<PAGE>


                                                                   EXHIBIT 10.50



                                 AMENDMENT NO. 1


         This Amendment No. 1 ("Amendment") to the Collaboration and License
Agreements effective October 29, 1998 between the parties hereto (the
"Agreements") is effective as of April 15, 1999, (the "Effective Date") and by
agreement of the parties as of the Effective Date amends the Agreements as
follows:

         1. All capitalized terms herein shall have the same meaning as in the
Agreements.

         2. The parties understand and agree that the mix of Phamacopeia
chemists and biologists specified in Section 2.5.1 is an initial estimate only,
and may vary throughout the course of the Collaboration as reasonably necessary
to carry out the Collaboration Research Plan.

         3. Section 2.9.4 is amended to read, in its entirety, as follows:

                  At the time that Schering and Pharmacopeia initiate the design
         and preparation of an Optimization Library, Schering shall identify the
         Target (in coded form only) and the relevant general therapeutic area
         for which the Optimization Library is being prepared. Notwithstanding
         the preceding sentence, in the event Schering wishes Pharmacopeia to
         prepare an Optimization Library based on a compound identified from
         Schering's screening of a Targeted Library pursuant to the
         Collaboration Agreement entered into by and between the parties
         effective as of December 22, 1994 as amended, Schering first shall
         disclose to Pharmacopeia the identity of the proposed Target for which
         the Optimization Library is to be prepared, in sufficient detail so
         that Pharmacopeia can ensure the avoidance of any conflict with any
         previous or current program. It is understood and agreed that if
         Pharmacopeia, at its sole discretion, determines that such a conflict
         exists, then Pharmacopeia shall not be obligated to prepare such
         Optimization Library.

         4. The remaining terms of the Agreements, except to the limited extent
modified by the terms of this Amendment and by the agreement letter dated March
29, 1999, shall remain in full force and effect.

         IN WITNESS WHEREOF, the parties hereto have caused this Amendment to be


<PAGE>


duly executed by their authorized representatives and delivered in triplicate
originals on the Effective Date.

SCHERING CORPORATION                PHARMACOPEIA, INC



By:      /s/ David Poorvin          By:      /s/ John J. Baldwin
   ------------------------------      ------------------------------

Name: DAVID POORVIN                 Name:  JOHN J. BALDWIN, Ph.D.
     ----------------------------        ----------------------------

Title: Vice President               Title: Chief Science and Technology Officer
      ---------------------------         -------------------------------------

SCHERING-PLOUGH, LTD.



By:      /s/ David Poorvin
   -----------------------------

Name: DAVID POORVIN
     ---------------------------

Title: Prokurist
      --------------------------



                                       2