Changing distribution metadata (such as install_requires) in setup.py according to some vague ideas on how (pip|setuptools|...) works is a horrid idea. More specifically, try this:

1. Use pip-tools (version 1.9 or later) to compile the following requirements.in on OSX:

ipython

2. Note that appnope (only useful on OSX) is included in the resulting requirements.txt, without any environment markers - it should be only for :sys_platform == "darwin".

I'll put together two PRs (one for master, the other for 5.x) that limits the insanity to old versions of pip (<6).