally active and those that are not for a large data set of compounds.[11] In particular, compounds which meet only the two criteria of:

10 or fewer rotatable bonds and

Polar surface area no greater than 140 Å2

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Some other polyketides of note: paclitaxel, a chemo drug and discodermolide, a tumor inhibitor. 

What would be the effect of opening some of the rings on paclitaxel, aside from increasing its molecular weight? What about closing the partial rings in discodermolide?

In general, closing rings would mean fewer rotatable bonds.