Document:

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                                                                    Exhibit 10.9

             Warrant to Purchase 89,797 Shares of Common Stock or
        such additional shares as this Warrant may entitle the holder
              to purchase pursuant to provisions of this Warrant.

                       WARRANT TO PURCHASE COMMON STOCK

                                      OF

                      3-DIMENSIONAL PHARMACEUTICALS, INC.

          This is to Certify That, FOR VALUE RECEIVED, Aetna Life Insurance
Company or assigns ("Holder") is entitled to purchase, subject to the provisions
of this Warrant, from 3-Dimensional Pharmaceuticals, Inc., a Delaware
corporation (the "Company"), 89,797 fully paid, validly issued and nonassessable
shares of Common Stock, par value $.001 per share, of the Company ("Common
Stock") at a price of $1.25 per share during the Exercise Period (as defined
below). The number of shares of Common Stock to be received upon the exercise of
this Warrant and the price to be paid for each share of Common Stock may be
adjusted from time to time as hereinafter set forth. The shares of Common Stock
deliverable upon such exercise, and as adjusted from time to time, are
hereinafter sometimes referred to as "Warrant Shares" and the exercise price of
a share of Common Stock in effect at any time and as adjusted from time to time
is hereinafter sometimes referred to as the "Exercise Price." This Warrant is
being issued in connection with the issuance by the Company of Warrants to
purchase shares of Common Stock and promissory notes in the aggregate principal
amount of up to $10,000,000 (the "Notes"), pursuant to a Note and Warrant
Purchase Agreement dated as of November 18, 1999 (the "Agreement").

     1.       EXERCISE OF WARRANT.

          a.       This Warrant may be exercised in whole or in part at any time
              or from time to time on or after November 18, 1999 until 5 p.m.
              New York City Time on November 18, 2000 (the "Exercise Period");
              provided, however, that if such day is a day on which banking
              institutions in the State of New York are authorized by law to
              close, then on the next succeeding day which shall not be such a
              day. This Warrant may be exercised by presentation and surrender
              hereof to the Company at its principal office, or at the office of
              its stock transfer agent, if any, with the Purchase Form annexed
              hereto duly executed and accompanied by payment of the Exercise
              Price for the number of Warrant Shares specified
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              in such form. As soon as practicable after each such exercise of
              the Warrants, but not later than seven (7) days from the date of
              such exercise, the Company shall issue and deliver to the Holder a
              certificate or certificates for the Warrant Shares issuable upon
              such exercise, registered in the name of the Holder or its
              designee. If this Warrant should be exercised in part only, the
              Company shall, upon surrender of this Warrant for cancellation,
              execute and deliver a new Warrant evidencing the rights of the
              Holder thereof to purchase the balance of the Warrant Shares
              purchasable thereunder. Upon receipt by the Company of this
              Warrant at its office, or by the stock transfer agent of the
              Company at its office, in proper form for exercise, the Holder
              shall be deemed to be the holder of record of the shares of Common
              Stock issuable upon such exercise, notwithstanding that the stock
              transfer books of the Company shall then be closed or that
              certificates representing such shares of Common Stock shall not
              then be physically delivered to the Holder.

          b.       At any time during the Exercise Period, the Holder may, at
              its option, exchange this Warrant, in whole or in part (a "Warrant
              Exchange") into the number of Warrant Shares determined in
              accordance with this Section (a)(ii), by surrendering this Warrant
              at the principal office of the Company or at the office of its
              stock transfer agent, accompanied by a notice stating such
              Holder's intent to effect such exchange, the number of Warrant
              Shares to be exchanged and the date on which the Holder requests
              that such Warrant Exchange occur (the "Notice of Exchange"). The
              Warrant Exchange shall take place on the date specified in the
              Notice of Exchange or, if later, the date the Notice of Exchange
              is received by the Company (the "Exchange Date"). Certificates for
              the shares issuable upon such Warrant Exchange and, if applicable,
              a new warrant of like tenor evidencing the balance of the shares
              remaining subject to this Warrant, shall be issued as of the
              Exchange Date and delivered to the Holder within seven (7) days
              following the Exchange Date. In connection with any Warrant
              Exchange, this Warrant shall represent the right to subscribe for
              and acquire the number of Warrant Shares (rounded to the next
              highest integer) equal to (i) the number of Warrant Shares
              specified by the Holder in its Notice of Exchange (the "Total
              Number") less (ii) the number of Warrant Shares equal to the
              quotient obtained by dividing (A) the product of the Total Number
              and the existing Exercise Price by (B) the Fair Market Value.
              "Fair Market Value" shall mean: (1) if the Common Stock is listed
              on a National Securities Exchange or admitted to unlisted trading
              privileges on such exchange or listed for trading on the NASDAQ
              system, the average of the last reported sale prices of the Common
              Stock on such exchange or system for the twenty (20) business days
              ending on the last business day prior to the date for which the
              determination is being made; or (2) if the
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              Common Stock is not so listed or admitted to unlisted trading
              privileges, the average of the means of the last reported bid and
              asked prices reported by the National Quotation Bureau, Inc. for
              the twenty (20) business days ending on the last business day
              prior to the date for which the determination is being made; or
              (3) if the Common Stock is not so listed or admitted to unlisted
              trading privileges and bid and asked prices are not so reported,
              an amount, not less than book value thereof as at the end of the
              most recent fiscal year of the Company ending prior to the
              Exchange Date, determined in such reasonable manner as may be
              prescribed by the Board of Directors of the Company.

     2.       RESERVATION OF SHARES. The Company shall at all times reserve for
          issuance and/or delivery upon exercise of this Warrant such number of
          shares of its Common Stock as shall be required for issuance and
          delivery upon exercise of the Warrants.

     3.       FRACTIONAL SHARES. No fractional shares or script representing
          fractional shares shall be issued upon the exercise of this Warrant.
          With respect to any fraction of a share called for upon any exercise
          hereof, the Company shall pay to the Holder an amount in cash equal to
          such fraction multiplied by the Fair Market Value of a share.

     4.       EXCHANGE, TRANSFER, ASSIGNMENT OR LOSS OF WARRANT.

              (i)  This Warrant is exchangeable, without expense, at the option
              of the Holder, upon presentation and surrender hereof to the
              Company or at the office of its stock transfer agent, if any, for
              other warrants of different denominations entitling the holder
              thereof to purchase in the aggregate the same number of shares of
              Common Stock purchasable hereunder. Subject to the restrictions
              set forth in subparagraph (ii) below, upon surrender of this
              Warrant to the Company at its principal office or at the office of
              its stock transfer agent, if any, with the Assignment Form annexed
              hereto duly executed and funds sufficient to pay any transfer tax,
              the Company shall, without charge, execute and deliver a new
              Warrant in the name of the assignee named in such instrument of
              assignment and this Warrant shall promptly be canceled. This
              Warrant may be divided or combined with other warrants which carry
              the same rights upon presentation hereof at the principal office
              of the Company or at the office of its stock transfer agent, if
              any, together with a written notice specifying the names and
              denominations in which new Warrants are to be issued and signed by
              the Holder hereof. The term "Warrant" as used herein includes any
              Warrants into which this Warrant may be divided or exchanged. Upon
              receipt by the Company of evidence satisfactory to it of the loss,
              theft, destruction or mutilation of this Warrant, and (in the case
              of loss, theft or destruction) of
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              reasonably satisfactory indemnification, and upon surrender and
              cancellation of this Warrant, if mutilated, the Company will
              execute and deliver a new Warrant of like tenor and date. Any such
              new Warrant executed and delivered shall constitute an additional
              contractual obligation on the part of the Company, whether or not
              this Warrant so lost, stolen, destroyed, or mutilated shall be at
              any time enforceable by anyone.

              (ii) This Warrant and the shares of Common Stock issuable upon
              exercise hereof have not been registered under the Securities Act
              of 1933, as amended, or state securities laws by reason of an
              exemption therefrom. The shares of Common Stock issuable upon
              exercise of this Warrant are not transferable except as provided
              in the Agreement and the Stockholders' Agreement dated as of
              January 6, 1998, as amended from time to time ("Stockholders'
              Agreement"). Shares of Common Stock issuable upon exercise of this
              Warrant will bear an appropriate legend to this effect. The
              restrictions contained herein shall be binding on any transferee
              of the Common Stock issuable upon exercise of this Warrant and the
              Company may require any such transferee to execute an instrument
              agreeing in writing to be bound by these restrictions as a
              condition to transfer.

     5.       RIGHTS OF THE HOLDER. The Holder shall not, by virtue hereof, be
          entitled to any rights of a shareholder in the Company, either at law
          or equity, and the rights of the Holder are limited to those expressed
          in the Warrant and are not enforceable against the Company except to
          the extent set forth herein.

     6.       ANTI-DILUTION PROVISIONS. The Exercise Price in effect at any time
          and the number and kind of securities purchasable upon the exercise of
          the Warrants shall be subject to adjustment from time to time upon the
          happening of certain events as follows:

          a.       In case the Company shall (i) declare a dividend or make a
              distribution on its outstanding shares of Common Stock in shares
              of Common Stock, (ii) subdivide or reclassify its outstanding
              shares of Common Stock into a greater number of shares, or (iii)
              combine or reclassify its outstanding shares of Common Stock into
              a smaller number of shares, the Exercise Price in effect at the
              time of the record date for such dividend or distribution or of
              the effective date of such subdivision, combination or
              reclassification shall be adjusted so that it shall equal the
              price determined by multiplying the Exercise Price by a fraction,
              the denominator of which shall be the number of shares of Common
              Stock outstanding after giving effect to such action, and the
              numerator of which shall be the number of shares of Common Stock
              outstanding immediately
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              prior to such action. Such adjustment shall be made successively
              whenever any event listed above shall occur.

          b.       In case the Company shall fix a record date for the issuance
              of rights or warrants to all holders of its Common Stock entitling
              them to subscribe for or purchase shares of Common Stock (or
              securities convertible into Common Stock) at a price (the
              "Subscription Price") (or having a conversion price per share)
              less than the Exercise Price on the record date mentioned below,
              the Exercise Price shall be adjusted so that the same shall equal
              the price determined by multiplying the Exercise Price in effect
              immediately prior to the date of issuance by a fraction, the
              numerator of which shall be the sum of the number of shares
              outstanding on the record date mentioned below and the number of
              additional shares of Common Stock which the aggregate offering
              price of the total number of shares of Common Stock so offered (or
              the aggregate conversion price of the convertible securities so
              offered) would purchase at the Exercise Price in effect
              immediately prior to the date of such issuance, and the
              denominator of which shall be the sum of the number of shares of
              Common Stock outstanding on the record date mentioned below and
              the number of additional shares of Common Stock offered for
              subscription or purchase (or into which the convertible securities
              so offered are convertible). Such adjustment shall be made
              successively whenever such rights or warrants are issued and shall
              become effective immediately after the record date for the
              determination of shareholders entitled to receive such rights or
              warrants; and to the extent that shares of Common Stock are not
              delivered (or securities convertible into Common Stock are not
              delivered) after the expiration of such rights or warrants the
              Exercise Price shall be readjusted to the Exercise Price which
              would then be in effect had the adjustments made upon the issuance
              of such rights or warrants been made upon the basis of delivery of
              only the number of shares of Common Stock (or securities
              convertible into Common Stock) actually delivered.

          c.       In case the Company shall hereafter distribute to the holders
              of its Common Stock evidences of its indebtedness or assets
              (excluding cash dividends or distributions and dividends or
              distributions referred to in Subsection (i) above) or subscription
              rights or warrants (excluding those referred to in Subsection (ii)
              above), then in each such case the Exercise Price in effect
              thereafter shall be determined by multiplying the Exercise Price
              in effect immediately prior thereto by a fraction, the numerator
              of which shall be the total number of shares of Common Stock
              outstanding multiplied by the Fair Market Value per share of
              Common Stock, less the fair market value (as determined by the
              Company's Board of Directors) of said assets or evidences of
              indebtedness so distributed or of such rights or warrants, and the
              denominator of which shall be the total number of shares
<PAGE>

              of Common Stock outstanding multiplied by the Fair Market Value
              per share of Common Stock. Such adjustment shall be made
              successively whenever such a record date is fixed. Such adjustment
              shall be made whenever any such distribution is made and shall
              become effective immediately after the record date for the
              determination of shareholders entitled to receive such
              distribution.

          d.       Whenever the Exercise Price payable upon exercise of each
              Warrant is adjusted pursuant to Subsections (i), (ii) or (iii)
              above, the number of Shares purchasable upon exercise of this
              Warrant shall simultaneously be adjusted by multiplying the number
              of Shares initially issuable upon exercise of this Warrant by the
              Exercise Price in effect on the date hereof and dividing the
              product so obtained by the Exercise Price, as adjusted.

          e.       No adjustment in the Exercise Price shall be required unless
              such adjustment would require an increase or decrease of at least
              5% in such price; provided, however, that any adjustments which by
              reason of this Subsection (v) are not required to be made shall be
              carried forward and taken into account in any subsequent
              adjustment required to be made hereunder. All calculations under
              this Section (f) shall be made to the nearest cent or to the
              nearest one-hundredth of a share, as the case may be. Anything in
              this Section (f) to the contrary notwithstanding, the Company
              shall be entitled, but shall not be required, to make such changes
              in the Exercise Price, in addition to those required by this
              Section (f), as it shall determine, in its sole discretion, to be
              advisable in order that any dividend or distribution in shares of
              Common Stock, or any subdivision, reclassification or combination
              of Common Stock, hereafter made by the Company shall not result in
              any Federal Income tax liability to the holders of Common Stock or
              securities convertible into Common Stock (including Warrants).

          f.       Whenever the Exercise Price is adjusted, as herein provided,
              the Company shall promptly but no later than 10 days after any
              request for such an adjustment by the Holder, cause a notice
              setting forth the adjusted Exercise Price and adjusted number of
              Shares issuable upon exercise of each Warrant, and, if requested,
              information describing the transactions giving rise to such
              adjustments, to be mailed to the Holders at their last addresses
              appearing in the Warrant Register, and shall cause a certified
              copy thereof to be mailed to its transfer agent, if any. The
              Company may retain a firm of independent certified public
              accountants selected by the Board of Directors (who may be the
              regular accountants employed by the Company) to make any
              computation required by this Section (f), and a

<PAGE>

              certificate signed by such firm shall be conclusive evidence of
              the correctness of such adjustment.

          g.       In the event that at any time, as a result of an adjustment
              made pursuant to Subsection (i) above, the Holder of this Warrant
              thereafter shall become entitled to receive any shares of the
              Company, other than Common Stock, thereafter the number of such
              other shares so receivable upon exercise of this Warrant shall be
              subject to adjustment from time to time in a manner and on terms
              as nearly equivalent as practicable to the provisions with respect
              to the Common Stock contained in Subsections (i) to (vi),
              inclusive above.

          h.       Irrespective of any adjustments in the Exercise Price or the
              number or kind of shares purchasable upon exercise of this
              Warrant, Warrants theretofore or thereafter issued may continue to
              express the same price and number and kind of shares as are stated
              in the similar Warrants initially issuable pursuant to the
              Agreement.

     7.       OFFICER'S CERTIFICATE. Whenever the Exercise Price shall be
          adjusted as required by the provisions of the foregoing Section, the
          Company shall forthwith file in the custody of its Secretary or an
          Assistant Secretary at its principal office and with its stock
          transfer agent, if any, an officer's certificate showing the adjusted
          Exercise Price determined as herein provided, setting forth in
          reasonable detail the facts requiring such adjustment, including a
          statement of the number of additional shares of Common Stock, if any,
          and such other facts as shall be necessary to show the reason for and
          the manner of computing such adjustment. Each such officer's
          certificate shall be made available at all reasonable times for
          inspection by the holder or any holder of a Warrant executed and
          delivered pursuant to Section (a) and the Company shall, forthwith
          after each such adjustment, mail a copy by certified mail of such
          certificate to the Holder or any such holder.

     8.       NOTICES TO WARRANT HOLDERS. So long as this Warrant shall be
          outstanding, (i) if the Company shall pay any dividend or make any
          distribution upon the Common Stock or (ii) if the Company shall offer
          to the Holders of Common Stock for subscription or purchase by them
          any share of any class or any other rights or (iii) if any capital
          reorganization of the Company, reclassification of the capital stock
          of the Company, consolidation or merger of the Company with or into
          another corporation, sale, lease or transfer of all or substantially
          all of the property and assets of the Company to another corporation,
          or voluntary or involuntary dissolution, liquidation or winding up of
          the Company shall be effected, then in any such case, the Company
          shall cause to be mailed by certified mail to the Holder, at least
          fifteen days prior to the date specified in (x) or (y) below, as the
          case may be, a notice containing a brief description of the proposed
<PAGE>

          action and stating the date on which (x) a record is to be taken for
          the purpose of such dividend, distribution or rights, or (y) such
          reclassification, reorganization, consolidation, merger, conveyance,
          lease, dissolution, liquidation or winding up is to take place and the
          date, if any is to be fixed, as of which the Holders of Common Stock
          or other securities shall receive cash or other property deliverable
          upon such reclassification, reorganization, consolidation, merger,
          conveyance, dissolution, liquidation or winding up.

     9.       RECLASSIFICATION, REORGANIZATION OR MERGER. In case of any
          reclassification, capital reorganization or other change of
          outstanding shares of Common Stock of the Company, or in case of any
          consolidation or merger of the Company with or into another
          corporation (other than a merger with a subsidiary in which merger the
          Company is the continuing corporation and which does not result in any
          reclassification, capital reorganization or other change of
          outstanding shares of Common Stock of the class issuable upon exercise
          of this Warrant) or in case of any sale, lease or conveyance to
          another corporation of the property of the Company as an entirety, the
          Company shall, as a condition precedent to such transaction, cause
          effective provisions to be made so that the Holder shall have the
          right thereafter by exercising this Warrant at any time prior to the
          expiration of the Warrant, to purchase the kind and amount of shares
          of stock and other securities and property receivable upon such
          reclassification, capital reorganization and other change,
          consolidation, merger, sale or conveyance by a holder of the number of
          shares of Common Stock which might have been purchased upon exercise
          of this Warrant immediately prior to such reclassification, change,
          consolidation, merger, sale or conveyance. Any such provision shall
          include provision for adjustments which shall be as nearly equivalent
          as may be practicable to the adjustments provided for in this Warrant.
          The foregoing provisions of this Section (i) shall similarly apply to
          successive reclassifications, capital reorganizations and changes of
          shares of Common Stock and to successive consolidations, mergers,
          sales or conveyances. In the event that in connection with any such
          capital reorganization or reclassification, consolidation, merger,
          sale or conveyance, additional shares of Common Stock shall be issued
          in exchange, conversion, substitution or payment, in whole or in part,
          for a security of the Company other than Common Stock, any such issue
          shall be treated as an issue of Common Stock covered by the provisions
          of Subsection (i) of Section (f)hereof.
<PAGE>

                                             3-DIMENSIONAL PHARMACEUTICALS, INC.

                                             By /s/ David C. U'Prichard
                                                --------------------------------
                                             Name:  David C. U'Prichard
                                             Title:  Chief Executive Officer

[SEAL]

Dated:  November 18, 1999

Attest:

/s/ Scott M. Horvitz
-----------------------------
Secretary
<PAGE>

                                 PURCHASE FORM
                                 -------------

                                                        Dated _____________,____

     The undersigned hereby irrevocably elects to exercise the within Warrant to
the extent of purchasing _________ shares of Common Stock and hereby makes
payment of in payment of the actual exercise price thereof

                                   ---------

                    INSTRUCTIONS FOR REGISTRATION OF STOCK
                    --------------------------------------

Name ____________________________________________
     (Please typewrite or print in block letters)

Address  _________________________________

Signature  ________________________________

                                   ---------

                                ASSIGNMENT FORM
                                ---------------

     FOR VALUE RECEIVED, __________________________ hereby sells, assigns and
transfers unto

Name _____________________________________________________
     (Please typewrite or print in block letters)

Address  __________________________________________________
the right to purchase Common Stock represented by this Warrant to the extent of
_____ shares as to which such right is exercisable and does hereby irrevocably
constitute and appoint ____________________ Attorney, to transfer the same on
the books of the Company with full power of substitution in the premises.

Date _____________, _____

Signature ____________________________<PAGE>

                                                                   EXHIBIT 10.10

             Warrant to Purchase 10,500 Shares of Common Stock or
        such additional shares as this Warrant may entitle the holder
              to purchase pursuant to provisions of this Warrant.

                       WARRANT TO PURCHASE COMMON STOCK

                                      OF

                      3-DIMENSIONAL PHARMACEUTICALS, INC.

          This is to Certify That, FOR VALUE RECEIVED, Henry Rothman or assigns
("Holder") is entitled to purchase, subject to the provisions of this Warrant,
from 3-Dimensional Pharmaceuticals, Inc., a Delaware corporation (the
"Company"), 10,500 fully paid, validly issued and nonassessable shares of Common
Stock, par value $.001 per share, of the Company ("Common Stock") at a price of
$1.25 per share during the Exercise Period (as defined below).  The number of
shares of Common Stock to be received upon the exercise of this Warrant and the
price to be paid for each share of Common Stock may be adjusted from time to
time as hereinafter set forth.  The shares of Common Stock deliverable upon such
exercise, and as adjusted from time to time, are hereinafter sometimes referred
to as "Warrant Shares" and the exercise price of a share of Common Stock in
effect at any time and as adjusted from time to time is hereinafter sometimes
referred to as the "Exercise Price."  This Warrant is being issued in connection
with the issuance by the Company of Warrants to purchase shares of Common Stock
and promissory notes in the aggregate principal amount of up to $10,000,000 (the
"Notes"), pursuant to a Note and Warrant Purchase Agreement dated as of November
18, 1999 (the "Agreement").

        1.          EXERCISE OF WARRANT.

                a.          This Warrant may be exercised in whole or in part at
                    any time or from time to time on or after November 18, 1999
                    until 5 p.m. New York City Time on November 18, 2000 (the
                    "Exercise Period"); provided, however, that if such day is a
                    day on which banking institutions in the State of New York
                    are authorized by law to close, then on the next succeeding
                    day which shall not be such a day. This Warrant may be
                    exercised by presentation and surrender hereof to the
                    Company at its principal office, or at the office of its
                    stock transfer agent, if any, with the Purchase Form annexed
                    hereto duly executed and accompanied by payment of the
                    Exercise Price for the number of Warrant Shares specified
<PAGE>

                    in such form. As soon as practicable after each such
                    exercise of the Warrants, but not later than seven (7) days
                    from the date of such exercise, the Company shall issue and
                    deliver to the Holder a certificate or certificates for the
                    Warrant Shares issuable upon such exercise, registered in
                    the name of the Holder or its designee. If this Warrant
                    should be exercised in part only, the Company shall, upon
                    surrender of this Warrant for cancellation, execute and
                    deliver a new Warrant evidencing the rights of the Holder
                    thereof to purchase the balance of the Warrant Shares
                    purchasable thereunder. Upon receipt by the Company of this
                    Warrant at its office, or by the stock transfer agent of the
                    Company at its office, in proper form for exercise, the
                    Holder shall be deemed to be the holder of record of the
                    shares of Common Stock issuable upon such exercise,
                    notwithstanding that the stock transfer books of the Company
                    shall then be closed or that certificates representing such
                    shares of Common Stock shall not then be physically
                    delivered to the Holder.

                b.          At any time during the Exercise Period, the Holder
                    may, at its option, exchange this Warrant, in whole or in
                    part (a "Warrant Exchange") into the number of Warrant
                    Shares determined in accordance with this Section (a)(ii),
                    by surrendering this Warrant at the principal office of the
                    Company or at the office of its stock transfer agent,
                    accompanied by a notice stating such Holder's intent to
                    effect such exchange, the number of Warrant Shares to be
                    exchanged and the date on which the Holder requests that
                    such Warrant Exchange occur (the "Notice of Exchange"). The
                    Warrant Exchange shall take place on the date specified in
                    the Notice of Exchange or, if later, the date the Notice of
                    Exchange is received by the Company (the "Exchange Date").
                    Certificates for the shares issuable upon such Warrant
                    Exchange and, if applicable, a new warrant of like tenor
                    evidencing the balance of the shares remaining subject to
                    this Warrant, shall be issued as of the Exchange Date and
                    delivered to the Holder within seven (7) days following the
                    Exchange Date. In connection with any Warrant Exchange, this
                    Warrant shall represent the right to subscribe for and
                    acquire the number of Warrant Shares (rounded to the next
                    highest integer) equal to (i) the number of Warrant Shares
                    specified by the Holder in its Notice of Exchange (the
                    "Total Number") less (ii) the number of Warrant Shares equal
                    to the quotient obtained by dividing (A) the product of the
                    Total Number and the existing Exercise Price by (B) the Fair
                    Market Value. "Fair Market Value" shall mean: (1) if the
                    Common Stock is listed on a National Securities Exchange or
                    admitted to unlisted trading privileges on such exchange or
                    listed for trading on the NASDAQ system, the average of the
                    last reported sale prices of the Common Stock on such
                    exchange or system for the twenty (20) business days ending
                    on the last business day prior to the date for which the
                    determination is being made; or (2) if the
<PAGE>

                    Common Stock is not so listed or admitted to unlisted
                    trading privileges, the average of the means of the last
                    reported bid and asked prices reported by the National
                    Quotation Bureau, Inc. for the twenty (20) business days
                    ending on the last business day prior to the date for which
                    the determination is being made; or (3) if the Common Stock
                    is not so listed or admitted to unlisted trading privileges
                    and bid and asked prices are not so reported, an amount, not
                    less than book value thereof as at the end of the most
                    recent fiscal year of the Company ending prior to the
                    Exchange Date, determined in such reasonable manner as may
                    be prescribed by the Board of Directors of the Company.

        2.          RESERVATION OF SHARES.  The Company shall at all times
                reserve for issuance and/or delivery upon exercise of this
                Warrant such number of shares of its Common Stock as shall be
                required for issuance and delivery upon exercise of the
                Warrants.

        3.          FRACTIONAL SHARES.  No fractional shares or script
                representing fractional shares shall be issued upon the exercise
                of this Warrant. With respect to any fraction of a share called
                for upon any exercise hereof, the Company shall pay to the
                Holder an amount in cash equal to such fraction multiplied by
                the Fair Market Value of a share.

        4.          EXCHANGE, TRANSFER, ASSIGNMENT OR LOSS OF WARRANT.

                (i)     This Warrant is exchangeable, without expense, at the
                option of the Holder, upon presentation and surrender hereof to
                the Company or at the office of its stock transfer agent, if
                any, for other warrants of different denominations entitling the
                holder thereof to purchase in the aggregate the same number of
                shares of Common Stock purchasable hereunder. Subject to the
                restrictions set forth in subparagraph (ii) below, upon
                surrender of this Warrant to the Company at its principal office
                or at the office of its stock transfer agent, if any, with the
                Assignment Form annexed hereto duly executed and funds
                sufficient to pay any transfer tax, the Company shall, without
                charge, execute and deliver a new Warrant in the name of the
                assignee named in such instrument of assignment and this Warrant
                shall promptly be canceled. This Warrant may be divided or
                combined with other warrants which carry the same rights upon
                presentation hereof at the principal office of the Company or at
                the office of its stock transfer agent, if any, together with a
                written notice specifying the names and denominations in which
                new Warrants are to be issued and signed by the Holder hereof.
                The term "Warrant" as used herein includes any Warrants into
                which this Warrant may be divided or exchanged. Upon receipt by
                the Company of evidence satisfactory to it of the loss, theft,
                destruction or mutilation of this Warrant, and (in the case of
                loss, theft or destruction) of
<PAGE>

                reasonably satisfactory indemnification, and upon surrender and
                cancellation of this Warrant, if mutilated, the Company will
                execute and deliver a new Warrant of like tenor and date. Any
                such new Warrant executed and delivered shall constitute an
                additional contractual obligation on the part of the Company,
                whether or not this Warrant so lost, stolen, destroyed, or
                mutilated shall be at any time enforceable by anyone.

                (ii)     This Warrant and the shares of Common Stock issuable
                upon exercise hereof have not been registered under the
                Securities Act of 1933, as amended, or state securities laws by
                reason of an exemption therefrom. The shares of Common Stock
                issuable upon exercise of this Warrant are not transferable
                except as provided in the Agreement and the Stockholders'
                Agreement dated as of January 6, 1998, as amended from time to
                time ("Stockholders' Agreement"). Shares of Common Stock
                issuable upon exercise of this Warrant will bear an appropriate
                legend to this effect. The restrictions contained herein shall
                be binding on any transferee of the Common Stock issuable upon
                exercise of this Warrant and the Company may require any such
                transferee to execute an instrument agreeing in writing to be
                bound by these restrictions as a condition to transfer.

5.              RIGHTS OF THE HOLDER.  The Holder shall not, by virtue hereof,
        be entitled to any rights of a shareholder in the Company, either at law
        or equity, and the rights of the Holder are limited to those expressed
        in the Warrant and are not enforceable against the Company except to the
        extent set forth herein.

6.              ANTI-DILUTION PROVISIONS.  The Exercise Price in effect at any
        time and the number and kind of securities purchasable upon the exercise
        of the Warrants shall be subject to adjustment from time to time upon
        the happening of certain events as follows:

        a.            In case the Company shall (i) declare a dividend or make a
                distribution on its outstanding shares of Common Stock in shares
                of Common Stock, (ii) subdivide or reclassify its outstanding
                shares of Common Stock into a greater number of shares, or (iii)
                combine or reclassify its outstanding shares of Common Stock
                into a smaller number of shares, the Exercise Price in effect at
                the time of the record date for such dividend or distribution or
                of the effective date of such subdivision, combination or
                reclassification shall be adjusted so that it shall equal the
                price determined by multiplying the Exercise Price by a
                fraction, the denominator of which shall be the number of shares
                of Common Stock outstanding after giving effect to such action,
                and the numerator of which shall be the number of shares of
                Common Stock outstanding immediately
<PAGE>

                prior to such action. Such adjustment shall be made successively
                whenever any event listed above shall occur.

        b.            In case the Company shall fix a record date for the
                issuance of rights or warrants to all holders of its Common
                Stock entitling them to subscribe for or purchase shares of
                Common Stock (or securities convertible into Common Stock) at a
                price (the "Subscription Price") (or having a conversion price
                per share) less than the Exercise Price on the record date
                mentioned below, the Exercise Price shall be adjusted so that
                the same shall equal the price determined by multiplying the
                Exercise Price in effect immediately prior to the date of
                issuance by a fraction, the numerator of which shall be the sum
                of the number of shares outstanding on the record date mentioned
                below and the number of additional shares of Common Stock which
                the aggregate offering price of the total number of shares of
                Common Stock so offered (or the aggregate conversion price of
                the convertible securities so offered) would purchase at the
                Exercise Price in effect immediately prior to the date of such
                issuance, and the denominator of which shall be the sum of the
                number of shares of Common Stock outstanding on the record date
                mentioned below and the number of additional shares of Common
                Stock offered for subscription or purchase (or into which the
                convertible securities so offered are convertible). Such
                adjustment shall be made successively whenever such rights or
                warrants are issued and shall become effective immediately after
                the record date for the determination of shareholders entitled
                to receive such rights or warrants; and to the extent that
                shares of Common Stock are not delivered (or securities
                convertible into Common Stock are not delivered) after the
                expiration of such rights or warrants the Exercise Price shall
                be readjusted to the Exercise Price which would then be in
                effect had the adjustments made upon the issuance of such rights
                or warrants been made upon the basis of delivery of only the
                number of shares of Common Stock (or securities convertible into
                Common Stock) actually delivered.

        c.            In case the Company shall hereafter distribute to the
                holders of its Common Stock evidences of its indebtedness or
                assets (excluding cash dividends or distributions and dividends
                or distributions referred to in Subsection (i) above) or
                subscription rights or warrants (excluding those referred to in
                Subsection (ii) above), then in each such case the Exercise
                Price in effect thereafter shall be determined by multiplying
                the Exercise Price in effect immediately prior thereto by a
                fraction, the numerator of which shall be the total number of
                shares of Common Stock outstanding multiplied by the Fair Market
                Value per share of Common Stock, less the fair market value (as
                determined by the Company's Board of Directors) of said assets
                or evidences of indebtedness so distributed or of such rights or
                warrants, and the denominator of which shall be the total number
                of shares
<PAGE>

                of Common Stock outstanding multiplied by the Fair Market Value
                per share of Common Stock. Such adjustment shall be made
                successively whenever such a record date is fixed. Such
                adjustment shall be made whenever any such distribution is made
                and shall become effective immediately after the record date for
                the determination of shareholders entitled to receive such
                distribution.

        d.            Whenever the Exercise Price payable upon exercise of each
                Warrant is adjusted pursuant to Subsections (i), (ii) or (iii)
                above, the number of Shares purchasable upon exercise of this
                Warrant shall simultaneously be adjusted by multiplying the
                number of Shares initially issuable upon exercise of this
                Warrant by the Exercise Price in effect on the date hereof and
                dividing the product so obtained by the Exercise Price, as
                adjusted.

        e.            No adjustment in the Exercise Price shall be required
                unless such adjustment would require an increase or decrease of
                at least 5% in such price; provided, however, that any
                adjustments which by reason of this Subsection (v) are not
                required to be made shall be carried forward and taken into
                account in any subsequent adjustment required to be made
                hereunder. All calculations under this Section (f) shall be made
                to the nearest cent or to the nearest one-hundredth of a share,
                as the case may be. Anything in this Section (f) to the contrary
                notwithstanding, the Company shall be entitled, but shall not be
                required, to make such changes in the Exercise Price, in
                addition to those required by this Section (f), as it shall
                determine, in its sole discretion, to be advisable in order that
                any dividend or distribution in shares of Common Stock, or any
                subdivision, reclassification or combination of Common Stock,
                hereafter made by the Company shall not result in any Federal
                Income tax liability to the holders of Common Stock or
                securities convertible into Common Stock (including Warrants).

        f.            Whenever the Exercise Price is adjusted, as herein
                provided, the Company shall promptly but no later than 10 days
                after any request for such an adjustment by the Holder, cause a
                notice setting forth the adjusted Exercise Price and adjusted
                number of Shares issuable upon exercise of each Warrant, and, if
                requested, information describing the transactions giving rise
                to such adjustments, to be mailed to the Holders at their last
                addresses appearing in the Warrant Register, and shall cause a
                certified copy thereof to be mailed to its transfer agent, if
                any. The Company may retain a firm of independent certified
                public accountants selected by the Board of Directors (who may
                be the regular accountants employed by the Company) to make any
                computation required by this Section (f), and a
<PAGE>

                certificate signed by such firm shall be conclusive evidence of
                the correctness of such adjustment.

        g.            In the event that at any time, as a result of an
                adjustment made pursuant to Subsection (i) above, the Holder of
                this Warrant thereafter shall become entitled to receive any
                shares of the Company, other than Common Stock, thereafter the
                number of such other shares so receivable upon exercise of this
                Warrant shall be subject to adjustment from time to time in a
                manner and on terms as nearly equivalent as practicable to the
                provisions with respect to the Common Stock contained in
                Subsections (i) to (vi), inclusive above.

        h.            Irrespective of any adjustments in the Exercise Price or
                the number or kind of shares purchasable upon exercise of this
                Warrant, Warrants theretofore or thereafter issued may continue
                to express the same price and number and kind of shares as are
                stated in the similar Warrants initially issuable pursuant to
                the Agreement.

    7.          OFFICER'S CERTIFICATE.  Whenever the Exercise Price shall be
        adjusted as required by the provisions of the foregoing Section, the
        Company shall forthwith file in the custody of its Secretary or an
        Assistant Secretary at its principal office and with its stock transfer
        agent, if any, an officer's certificate showing the adjusted Exercise
        Price determined as herein provided, setting forth in reasonable detail
        the facts requiring such adjustment, including a statement of the number
        of additional shares of Common Stock, if any, and such other facts as
        shall be necessary to show the reason for and the manner of computing
        such adjustment. Each such officer's certificate shall be made available
        at all reasonable times for inspection by the holder or any holder of a
        Warrant executed and delivered pursuant to Section (a) and the Company
        shall, forthwith after each such adjustment, mail a copy by certified
        mail of such certificate to the Holder or any such holder.

    8.           NOTICES TO WARRANT HOLDERS.  So long as this Warrant shall be
        outstanding, (i) if the Company shall pay any dividend or make any
        distribution upon the Common Stock or (ii) if the Company shall offer to
        the Holders of Common Stock for subscription or purchase by them any
        share of any class or any other rights or (iii) if any capital
        reorganization of the Company, reclassification of the capital stock of
        the Company, consolidation or merger of the Company with or into another
        corporation, sale, lease or transfer of all or substantially all of the
        property and assets of the Company to another corporation, or voluntary
        or involuntary dissolution, liquidation or winding up of the Company
        shall be effected, then in any such case, the Company shall cause to be
        mailed by certified mail to the Holder, at least fifteen days prior to
        the date specified in (x) or (y) below, as the case may be, a notice
        containing a brief description of the proposed
<PAGE>

        action and stating the date on which (x) a record is to be taken for the
        purpose of such dividend, distribution or rights, or (y) such
        reclassification, reorganization, consolidation, merger, conveyance,
        lease, dissolution, liquidation or winding up is to take place and the
        date, if any is to be fixed, as of which the Holders of Common Stock or
        other securities shall receive cash or other property deliverable upon
        such reclassification, reorganization, consolidation, merger,
        conveyance, dissolution, liquidation or winding up.

    9.           RECLASSIFICATION, REORGANIZATION OR MERGER.  In case of any
        reclassification, capital reorganization or other change of outstanding
        shares of Common Stock of the Company, or in case of any consolidation
        or merger of the Company with or into another corporation (other than a
        merger with a subsidiary in which merger the Company is the continuing
        corporation and which does not result in any reclassification, capital
        reorganization or other change of outstanding shares of Common Stock of
        the class issuable upon exercise of this Warrant) or in case of any
        sale, lease or conveyance to another corporation of the property of the
        Company as an entirety, the Company shall, as a condition precedent to
        such transaction, cause effective provisions to be made so that the
        Holder shall have the right thereafter by exercising this Warrant at any
        time prior to the expiration of the Warrant, to purchase the kind and
        amount of shares of stock and other securities and property receivable
        upon such reclassification, capital reorganization and other change,
        consolidation, merger, sale or conveyance by a holder of the number of
        shares of Common Stock which might have been purchased upon exercise of
        this Warrant immediately prior to such reclassification, change,
        consolidation, merger, sale or conveyance. Any such provision shall
        include provision for adjustments which shall be as nearly equivalent as
        may be practicable to the adjustments provided for in this Warrant. The
        foregoing provisions of this Section (i) shall similarly apply to
        successive reclassifications, capital reorganizations and changes of
        shares of Common Stock and to successive consolidations, mergers, sales
        or conveyances. In the event that in connection with any such capital
        reorganization or reclassification, consolidation, merger, sale or
        conveyance, additional shares of Common Stock shall be issued in
        exchange, conversion, substitution or payment, in whole or in part, for
        a security of the Company other than Common Stock, any such issue shall
        be treated as an issue of Common Stock covered by the provisions of
        Subsection (i) of Section (f)hereof.
<PAGE>

                              3-DIMENSIONAL PHARMACEUTICALS, INC.

                              By /s/ David C. U'Prichard
                                 -------------------------------------
                              Name:  David C. U'Prichard
                              Title:  Chief Executive Officer

[SEAL]

Dated:  November 18, 1999

Attest:

/s/ Scott M. Horvitz
-----------------------------
Secretary
<PAGE>

                                 PURCHASE FORM
                                 -------------

                                                     Dated _____________, ____

     The undersigned hereby irrevocably elects to exercise the within Warrant to
the extent of purchasing _________ shares of Common Stock and hereby makes
payment of in payment of the actual exercise price thereof

                                   ---------

                    INSTRUCTIONS FOR REGISTRATION OF STOCK
                    --------------------------------------

Name ____________________________________________
     (Please typewrite or print in block letters)

Address  _________________________________

Signature  ________________________________

                                   ---------

                                ASSIGNMENT FORM
                                ---------------

     FOR VALUE RECEIVED, __________________________ hereby sells, assigns and
transfers unto

Name _____________________________________________________
     (Please typewrite or print in block letters)

Address  __________________________________________________
the right to purchase Common Stock represented by this Warrant to the extent of
_____ shares as to which such right is exercisable and does hereby irrevocably
constitute and appoint ____________________ Attorney, to transfer the same on
the books of the Company with full power of substitution in the premises.

Date _____________, _____

Signature ____________________________

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