Combinatorial libraries?

Reviewing the 1996 article in C&E News titled: Combinatorial chemistry becoming core technology at drug discovery companies, one wonders what became of the patent rush on patenting combinatorial libraries?

The article began:

Modern drug discovery efforts are exploiting at least three core technologies aimed at increasing the efficiency of finding drug leads: genomics, high-throughput screening, and combinatorial chemistry. Research aimed at deciphering the human genome is rapidly multiplying the number of known disease targets. Screening methods using biological assays can quickly show if a compound is a "hit"; that is, if it has activity against a target.

And combinatorial chemistry methods can produce and help optimize the compounds used in screening. Many pharmaceutical companies view this hot area as technology they must have to compete.

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One commenter wrote in:

M'thinks you are rightfully skeptical...I never thought combinatorial
libraries were going to be a godsend to pharma....

A) They are best at making "chains" A-B-A-C-B-C..... and an awful
lot
of good drugs are not polypeptides.
B) This was "brute force", with no "thinking" or insight as to the
shape or 3-d shape of active site, etc. Just random shots in the
dark.
C) It got around a bottleneck (doing things one at a time, at gram
quantities), but it simply shifted the bottleneck elsewhere. Yes, you
could make a collection 1000x faster, but processing elsewhere,
screening, etc. was not sped up 1000x faster.

So everybody ended up with libraries, none of which worked for their
particular "problem or disease"...so the next best thing to do was to
sell them to other dopes....

So, they "failed fast" rather than failed slow....it was still
"failure"
to deliver mucho big hits.