EXHIBIT 3.6


                            CERTIFICATE OF AMENDMENT
                                       OF
                   SIXTH RESTATED CERTIFICATE OF INCORPORATION
                                       OF
                                 NITROMED, INC.

                         Pursuant to Section 242 of the
                General Corporation Law of the State of Delaware
                            ------------------------

         NitroMed, Inc. (hereinafter called the "Corporation"), organized and
existing under and by virtue of the General Corporation Laws of the State of
Delaware, does hereby certify as follows:

         At a duly called meeting of the Board of Directors, a resolution was
duly adopted pursuant to Section 242 of the General Corporation Law of the State
of Delaware, setting forth an amendment to the Sixth Restated Certificate of
Incorporation of the Corporation and declaring said amendment to be advisable.
The stockholders of the Corporation duly adopted said amendment by written
consent in accordance with Sections 228 and 242 of the General Corporation Law
of the State of Delaware. The resolution setting forth the amendment is as
follows:

         RESOLVED: That Article III, Part A, of the Sixth Restated Certificate
of Incorporation of the Corporation shall be amended as follows:

         (1) Article III, Part A, Section A.3(a) of the Sixth Restated
Certificate of Incorporation of the Corporation be amended and restated in its
entirety as follows:

                  "A.3(a) The holders of shares of Series E Stock shall be
         entitled to receive, out of funds legally available therefor, dividends
         of $0.5763 per share per annum (subject to appropriate adjustment in
         the event of any stock dividend, stock split, combination or other
         similar recapitalization affecting such shares), payable when and as
         declared by the Board of Directors of the Corporation. Such dividends
         shall accrue and shall be cumulative from the date of issuance of each
         share of Series E Stock, whether or not declared, provided, however, if
         the Corporation consummates an initial firm commitment underwritten
         public offering of its Common Stock registered under the Securities Act
         of 1933, as amended (an "IPO") on or before December 31, 2003, such
         dividends shall be deemed to have accrued from the date of issuance of
         each share of Series E Stock up to and including October 31, 2003,
         whether or not declared, irrespective of the actual consummation date
         of the IPO. The Corporation shall not declare or pay any dividend on
         shares of Series A, B, C and D Preferred Stock, Series F Junior Stock
         or Common Stock until the holders of Series E Stock then outstanding
         shall have first received a dividend at the rate specified in this
         Section A.3(a)."

         (2) Article III, Part A, Section A.7(a)(ii) of the Sixth Restated
Certificate of Incorporation of the Corporation be amended and restated in its
entirety as follows:

                  "A.7(a)(ii) In the event any Series Preferred Stockholder
         exercises the right to convert shares of Series Preferred Stock into
         shares of Common Stock, pursuant to this Section A.7, all accrued or
         declared but unpaid dividends payable pursuant to Section A.3(a) and/or
         A.3(b) herein, as the case may be, with respect to each share of Series
         Preferred Stock so converted shall be converted into that number of
         fully paid and nonassessable shares of Common Stock equal to the
         quotient of the aggregate dollar amount of accrued or declared but
         unpaid dividends on such share of Series Preferred Stock divided by the
         Dividend Conversion Price. The "Dividend Conversion Price" shall be (i)
         $12.50 per share (subject to adjustment to reflect stock splits, stock
         dividends, stock combinations, recapitalizations and like occurrences),
         if such conversion occurs on or before December 31, 2003; or (ii) fair
         market





         value of the Common Stock as determined by the Board of Directors of
         the Corporation, if such conversion occurs on or after January 1,
         2004."

         (3) Article III, Part A, Section A.7(j) of the Sixth Restated
Certificate of Incorporation of the Corporation be amended and restated in its
entirety as follows:

                  "A.7(j) Upon either (1) the consummation of an IPO pursuant to
         which (A) Common Stock is offered to the public at a price of at least
         $14.4074 per share (subject to adjustment to reflect stock splits,
         stock dividends, stock combinations, recapitalizations and like
         occurrences), and (B) the net proceeds to the Corporation are at least
         $15,000,000, or (2) the written election of the holders of at least
         sixty six and two-thirds percent (66 2/3rd %) of the Series Preferred
         Stock then outstanding, voting together as one class, each share of
         Series Preferred Stock then outstanding shall, by virtue of and
         immediately prior to the closing of such IPO or at the time specified
         by such written election and without any action on the part of the
         holder thereof, be deemed automatically converted into that number of
         shares of Common Stock in which the Series Preferred Stock would be
         convertible if such conversion were to occur at the time of the IPO or
         at the time specified by such written election. The holder of any
         shares of Series Preferred Stock converted into Common Stock pursuant
         to this Section A.7(j) shall be entitled to payment of all declared but
         unpaid dividends, if any, payable on or with respect to such shares up
         to and including the date of the closing of such IPO which shall be
         deemed the Conversion Date for purposes of this Section A.7(j).

                  Notwithstanding anything herein to the contrary (including
         without limitation, the antidilution provisions of Section A.7 of this
         Part A), upon conversion of the Series E Stock and Series F Preferred
         Stock in connection with an IPO (whether such conversion is pursuant to
         subsection (1) or (2) above) that is consummated:

                  (A) on or before December 31, 2003, each share of Series E
         Stock outstanding immediately prior to the IPO shall be converted into
         1.1526 shares of Common Stock and each share of Series F Stock shall be
         converted into 1.073364 (subject to adjustment to reflect stock splits,
         stock dividends, stock combinations, recapitalizations or like
         occurrences); or

                  (B) on or after January 1, 2004, each share of Series E Stock
         outstanding immediately prior to the IPO shall be converted into a
         number of shares of Common Stock equal to the quotient of $14.4074
         (subject to adjustment to reflect stock splits, stock dividends, stock
         combinations, recapitalizations or like occurrences) divided by the
         price per share at which Common Stock is offered to the public in the
         IPO (exclusive of underwriter discounts and commissions, the "IPO Share
         Price")), rounded up to the nearest one-tenth of a share (e.g., if the
         IPO Share Price is $10.00, then each share of Series E Stock shall
         convert into 1.4407 shares of Common Stock [$14.4074 / $10.00 =
         1.4407]) and each share of Series F Stock shall be converted into a
         number of shares of Common Stock at the then effective Series F
         Conversion Price."

         IN WITNESS WHEREOF, the Corporation has caused this Certificate of
Amendment to be signed by its Chief Executive Officer on this 26th day of
September, 2003.


                                             NITROMED, INC.


                                             By: Michael D. Loberg
                                                 --------------------------
                                             Name:  Michael D. Loberg
                                             Title: Chief Executive Officer




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