NOVEL CC-1065 ANALOGS

Abstract: This invention provides some new synthetically obtained compounds of formula (I and II), which are useful as chemical intermediates. Representative formula (I or II) compounds have also been shown to possess useful ranges of antitumor activity in standard laboratory animal tests. In addition, the compounds of formula (I or II) can be linked to monoclonal antibodies, either directly or via known linking group, as a means of selectively delivering the CC-1065 analogs (Compounds of Formula I and II) to those target cells expressing the target antigen and thus selectively eliminating those diseased cells from the animal or human. Further, the compounds of formula (I and II) can be linked to soluble human CD4 or a soluble human CD4 protein fragment capable of binding to the gp120 envelope protein of the human immuno-virus and thus eliminate virally infected cells.

Description: NOVEL CC-1065 ANALOGS BACKGROUND OF THE INVENTION Antibiotic CC-1065, (7bR,8aS)-7-[[l ,6-dihydro-4-hydroxy-5-methoxy-7-[(4,5,8,8a- tetrahydro-7-methyl-4-oxocyclopropa[c]pyrrolo[3,2-e]indol-2(lH)-yl)carbonyl]benzo[l,2-b:4,3- b']dipyrrol-3(2H)-yl]carbonyl]l,6-dihydro-4-hydroxy-5-methoxy-benzo[l,2-b:4,3-b']dipyrrole- 3(2H)-carboxamide, is disclosed and claimed in L . Hanka et al U.S. Patent No. 4,169,888 together with a process for preparing antibiotic CC-1065 by aerobic fermentation procedures, and recovering antibiotic CC-1065 therefrom. In The Journal of Antibiotics, 1985, 38, 746, D.G. Martin et al reported that acetic acid adds across the spirocyclopropylcyclohexadienyl (SCPCH) system of CC-1065 to produce the phenolic, acetic acid product (AAP), 7-[[7-[[l-[(acetyloxy)methyl]-l,6-dihydro-5-hydroxy-8- meώylbenzo[l,2-b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-l,6-dihydro-4-hydroxy-5-methoxybenzo[l,2- b:4,3-b']-dipyrrol-3(2H)-yl]carbonyl]-l,6-dihydro-4-hydroxy-5-methoxy-benzo[l,2-b:4,3- b']dipyrrole-3(2H)-carboxamide. AAP was tested in vitro and in vivo and found to be less potent than CC-1065 by a factor of 10 3 to 10 depending upon the particular test system and therefore tended to divert attention from adducts of the SCPCH system as useful antitumor agents or as prodrugs to CC-1065 analogs. In J. Am. Chem. Soc, 103, No. 18, 1981, W. Wierenga published a "Synthesis of the Left-Hand Segment of the Antitumor Agent CC-1065". EP Application 0 154445 (published 11.09.85) discloses various analogs of antibiotic CC- 1065, including compounds of formula EP-I and EP-II (see General Formula chart of EP 0154 445), wherein R j in formula EP-II is CH 3 -, -CH 2 Ph, CH=CHCH 2 -, -CH 2 SCH 3 , -CH 2 OCH 3> -CH 2 OCH 2 CH 2 OCH 3 , -CH 2 CC1 3 , -CH j CH^itR^, or H, where Ph is phenyl; R is alkyl(Cι~C5), phenyl, or H; R 2 ' is C j to C5-aIkyl, phenyl or hydrogen, and is not necessarily the same as R in one compound; R 3 is alkylζC j -^), phenyl, or H; and X is Cl, Br, or I-, or OS - j R^, where R^ is C j to C 5 -alkyl, phenyl, tolyl, bromophenyl, nitrophenyl, or trifluromethyl. (See also U.S. Patent No. 4,912,227.) The O-protected compounds of formula EP-II are chemically stable and only removable under specific chemical conditions. However, when the compounds of formula EP-II are 0-deprotected, they can be cyclized to yield the compounds of EP-I. Other analogs of antibiotic CC-1065 are disclosed in EP Application 340- 243A (published 08 11.89). EP Application 0 154 445 also discloses CPI dimers joined by -CO- CH-^n j -CO- where n χ is 2-12 and CPI dimers joined by the tether -C(O)-(-R π -)-C(O)-X 7 -(-CH 2 CH 2 - X 7 )n4-C(O)-(-R n -)-C(O)- where R π = CH 2 CH 2 , CH=CH; and X 7 = O, NH, and n4 = 1-4, and the HC1 and Mel salts for X 7 = NH. Additional dimers of CPI prodrugs joined by -CO-(CH 2 )n!-CO- where n j is 2-12 and CPI dimers joined by the tether -C(O)-(-R 11 -)-C(O)-X 7 -(-CH 2 CH 2 -X 7 )n4-C(O)-(-R 11 -)-C(O)- where R u = CH 2 CH 2 , CH=CH; and X 7 = O, NH, and n4 = 1-4, and the HC1 and Mel salts for X 7 = NH are disclosed in U.S. Patent Application 944,633, filed 19 December 1986, now abandoned, and PCT/US Application 87/03227, filed 11 December 1987, published 14 July 1988. Various oral and poster presentations of material in U.S. patent application Serial No. 944,633, filed 19 December 1986 and EP Application 340 243A, published 08.11.89, have been made. Various oral and poster presentations of the CC-1065 analogs having two CPI subunits disclosed in U.S. patent application Serial No. 07/243,350, filed 12 September 1988 (now abandoned) and EP Application PCT/US89/03329, filed 7 August 1989 (Case 4305.P). The use of tumor-associated monoclonal antibody (Mab)-conjugates and Mab-toxin conjugates for the treatment of cancer is described in many publications. For example, European Patent Application 87304516.5 (Publication No. 70 247792) discloses immunoglobulin conjugates formed by reaction of an antineoplastic indole-dihydroindole vinca alkaloid containing a hydrazide group with an oxidized glycoprotein containing aldehyde groups. Other European Patent Applications disclosing antibody conjugates include EP 83400461.6 (Publication No. 0 088 695), 85401695.3 (Publication No. 0 173 629, see also US Patent 4,741,900) and 85401776.1 (Publication No. 0 175 617). SUMMARY OF THE INVENTION This invention provides some new synthetically obtained compounds of formula I and π (see General Formulae Chart), as defined hereinafter, which are useful as chemical intermediates. Representative formula I and II compounds have also been shown to possess useful ranges of antitumor activity in standard laboratory animal tests. The compounds of this invention are ob¬ tained by chemical processes shown in Schemes 1-15 and detailed in the examples. In addition, the compounds of formula I or U can be linked to monoclonal antibodies, either directly or via known linking group, as a means of selectively delivering the CC-1065 analogs (Compounds of Formula I and II) to those target cells expressing the target antigen and thus selectively eliminating those diseased cells from the animal or human. Further, the compounds of formula I and II can be linked to soluble human CD4 or a soluble human CD4 protein fragment capable of binding to the gp 120 envelope protein of the human immuno-virus and thus eliminate virally infected cells. DETAILED DESCRIPTION OF THE INVENTION More specifically, this invention provides new chemical compounds of Formula I or II (see FORMULAE sheet) wherein W is selected from C j ^ alkyl, phenyl or hydrogen; wherein X is selected from azido, a halogen atom, cyanate, thiocyanate, isocyanate, thioisocyanate, phosphate diester (O-POζOR)-^, phosphonyl (-O-PO 2 R), thiophosphonyl (-O-PSOR), sulfinyl (-O-SOR) or sulfonyl (-O-SC^R); wherein D is R^ or R'ι 5 ; wherein Q is Y when D is R' 15 ; wherein Q is Y' when D is R 15 ; wherein Y is selected from hydrogen, -C(O)R, -C(S)R, -C(O)OR j , -S(O) 2 R l5 -C(O)NR 2 R 3 , -C(S)NR 2 R 3 , -C(O)NHSO 2 R 4 , -C(O)CH 2 (OCH 2 CH 2 ) n7 O(C 1 -C 3 alkyl) and n7 is 0-5 (preferably 2 or 3), or -C(O)(CH 2 ) n8 C(O)R b where n8 is 0-10 (preferably 2, 3 or 4) and R b is selected from -OH (or a metal or amine salt thereof), -OR,, where R c is -CH 2 C(CH 2 OH) 3 or R 70 , and -N(R d ) R e where R d is hydrogen or C j ^ alkyl, and is selected from -C(CH 2 OH) 3 , -CH 2 C(CH 2 OH) 3 , -CH 2 C(CH 2 NH2) 3 , R 70 , R 71 or R 72 where n9 is 1 or 2 and nlO is 1-3; wherein Y' is selected from -C(O)R 10 , -C(S)R 10 , -C(O)OR 10 , -S(O) 2 R 10 , -C(O)NR 12 R 13 , -C(S)NR 12 R 13 , or -C(O)NHSO 2 R 14 ; wherein Z is selected from the group consisting of C j ^ alkyl, phenyl or hydrogen; wherein R is selected from the group consisting of C j -C^ alkyl; C^-Cg alkenyl; C2-C 6 alkynyl; phenyl optionally substituted with one, 2 or 3 Cι-C 4 alkyl, C j -C 3 alkoxy, halo, C\-C-- alkylthio, trifluoromethyl, C^-Cg dialkylamino, or nitro; naphthyl optionally substituted with one or 2 C j - 4 alkyl, C j -C 3 alkoxy, halo, trifluromethyl, C^-Cg dialkylamino, C-*^ alkylthio or nitro; wherein R j is selected from C j -C^ alkyl or phenyl optionally substituted with one, 2 or 3 CJ-C4 alkyl, C;t-C 3 alkoxy, halo, C j -^ alkylthio, trifluoromethyl, C 2 -C 6 dialkylamino, or nitro; wherein R 2 and R 3 , being the same or different, are selected from hydrogen, C j -C^ alkyl, or phenyl optionally substituted with one, 2 or 3 0^4 alkyl, C 1 -C 3 alkoxy, halo, C j -C^ alkylthio, trifluoromethyl, C^-Cg dialkylamino, or nitro; with the proviso that both R 2 and R 3 can not be phenyl or substituted phenyl; wherein R is selected from CJ-CJ Q alkyl; phenyl optionally substituted with one, 2 or 3 CJ-C4 alkyl, C C 3 alkoxy, halo, C j -C 3 alkylthio, trifluoromethyl, C^-Cg dialkylamino, or nitro; naphthyl optionally substituted with one or 2 C j ^ alkyl, C r C 3 alkoxy, halo, trifluromethyl, C-,- C 6 dialkylamino. C1-C3 alkylthio or nitro; wherein R 10 , R 13 and R 14 , being the same or different, are selected from -(^-C^ Q alkylXCH^ j ^ Q or -(phenyl optionally substituted with one or two C j ^ alkyl, C j -^ alkoxy, halo, C\-C $ alkylthio, trifluoromethyl, ^^ dialkylamino, or nitro)(CH 2 ) n R5 0 ; wherein n is 0-10; wherein R 50 is selected from the group consisting of (i) -CO 2 H; (ii) -CH 2 NH 2 ; (iii) -SH; (iv) -C(R Q ) R6I)-SH wherein Rg Q and R^, being the same or different, are C j ^ alkyl or H; (v) wherein R and R 61 are defined above and n j is O-5; (vi) -C(O)NHNH 2 (hydrazido); (vii) -NHNH 2 (hydrazino); (viii) -CH 2 OH (hydroxymethyl); (ix) -NHC(S)NH 2 (thioureido); (x) -CH 2 NHC(O)NH 2 ; (xi) -NHC(S)NHNH 2 ; (xii) -C(O)CH 2 X 1 (Xi is a halogen); (xiii) -CH 2 X j (halomethyl) wherein X j is a halogen; (xiv) -CHO (aldehyde); -C(0)-0-N j (N-hydroxysιιcciaidyi); (xv) (aaleiuide); (xvii) -C R o) 6i)C(O)NHNH 2 wherein Rg and Rg j , being the same or different, are 0^4 alkyl or H; (xviii) -O(CH 2 ) nl C(R 60 )(R 61 )C(O)NHNH 2 wherein R^, R^, and ^ are defined above; (xix) -N(R 62 )(CH 2 ) nl C(R 60 )(R 61 )C(O)NHNH 2 wherein Rg Q , R^ and R^ are independently selected from C j ^ alkyl or H and n x = O-5; (xx) -O(CH 2 ) n 2C(R 60 )(R 6 ,)C(O)NHNH 2 (n 2 = 1-5); (xxi) -NHR 51 ; (xxii) -C(O)NHNHR 51 ; (xxiii) -NHNHR 51 ; wherein R 51 is an amine protecting group such as BOC (t-butoxycarbonyl), FMOC (9-fluorenylmethyloxycarbonyl), TFA (trifluoroacetate)amide), ALLOC (alloxycarbonyl), CBZ (benzoxycarbonyl), or TROC (trichloroethoxycarbonyl); (xxiv) -NHC(=NH)NH 2 (guanadinyl); or (xxv) -B-M-(CH 2 )n 3 R 52 wherein n 3 = O-5; R5 2 is the same as R 50 above (groups (i) - (xxiv) only); wherein B is an ester [-OC(O)- or -C(O)O-] or amide [-NHC(O)- or -C(O)NH-] bond; wherein M is defined below as any compatible peptide, carbohydrate, or other organic moiety imparting to the embodiment of this invention specific properties (e.g. chemical, photochemical, or enzymatic cleavability; branching for multiple site attachment of additional therapeutic agents of die invention; optimal spacing between therapeutic agent and antibody); for cleavage of linkers by serum compliment M can be chosen from Table IE; wherein in Table HI (a. a) represents any naturally occurring amino acid (and can be the same or different) and 114 = 0-5; wherein R 12 is selected from hydrogen, C j -C^ alkyl, or phenyl optionally substituted with one, 2 or 3 Cy ^ alkyl, C 3 alkoxy, halo, C C 3 alkylthio, trifluoromethyl, C 2 -C 6 dialkylamino, o nitro; wherein R 15 is a carbonylaryl group selected from the group consisting of Formula (a) wherein X 8 is -O-, -S-, -NH-; Xg is -CH- or N; X 10 is -O-, -S-, -NH-; X n is -CH- or -N-; X 5 may be the same or different and is H, OCH 3 , NO 2 , NHC(O)CH 3 , OH, halo, C!-C 4 alkyl, C^ alkoxy, C2-C 6 dialkylamino, or NHC(O)C 6 H 5 ; and X 6 is H, OCH 3 , NO 2 , NHC(O)CH 3 , OH, halo, C r C 4 alkyl, C r C 3 alkoxy, C 2 -C 6 dialkylamino, or NHC(O)C 6 H 5 ; Formula (b) wherein X 5 , X 8 , X have the meanings defined above; Formula (c) wherein X 5 , X 6 , X 8 , X have d e meanings defined above; wherein R * 15 is a carbonylaryl group selected from the group consisting of Formula (d) wherein X 8 is -O-, -S-, -NH-; X 9 is -CH- or N; X 10 is -O-, -S-, -NH-; X π is -CH- or -N-; X 5 can be the same or different and is H, OCH 3 , NO 2 , NHC(O)CH 3 , OH, halo, C r C 4 alkyl, C r C 3 alkoxy, ^-Cg dialkylamino, or NHC(O)C 6 H 5 ; X 6 is H, OCH 3 , NO 2 , NHC(O)CH 3 , OH, halo, C r C 4 alkyl, C r C 3 alkoxy, (^-Cg dialkylamino, or NHC(O)C 6 H 5 ; n and R50 have the meanings defined above; Formula (e) wherein X 8 is -O-, -S-, -NH-; X 9 is -CH- or N; X 10 is -O-, -S-, -NH-; X n is -CH- or -N-; X 5 is H, OCH 3 , NO 2 , NHC(O)CH 3 , OH, halo, C r C 4 alkyl, C r C 3 alkoxy, C 2 - C 6 dialkylamino, or NHC(O)C 6 H 5 ; X 6 is H, OCH 3 , NO 2 , NHC(O)CH 3 , OH, halo, C^ alkyl, C r C 3 alkoxy, C 2 -C 6 d ialkylamino, or NHC(O)C 6 H 5 ; n and R 50 have the meanings defined above; Formula (f) wherein X 5 , X 8 , X 9 , n and R50 have the meanings defined above; Formula (g) wherein X 5 , X 6 , X 8 , X 9 , n and R 50 have the meanings defined above; and Formula (h) wherein X 5 , X 6 , X 8 , Xg, n and R50 have the meanings defined above. (Formulae a-h are set forth in the General Formulae Sheets). W is preferably methyl. X is preferably halogen, more preferably chloro or bromo. Z is preferably hydrogen. R j 5 is preferably Formula aa (General Formulae Sheet), wherein X 5 and X 6 are hydrogen and X 10 is -O- or -NH-; or any of the foregoing optionally substituted with X 5 and/or X 6 , independently selected from N j , halogen, OH, C j -C 3 alkoxy or C^-Cg dialkylamino. R' 15 is preferably Formula dd, ddd, or dddd (General Formulae Sheet), wherein X 5 and X are hydrogen, or any of the foregoing optionally substituted with X 5 and/or Xg, independently selected from NC^, NHX(O)CCH 3 , halogen, C-^ alkyl, C j -C 3 alkoxy or C 2 -C 6 dialkylamino. -(CH2) m R5 0 is preferably -(CH^-C^^C^NHNH^ -NHCflDMCH^- C(R 60 )(R 61 )SH; or -(CH 2 ) m2 C(R 60 )^ 61 )SH, wherein R ω and R 6l are independently metfiyl or H, m is 1-3, and m 2 is 0-3. Q is preferably Y. Y is preferably hydrogen, 3,6,9-trioxadecanoyl, N-[2-hydroxy-l, l- bis(hydroxymethyl)ethyl]glutaτamyl, 7-glutaramyl-naphthalene-l,3-disulfonic acid salts, -C(O)R, -CCO R-J, -SO 2 R! or -C(O)NR 2 R 3 wherein R, R χ and R 2 is phenyl optionally substituted with one, two or three halogen, NO-*., CJ-C-4 alkyl, C--^ alkoxy, Cj-03 thioalkyl, trifluoromethyl or C 2 -C 6 dialkylamino. Xg is preferably hydrogen, NO 2 , halo (most preferably chloro), methyl, ethyl, methoxy, ethoxy, dimethylamino, diethylamino, dipropylamino or dibutylamino. Xg is preferably -CH-. Xg is preferably -NH-. X tl is preferably -CH-. X 10 is preferably -NH- or -O-. Halogen atom (halo) refers to a bromo, chloro, iodo or fluoro atom. Examples of CJ-0-. Q alkyl are methyl, ethyl, propyl, butyl and the like, including isomeric forms thereof. Examples of C j -C 3 alkoxy are methoxy, ethoxy, propoxy and isomeric forms thereof. Examples of C^-Cg dialkylamino are dimethylamino, diethylamino, methylethylamino, dipropylamino and ethylpropylamino. The compounds of formula I and II on the FORMULAE sheet can be named as derivatives of the numbering system B j and B^ shown on the FORMULAE sheet. Such compounds will containthe l,2,3,6-tettahydro-3-R5-8-W-5-Y-benzotl,2-b:4,3-b']dipyrrol-l-[Z-CH(X)]-structure. The compounds of Formula I and π are drawn as the racemic mixture and include the natural isomer of Formula la and Ila, which can be resolved from the racemic mixture and/or prepared from starting materials or intermediates of the natural, i.e. l(S)-configuration. Examples of compounds of Formula I and π of this invention include: (S)-2-[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-2-benzofuran-5-carboxylic acid phenylmethyl ester (Cpd #1); (S>2-[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-2-benzofuran-5-carboxylic acid (Cpd #2); (S)-2-[[[2-[(4,5,8,8a-tetrahydro-7-me-hyl-4-oxocyclopropa-[c]pyrrol[3,2-e]indol-2(lH)-yl)- carbonyl]-lH-indol-5-yl]amino]carbonyl]-2-benzofuran-5-carboxylic acid (Cpd #3); (S)-2-[[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-lH-indol-5-yl]-carbamicacid, 1 , 1-dimethylethyl ester (Cpd #4); (S)-N-[2-[[l-(chloromethyl)-l,6-dihydro-8-methyl-5-[[[[4-[[[(l,l-dimethylethyl)oxy]- carbonyl]aminomethyl]phenyl]amino]car-bonyl]oxy]benzo[l,2-b:4,3-b']-dipyrrol-3(2H)- yl]carbonyl]-lH-indol-5-yl]-2-benzofurancarboxamide (Cpd #5); 5-[(2-mercaptopropionyl)amino]-N-[2-(4,5,8,8a-tetrahydro-7-methyl-4-oxocyclopropa- [c]pyrrolo[3,2-e]indol-2(lH)-yl)-lH-indol-5-yl]-lH-indole-2-carboxamide (Cpd #8); (S)-N-[2-[[l-(chloromethyl)-l,6-dihydro-8-methyl-5-[[[[4-[[(phenylmethyl)oxy]carbonyl] phenyl]amino]carbonyl]oxy]benzo[l,2-b: 4,3-b']dipyrrol-3(2H)-2-yl]carbonyl]-lH-indol-5-yl]-2- bcnzofurancarboxamide (Cpd #10); (S 2-[[[2-[[l-(chloromethyl)-l ,6-dihydro-5-hydroxy-8-methylbenzo[l ,2-b:4,3-b']dipyrrol- 3(2H yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[[2-[[(l,l-dimedιylethyl)oxy]carbonyl]hydra- zino]carbonyl]-lH-indol (Cpd #11 A); (S)-2-[[[2-[[l-(chloromethyl)-l,6-<iihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-(hydrazinocarbonyl)-lH-indol monohydrochloride (Cpd #11B); (S)-N-[2-[[l-(chloromethyl)-l,6-dihydro-8-methyl-5-[[[[4-[[2-[[(l,l-dimethylethyl)- oxy]carbonyl]hydrazino]carbonyl]phenyl]amino]carbonyl]oxy]benzo[l,2-b:4,3-b']dipyrrol-3(2H)- yl]carbonyl]-lH-indol-5-yl]-2-benzofurancarboxamide (Cpd #12); (S)-N-[2-[[l-(chloromethyl)-l,6-dihydro-8-methyl-5-[[[[4-[[[2-[[(l,l-dimethylethyl- )oxy]carbonyl]hydrazino]carbonyl]ediyl]phenyl]amino]carbonyl]oxy]benzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]-2-benzofurancarboxamide (Cpd #13); (S)-N-[2-[[l-(chloromethyl)-l,6-dihydro-8-methyl-5-[[[[4-[2-[(hydrazinocarbonyl)ethyl] phenyl]amino]carbonyl]oxy]benzo[l,2-b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]-2- Benzofurancarboxamide, monohydrochloride (Cpd #14); (S)-[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2-[[(l,l-dimethylethyl)oxy]carbonyl] hydrazino]carbonyl]ethyl]-2-Benzofuran (Cpd #15); (S)-[[[2-[[l-(chloromethyl)-l,6-dihydro-5-iydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl-5-[2-0ιydrazinocarbonyl)ethyl]-2-benzofuran monohydrochloride (Cpd #16); (7bR)-N-[2-[[4,5,8,8a-tefrahydro-7-meώyl-4-oxocyclopropa c]pyrrolo[3,2*^]indol-2(lH)-yl- carbonyl]-lH-indol-5-yl]aminocarbonyI]-5-[2-[[2-[(l,l-dimethylethyI)oxy]carbonyl]hydrazino] carbonyl]ethyl-2-benzofuran (Cpd #17); (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2-[[(l,l-dimethyIethyl)oxy]carbonyl] hydrazino]carbonyl]ethyl-2-benzofuran 3,6,9-trioxadecanoic acid ester (Cpd #18); (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-med ylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carrκ)nyl]-5-[2-(hydrazino)carbonyl]ethyl-2-benzofuran 3,6,9-trioxadecanoic acid ester (Cpd #19); (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-meύ ylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]ammo]carto^ zino]carbonyl]ethyl]-2-benzofiιran glutaric acid monoester (Cpd #20); (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-mdol-5-yl]amino]carbonyl]-5*^ zino]carbonyl]ethyl]-2-benzofuran ester of N-[2-hydroxy-l,l-bis0ιydroxymethyl) ethyl]glutaramic acid (Cpd #21); (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-mediylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-(hydrazino)carbonyl]ethyl-2-benzoruran ester of N-[2-hydroxy-l,l-bis(hydroxymeu yl)ethyl]glutaramic acid (Cpd #22); (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]∞rbonyl^ zino]carbonyl]ediyl]-2-benzofuran glutaric acid monoester mono amide of 7-amino-naphthalene-l ,3- disulfonic acid disodium salt (Cpd #23); and (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-(hydrazino)carbonyl]ethyl-2-benzofuran glutaric acid monoester mono amide of 7-amino-naphthalene- 1 ,3-disulfonic acid disodium salt (Cpd #24). An embodiment of the subject invention are compounds of Formula I, wherein W is methyl; Z is hydrogen; X is halogen (most preferably a chloro atom); and Q is Y' and Y' is selected from -C(O)R 10 , -SO 2 R 10 , -C(O)NR 12 R 13 ; R 10 and R 13 are selected from -(phenyl optionally substituted one or two C!-C alkyl, C j -C- j alkoxy, halo, Ci-C 3 alkylthio, trifluoromethyl, C^-Cg dialkylamino, or nitroXCH^ j ^ Q wherein n is zero, one or two, and R 50 is -CO 2 H, -CH 2 NH 2 , -SH, -C(R 60 )(R 61 )SH, -C(O)NHNH 2 , -CH 2 OH, -C(R 60 )(R 61 )C(O)NHNH 2 , -N(R 62 )(CH 2 ) nl C(R 60 )(R 61 )C(O)NHNH 2 , -O(CH 2 )n 2 C(R 60 )(R 61 )C(O)NHNH 2 ; wherein n χ is 1-3; n 2 is 0-2; R 60 , Rg j and R 2 , being the same or different, are H, methyl or ethyl; R 12 is hydrogen; and R j 5 is (aa) (see General Formulae Chart) wherein X 10 is -NH- or -O-; X5 and X 6 , being the same or different are hydrogen, OCH 3 , NO 2 , NHC(O)CH 3 , halo, C^ alkyl, C j -C 3 alkoxy or C 2 -Cg dialkylamino. A preferred embodiment of the subject invention are compounds of Formula I, wherein W is meύ yl; Z is hydrogen; X is halogen (most preferably a chloro atom); and Q is Y' and Y' is selected from -C(O)R 10 , -SO 2 R 10 , -C(O)NR 12 R 13 ; R 10 and R 13 are selected from -(phenyl optionally substituted one or two C1-C4 alkyl, C j -^ alkoxy, halo, C j ^ alkylthio, trifluoromethyl, C^-C dialkylamino, or nitroXCH^^ Q wherein n is zero, one or two, and R 50 is -CO 2 H, -CH 2 NH 2 , -SH, -C(R 60 )(Rg 1 )SH, -C(O)NHNH 2 , -CH 2 OH, -C(R 60 )(R 61 )C(O)NHNH 2 , -N(R 62 )(CH 2 ) nl C(R6 0 )(R 61 )C(O)-NHNH 2 , -O(CH 2 )n 2 C(R 60 )(Rg 1 )C(O)NHNH 2 ; wherein n χ is 1-3; n 2 is 0-2; R 60 , R 61 and Rg 2 , being the same or different, are H, methyl or ethyl; R 12 is hydrogen; and R j 5 is (aa) (see General Formulae Chart) wherein X 10 is -NH- or -O-; X 5 and X 6 are hydrogen. Another embodiment of the subject invention are compounds of Formula I, wherein W is methyl; Z is hydrogen; X is halogen (most preferably a chloro atom); and Q is Y' and Y' is selected from -C(O)R 10 , -SO 2 R 10 , -C(O)NR 12 R 13 ; R 10 and R 13 are selected from -(phenyl optionally substituted one or two C1-C4 alkyl, C!-C 3 alkoxy, halo, C1-C3 alkylthio, trifluoromethyl, C2-C 6 dialkylamino, or nitroXCH^J^ Q wherein n is zero, one or two, and R 50 is N-hydroxysuccimidyl or maleimide; R 12 is hydrogen; and R j 5 is (aa) (see General Formulae Chart) wherein X 10 is -NH- or -O-; X5 and X 6 , being the same or different are hydrogen, OCH 3 , NO 2 , NHC(O)CH 3 , halo, C r C 4 alkyl, C r C 3 alkoxy or C 2 -Cg dialkylamino. Another embodiment of die subject invention are compounds of Formula I wherein W is methyl; Z is hydrogen; X is halogen; and Q is Y' and Y' is selected from -C(O)NR 12 R 13 , -C(O)R 10 , -SO 2 R 10 , -C(O)NR 12 R 13 ; R 12 is hydrogen, R 10 and R 13 are selected from -(phenyl optionally substituted wiui one or two C1-C4 alkyl, C f -C^ alkoxy, halo, C-1-C3 alkylthio, trifluoromethyl, C^-C dialkylamino, or nitro)(CH 2 ) n R5 0 ; n is zero or one; R50 is -B-M- (CH 2 )n 3 R 52 wherein R 52 is -NH 2 , -C(O)NHNH 2 , -CO 2 H, or -SH; and R 15 is (aa) (see General Formulae Chart) wherein X 10 is -NH- or -O-; X 5 and Xg, being the same or different are hydrogen, OCH 3 , NO 2 , NHC(O)CH 3 , halo, ^-€4 alkyl, C r C 3 alkoxy or C 2 -C 6 dialkylamino. Another embodiment of the subject invention are compounds of Formula I wherein W is ethyl; Z is hydrogen; X is halogen (most preferably a chloro atom); and Q is Y and Y is selected from hydrogen, -C(O)R, -SO- T RJ, -C(O)NR 2 R 3 ; R 3 is hydrogen, R and R and R 2 (being the same or different) are selected from phenyl optionally substituted with one to three C j -C4 alkyl, C j -^ alkoxy, halo, C^C- j , alkylthio, trifluoromethyl, C^-Cg dialkylamino, or nitro; and R' 15 is selected from (dd), (ddd), (dddd), (ee) or (eee) wherein n is 0-6; X 10 is -NH- or -O-; X 5 and Xg are independently H, OH, NC^, NHC(O)CH 3 , halo, CyC alkyl, C r C 3 alkoxy or C 2 -C 6 dialkylamino; and R 50 is selected from eiti er i) N-hydroxysuccimidyl or maleimidyl; ii) -B-M- (CH 2 ) n3 R5 2 wherein R 52 is -NH 2 , -C(O)NHNH 2 , -CO 2 H, or -SH; or iii) -CO 2 H, -CH 2 NH 2 , -SH, -C(R 60 )(Rgι)SH, -NHC(O)-(CH 2 ) nI -C(R 60 )(R 61 )-SH, -C(O)NHNH 2 , -CH 2 OH, -C (R 60 ) (R 6 ι)C (O)NHNH 2 , -N(R 62 ) (CH 2 ) n l C (R 60 ) (R 6 1 )C(O)-NHNH2 , -O(CH 2 )n 2 C(R 60 )(R 61 )C(O)NHNH 2 ; wherein n λ is 1-3; n 2 is 0-2; and Rgø, R 61 and Rg 2 , being die same or different, are H, meti yl or etfiyl. Another preferred embodiment of d e subject invention are compounds of Formula I wherein W is memyl; Z is hydrogen; X is halogen (most preferably a chloro atom); and Q is Y and Y is selected from hydrogen, -C(O)R, -SO^, -C(O)NR 2 R 3 ; R 3 is hydrogen, R and R λ and R 2 (being me same or different) are selected from phenyl optionally substituted widi one to ϋ ree C j -C 4 alkyl, C 1 -C 3 alkoxy, halo, C j ^, alkylϋ io, trifluoromethyl, C-r-Cg dialkylamino, or nitro; and R' 15 is selected from (dd), (ddd), (dddd), (ee) or (eee) wherein n is 0-6; X 10 is -NH- or - -; X 5 and Xg are both hydrogen; and R50 is selected from ei er i) N-hydroxysuccimidyl or maleimidyl; ii) -B-M-(CH2 n 3 R 52 wherein R 52 is -NH 2 , -C(O)NHNH 2 , -CO 2 H, or -SH; or iii) -CO 2 H, -CH 2 NH 2 , -SH, -C(R 60 )(R 61 )SH ) -NHC(O)-(CH 2 ) nl -C(R6 0 )(R6 1 )-SH, -C(O)NHNH 2 , -CH 2 OH, -C(R6 0 )(R 61 )C(O)NHNH 2 , -N(R 62 )(CH 2 ) nl C(R 60 )(R 61 )C(O)-NHNH 2 , -O(CH 2 )n 2 C(Rg 0 )(R 61 )C(O)NHNH 2 ; wherein n χ is 1-3; n 2 is 0-2; and Rg 0 , R 61 and Rg 2 , being die same or different, are H, methyl or ethyl. Another embodiment of d e subject invention are compounds of Formula π wherein W is methyl; Z is hydrogen; and R' 15 is selected from (dd), (ddd), (dddd), (ee) or (eee) wherein n is 0-6; X 10 is -NH- or -O-; X 5 and X 6 are independendy H, OH, NO 2 , NHC(O)CH 3 , halo, C^ alkyl, C r C3 alkoxy or C 2 -C 6 dialkylamino; and R 50 is preferably -CO 2 H, -CH 2 NH 2 , -SH, -C(R6 0 )(R 61 )SH, -NHC(O)-(CH 2 ) nl -C(Rg 0 )(R 61 )-SH, -C(O)NHNH 2 , -CH 2 OH, -C(Rg 0 ) (R 61 )C(O)NHNH 2 , -N (R 62 ) (CH 2 ) n l C (R6 0 ) (Rg 1 )C(O)-NH NH 2 , wherein n χ is 1-3; n 2 is 0-2; R 60 , R 61 and Rg 2 , being the same or different, are H, memyl or etiiyl. A preferred embodiment of die subject invention are compounds of Formula II wherein W is metiiyl; Z is hydrogen; and R' 15 is selected from (dd), (ddd), (dddd), (ee) or (eee) wherein n is 0-6; X 10 is -NH- or -O-; X 5 and X 6 are bo hydrogen; and R 50 is preferably -CO 2 H, -CH 2 NH 2 , -SH, -C(Rg 0 )(R 6 ι)SH, -NHC(O)-(CH 2 ) nl -C(R 60 )(R 61 )-SH, -C(O)NHNH 2 , -CH 2 OH, -C(Rg 0 )(R 61 )C(O)NHNH 2 , -N(R 62 )(CH 2 ) nl C(Rg 0 )(Rg 1 )C(O)-NHNH 2 , -©(CH^C^NHNH j ; wherein n t is 1-3; n 2 is 0-2; R 60 , Rg j and R 62 , being me same or different, are H, memyl or ethyl. Another embodiment of me subject invention are compounds of Formula II wherein W is methyl; Z is hydrogen; and R' 15 is (dd); X 10 is -NH- or -O-; X 5 and X 6 are independently H, OH, NO 2 , NHC(O)CH 3 , halo, C r C 4 alkyl, C r C 3 alkoxy or C 2 -C 6 dialkylamino; and R 50 is preferably -CO 2 H, -CH 2 NH 2 , -SH, -C(Rg 0 )(R 61 )SH, -NHC(O)-(CH 2 ) nl -C(Rg 0 )(R 61 )-SH, -C(O)NHNH 2 , -CH 2 OH, -C(Rg 0 )(R 61 )C(O)NHNH 2 , -N(R 62 )(CH 2 ) nl C(R6 0 )(R 61 )C(O)-NHNH 2 , -O(CH 2 )n2 C ( R 6θ(^6l) C ( 0 ) NHN 2ϊ herein n l is --- ■ > ' n 2 is °- 2 » R 60> -^l ^^ R 62> bein S Λe same or different, are H, methyl or etfiyl. A preferred embodiment of die subject invention are compounds of Formula II wherein W is methyl; Z is hydrogen; and R' 15 is (dd) wherein n is 0-6; X 10 is -NH- or -O-; X 5 and X 6 are both hydrogen; and R 50 is preferably i) -CO 2 H, -CH 2 NH 2 , -SH, -CfRgo^^SH, -NHC(O)- (CH 2 ) nl -C(R 60 )(Rg 1 )-SH, -C(O)NHNH 2 , -CH 2 OH, -C(R 60 )(R 61 )C(O)NHNH 2 , -N(R 62 )(CH 2 ) nl C(R6 0 )(R 61 )C(O)-NHNH 2 , wherein n x is 1-3; n 2 is 0-2; R 60 , R 61 and Rg 2 , being the same or different, are H, memyl or ediyl; or ii) N- hydroxysuccimidyl or maleimide. Anod er embodiment of the subject invention are compounds of Formula I wherein Y is selected from hydrogen, -C(O)R, -C(S)R, -C(O)OR lt -5(0)^, -C(O)NR 2 R 3 , -C(S)NR 2 R 3 , -C(O)NHSO 2 R 4 , -C(O)CH 2 (OCH 2 CH 2 ) n7 O(C 1 -C 3 alkyl) and n7 is 0-5 (preferably 2 or 3), or -C(O)(CH2) n8 C(O)R b where n8 is 0-10 (preferably 2, 3 or 4) and R b is selected from -OH (or a metal or amine salt ereof), -OR c where R c is -CH 2 C(CH 2 OH) 3 or R 70 , and -N(R d ) R e where R d is hydrogen or C r C 4 alkyl, and , is selected from -C(CH 2 OH) 3 , -CH 2 C(CH 2 OH) 3 , -CH 2 C(CH 2 NH2) 3 , R 70 , R 71 or R 72 where n9 is 1 or 2 and nlO is 1-3. Examples of preferred compounds include the relatively more water soluble compounds of Formula I include those where Y is 3,6,9-trioxadecanoyl, N-[2-hydroxy-l,l- bis(hydroxyme yl)edιyl]glutaramyl or 7-glutaramyl-naphthalene-l,3-disulfonic acid salts. See for example, compounds 18, 19 and 21-24. The compounds of Formula I and II are readily prepared by reacting me appropriate spirocyclopropylcyclohexadienyl analog (Formula II) with die Y'-X reagent or with H-X and then acylating widi Y-X' where X' is an active leaving group, for example halide, azide, sulfonate, and the like. The starting spirocyclopropylcyclohexadienyl analog (Formula II) is dissolved in an inert solvent such as me ylene chloride, tetrahydrofuran (THF), N,N-dimemylformamide (DMF, DMFA), dimethylacetamide (DMA), pyridine, dioxane, N-methylpyrrolidone and the like. The resultant solution is treated widi the reagent Y'-X and die solution stirred at ambient temperature until thin layer chromatography (TLC) shows the reaction to be complete (normally for reactive acyl halides in a few minutes but for weak acids or acylating agents a few hours or days may be required. For very reactive reagents the temperature may be lowered to -20°C or less and for relatively unreactive addents the temperature may be raised to 80°C or higher depending upon die solvent). When the reaction is complete, the solution is diluted widi an appropriate solvent (mediylene chloride, e yl acetate, e ier, THF (widi brine), and die like. The organic layer is extracted with a mild base such as sodium or potassium bicarbonate, washed with water, dried by a suitable drying agent such as anhydrous magnesium sulfate or anhydrous sodium sulfate. Filtra¬ tion of the drying agent and evaporation of me solvent leaves the desired product which may be used as such or purified by crystallization or chromatography by mediods well know to mose skilled in the art. Example 1 Preparation of (S)-2-[[[2-[[l-(chloromedιyl)-l ,6-dihydro-5-hydroxy-8-methylbenzo[l ,2- b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-2-benzofuran-5-carboxylic acid phenylmediyl ester (Cpd #1); Part A. Preparation of benzofuran-2,5-dicarboxylic acid bis-φhenylmethyl) ester (Formula B, General Formulae Chart). A 2.48g (12mmole) quantity benzofuran-2,5-dicarboxylic acid (Formula A: General Formulae Chart) is stirred at room temperature (~ 25 °C) under nitrogen in 20ml dimethyl acetamide. To this is added 1.29ml (12mmoles) benzyl alcohol, 170mg dimetiiylaminopyridine and 2.49g l-edιyl-3-(3-dimethylaminopropyl)carbodiimide. The reaction is left to react for 24 hours, when TLC shows some starting material left, some bis ester but mostly a mono ester-mono acid. The reaction mixture is partitioned between e yl acetate- water. The layers are separated and e aqueous layer reextracted widi e yl acetate. The organic layers are combined, dried over sodium sulfate and evaporated under vacuum. The crude product is redissolved in eu yl acetate and die solution evaporated under vacuum onto 40 g of silica gel. This as added to the top of a 400 g silica gel column and eluted with 15% emyl acetate, 83% hexane, 2% acetic acid. A forerun of 400 mL is collected followed by 50 mL fractions. The desired bis benzyl ester elutes in fractions 24-43. Evaporation of ese fractions leaves 308 mg of benzofuran 2,5-dicarboxylic acid bis benzyl ester. TLC: Silic gel: Uv visualization; 15% emyl acetate, 85% hexane, 2% acetic acid; R f 0.54. Mass Spectrum: M+H and M at 387 and 386 respectively. Other fragment ions at 279 and 91. NMR(CDC1 3 , TMS) δ 5.39 (S, 2H); 5.43 (s, 2H); 7.30-7.53 (m, 10H); 7.57-7.69 (d+s, 2H); 8.16-8.25 (dd, 1H); 8.45 and 8.46 (d, 1H). The elution is continued widi 25% ediyl acetate, 73% hexane, 2% acetic acid. The benzofuran 2,5-dicarboxylic acid 2-phenylmethyl ester is isolated by evaporation of fractions 56- 208 (1.53 g). TLC: Silic gel: Uv visualization; 15% ethyl acetate, 85% hexane, 2% acetic acid; R f 0.36. NMR(CDC1 3 , TMS): δ 2.7-3.2 (bs, 1H); 5.45 (s, 2H); 7.3-7.5 (m, 3H); 7.5-7.6 (m, 2H); 7.75 and 7.78 (d, 1H); 7.85 (d, 1H); 8.17-8.23 (dd, 1H); 8.53 (d, 1H). Resubmission of the above benzofuran-2,5-dicarboxylic acid 2-phenyl memyl ester to the esterification conditions of part A gives me benzofuran 2,5-dicarboxylic acid bis phenylmethyl ester in 80% yield. Part B: Preparation of me benzofuran-2,5-dicarboxylic acid 5-phenylmemyl ester (Formula C, General Formulae Chart). A l.llg (2.87mmole) quantity of the bis benzyl ester (Part A; Formula B), is dissolved wi stirring at room temperature (~25°C) under nitrogen in 20ml THF- 5ml DMF. To mis added two 2.5ml batches of IN NaOH, following the reaction by TLC to make sure the reaction is stopped at die mono ester stage. After 45 minutes reaction time 6ml IN HC1 is added. The reaction is partitioned between eώyl acetate - brine. The layers are separated and the aqueous layer reextracted widi ethyl acetate. The organic layers are combined, dried over sodium sulfate and evaporated, using high vacuum at the end. The crude product is coated on lOg silica gel and chromatographed over lOOg silica gel. Elute wi 700ml 30% ediyl acetate- 2% acetic acid- 68% hexane, followed by 800ml 40% ethyl acetate- 2% acetic acid- 58% hexane. Fractions of 20ml are collected, analyzing diem by TLC. The product is found in fractions 28-54, which upon combining and evaporating leaves 870mg solid, 94% yield. TLC: silica gel; UV visualization; 15% emyl acetate- 85% hexane- 2% acetic acid; Rf: 0.08 Mass spectrum: Major ions at 296, 278, 251, 189, 91. NMR(d 6 -acetone, TMS): δ 5.42 (s, 2H); 7.3-7.5 (m, 3H); 7.5-7.6 (m, 2H); 7.75 and 7.78 (d, 1H); 7.8 (d, 1H); 8.19-8.25 (dd, 1H); 8.54 (d, 1H). Part C: Preparation of die amide of Formula E (General Formulae Chart). A 40mg (0.13mmole) quantity of the amine of Formula D (General Formulae Chart) is stirred at room temperature (~25°C) in me dark and under nitrogen in 1ml DMF. To this solution is added 39mg (0.13mmole) of the acid (Formula C) and 27mg l-edιyl-3-(3-dimethyl- aminopropyl)carbodiimide. The reaction starts out as two phases but everything dissolves during me 17 hour reaction time. After the given reaction time the reaction mixture is partitioned between ethyl acetate- water. The layers are separated and the aqueous layer reextracted widi emyl acetate. The organic layers are combined, dried over sodium sulfate and evaporated under vacuum. The crude product is coated on lg silica gel and chromatographed over 9g silica gel. The column is eluted wi the following amounts of emyl acetate-hexane: 80ml 30-70, 40ml 40-60, 60ml 50-50, 20ml 60*40, 20ml 70-30, 20ml 80-20, 20ml 90-10, and 100ml pure ethyl acetate, the product dragging off due to insolubility. Fractions of 2ml are collected, analyzing mem by TLC. Product is found in fractions 26-110, which upon combining and evaporating under vacuum leave 68mg (89% yield) solid. Mass spectrum: M+H at 585, 587, 589; odier major ions at 279, 91. TLC: silica gel; UV visualization; 30% emyl acetate- 70% hexane; Rf: 0.59 NMR(d 6 -DMSO, TMS): δ 5.19 (s, 2H); 5.41 (s, 2H); 7.3-7.6 (m, 7H); 7.66-7.74 (d, IH); 7.83-7.90 (d, IH); 7.90 (s, IH); 8.10-8.17 (d, IH); 8.23 (s, IH); 8.54 (s, IH); 10.65 (s, IH); 12.17 (s, IH). Part D: Hydrolysis of die trichloroethyl ester (Formula E, Part C). A 50mg (0.085mmole) quantity of the trichloroediyl ester (Formula E, General Formulae Chart) is stirred at 60 C under nitrogen in 10ml acetic acid. To mis partially solubilized mixture is added 75mg zinc. After a few minutes most of me solids dissolve and men a new solid forms. The reaction is left to react for one hour at 60°C and men cooled to room temperature (~25°C), diluted wim DMF and filtered. The solid is washed wim DMF, combining filtrate and wash and evaporating under high vacuum. The above crude product is coated on 500mg silica gel and chromatographed over 5g silica gel. The column is eluted with 30ml 10%DMF- 90% toluene- 2% acetic acid and 50ml of 20-80-2 of the same solvents. Fractions of 2ml are collected, analyzing them by TLC. Fractions 12-30 contained die major product (Formula F, General Formulae Chart) and are combined and evaporated under vacuum. This leaves 25mg solid, 67% yield. Mass spectrum: M+Na at 477; M+H at 455; other major ion at 279. TLC: silica gel; UV visualization; 10% DMF- 90% toluene- 2% acetic acid; Rf: 0.16. NMR: dg-DMSO, TMS: δ 5.41 (s, 2H); 7.10 (s, IH); 7.3-7.7 (m, 7H); 7.85 and 7.88 (d, IH); 7.89 (s, IH); 8.12 and 8.15 (d, IH); 8.17 (s, IH); 8.54 (s, IH); 10.58 (s, IH); 11.77 (s, IH); 12.6-13.1 (bs, IH). Part E: Preparation of (S)-2-[[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2- b:4,3-b')dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-2-ben2«furan-5-carboxylic acid phenylmethyl ester (Cpd #1), A 56mg (0.17mmole) quantity, (S)-l-(chloromethyl)-l,6-dihydro-5- hydroxy-8-memyl- benzo[l,2b:4,3-b']dipyrrole-3(2H)-carboxylic acid 1,1-dimedιyl ester (BOC chlorophenol), is stirred at room temperature (— 25 °C) in the dark and under nitrogen for one hour in 2ml ethyl acetate and 3ml ethyl acetate saturated wim gaseous HCl. Silica gel TLC in 30% emyl acetate- 70% hexane shows all of the starting material spot is replaced by a spot at me origin. The solvent is men evaporated under vacuum, and men methylene chloride is added to the residue which is reevaporated under vacuum. The resultant solid residue is dissolved in 1.5ml dimethylacetamide. To this solution is added 77mg (0.17mmoles) of me acid (Formula F) and 32mg (0.17mmoles) l-emyl-3-(3- dimethylaminopropyl)-carbodiimide (EDC). The solution is left to react for one hour, after which is added 20mg more acid and 8mg more EDC. The reaction is allowed to react for 3 hours more. The reaction mixture is partitioned between brine- ethyl acetate- THF. The layers are separated and d e aqueous layer reextracted with ethyl acetate. The organic layers are combined, dried over sodium sulfate and evaporated. The crude product is coated on lg silica gel and chromatographed over lOg silica gel. The column is eluted with a gradient of 10% DMF- 90% toluene to 20% DMF- 80% toluene. Fractions of 2ml are collected, analyzing em by TLC. The product is found in fractions 30-43, which upon combining and evaporating under high vacuum leave 84mg yellow solid, a 74% yield. TLC: silica gel; UV visualization; 10% DMF- 90% toluene; RF: 0.30 UV(MeOH): 295nm (35,670); 340nm (24,900). Mass spectrum: M+H at 673, 675; M at 672, 674; odier major ions at 437, 279, 237, 236, 199, 187. NMR: dg-DMSO, TMS: δ 2.36 (s, 3H); 3.5-3.67 (t, IH); 3.83-3.95 (d, IH); 3.95-4.07 (t, IH); 4.47-4.59 (d, IH); 4.59-4.74 (t, IH); 5.41 (s, 2H); 7.06 (s, IH); 7.16 (s, IH); 7.32-7.75 (m, 8H); 7.86 and 7.89 (d, IH); 7.90 (s, IH); 8.12 and 8.15 (d, IH); 8.22 (s, IH); 8.54 (s, IH); 9.82 (s, IH); 10.61 (s, IH); 10.75 (s, IH); 11.73 (s, IH). Example 2 Preparation of (S)-2-[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2- b:4,3-b')dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-2-benzofuran-5-carboxylic acid (Cpd #2); A lOmg (O.OlSmmole) quantity of (S)-2-[[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8- memylbenzo[l,2-b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH^ 5-carboxylic acid phenylmethyl ester (Cpd #1) is stirred at room temperature (~ 25 °C) in 0.3ml THF- 0.1ml MeOH in the dark. To mis solution is added lOmg 10% palladium on carbon and 8mg ammonium formate. The mixture is heated to 50 C for 15 minutes, when TLC shows me reaction to he complete. The reaction is cooled to room temperature ( ~ 25 °C) and partitioned between emyl acetate, lml IN HCl- 25ml water. The layers are separated and die aqueous layer reextracted wi ediyl acetate. The organic layers are combined, dried over sodium sulfate and evaporated under vacuum, leaving 8mg (S)-2-[[[[2-[[l-(chloromemyl)-l,6-dihydro-5-hydroxy-8-memylbenzo[l,2- b:4,3-b']dipyrtol-3(2H yl]carbonyl]-lH-mdol-5^ acid, 89% yield. NMR(d 6 -DMSO, TMS): δ 2.36 (s, 3H); 3.53-3.67 (m, IH); 3.86-3.97 (d, IH); 3.97-4.09 (t, IH); 4.48*4.60 (d, IH); 4.604.75 (t, IH); 7.05 (s, IH); 7.15 (s, IH); 7.44-7.54 (s, IH); 7.56- 7.64 (d,lH); f7.65 (bs, IH); 7.78-7.87 (d, IH); 7.90 (s, IH); 8.05-8.13 (d, IH); 8.21 (s, IH); 8.48 (s, IH); 9.83 (s, IH); 10.59 (s, IH); 10.75 (s, IH); 11.71 (s, IH); 12.6-13.3 (bs, IH). UV(MeOH): 340nm (21,860); 294nm (32,360). Mass spectrum: M+H at 583, 585; M at 582, 584. Other ions at 347, 237, 236. TLC: silica gel; UV visualization; 20% DMF- 80% toluene- 2% acetic acid; Rf: 0.44. Example 3 Preparation of (S)-2-[[[2-[(4,5,8,8a-tetrahydro-7-memyl4-oxocyclopropa[c]pyrrol[3,2- e]indol-2(lH)-yl)-carbonyl]-lH-indol-5-yl]amino]carbonyi]-2-benzofiiran-5-carboxylic acid (Cpd #3); A 61mg (O.Olmmole) quantity of (S)-2-[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8- meώylbenzo[l,2-b:4,3-b']dipyrcol-3(2H)-yl]carbonylH^ 5-carboxylic acid (Cpd #2); is stirred at room temperature (~25°C) in the dark under nitrogen in 2.4ml acetonitrile, 1.2ml triethylamine, 1.2ml water for 30 minutes, resulting in complete solution. The reaction mixture is partitioned between emyl acetate- water. The organic layer is dried over sodium sulfate and evaporated. Insufficient material is recovered by e above extraction. Thus, the aqueous layer is acidified widi pH3 phosphate buffer and extracted twice wim a 50-50 mixture of ethyl acetate and freshly distilled THF. The organic layers are dried over sodium sulfate, combined wim the first ethyl acetate extract and evaporated under vacuum. This leaves 53mg product (Cpd #3), 93% yield. TLC: silica gel; UV visualization; 20% DMF- 80% toluene- 2% acetic acid: Rf: 0.37. NMR(d 6 -DMSO, TMS): δ 1.42-1.52 (m, IH); 1.95-2.05 (m, IH); 2.05 (s, 3H); 3.15-3.30 (m, IH); 4.454.55 (d, IH); 4.56-4.67 (dd, IH); 6.77 (s, IH); 6.94 (s, IH); 7.27 (s, IH); 7.48- 7.58 (d, IH); 7.64-7.75 (d, IH); 7.84-7.92 (d, IH); 7.93 (s, IH); 8.10-8.20 (d, IH); 8.28 (s, IH); 8.52 (s, IH); 10.64 (s, IH); 11.60 (s, IH); 11.89 (s, IH). UV(MeOH): 356nm (19670); 309nm (26,230). Mass spectrum: M+H at 547; other ions at 347, 201. Adding HCl gives an M+HC1+H at 583. Example 4 Preparation of (S)-2-[[[[2-[[l-(chloromethyl)-l ,6-dihydro-5-hydroxy-8-methylbenzo[l ,2- b:4,3-b']dipyrtol-3(2H)-yl]carbonyI]-lH-indol-5-yl]amino]carbonyl]-lH-indol-5-yl]-carbamic acid, 1,1-dimemylethyl ester (Cpd #4); Part A: Preparation of Formula H (General Formulae Chart). A 0.5g (2.45mmole) quantity of the amine (Formula G: General Formulae Chart), is stirred at room temperature (~25°C) in the dark under nitrogen in 5ml freshly distilled THF. To this is added 610mg (2.45mmole) BOC-ON and 350ul (2.45mmole) triethylamine. After 3 days at room temperature (~25°C) die reaction is found by TLC to be essentially completed. The reaction is men partitioned between emyl acetate, brine. The layers are separated and die aqueous layer reextracted wim ethyl acetate. The combined organic layers are dried over sodium sulfate and evaporated under vacuum. The crude product is coated on lOg silica gel and chromatographed over 90g silica gel. The column is eluted widi a gradient of 10% emyl acetate- 90% hexane to 25% ethyl acetate- 75% hexane. Fractions of 15ml are collected, analyzing mem by TLC. The product is found in fractions 55-119 which upon combining and evaporating under vacuum leaves 617mg solid, (Formula H), 83% yield. TLC: silica gel; UV visualization; 30% ethyl acetate- 70% hexane; Rf: 0.63. Mass spectrum: Major ions at 304, 248, 202, 158, 130, 102, 57. NMR(CDC13), TMS): δ 1.38-1.47 (t, 3H); 1.53 (s, 9H); 4.354.45 (q, 2H); 6.50 (s, IH); 7.13-7.16 (d, IH); 7.18-7.24 (dd, IH); 7.30-7.38 (d, IH); 7.79 (s, IH); 8.85 (bs, IH). Part B: Hydrolysis of the ethyl ester (Formula H). A 617mg (2.03mmole) quantity of die ediyl ester (Part A, Formula H) is stirred at room temperature (~25°C) under nitrogen in 10ml pyridine-lOml MeOH-lOml water-5ml IN NaOH, resulting in complete solution. The reaction is followed by TLC and is found to be complete after 20 hours. The reaction is then treated wim 5ml IN HCl and evaporated under vacuum. The residue is partitioned between ethyl acetate- water- 3ml IN HCl. The layers are separated and the aqueous layer reextracted widi ediyl acetate. The organic layers are combined, dried over sodium sulfate and evaporated under vacuum. This leaves 620mg solid (Formula J), 100% yield. TLC: silica gel; UV visualization; 30% ethyl acetate- 70% hexane- 2% acetic acid; Rf: 0.25. Mass spectrum: major ions at 276, 220, 202, 176, 158, 130. NMR(d 6 -DMSO, TMS): δ 1.50 (s, 9H); 7.13-7.17 (d, IH); 7.37-7.49 (m, 2H); 7.97 (s, IH); 8.31(bs, IH); 10.77 (bs, IH). Part C: Preparation of the ethyl ester (amide) (Formula L, General Formulae Chart). A 620mg (2.03mmoles) quantity of the acid (Part B: Formula J, General Formulae Chart), is stirred at room temperature (~25°C) under nitrogen and in die dark wim 4ml dry DMF, giving a complete solution. To this is added 415mg (2.03mmoles) amine and 390mg l-ethyl-3-(3- dimethylaminopropyl) carbodiimide. After 5 days die reaction mixture is partitioned between ediyl acetate- water. The layers are separated and the aqueous layer reextracted widi emyl acetate. The organic layers are combined, dried over sodium sulfate and evaporated under vacuum. The crude product is coated on lOg silica gel and chromatographed over 90g silica gel. The column is eluted wim 10% DMF- 90% toluene. Fractions of 20ml are collected, analyzing them by TLC. Fractions 24-53 contained e product and are combined and evaporated under vacuum. This leaves 890mg solid (Formula L), 95% yield. TLC: silica gel; UV visualization; 10% DMF- 90% toluene; Rf: 0.45. Mass spectrum: major ions at 539, 463, 462, 407, 406, 259, 204, 203, 159, 158, 57. NMR(d 6 -DMSO, TMS): δ 1.3-1.4 (t, 3H); 1.49 (s, 9H); 4.34.4 (q, 2H); 7.16 (s, IH); 7.20-7.27 (d, IH); 7.28-7.38 (m, 2H); 7.4-7.5 (d, IH); 7.55-7.64 (d, IH); 7.80 (s, IH); 8.14 (s, IH); 9.17 (s, IH); 10.13 (s, IH); 11.58 (s, IH); 11.89 (s, IH). Part D: Hydrolysis of ediyl ester (Formula L). An 890mg (1.92mmole) quantity of me emyl ester (Part C, Formula L), is stirred at room temperature (~25°C) under nitrogen and in the dark in 10ml pyridine- 3ml IN NaOH, giving a complete solution. The reaction is followed by TLC and after 20 hours shows no starting material left. At this time 3ml IN HCl is added and die mixture evaporated under vacuum. The residue is partitioned between brine- 5ml IN HCl- freshly distilled THF- emyl acetate. The layers are separated and the aqueous layer reextracted with ethyl acetate. The organic layers are combined, dried over sodium sulfate and evaporated under vacuum. The crude product is coated on lOg silica gel and chromatographed over 70g silica gel. The column is eluted with 500ml 20% DMF- 80% toluene-2% acetic acid, followed by 300ml 30- 70-2 and 40-60-2 of die same. A forerun of 100ml is collected, followed by 15ml fractions. The fractions are analyzed by TLC and product is found in fractions 30-52. These are combined and evaporated under vacuum, leaving 930mg (Formula M), 100% yield. Mass spectrum: major ions at 435, 434, 379, 378, 361,177, 176, 159, 158, 57. TLC: silica gel; UV visualization; 20% DMF- 80% toluene- 2% acetic acid; Rf: 0.35. NMR(d 6 -DMSO, TMS): δ 1.49 (s, 9H); 7.08 (s, IH); 7.18-7.27 (d, IH); 7.27-7.38 (m, 2H); 7.38-7.46 (d, IH); 7.5-7.6 (d, IH); 7.80 (s, IH); 7.95 (s, IH); 8.12 (s, IH); 9.16 (s, IH); 10.10 (s, IH); 11.58 (s, IH); 11.73 (s, IH). Part E: Preparation of (S)-2-[[[[2-[[l-(chloromemyl)-l,6-dihydro-5-hydroxy-8-m^hylbenzo[l,2- b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-lH-indoI-5-yl]-carbamic acid, 1,1-dunethylethyl e-ster (Cpd #4). A 120mg (0.36mmole) quantity of (S)-l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methyl- benzo[l,2b:4,3-b']dipyrrole-3(2H)-carboxylic acid 1,1-dimedιyl ester (BOC chlorophenol), is stirred for 1.5 hours at room temperature (~25°C) in the dark and under nitrogen in 4ml ethyl acetate- 6ml ethyl acetate samrated widi gaseous HCl. TLC shows all of the starting material to have reacted at that time. The solvent is evaporated under vacuum. Memylene chloride is added to the residue and d e mixture reevaporated under vacuum. The residue is dissolved in 4ml dimethylacetamide. A 1.7ml aliquot of the DMA solution (0.15mmoles) is stirred at room temperature (~-25°C) in die dark under nitrogen, and treated widi 65mg (0.15mmoles) acid (Part D: Formula M) and 28mg l-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). After 45 minutes an additional 16mg of acid and 7mg of EDC are added. After an additional 3 hrs the reaction mixture is partitioned between ethyl acetate- THF- brine. The layers are separated and die aqueous layer reextracted widi THF- ethyl acetate. The organic layers are combined, dried over sodium sulfate and evaporated under vacuum. The crude product is coated on lg silica gel and chromatographed over lOg silica gel. The column is eluted with a gradient of 10% DMF- 90% toluene to 20% DMF- 80% toluene. Fractions of 2ml are collected, analyzing them by TLC. The product is found in fractions 16-30, which upon combining and evaporating under vacuum leaves 92mg solid, 94% yield. UV(MeOH): 298nm (35,920); 340nm (30,040). TLC: silica gel; UV visualization; 10% DMF- 90% toluene; Rf: 0.21. NMR(d 6 -DMSO, TMS): δ 1.50 (s, 9H); 2.08 (s, 3H); 3.54-3.66 (t, IH); 3.85-3.95 (d, IH); 3.984.09 (t, IH); 4.54.6 (d, IH); 4.^4.74 (t, IH); 7.06 (s, IH); 7.15 (s, IH); 7.20-7.29 (d, IH); 7.3-7.4 (m, 2H); 7.45-7.53 (d, IH); 7.53-7.60 (d, IH); 7.67 (bs, IH); 7.83 (s, IH); 7.95 (s, IH); 8.23 (s, IH); 9.17 (s, IH); 9.81 (s, IH); 10.15 (s, IH); 10.74 (s, IH); 11.63 (s, IH); 11.69 (s, IH). Mass spectrum: M+H at 653, 655; M at 652, 654; omer major ions at 729, 597, 361, 237, 236, 159, 57. Example 5 Preparation of (S)-N-[2-[[l-(chloromethyl)-l,6-dihydro-8-methyl-5-[[[[4-[[[(l,l- dimemylemyl)oxy]carbonyl]ammomemyl]phenyl]amino]carbonyl]oxy]benzo[l,2-b:4,3-b']*^ipyπ , ol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]-2-benzofurancarboxamide (Cpd #5). Part A: Preparation of Formula N (General Formulae Chart). A l.Og (5.3mmoles) quantity p-nitrobenzylamine hydrochloride is stirred at room temperature (~-25°C) under nitrogen in 14ml freshly distilled THF in the dark. To this is added 1.51ml triethylamine and 1.32g BOC-ON. This results in a mixmre which does not completely dissolve in 24 hrs, so 15ml more THF is added. The reaction still does not dissolve after another 24 hrs stirring. At is point, the reaction mixture is partitioned between ethyl acetate -brine. The layers are separated and me aqueous layer reextracted wi emyl acetate. The organic layers are combined, dried over sodium sulfate and evaporated under vacuum. The crude product is chromatographed over lOOg silica gel, eluting wim 20% emyl acetate- 80% hexane. Fractions of 15ml are collected, analyzing them by TLC. The following fractions are combined and evaporated under vacuum: Fractions 3344, desired product and side product Fractions 45-67, desired product Other TLC systems tried for separating mixed fractions: 10% acetone- 90% hexane (worse); toluene (worse); methylene chloride (worse); 10% ethyl acetate- 90% toluene (similar). Fractions 3344 are flash chromatographed over lOOg silica gel 60, eluting with 10% emyl acetate- 90% toluene. A forerun of 100ml is collected, followed by 20ml fractions. TLC analysis shows fractions 18-23 to be mixed and fractions 24-42 to be pure product, me latter combined wim pure product above. The mixed fractions are rechromatographed over die same column, pure product being found in fractions 2142. These are combined witii pure product above to give a total of 1.28g, 95% yield. TLC: silica gel; UV visualization; 10% ediyl acetate- 90% hexane; Rf: 0.10 Mass spectrum: major ions at 252, 237, 197, 196, 179, 57. NMR(CDC13), TMS): δ 1.50 (s, 9H); 4.354.48 (d, 2H); 5.01 (bs, IH); 7.43 and 7.46 (d, 2H); 8.18 and 8.21 (d, 2H). Part B: Preparation of Formula O (General Formulae Chart). A 500mg (1.98mmole) quantity of the nitro compound (Part A: Formula P), is dissolved in 5ml freshly distilled THF and 15ml absolute emanol. The solution is treated widi 75mg platinum oxide and hydrogenated under pressure at room temperamre (~25°C) for 2 hours. The reaction mixture is filtered and me catalyst washed wim more freshly distilled THF. The filtrate and wash are combined and evaporated under vacuum, giving a solid in a 100% yield. TLC: silica gel; UV visualization; 20% ethyl acetate- 80% hexane; Rf: 0.28. Mass spectrum: major ions at 222, 165, 121, 106, 77, 57. NMR(CDC13), TMS): δ 1.45 (s, 9H); 3.5-3.8 (bs, 2H); 4.134.20 (d, 2H); 4.704.85 (bs, IH); 6.60-6.65 (d, 2H); 7.03-7.10 (d, 2H). Part C: Preparation of (S)-N-[2-[[l-(chloromethyl)-l,6-dihydro-8-methyl-5-[[[[4-[[[(l,l- dimedιyledιyl)oxy]carbonyl]aminomemyl]phenyl]ammo]carbonyl]oxy]benzo[l,2-b:4,3-b']*dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]-2-benzofurancarboxamide (Cpd #5). A 5ml quantity 20% phosgene in toluene (1.93 molar, 9.65mmoles) is stirred at room temperature (~25°C) under nitrogen. To this is added dropwise over one minute 47mg (0.21mmoles) amine (Part B: Formula O) dissolved in 1ml ethyl acetate. After one hour reaction time die solvent is evaporated under vacuum. The resultant residue is stirred at room temperature (~25°C) under nitrogen with 1ml freshly distilled THF. To this is added 57mg (0.105mmoles) (S)-N-[2-[[l-(chloromethyl)-l,6- dihydro-5-hydroxy-8-methylbenzo[l,2-b:4„3-b']dipyrrol-3(2H0-yl]carbonyl]-lH-indol-5-yl]-2- benzofurancarboxamide (see U.S. Patent 4,912,227; incorporated herein by reference) dissolved in 1ml freshly distilled THF, following by the dropwise addition of 14ul triethylamine to the isocyanate-urea mixture during one minute. The reaction is heated to 65 C for 3 hours, and die reaction followed by TLC. lOul more triethylamine is added and die heating continued for 2 hours more. The reaction is then allowed to cool to room temperature (~25°C) overnight followed by 2 hrs more heating at 65 °C. At this point the reaction is cooled to room temperature (~25°C), filtered, and me solid washed wim THF. The filtrate and wash are combined and evaporated under vacuum. The crude residue from evaporation is coated on lg silica gel and chromatographed over 9g silica gel. The column is eluted wi i 40% acetone- 60% hexane, followed by 50-50 of die same. Fractions of 2ml are collected, analyzing them by TLC. The following fractions are combined and evaporated: Fractions 3542, desired product, 29mg Fractions 29-34 and 43-56, desired product plus impurities The mixed fractions are rechromatographed as above except eluting wim 10% DMF- 90% toluene. Product (Cpd #5) is found in fractions 20-35, giving 28mg. This gives a total yield of 57mg or 69% based on (S)-N-[2-[[l-(chloromemyl)-l,6-dihydro-5-hydroxy-8-memylbenzo[l,2- b:4„3-b']dipyrrol-3(2H0-yl]carbonyI]-lH-indol-5-yl]-2-benzorurancarboxamide. TLC: silica gel; UV visualization; 50% acetone- 50% hexane; RF: 0.49. UV(MeOH): 320nm (31,490); 292nm (40,150). Mass spectrum: M at 787, 789; other major ions at 687, 670, 538, 303, 236, 200, 199, 187, 145, 106, 57. NMR(d 6 DMSO, TMS): δ 1.40 (s, 9H); 2.42 (s, 3H); 3.70-3.82 (t, IH); 3.95-3.15 (m, 3H); 4.134.24 (t, IH); 4.594.68 (d, IH); 4.704.84 (t, IH); 7.17-7.25 (m, 4H); 7.30-7.44 (m, 2H); 7.44-7.57 (m, 4H); 7.57-7.66 (d, IH); 7.73-7.78 (d, IH); 7.79 (s, IH); 7.81-7.87 (d, IH); 7.91 (bs, IH); 8.23 (s, IH); 10.33 (s, IH); 10.50 (s, IH); 11.22 (s, IH); 11.74 (s, IH). Example 6 Preparation of Formula P (General Formulae Chart). A 1.85g (lOmmole) quantity of p-nitrobenzoyl chloride is stirred about 10 min at room temperature (~25°C) under nitrogen in 20ml pyridine. To d e solution is then added 1.08g benzyl alcohol and die resultant solution is left to react about 65 hrs. At thi« point water is added resulting in the precipitation of a white solid. The solid (Formula P) is collected by filtration, washed widi water and dried under vacuum, giving 1.79g product, 70% yield. TLC: silica gel; UV visualization; 20% ethyl acetate- 80% hexane; Rf: 0.75 NMR(CDC13, TMS): δ 5.41 (s, 2H); 7.31-7.50 (m, 5H); 8.20-8.34 (m, 4H). UV(EtOH): 217nm (9,780); 259nm (13,850). IR (Mull): major peaks at 1713, 1523, 2925, 716, 1282, 2953, 745, 1348, 2855, 1123, 695, 2869, 1104, 1323, 1381, 1455, 870, 1605, 1299, 851, 1363, 954, 3114, 787, 1023 cm" 1 . Mass spectrum: major ions at 257, 150, 91. Example 7 Preparation of Formula Q (General Formulae Chart), the amine. A 500mg (1.94mmoles) quantity of Formula P (Example 6), is dissolved in 5ml THF-15ml 95% ethanol. To this is added 75mg platinum oxide and die mixmre hydrogenated under pressure at room temperature (~25°C) for 80 minutes. TLC shows no starting material but two more polar products, one moving off the origin only with acid present in me developing solvent. The catalyst is filtered off, washing it widi THF. The filtrate and wash are combined and evaporated under vacuum. The crude product is coated on 5g silica gel and chromatographed over 50g silica gel. The column is eluted wi 30% e yl acetate - 70% hexane until the less polar product has come off. Then the solvent is switched to 40% ethyl acetate- 60% hexane- 2% acetic acid. Fractions of 15ml are collected, analyzing diem by TLC. The following fractions are combined and evaporated under vacuum. Fractions 11-17, 287mg, 65% yield, desired product Fractions 33-47, 140mg, 53% yield, side product TLC and NMR data indicate the side product to be p-amino benzoic acid from hydrogenolysis of die benzyl ester. Reducing the hydrogenation time to 20 min. still shows all of the starting material gone as well as overhydrogenation and a 69% yield of desired product. TLC: silica gel; UV visualization; 20% ediyl acetate- 80% hexane; Rf: 0.27 NMR(CDC13), TMS): δ 4.06 (s, 2H); 5.31 (s, 2H); 6.6-6.7 (d, 2H); 7.3-7.6 (m, 5H); 7.85-7.94 (d, 2H). JJR(Mull): major peaks at 1282, 1171, 3361, 1687, 3457, 1601, 1633, 1118, 2926, 1311, 1381, 2954, 1317, 1519, 730, 2855, 772, 1437, 2868, 1572, 694, 703, 847, 1453, 3225 cm' 1 . UV(EtOH): 215nm (12,400;) 223nm (9,000); 296nm (21,660). Example 8 Preparation of 5-[(2-mercaptopropionyl)amino]-N-[2-(4,5,8,8a-tetrahydro-7-memyl4- oxocyclopropa[c]pyrrolo[3,2-e]indol-2((lH)-yl)-lH-indol-5-yl]-lH-indole-2-carboxamide, (Cpd #8). A 2 mg (.003mmole) quantity of (S)-2-[[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8- medιylbenzo[l,2-b:4,3-b']dipyιτol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-lH-indol-5- yl]-carbamic acid, 1, 1-dimethylethyl ester (Cpd #4, Example 4) is dissolved in the dark in lOOul trifluoroacetic acid. TLC after 5 min shows all of the starting material to have reacted. After 30 min reaction time the sample is evaporated under a stream of nitrogen. lg Dowex 2-X8 anion exchange resin (50-100 mesh, chloride form, quaternary ammonium styrene type, 3.2 meg/dry frame capacity) is mixed widi 10 ml IN HCl, filtered off and washed with deionized water until die pH of die effluent is 6. To mis mixture is added 10 ml DMF, mixed well. The resultant mixture is allowed to sit for 5 min, then me solvent is removed by filtration under vacuum. The resin is placed in a small column. The evaporate residue from the above steps is dissolved in lOOul DMF and applied to resin and eluted with 5 ml DMF to give the product (Compound JJ). TLC: reverse phase C18, 80% DMF-20% water, UV visualization, Rf of starting material and product are 0.39 and 0.73 respectively. NMR(DMSO, TMS): δ 2.50, (s,3H); 3.54-3.65 (t, IH); 3.86-3.94 (d, IH); 3.964.08 (t, IH); 4.474.58 (d, IH); 4.594.73 (t, IH); 7.06 (s, IH); 7.11-7.23 (m, 2H); 7.43-7.53 (m, 2H); 7.53-7.70 (m, 4H); 8.21 (s, IH); 9.80 (s, IH); 9.76-9.98 (bs, 2H); 10.30 (s, IH); 10.74 (s, IH); 11.70 (s, IH); 12.07 (s, IH). Part B: Preparation of thioacetate analog. A 0.043mmole quantity of (S)-5-amino-2-[[[2-[[l-(chloromethyl)-l ,6-dihydro-5-hydroxy-8- medιylbenzo[l,2-b:4,3-b']dipyrrol-3(2H yl]^ (Cpd JJ, Part A) is dissolved in 200 ul DMA in the dark widi stirring under nitrogen. To this is added 7 mg (0.047mmole) of S-acetyl-roiolactic acid (Chem. Ber. 1966, 99, 1523, 1528) and lOmg (0.053mmole) of EDC. The mixture is left to react for 18 hrs and 3mg more of EDC is added. The reaction is stirred for an additional 5 hrs. The reaction mixture is then coated on 500mg silica gel and chromatographed over 5mg silica gel, eluted wi 20% DMF-80% toluene, to give 17mg solid, which by NMR appears to be a 1:1 mixmre of product and starting acid. The impure product is chromatographed over 1.5g reverse phase C18 silica gel, and eluted with 70% DMF-30% water to give 8mg of product. NMR and HPLC of die product shows an impurity (12%) which could be increased on treatment with acetonitrile-water-triethylamine and which shows me appearance of a new UV peak at 364nm, the impurity being the cyclopropyl compound, formed during me chromatography. TLC: UV visualization; reverse phase C18 silica gel, 75% DMF-25% water, Rf 0.44; regular silica gel, 20% DMF-80% toluene, Rf 0.38. HPLC: Altex Ultrashere, 1.5ml/minute, 295nm, 55% acetonitrile45% water- 0.1 % TFA; two major peaks adding up to more than 95%, wim the following retention times and percentages: 3.49 minutes, 12.4%; 6.38 minutes, 87.6%. UV(MeOH): 324nm (35,047). Mass spectrum: M+H at 683,685; other ions at 705, 682, 669, 647, 447, 405, 187. Part C: Hydrolysis of thioacetate and cyclopropyl ring closing of Part B. A sample of Part B is stirred at RT in the dark and under nitrogen in acetonitrile-water- triethylamine. The reaction mixture is diluted wid e yl acetate-water which has been purged wid nitrogen and keeping everything under nitrogen me layers are separated, the organic layer dried over sodium sulfate and evaporated to yield 5-[(2-mercaptopropionyl)amino]-N-[2-(4,5,8,8a- te rahydro-7-medιyl4-oxocyclopropa[c]pyrtolo[3,2-e]indol-2((lH)-yl)-lH-indol-5-yl]-lH-indole-2- carboxamide (Cpd #8). UV: Acetonitrile-water-triethylamine; 318 nm, 28,410; 364 nm; 22,860. Example 10 Preparation of (S)-N-[2-[[l-(chloromethyl)-l,6-dihydro-8-methyl-5-[[[[4- [[(phenylmethyl)oxy]carbonyl]phenyl]amino]carbonyl]oxy]benzo[l,2-b:4,3-b']dipyrrol-3(2H)-2- yl]carbonyl]-lH-indoI-5-yl]-2-benzofurancarboxamide (Cpd #10). A 5ml solution of phosgene (20% in toluene, 1.93 molar, 9.65mmoles) is stirred at room temperature (~25°C) under nitrogen. To mis is added slowly from a syringe 48mg (0.21mmoles) of the compound of Formula S (General Formulae Chart) dissolves in 1ml EtOAc. Some solid is formed at first which dissolves during d e one hour reaction time. The reaction is then evaporated under vacuum, high vacuum at end. The residue is stirred at room temperature (~25°C) under nitrogen in 1ml freshly distilled THF. To this is added slowly from a syringe 57mg (0.105 mmoles) (S)-N-[2-[[l-(dιloromethyl)- l,6^ihydro-5*4iydroxy-8-memylberao[l,2-b:4,,3-b']dipyrrol-3(2H yl]carbonyI]-lH-indol-5-yl]-2- benzofiirancarboxamide (see US Patent 4,912,227, Chart IV), in 1ml freshly distilled THF and 14ul triemylamine. The reaction mixture is heated to 65 °C for 2.5 hours when TLC shows me reaction to be complete. The reaction mixture is cooled to room temperature (~25°C), coated on lg silica gel and chromatographed over 9g silica gel. Elute wim a gradient of 40% acetone- 60% hexane to 50% acetone- 50% hexane. Fractions of 2ml are collected, analyzing them by TLC. The product is found in fractions 1745, which upon combining and evaporating leave 68mg, 82% yield based on (S)-N-[2-[[l-(chloromemyl)-l,6-dihydro-5*ydro^ carbonyl]-lH-indol-5-yl]-2-benzofurancarboxamide (see US Patent 4,912,227, Chart IV). TLC: UV visualization; silica gel; 40% acetone- 60% hexane; Rf: 0.42 UV(MeOH): 285nm (46,740); sh 325nm (30,100). NMR( c -DMS : TMS): δ 2.43 (s, IH); 3.70-3.83 (t, IH); 3.95-4.07 (d, IH); 4.154.27 (t, IH); 4.62-4.71(d, IH); 4.72-4.84 (t, IH); 5.35 (s, 2H); 7.21 (s, IH); 7.23 (s, IH); 7.33-7.57 (m, 8H); 7.63, 7.66 (d, IH); 7.70-7.78 (m, 3H); 7.80 (s, IH); 7.83, 7.85 (d, IH); 7.98 (bs, IH); 8.01 (s, IH); 8.04 (s, IH); 8.28 (s, IH); 10.52 (s, IH); 10.83 (s, IH); 11.29 (s, IH); 11.77 (s, IH). Mass spectrum: Major ions at 794, 792, 684, 538, 303, 237, 236, 199, 187, 145, 91. Exa ple 11A Part A: Preparation of Hydrazide. A 200mg quantity (0.86mmoles) of impure acid (Formula T, General Formulae Chart) is stirred at RT under nitrogen in 5ml dry DMF. To die solution is added 165mg (0.86mmoles) EDC and 114mg (0.86mmoles) t-butylcarbazate giving a complete solution. After 24 hrs me reaction mixture is partitioned between emyl acetate- water. The layers are separated and me water layer reextracted wid ethyl acetate. The organic layers are combined, dried over sodium sulfate and evaporated under vacuum. The residue is coated on 3g silica gel and chromatographed over 30g silica gel, eluting with 40% ediyl acetate- 60% hexane followed by 50% ediyl acetate-50% hexane. Fractions of 5ml are collected analyzing them by TLC. Impure product is found in fractions 49-84 which are combined and evaporated. This material is rechromatographed tiiree times over 5g silica gel, eluting with 30% acetone-70% hexane, separating out pure product (Formula U, General Formulae Chart) each time to give a total of 131mg, 44% yield. TLC: silica gel; UV visualization; 50% ediyl acetate- 50% hexane; Rf: 0.42. Mass spectrum: Major ions at 424, 348, 292, 248, 216, 202, 57. NMR(d 6 -acetone, TMS): δ 1.33-1.43 (t, 3H); 1.46 (s, 9H); 4.334.46 (q, 2H); 7.30 (s, IH); 7.59 (s, IH); 7.62 (s, IH); 7.87 (s, IH); 7.90 (s, IH); 7.97 (bs, IH); 8.35 (s, IH); 9.43 (bs, IH); 11.24 (bs, IH). Part B: Ediyl ester hydrolysis. A lOOmg (0.29mmoles) quantity ediyl ester is (Formula U) stirred at room temperature under nitrogen in 2ml MeOH- 1ml IN NaOH- 1ml water for 5 hours, when TLC shows the reaction not quite complete. At this point 0.5ml IN HCl is added and the reaction allowed to stand. After 16 hrs TLC shows die reaction to be finished. The reaction mixture is partitioned between ediyl acetate- water. TLC shows the ediyl acetate layer to contain impurity only and is discarded. The water layer is acidified widi 1ml IN HCl and extracted twice widi ediyl acetate. No product is left in die water layer as seen by TLC. The organic layers are combined, dried over sodium sulfate and evaporated under vacuum. This leaves 85mg (Formula V, General Formulae Chart), 92% yield. TLC: silica gel; UV visualization; 50% ethyl acetate- 50% hexane- 2% acetic acid; Rf: 0.28. Mass spectrum: major ions at: 474, 396, 320, 264, 220, 188, 57. UV(EtOH): 210nm (11,230); 252nm (48,600); 305nm (10,760); 315nm, si sh (8,470). NMR(d 6 -DMSO, TMS): δ 1.44 (s, 9H); 7.21 (s, IH); 7.46, 7.49 (d, IH); 7.75, 7.77 (d, IH); 8.25 (s, IH); 8.88 (s, IH); 10.12 (s, IH); 12.07 (s, IH); 12.9-13.3 (bs, IH). Part C: Amide preparation. An 85mg (0.27mmoles) quantity acid (Formula V) is stirred at RT under nitrogen in the dark in 1ml dry DMF. To mis is added 55mg (0.27mmoles) amine (Formula G, General Formulae Chart) and 52mg (0.27mmoles) EDC and die mixture allowed to react for 3 days. TLC at diis time indicates incomplete reaction and another lOmg EDC is added and reaction continued for 2 days at which point the reaction appears to be complete. The crude reaction mixture is coated on lg silica gel and chromatographed over 15g silica gel, eluting wim a gradient of 10-90 to 20-80 DMF-toluene to give 138 mg of product (Formula X, General Formulae Chart). TLC: silica gel; UV visualization; 10%DMF- 90% toluene; Rf: 0.28. Mass spectrum: major ions at 506, 406, 374, 302, 57. NMR(d 6 -DMSO, TMS): δ 1.30-1.41 (t, 3H); 1.46 (s, 9H); 4.30-4.43 (q, 2H); 7.22 (s, IH); 7.50-7.74 (m, 4H); 7.77-7.87 (d, IH); 8.24 (s, IH); 8.35 (s, IH); 8.94 (s, IH); 10.19 (s, IH); 10.33 (s, IH); 11.94 (s, IH); 12.08 (s, IH). Part D: Ester hydrolysis. A 138mg (0.27mmole) quantity e yl ester (Formula X) is dissolved in 2ml freshly distilled THF wim stirring at RT under nitrogen. To this is added 1ml EtOH and 1ml IN NaOH. Reaction is allowed to proceed for 21 hours when TLC shows it to be complete. The reaction mixture is treated wim 1ml IN HCl and evaporated under vacuum. The residue is treated widi 20ml water containing 1ml IN HCl. The resultant suspension is transferred to a eentrifugation tube and spun down. The supernatant is decanted and e solid mixed wid water. The suspension is again spun down and the liquid decanted. The solid is dried under vacuum, leaving 106mg (Formula Y, General Formulae Chart), 82% yield. TLC: silica gel; UV visualization; 20% DMF-80% toluene- 2% HOAc; Rf: 0.32. Mass spectrum: major ions at 500, 478, 422, 346, 144, 57. NMR(d 6 -DMSO, TMS): δ 1.45 (s, 9H); 7.09 (s, IH); 7.40-7.61 (m, 4H); 7.73-7.78 (d, IH); 8.16 (s, IH); 8.27 (s, IH); 8.86 (s, IH); 10.11 (s, IH); 10.29 (s, IH); 11.73 (s, IH); 12.05 (s, IH). Part E: Preparation of (S)-2-[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2- b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[[2-[[(l, l- dimethylethyl)oxy]carbonyI]hydrazino]carbonyll-lH-indol (Cpd 11 A). A 57mg (.17mmole) quantity of (S)-l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methyl- benzo[l,2b:4,3-b']dipyrrole-3(2H)-carboxylic acid 1 , 1-dimethyl ester (BOC chlorophenol) is stirred at RT in me dark and under nitrogen for one hour in 2ml EtOAc and 3ml EtOAc saturated with gaseous HCl. TLC in 30% ediyl acetate- 70% hexane shows all of the starting material spot to have moved to me origin, indicating complete reaction. The reaction is men evaporated under vacuum, and d e residue treated wid methylene chloride and reevaporated under vacuum. The solid residue is dissolved in 1.5ml DMA, giving a dark brown solution. To this is added 81mg (.17mmoles) acid (Formula Y) and 32mg EDC. The resultant mixture is stirred at RT under nitrogen in the dark for one hour, followed by the addition of 20mg more acid and 8mg more EDC and stirred for 3 more hours. The reaction mixture is transferred to a centrifuge tube and d e product precipitated widi water. The solid is spun down and die liquid phase decanted. The cloudy liquid from decantation is extracted with EtOAc-THF. The organic layer is dried over sodium sulfate and evaporated under vacuum. The residue from this is combined widi me solid from decantation. The crude product is coated on lg silica gel and chromatographed over 13g silica gel, eluting widi 30% DMF- 70% toluene to give 90 mg (76%) of product (Cpd #11 A). TLC: silica gel; UV visualization; 30% DMF- 70% toluene; Rf: 0.47. NMR(d 6 -DMSO, TMS): δ 1.45 (s, 9H); 2.37 (s, 3H); 3.55-3.68 (t, IH); 3.87-3.97 (d, IH); 4.00-4.10 (t, IH); 4.514.60 (d, IH); 4.634.77 (t, IH); 7.06 (s, IH); 7.16 (s, IH); 7.46- 7.83 (m, 6H); 8.25 (s, IH); J8.31 (s, IH); 8.91 (s, IH); 9.83 (s, IH); 10.15 (s, IH); 10.30 (s, IH); 10.76 (s, IH); 11.71 (s, IH); 12.08 (s, IH). UV(MeOH): 319 nm (34,810); 293nm (36,550). Mass spectrum: major ions at 772, 696, 695, 595, 564, 360, 237, 236, 199, 187, 170, 144, 57. Example 11B Preparation of (S)-2-[[[2-[[l-(chlorome yl)-l,6-dihydro-5-hydroxy-8-memylbenzo[l,2- b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carrx)nyI]-5-φydrazinocarbonyl)-lH-indol monohydrochloride (Cpd #11B). A5.14mg(0.0074mmole) quantity of (S)-2-[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy- 8-methylbenzo[l,2-b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[[2- [[(l,ldimetiιyledιyl)oxy]carbonyl]hydrazino]carbonyl]-lH-indol (Cpd #11 A) is stirred at room temperature (~ 25 °C) under nitrogen in die dark wim 2ml ethyl acetate saturated widi gaseous HCl for one hour. TLC in 20% DMF-80% toluene shows all of the starting material spot to move to the origin. The reaction mixmre is evaporated under vacuum, and die residue treated widi methylene chloride and reevaporated under high vacuum. UV(MeOH): 320nm (30,360); 293nm (32,890). Mass spectrum: M+H at 596, 598; M at 595, 597. HPLC: Altex Ultrasphere C18; 1.5ml/min; 295nm; 40% acetonitrile-60% water- 0.2% TFA; 98% pure; retention time: 5.13 min. NMR(d 6 -DMSO, TMS): δ 2.36 (s, 3H); 3.56-3.70 (m, IH); 3.85-3.96(d, IH); 3.984.10 (t, IH); 4.504.60 (d, IH); 4.624.75 (t, IH); 7.06 (s, IH); 7.15 (s, IH); 7.47-7.54 (d, IH); 7.55- 7.73 (m, 4H); 7.77-7.87 (d, IH); 8.24 (s, IH); 8.38 (s, IH); 9.77-9.90 (bs, IH); 10.39 (s, IH); 10.4-10.7 (bs, 2H); 10.78 (s, IH); 11.46 (s, IH); 11.72 (s, IH); 12.25 (s, IH). Example 12 Preparation of (S)-N-[2-[[l-(chloromethyl)-l,6-dihydro-8-methyl-5-[[[[4-[[2- [[(l,ldimedιyledιyl)oxy]carbonyl]hydrazino]carbonyl]phenyl]amino]carbonyl]oxy]benzo[l,2-b:4,3- b']dipyrtol-3(2H)-yl]carbonyl]-lH-indol-5-yl]-2-benzofurancarboxamide (Cpd #12); Part A: BOC hydrazide. A 500mg (2.76mmole) quantity 4-nitrobenzoic hydrazide is stirred at room temperamre (~25°C) under nitrogen in 5ml freshly distilled THF. 680mg (2.76mmoles) of [2-(tert- butoxycarbonyloxyimino)-2-phenylacetonitrile] (BOC-ON) and 385ul (2.76mmoles) triethylamine are added. The resulting mixture is then treated widi 3ml more THF, followed by 2ml DMF, stirred for 48 hours, then heated to 50°C for 8 hrs, and allowed to proceed at room temperature (~25°C) 16 additional hrs. The reaction is men condensed to about 1/2 volume by passing a stream of nitrogen above the liquid widi heating to 50°C. Then 380ul of triethylamine is added and the reaction allowed to stand for 4 days at room temperamre (~25°C). TLC shows almost complete reaction. The reaction mixture is partitioned between methylene chloride-water. The layers are separated and die aqueous layer reextracted wid ethyl acetate. The organic layers are combined, dried over sodium sulfate and evaporated under vacuum. The crude product is coated on lOg silica gel and chromatographed over lOOg silica gel, eluting with ethyl acetate- hexane: 300ml, 20-80; 250ml, 30-70; 250ml, 40-60; 500ml, 50-50; and 250ml, 6040 to give 661 mg (85%) of desired product (Compound Z in General Formulae Chart). TLC: silica gel; UV visualization; 20% ethyl acetate-80% hexane; Rf: 0.14 IR(Mull): peaks at 2925, 1525, 1675, 3325, 3320, 2953, 1719, 3399, 1278, 2855, 1159, 1731, 1256, 1510, 2869, 1484, 1350, 1370, 1373, 606, 851, 3235, 2986, 1460, 1456. Mass spectrum: major ions at: 435, 282, 226, 182, 150, 57. UV(EtOH): 212nm sh (8,460); 262nm (11,850). NMR(d 6 -acetone, TMS): δ 1.46 (s, 9H); 8.10-8.23(d+s, 3H); 8.33-8.41 (d, 2H); 9.81 (s, IH). Part B: Preparation of Formula AA (General Formulae Chart) amine. A lOOmg (0.35mmole) quantity of Formula Z (General Formulae Chart) (Part A) compound is dissolved in 2ml THF. To this is added 5ml 95% EtOH and 20mg platinum oxide. The mixmre is hydrogenated at room temperamre (~25°C) under pressure for 50 minutes. The reaction mixmre is filtered, washing the solid wi etiianol. The combined filtrate and wash is evaporated under vacuum, leaving 87mg solid (Formula A). TLC: silica gel; UV visualization; 60% ethyl acetate-40% hexane; Rf: 0.47. NMR(d 6 acetone, TMS): δ 1.43 (s, 9H); 5.17-5.3 (d, 2H); 6.65-6.72 (d, 2H); 7.65-7.74 (d, 2H); 7.77 (bs, IH); 9.05 (bs, IH). Mass spectrum: major ions at 252, 251, 196, 178, 120, 57. IR(Mull): peaks at 1719, 1631, 1607, 2925, 1274, 1518, 2954, 1487, 3356, 1259, 1167, 2855, 3239, 1182, 2869, 1371, 2981, 3374, 1306, 3438, 1463, 1460, 1574, 839, 779 cm "1 . UV(EtOH): 213nm (11,800); 285nm (16360). Part C: Preparation of (S)-N-[2-[[l-(chloromethyl)-l,6-dihydro-8-methyl-5-[[[[4-[[2-[[(l,l- dimethyIeuiyl)oxy]carbonyl]hydrazino]carbonyl]phenyl]amino]carbonyl]oxy]benzot 1 ,2-b :4,3- b']dipyιτol-3(2H)-yl]carbonyl]-lH-indol-5-yl]-2-benzorurancarboxamide (Cpd #12). A 4ml quantity phosgene in toluene (20%, 1.93 molar) is stirred at room temperamre (~25°C) under nitrogen. To mis is added 50mg (0.20mmoles) of me amine (Part B, Formula A), dissolved in 2ml dry THF, by syringe during one minute. After 5 minutes, the reaαion is still clear and 28ul triediylamine is added. A precipitate forms. After 2 hrs another 28ul triediylamine is added and reaction continued for 17 hours. A lOOul aliquot is removed and evaporated under vacuum. The residue is dissolved in 0.5ml THF and an IR spectrum run. An isocyanate peak is seen at 2250. The remainder of me reaction mixture is evaporated under vacuum. The residue is stirred under nitrogen in 1ml dry THF. To mis is added 57mg (S)-N-[2-[[l-(chloromethyl)-l,6-dihydro-5- hydroxy-8-methylbenzo[l,2-b:4„3-b']dipyrrol-3(2H-yl]carbonyl]-lH-indol-5-yl]-2-benzofurancar- boxamide (see US Patent 4,912,227, Chart IV), (0.106mmoles) in 15ul triediylamine and 2ml dry THF. The resultant mixture is heated to 70°C for one hour when anotiier lOul triethylamine is added. Heating is continued for one hour more. The resultant mixmre is cooled to room temperature ( ~ 25 C C) and die solid filtered off by washing it with THF. The combined filtrate and wash are evaporated under vacuum. The residue is coated on lg silica gel and chromatographed over lOg silica gel, eluting wim 20%DMF-80% toluene to give a major product (71mg of solid) which is still impure. The impure product is coated on lg Celite and chromatographed over 7g preparative C18 reverse phase silica gel (Waters, 55-105 microns). The column is eluted with 10ml 60% acetone - 40% water, followed by 70-30 of same to give 31 mg (36%) of product (Cpd #12). TLC: silica gel; UV visualization; 10%DMF-90% toluene; Rf: 0.21 IJV(MeOH): 330nm (21,220); 280nm (31.830). NMR(d 6 -DMSO, TMS): δ 1.44 (s, 9H); 3.72-3.83 (t, IH); 3.95-4.08 (d, IH); 4.15- 4.28 (t, IH); 4.604.72 (d, IH); 4.73- J4.84 (t, IH); 7.21 (s, IH); 7.23 (s, IH); 7.35-7.45 (t, IH); 7.45-8.00 (m, 11H); 8.25 (s, IH); k8.91 (s, IH); 10.13 (s, IH); 10.52 (s, IH); 10.73 (s, IH); 11.28 (s, IH); 11.76 (s, IH). Mass spectrum: major ions at 819, 818, 817, 816, 684, 538, 303, 237, 236, 199, 187, 177, 145, 120, 57. Example 13 Preparation of (S)-N-[2-[[l-(chloromethyI)-l ,6-dihydro-8-methyl-5-[[[[4-[[[2-[[(l, 1- dimeώylethyl)oxy]carrx)nyl]hydrazino]carbonyl]ethyl]phenyl]ammo]carbonyl]oxy]benzo[l,2-b:4,3- b']dipyrtol-3(2H)-yl]carbonyl]-lH-indol-5-yl]-2-benzorurancarboxamide (Cpd #13). Part A: Ester hydrolysis. A 2g quantity of p-nitro ethyl cinnamate (9.04mmoles) is stirred at room temperature (~25°C) under nitrogen in 20ml THF-lOml MeOH- 20ml IN NaOH for 30 minutes at which time everydiing has gone into solution and TLC shows no starting material left. A 20ml volume of IN HCl is then added resulting in the precipitation of a solid. The solid (Formula BB, General Formulae Chart), is collected by filtration and dried under vacuum to give Crop 1: 1.58g, 90% yield. The filtrate is concentrated under vacuum and a second crop is obtained: 40mg, 2% yield. Total yield 92%. TLC: silica gel; UV visualization; 50% EtOAc-50% hexane; Rf: origin. IR(Mull): peaks at 1351, 1687, 2924, 1532, 1631, 1521, 1343, 849, 1310, 2953, 2855, 2869, 1622, 1429, 988, 717, 1321, 1285, 1606, 1597, 713, 961, 1497, 760, 3054 cm 4 . UV(EtOH): 211nm, sh(14,690); 222nm, sh(10,130); 302nm (18,930). Mass spectrum: ions at 193, 176, 147, 146, 102, 91, 77. Part B: Preparation of Formula CC (General Formulae Chart). A 0.5g quantity (2.6mmoles) of Formula BB (Part A) acid is stirred at room temperamre (~25°C) under nitrogen in 10ml dry DMF, resulting in a partial solution. To mis is added 396mg (3mmoles) of i-butylcarbazate and 575mg (3mmoles) of EDC. The mixmre is left to react for 1.5 hours, during which time everything dissolves. Anotiier 192mg of EDC is added and die reaction allowed to continue for 3.5 days. At mis time die reaction mixmre is partitioned between emyl acetate-water. The layers are separated and d e water layer reextracted widi ediyl acetate. The organic layers are combined, dried over sodium sulfate and evaporated under vacuum. The crude product is coated on lOg sflica gel and chromatographed over lOOg silica gel. The column is eluted wim a gradient of 40-60 to 6040 e yl acetate-hexane, giving 623mg of product (Formula CC) as a solid, 78% yield. TLC: silica gel; UV visualization; 50% ethyl acetate-50% hexane; Rf: 0.72 ΪR(Mu11V peaks at 1515, 2925, 1675, 1348, 2954, 3299, 1715, 2855, 1252, 1637, 1367, 2867, 1166, 1297, 3218, 1282, 1373, 1149, 1543, 835, 1456, 989, 1594, 848, 719 cm -1 . UV(EtOH): 212nm (15400); 223nm sh(11400); 244nm sh(13100); 307nm, 22440. Mass spectrum; peaks at 307, 251, 234, 207, 176, 57. Part C: Preparation of Formula DD (General Formulae Chart). A 200mg (0.65mmole) quantity of Formula CC (Part B) is dissolved in 4ml freshly distilled THF. TO this is added lOml 95% EtOH and 40mg platinum oxide and the mixmre hydrogenated at room temperature (~25°C) under pressure for 45 minutes. The reaction mixture is filtered, washing the solid wid THF. The combined filtrate and wash is evaporated under vacuum, treated wim toluene and reevaporated twice, leaving 201mg, 100% yield of product (Formula DD). TLC: silica gel; UV visualization; 50% ethyl acetate- 50% hexane; Rf: 0.31 NMR(CDC13, TMS): δ 1.46 (s, 9H); 2.40-2.5 (t, 2H); 2.80-2.90 (t, 2H); 3.59 (bs, 2H); 6.58-6.64 (d, 2H); 6.92-7.00 (d, 2H). Mass spectrum: major ions at 559, 279, 224, 180, 106, 57. IR(Mull): major peaks at 2926, 2955, 2856, 1672, 1730, 1519, 1168, 2868, 1237, 1715, 1368, 3285, 1456, 1466, 1272, 1258, 1484, 1288, 1298, 3327, 1393, 1617, 1632, 831, 3389 cm "1 . UV(EtOH): 238nm (9580); 290nm (1360). Part D: Preparation of (S)-N-[2-[[l-(chloromethyl)-l,6-dihydro-8-methyl-5-[[[[4-[[[2-[[(l,l- dimethylemyl)oxy]carbonyl]hydrazino]carbonyl]emyl]phenyl]amino]carbonyl]oxy]benzo[l,2-b:4,3- b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]-2-benzofurancarboxamide (Cpd #13). A 1ml quantity phosgene in toluene (20%, 1.93 molar) is stirred at room temperature (~ 25 °C) under nitrogen. A total of 50mg (0. lδmmoles) of Formula DD (Part C) amine dissolved in 80ul triethylamine and 1ml dry THF is added over 1 minute via syringe. The reaction is stirred for 5 hrs whereupon another 50ul of triediylamine is added and die reaction stirred anotiier hour. The reaction is tiien evaporated under reduced pressure. The residue is then stirred under nitrogen in 2ml dry THF, giving a suspension. To this is added 30mg (0.056mmoles) (S)-N-[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8- medιylbenzo[l,2-b:4,,3-b']dipyπol-3(2H-yl]carbonyl]-lH-indol-5-yl]-2-benzofuranc^^ (see US Patent 4,912,227, Chart IV), dissolved in 1ml dry THF and lOul triediylamine. The mixture is heated to 70°C for two hours, when 5ul more triethylamine is added. The reaction is men cooled to room temperature (~25°C) and allowed to proceed. After 16 hr me reaction is reheated to 70°C for 2 hours more and again cooled to room temperature (~25°C). The crude product is coated on lg silica gel and chromatographed over lOg silica gel, eluting with a gradient of 5% DMF- 95% toluene to 10% DMF- 90% toluene to give impure product. This material is coated on lg Celite and chromatographed over lOg reverse phase C18 silica gel (waters, 55-105 microns). The column is made up in acetone and conditioned widi 10ml each of 90-10, 80-20, 70-30, and 6040 acetone-water. The product is tiien eluted widi 10ml 60% acetone 40% water, 100ml 70-30 and 20ml 80-20 of me same solvents to give 28 mg (60%) of pure product (Compound 13). TLC: silica gel; UV visualization; 10% DMF- 90% toluene; Rf: 0.53 UV(MeOH): 320nm (41,370); 292nm (54,030). NMR(d 6 -acetone, TMS): δ 1.57 (s, 9H); 2.44 (s, 3H); 2.83-3.05 (m, 6H); 3.67-3.77 (t, IH); 3.964.04 (dd, IH); 4.184.28 (t, IH); 4.734.87 (m, 2H); 7.11 (s, IH); 7.23 (s, IH); 7.28 (s, IH); 7.31 (s, IH); 7.33-7.41 (t, IH); 7.46-7.54 (t, IH); 7.54-7.70 (m, 6H); 7.77-7.83 (d, IH); 8.14 (s, IH); 8.42 (s, IH); 9.30 (s, IH); 9.69 (s, IH); 10.47 (s, IH); 10.98 (s, IH). Mass spectrum: major ions at 844, 770, 539, 538, 303, 237, 236, 199, 187, 145, 73, 57. Example 14 Preparation of (S)-N-[2-[[l-(chloromethyl)-l,6-dihydro-8-methyl-5-[[[[4-[2- [(hydrazinocarbonyl)emyl]phenyl]amino]carbonyl]oxy]benzo[l,2-b:4,3-b']dipyrrol-3(2H)- yl]carbonyl]-lH-indol-5-yl]-2-Benzofurancarboxamide, monohydrochloride (Cpd #14). A 5.32mg (0.0063mmole) quantity of (S)-N-[2-[[l-(chloromethyl)-l,6-dihydro-8-memyl-5- [[[[4-[[[2-[[(l,l-dimethylediyl)oxy]carbonyl]hydrazino]carbonyl]ediyl]phenyl]amino]carbonyl] oxy]benzo[l,2-b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]-2-benzofurancarboxamide (Cpd #13), is stirred at room temperamre (~25°C) in the dark under nitrogen in 2ml ethyl acetate saturated widi gaseous HCl for one hour. TLC in 20% DMF-80% toluene shows all of the starting material spot to have moved to me origin. The solvent is evaporated under vacuum. The residue is extracted witii methylene chloride and reevaporated under high vacuum to give Compound 14. UV(MeOH): 320nm (31,230); 292nm (39,420). HPLC: Altex Ultrasphere C18; 1.5ml/min; 295nm; 55% acetonitrile45% water- 0.2% TFA; 91% pure; retention time: 10.22 min. NMR(DMSO, TMS): δ 2.42 (s, 3H); 2.76-2.93 (m, 4H); 3.70-3.82 (t, IH); 3.964.05 (d,lH); 4.13-4.25 (t, IH); 4.584.67 (d, IH); 4.704.84 (t, IH); 7.15-7.25 (m, 4H); 7.34-7.43 (t, IH); 7.43-7.54 (m, 4H); 7.55-7.64 (d, IH); 7.70-7.93 (m, 4H); 8.23 (s, IH); 10.33 (s, IH); 10.51 (s, IH); 11.22 (s, IH); 11.75 (s, IH); 12.07 (s, IH). Example 15 Preparation of (S)-[[[2-[[l-(chloromediyl)-l,6-dihydro-5-hydroxy-8-memylbenzo[l,2-b: 4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2-[[(l , l- dimethyledιyl)oxy]carbonyl]hydrazino]carbonyl]edιyl]-2-Benzofuran (Cpd #15). Part A: Preparation of 3-[(benzofuran-2-carboethoxy)-5-yl]-propenoic acid. A mixmre of 5-bromobenzofuran-2-carboxylic acid ediyl ester (0.76 mM), palladium acetate (0.14 mM), triphenylphosphme (0.31 mM), acrylic acid (7.3 mM), distilled triethylamine (14.3 mM) and dimethylformamide (0.3 ml) is heated under argon at 110°C for 1.5 hours. The reaction is cooled and partitioned between IN HCl and ediyl acetate. The acidic product is extracted into 5% sodium bicarbonate solution. Acidification and extraction of the bicarbonate solution gives after drying and concentration 279 mg of crude yellow solid. The product is chromatographed on reversed phase C18 silica in methanol-water-acetic acid mixtures. A 20% yield of desired product is obtained. NMR(d 4 -MeOH, TMS): δ 1.41(t,3H); 4.41(q,2H); 6.53(d,lH,J= 18hz); 7.62(m,2H); 7.76(m,2H); 7.99(s,lH). C-13 NMR(DMSO-d 6 , TMS): δ 14.15, 61.43, 112.80, 114.19, 119.32, 123.66, 127.24, 127.75, 130.68, 143.49, 146.08, 155.89, 158.54, 167.69. MS(EI): M+. at m/z 260; major ions at m/z 232, 215, 188, 159. TLC(RP C18 silica): Rf = 0.28 in (70-30-0.2) medianol-water-acetic acid. Part B: Preparation of 3-(5-benzofuran-2-carboetiιoxy)-propanoic acid. The olefin of Part A (0.18 mM) is dissolved in THF (1 ml) and medianol (1 ml). The resultant solution is treated wim 10% palladium on carbon (36 mg). Four aliquots of ammonium formate (approximately 50 mg each) are added over die course of 3.8 hrs. The reaction is filtered, and die solids washed widi methanol. The filtrate is evaporated, redissolved in ethyl acetate, and washed with water and brine. The ediyl acetate solution is dried over anhydrous sodium sulfate and evaporated. An 82% yield of desired product is obtained. Mp 96-108°C. NMR (d 4 -MeOH, TMS): δ 1.40 (t,3H); 2.64(t,2H); 3.02(t,2H); 4.40 (q,2H); 7.37(dd,lH); 7.55(m,3H). C-13NMR (d 4 -MeOH, TMS): δ 14.60, 31.87, 37.15, 62.57, 112.81, 114.78, 123.20, 128.50, 129.72, 138.19, 147.13, 155.92, 161.02, 176.69. MS(EI): M+. at ml 262. Other ions at m/z 217, 203, 175, 115. TLC (Silica gel GF, acetic acid washed): Rf = 0.55 in (20-80) ethyl acetate-toluene. Part C: Coupling of Propanoic acid-3-(5-benzofuran-2-carboedιoxy) widi t-butyl carbazate. The acid of Part B (0.14 mM) is dissolved in N,N-dimethyIacetamide (0.5 ml) is treated with tert-butyl carbazate (0.28 M). Approximately one half of a weighed quantity of l-etiιyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC, 0.32 mM) is added to die reaction and it is stirred at room temperamre (~25°C) for 1.3 h. The remainder of the EDC is added and stirring is continued overnight. The reaction is partitioned between ethyl acetate and water. The organic layer is washed widi 0.1N HCl and brine, dried and evaporated. The crude product is chromatographed on 5 g HPLC grade silica in emyl acetate-toluene mixtures. An 83% yield of product (Formula EE, General Formulae Chart) is realized. NMR(CDC1 3 , TMS): δ 1.42(s+t, 12H); 2.57(t,2H); 3.06(t,2H); 4.43(q,2H); 6.82(bs,lH); 7.26(dd,lH); 7.45(m,3H); 8.16(bs, IH). C-13 NMR(CDC1 3 . TMS): δ 14.18, 27.96, 30.81, 35.82, 61.39, 81.73, 112.10, 113.51, 121.90, 127.03, 128.19, 136.03, 145.78, 154.39, 155.67, 159.48, 171.60. MS(CI): M+. at m/z 376. Other ions at m z 276,203, 175, 57. TLC(Silica gel GF): Rf = 0.08 in (20-80) ethyl acetate-toluene. Part D: Hydrolysis of Ediyl Ester. The product of Part C (Formula EE, 0.11 mM) is stirred in a mixture of pyridine (1 ml) and IN NaOH (0.25 mL) at room temperature (~25 C C) for 4 h. The reaction is diluted wim 1 N HCl and ethyl acetate. The ethyl acetate layer is dried and evaporated to give a white solid of Formula FF (93% yield) which is used in me next reaction without further purification. NMR(MeOH-d 4 , CDC1 3 , TMS): δ 1.47(s,9H); 2.57(t,2H); 3.07(t,2H); 7.33(dd,lH); 7.50(m,4H). Part E: Coupling of 5-Amino-2-carboxyethyl-benzofuran widi 5-Aminoindole-2-Carboxylic Acid Ethyl Ester. A mixmre of the acid (Formula FF, General Formulae Chart) (0.10 mM), the (Formula GG) amine (0.13 mM), and EDC (0.15 mM) in N,N-dimethylacetamide (0.2 ml) is stirred at room temperamre (~ 25°C) in subdued light for 4 days. The reaction is partitioned between ethyl acetate and water. The ediyl acetate layer is washed widi brine, dried and evaporated. The crude product is purified chromatographically on HPLC grade silica gel in ethyl acetate-toluene mixtures. A 72% yield of white solid product (Formula HH, General Formulae Chart) is obtained. Mp 132-135 C. NMR(CDCl 3 ,MeOH-d 4 , TMS): δ 1.44(t,3H); 1.48(s,9H); 2.59(t,2H); 3.09 (t,2H); 4.41(q,2H); 7.18-7.45(m,7H);8.17(s,lH). C-13 NMR(CDCl 3 ,MeOH-d 4 , TMS): 15.35, 29.16, 32.39, 37.16, 62.29, 82.51, 109.87, 112.14, 113.01, 113.84, 115.86, 121.62, 123.17, 128.56, 129.19, 129.79, 131.56, 136.65, 137.77, 150.31, 155.31, 157.63, 159.26, 163.73, 174.59. MS(FAB): {m+H}+ at m/z 535; other ions at m/z 479, 435, 361. TLC(Silica gel GF): Rf = 0.20 in (30-70) ethyl acetate-toluene. Part F: Ester Hydrolysis. A solution of the ester (Formula HH, General Formulae Chart), (0.07 mM) in pyridine (1 ml) and IN NaOH (0.3 ml) is stirred at room temperature (~25°C) for 18 hours. The reaction is acidified widi IN HCl and extracted widi ediyl acetate. Drying and concentration of the ethyl acetate solution gives 38 mg of white solid product. It is used in die next step without further purification. NMR(DMF-d 7 TMS): δ 1.43(s,9H); 2.58(t,2H); 3.05(t,2H); 7.19(s,lH); 7.43(d,lH); 7.56(m,2H); 7.71(m,2H); 7.79(dd,lH); 8.37(s,lH); 8.72(bs,lH); 9.64(bs,lH); 10.55(bs,lH); 11.78(bs,lH). Part G: Preparation of (S)-[[[2-[[l-(chloromethyl l,6-dihydro-5-hydroxy-8-memylbenzo[l,2- b:4,3-b']dipyrrol-3(2H)-yncarbonyl]-lH-indol-5-yll-amino]carbonyll-5-r2-[[2-r[(l, l- dimethyledιyl)oxy]carbonyl]hydrazino]carbonyl]ethyl]-2-benzofuran (Cpd #15). Hydrogen chloride is bubbled into an emyl acetate for approximately 20 minutes. (S)-l- (chloromemyl)-l,6-dihydro-5-hydroxy-8-methyl-benzo[l,2b:4,3-b']dipyrrole-3(2H)-carboxylic acid 1,1-dimediyl ester BOC(CPI) chlorophenol (0.105 mM) in emyl acetate (0.5 ml) is treated wim 1 ml of the above HCl solution. The reaction is stirred at room temperamre (~25°C) under an inert atmosphere for 45 minutes. The reaction is evaporated under reduced pressure to dryness. Contact of the product widi air is avoided. The residue is treated widi methylene chloride and re-evaporated twice. A solution of die acid of Part F, (0.075 mM) in N,N-dimethylacetamide (1 ml) is added to die residue followed by approximately one-half of a weighed quantity of EDC (0.19 mM). After the reaction has been stirred for one hr at room temperature (~25°C), the remainder of die EDC is added. One hour later, die reaction is diluted widi ediyl acetate and washed with water. The organic layer is dried over anhydrous sodium sulfate and evaporated. The residue is adsorbed onto silica gel (1 g) and flash chromatographed on HPLC grade silica gel (7 g) in (20-80) and (30-70) dimemylformamidetoluene to give 72% of a yellow solid product. NMR(DMSO-d 6 ) δ 1.41(s,9H); 2.36(s,3H); 2.45(t,2H); 2.96(t,2H); 3.61(t,lH); 3.91(m,lH); 4.04(m,lH); 4.53(m,lH); 4.67(m,lH); 7.05(s,lH); 7.14(s,lH); 7.37(d,lH); 7.47(d,lH); 7.62(m,5H); 8.20(s,lH); 8.73(bs,lH); 9.58(bs,lH); 9.79(s,lH); 10.45(s,lH); 10.73(bs,lH); 11.69(bs,lH). MS(FAB): Calc'd for C38H37C1N6O7: 724.2412; measured: 724.2393. Major ions at m z 625, 389, 357, 347, 236, 199. UV(DMA, MeOH): cmax 294 (36000), shoulder at 335 (22000). TLC(Silica gel GF): Rf= 0.45 in (30-70) DMF-toluene. Example 16 Preparation of (S)-2-[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2- b:4,3-b']dipyn-ol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-^ydrazinocarix)nyl)ethyl]- 2-benzofuran monohydrochloride (Cpd #16). Removal of t-BOC Protecting Group (S)-[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]-amino]carbonyl]-5-[2-[[2-[(l , l-dimethylethyl)oxy]- carbonyl]hydrazino]carbonyl]ediyl]-2-benzofuran (Cpd #15), (3 mg, 4.1x10-6 mole) is dissolved in a minimal amount of dimethylformamide. The solution is treated widi 1 ml of HCl-saturated ediyl acetate and stirred in subdued light at room temperature (~25°C) for 20 minutes. The solvent is men removed under vacuum to give (S)-[[[2-[[l-(chlorometiiyI)-l,6-dihydro-5-hydroxy-8- methylbenzo[l,2-b:4,3-b']diρyrrol-3(2H)-yl]carbonyl]-lH-indoI-5-yl]amino]carbonyl-5-[2- (hydrazinocarbonyl)e-thyl]-2-benzofuran monohydrochloride (Cpd #16), as a solid. NMR(DMSO-d 6 , TMS): δ 2.36(s,3H); 2.60(t,2H); 3.00(t,2H); 3.60(t,lH); 3.92(dd,lH); 4.03(dd,lH); 4.53(d,lH); 4.68(t,lH); 7.05(s,lH); 7.13(s,lH); 7.39(d,lH); 7.48(d,lH); 7.64(m,5H); 7.73(s,lH); 8.20(s,lH); 9.79(s,lH); 10.46(s,lH); 10.62(bs,lH); 10.74(s,lH); 11.69(s,lH). HPLC (Altex Ultrashere ODS, 5μ C18 column, 4.6x150 mm; 295nm detection; Solvents: 40% CH 3 CN + 0.2% TFA : 60% H 2 0 + 0.2% TFA; pump rate 1.5 ml/min): Retention time = 8.19 min. Example 17 Preparation of (7bR)-N-[2-[[4,5,8,8a-tetrahydro-7-methyl4-oxocyclopropa[c]pyrrolo[3,2- e]indol-2(lH)-yl-carbonyl]-lH-indol-5-yl]aminocarbonyl]-5-[2-[[2-[(l,l-dimethylethyl)oxy] carbonyl]hydrazino]carbonyl]edιyl-2-benzofuran (Cpd #17). A 50 mg (0.069 mmole) quantity of (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8- methylbenzo[l,2-b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2- [[(l,l-dimemylediyl)oxy]carbonyl]hydrazino]carbonyl]ethyl]-2-benzofuran(Cpd#15) is treated with 10 mL of (25-25-50) triethyl amine-acetonitrile-water and die resultant solution stirred at 25°C for 25 min. The reaction mixmre is then partitioned between THF, e yl acetate and water. The water layer is separated and reextracted widi THF-etiiyl acetate. The combined organic extracts are dried over sodium sulfate. To mis solution is added 500 mg of silica gel and then die mixmre concentrated under vacuum. The residue is added to the top of a 5 g silica gel column and die column eluted wim (20-80) DMF-toluene, collecting 2 mL fractions. The fractions containing product as determined by TLC (19-28) are combined and evaporated under vacuum leaving 37 mg of (7bR)-N-[2-[[4,5,8,8a-tetrahydro-7-memyl4-oxocyclopropa[c]pyrrolo[3,2-e]indol-2(lH)-yl- carbonyl]-lH-indol-5-yl]aminocarbonyl]-5-[2-[[2-[(l,l-dimethylethyl)oxy]carbonyl]hydra- zino j carbonyl] ethyl-2-benzofuran. NMR (DMSO-dg): δ 1.32(s,lH); 1.41(s,9H); 1.90-2.04(m,lH); 2.01(s,3H); 2.38- 2.52(t,2H); 2.90-3.02(t,2H); 3.12-3.23(m,lH); 4.41-4.51(d,lH); 4.524.60(dd,lH); 6.72(s,lH); 6.90(s,lH); 7.22(s,lH); 7.33-7.41(dd,lH); 7.44-7.51(d,lH); 7.62(s,lH); 7.65(s,lH); 7.70(s,lH); 8.22(s,lH); 8.75(s,lH); 9.59(s,lH); 10.48(s,lH); 11.56(s,lH); 11.83(s,lH). TLC: R f = 0.36 in (20-80) DMF-toluene. Example 18 Preparation of (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b: 4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2-[[(l , l- dimethylethyl)oxy]carbonyl]hydrazino]carbonyl]ethyl-2-benzofuran3,6,9-trioxadecanoic acid ester (Cpd #18). Part A: Preparation of 3,6,9-trioxadecanoic acid (23899-IG-154) A 0.5 g quantity of platinum oxide is hydrogenated in 60 mL of water at 25°C and atmospheric pressure until the uptake of hydrogen ceases. To die resultant mixmre is added a mixmre of 0.6 g (7.14 mmoles) of sodium bicarbonate and 1.0 g (6.1 mmoles) of triethylene glycol monomethyl ether dissolved in 20 mL of water. Air is bubbled dirough the above mixture for 4 hr following the consumption of starting material by TLC. The reaction is then filtered though Celite and die Celite washed widi water. The combined washes are treated widi 7.2 mL (7.2 mmoles) of 1 N hydrochloric acid and the resultant solution freeze-dried. The residue is washed widi acetone and filtered. The filtrate is evaporated to dryness under vacuum. The residual oil is chromatographed over 100 g of CC4 silica gel eluted widi (50-50)acetone-methylene chloride, collecting 20 mL fractions. Concentration of fractions 11-16 gives 0.92 g of the desired 3,6,9- trioxadecanoic acid. NMR (acetone-dg): δ 3.30(s,3H); 3.40-3.75(m,8H); 4.12(s,2H). TLC: R f = 0.13 in (40-60-2) acetone-hexane-acetic acid. Part B: A 40 mg (0.22 mmole) quantity of 3,6,9-trioxadecanoic acid (Part A) is treated widi 0.5 mL of thionyl chloride and die mixmre heated to reflux under a nitrogen atmosphere for 1 hr. The reaction is then cooled and concentrated under vacuum at 25 °C. The residue is redissolved in carbon tetrachloride and again evaporated under vacuum. The residual acid chloride is treated widi 1.0 mL of dry pyridine and this solution added to a solution of 30 mg (0.043 mmole) quantity of (7bR)-N-[2-[[4,5,8,8a-tetrahydro-7-memyl-4-oxocyclopropa [c]pyrrolo[3,2-e]indol-2(lH)-yl- carbonyl]-lH-indol-5-yl]aminocarbonyl]-5-[2-[[2-[(l,l-dimethylethyl)oxy]carbonyl]hydra- zino]carbonyl]ed yl-2-benzofuran (Cpd #17). After stirring 16 hr at 25°C, the reaction is treated widi 0.3 mL of 5% aqueous sodium bicarbonate and the total mixmre evaporated under vacuum onto 0.5 g of silica gel. The residual silica gel and compound are added to the top of a 7 g silica gel column which is then eluted witii (15-85) DMF-toluene, coiiecting fractions of 2 mL. Evaporation of fractions 13-20 leaves 9 mg of (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8- memylbenzo[l,2-b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2- [[(l,l-dimethylethyl)oxy]carbonyl]hydrazino]carbonyI]ediyl-2-benzofuran 3,6,9-trioxadecanoic acid ester (Cpd #18). NMR (DMSO-dg): δ 1.41(s,9H); 2.41(s,3H); 2.40-2.50(t,2H); 2.90-3.00(t,2H); 3.25(s,3H); 3.42-3.50(m,2H); 3.53-3.65(m,4H); 3.70-3.80(m,3H); 3.944.03(d,lH); 4.13- 4.24(t,lH); 4.57(s,2H); 4.564.66(d, IH); 4.684.81(t,lH); 7.18(s,lH); 7.26(s,lH); 7.32- 7.40(dd,lH); 7.45-7.53(d,lH); 7.56-7.67(m,3H); 7.86(s,lH); 8.22(s,lH); 8.72(s,lH); 9.59(s,lH); 10.47(s,lH); 11.15(s,lH); 11.69(s,lH). TLC: R f = 0.44 in (20-80) DMF-toluene. Example 19 Preparation of (SHt^fJI-^hlornme hyl l^- ihy ro-^-hy rox -g- eth ihe z Ji ,?-b: 4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-^ιydrazino)carbonyl]edιyl-2- benzofuran 3,6,9-trioxadecanoic acid ester (Cpd #19). A 4 mg (0.0045 mmole) quantity of (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8- methylbenzo[l,2-b:4,3-b , ]dipyrroI-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2- [[(1 , l-dimethylethyl)oxy]carbonyl]hydrazino]carbonyl]ethyl-2-benzofuran 3,6,9-trioxadecanoic acid ester (Cpd #18) is treated widi 0.2 mL of trifluoroacetic acid at 25°C. After 2 min the reaction is evaporated under vacuum (< 0.2 mm Hg) and me residue immediately dissolved in 0.25 mL of DMF and he solution added to die top of a 1.25 g Dowex 2-X8 (50-100 mesh) ion exchange column in the chloride form. The column is eluted widi DMF, collecting fractions of 0.25 mL. The fractions are analyzed by HPLC on a Altex Ultrasphere 5μ ODS 4.6x150 mm column eluted at 1.5 mL/min widi (45-55-0.1) acetonitrile-water-TFA, following peak elution by UV at 295 nm. Under these conditions die starting material elutes in 7.7 min and (S)-[[[-2[[l- (chloromemyl)-l,6-dihydro-5 ιydroxy-8-medιylbenzo[l,2-b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH- indol-5-yl]amino]carbonyl]-5-[2-0iydrazino)carbonyl]ethyl-2-benzofuran 3 ,6,9-trioxadecanoic acid ester in 5.2 min. The fractions containing product are combined and concentrated under high vacuum (<0.2 mm Hg). TLC: Rf = 0.40 in (50-50) acetonitrile-water on C-18 reversed phase silica gel plates. Example 20 Preparation of (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b: 4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2-[[(l , l- dimethyletiιyl)oxy]carbonyl]hydrazino]carbonyl]ethyI]-2-benzofuran glutaric acid monoester (Cpd #20). A 30 mg (0.041 mmole) quantity of (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8- methylbenzo[l,2-b:4,3-b']dipyrrol-3(2H)-ylJcarbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2- [[(l,l-dimethylethyl)oxy]carbonyl]hydrazino]carbonyl]ethyl]-2-benzofuran (Cpd #15), 7 mg of glutaric anhydride and 3 mg of 4-N,N-dimethylaminopyridineare dissolved in 0.20 mL of pyridine and the solution heated to 65°C under a nitrogen atmosphere for 3 hr followed by stirring for 64 hr at 25°C. The reaction is en added to 0.5 g of silica gel and evaporated under vacuum. The residue is added to me top of a 5 g silica gel column and me column eluted widi (20-80) DMF- toluene until the TLC shows the starting (Cpd #15) is eluted. The solvent is tiien switched to (20- 80-2) DMF-toluene-acetic acid and 2 mL fractions are collected. Evaporation, under vacuum (<0.2 mm Hg), leaves 27 mg of (S)-[[[-2[[l-(chloromemyl)-l,6-dihydro-5-hydroxy-8- methylbenzo[l,2-b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2- [[(l,l-dimedιyled yl)oxy]carbonyl]hydrazino]carbonyl]edιyl]-2-benzofuranglutaricacidmonoester. NMR (DMSO-dg): δ 1.41(s,9H); 1.85-1.98(q,2H); 2.33-2.44(t,2H); 2.41(s,3H); 2.45- 2.53( 2H): 2.73-2.83(t,2H); 2.92-3.04(t,2H); 3.67-3.80(t,lH); 3.934.05(d,lH); 4.144.24(t,lH); 4.564.66(d,lH); 4.704.81(t,lH); 7.20(s,lH); 7.25(s,lH); 7.34-7.41(dd,lH); 7.45-7.53(d,lH); 7.55-7.70(m,3H); 7.71(s,lH); 7.85(s,lH); 8.23(s,lH); 8.75(s,lH); 9.60(s,lH); 10.47(s,lH); 11.13(s,lH); 11.71(s,lH). TLC: R f = 0.14 in (20-80) DMF-toluene. TLC: R f = 0.57 in (20-80-2) DMF-toluene-acetic acid. Example 21 Preparation of (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b: 4,3-b , ]dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2-[[(l,l-dimethyIethyl) oxy]carbonyl]hydrazino]carbonyl]ethyl]-2-benzofuran ester of N-[2-hydroxy-l, l- bis(hydroxymethyl)ethyl]glutaramic acid (Cpd #21). A 25 mg (0.03 mmole) quantity of (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8- methylbenzo[l,2-b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2- [[(l,l-dimemylemyl)oxy]carbonyl]hydrazino]carbonyl]emyl]-2-benzofuran glutaric acid monoester (Cpd #20), 7 mg of hydroxybenzotriazole, 7 μL of triethylamine, and 9 mg of ethyl dimethylaminopropylcarbodiimide are dissolved in 0.20 mL of DMA and d e reaction allowed to stand in e dark for 1.5 hr. The reaction is then treated witii 7 mg of trihydroxymethylaminomethane and die reaction stirred in the dark at 25 °C for 21 hr. The reaction is tiien evaporated onto 0.5 g of silica gel under high vacuum (<0.2 mm Hg). The residue is added to d e top of a 5 g silica gel column and eluted with (20-80) DMF-toluene, collecting 2 mL fractions. Evaporation of fractions 2244 under high vacuum (< 0.2 mm Hg) leaves 18 mg of ((S)- [[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol-3(2H)- yl] carbonyl] - l H-indol-5-yl]amino]carbonyl]-5-[2-[[2-[[(l , 1 -dimethylethyl) oxy]carbonyl]hydrazino]carbonyl]ethyl]-2 -benzofuran ester of N-[2-hydroxy-l,l- bis(hydroxymethyl)ethyl]glutaramic acid (Cpd #21). NMR (DMSO-dg): δ 1.41(s,9H); 1.84-1.99(q,2H); 2.24-2.36(t,2H); 2.41(s,3H); 2.41- 2.50(t,2H); 2.70-2.80(t,2H); 2.90-3.02(t,2H); 3.56 & 3.58(d,6H); 3.66-3.77(t,lH); 3.92- 4.03(d,lH); 4.134.24(t,lH); 4.544.65(d,lH); 4.674.80(2t,4H); 7.18(s,lH); 7.23(s,2H); 7.33- 7.40(dd,lH); 7.44-7.53(d,lH); 7.56-7.69(m,3H); 7.71(s,lH); 7.84(s,lH); 8.22(s,lH); 8.73(s,lH); 9.58(s,lH); 10.46(s,lH); 11.09(s,lH); 11.69(s,lH). TLC: R f = 0.60 in (30-70) DMF-toluene. HPLC: RT = 4.06 min on 4.6x150 mm Altex Ultrasphere 5μ ODS column eluted at 1.5 mL/min with (45-55-0.1) acetonitrile-water-TFA; RT = 6.51 min on 4.6x150 mm Altex Ultrasphere 5μ ODS column eluted at 1.5 mL/min with (43-57-0.1) acetonitrile-water-TFA. Example 22 Prepartation of (S)-[[[-2[[l-(chloromemyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b: 4.3-h']dinyrrnl-3(2H)-yl]carbonyl]-lH-indol-5-yl]am o]ωrto^ benzofuran ester of N-[2-hydroxy-l,l-bis(hydroxymethyl)ethyl]glutaramic acid (Cpd #22). A 16 mg (0.017 mmole) quantity of (Cpd #22) is treated with 0.90 mL of trifluoroacetic acid at 25 C C. After 2 min die mixture is evaporated under high vacuum (<02. mm Hg). The residue is immediately dissolved in 1 mL of DMF and added to me top of a 5 g Dowex 2-X8 (50- 100 mesh) ion exchange column in the chloride form. The column is eluted witii DMF, collecting fractions of 1 mL. Evaporation of fractions 3-7 under high vacuum (<0.2 mm Hg) leaves 15 mg of slightly impure ((S)-[[[-2[[l-(chloromemyl)-l,6-dihydro-5-hydroxy-8-mediylbenzo[l,2-b:4,3- b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2- iydrazino)carbonyl]emyl-2- benzofuran ester of N-[2-hydroxy-l,l-bis(hydroxymethyl)ethyl]glutaramic acid, Cpd #22). This material is dissolved in 0.6 mL of DMF and the solution diluted widi 0.4 mL of water. This mixmre is chromatographed over 2 g of C-18 reversed phase silica gel, eluting with 3 mL of (60- 40) DMF-water followed by 30 mL of (70-30) DMF-water. Fractions of 1 mL are collected. Evaporation of fractions 9-13 leaves 3 mg of ((S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8- methylbenzo[l,2-b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2- (hydrazino)carbonyl] ethyl-2-benzofuran ester of N-[2-hydroxy- l , l - bis(hydroxymethyl)ethyl]glutaramic acid (Cpd #22). NMR (DMSO-dg): δ 1.84-1.98(q,2H); 2.25-2.35(t,2H); 2.36-2.44(t,2H); 2.41(s,3H); 2.67- 2.77(t,2H); 2.90-3.00(t,2H); 3.55 & 3.57(d,6H); 3.67-3.77(t,lH); 3.944.04(d,lH); 4.13- 4.25(t,lH); 4.574.65(d,lH); 4.704.82(2t,4H); 7.18(s,lH); 7.23(s,2H); 7.30-7.37(d,lH); 7.44- 7.51(d,lH); 7.56-7.66(m,4H); 7.71(s,lH); 7.84(s,lH); 8.22(s,lH); 8.99(s,lH); 10.45(s,lH); 11.09(s,lH); 11.69(s,lH). TLC: R f = 0.60 in (70-30) DMF-water on C-18 silica gel reversed phase TLC plates. Example 23 Preparation of (S)-[[[-2[[l-(chloromethyl l ,6-dihydro-5-hydroxy-8-methylbenzo[l ,2-b: 4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2-[[(l , l- dimethylethyl)oxy]carbonyl]hydrazino]carbonyl]ediyl]-2-benzofuran glutaric acid monoester mono amide of 7-amino-naphthalene-l,3-disulfonic acid disodium salt (Cpd #23). A 25 mg (0.03 mmole) quantity of (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8- memylbenzo[l,2-b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2- [[(l,l-dimemylemyl)oxy]carbonyl]hydrazino]carbonyl]ediyl]-2-benzofuran glutaric acid monoester (Cpd #20), 7 mg of hydroxybenzotriazole, 7 μL of triediylamine, and 9 mg of emyl dimethylaminopropylcarbodiimide are dissolved in 0.20 mL of DMA and die solution stirred at 25°C for 1.5 hr. To the reaction is then added 10 mg (0.033 mmole) of 7-amino-l,3- naphthalenedisulfonic acid dissolved in 10 μL of triethyl amine and 20 μL of water, the residual solution being washed in widi 100 μL of DMF. The reaction is stirred in die dark at 25 °C for 21 hr. The reaction is then evaporated onto 0.5 g of Celite under high vacuum (<0.2 mm Hg). The residue is added to die top of a 5 g C-18 reverse phase silica gel column and eluted witii 10 mL of (10-90) DMF-1% sodium chloride in water, and subsequentiy wim 10 mLs each of solvent changing from 10%-80% DMF in water in increaments of 10%. Fractions of 2 mL are collected. The desired (S)-[[[-2[[l-(cWoromethyl)-l,6^ihydro-5*4iydroxy-8*m^ylbenzo[l,2-b:4,3-b']dipyrrol- 3 (2H ) -y l ] carb o nyl] - l H -indol -5 -yl] amino] carbo nyl ] -5 -[2- [ [2- [ [ ( l , l - dimethylemyl)oxy]carbonyl]hydrazino]carbonyl]ethyl-2-benzofuran glutaric acid monoester mono amide of 7-amino-naphthalene-l ,3-disulfonic acid disodium salt is obtained as a solid residue by evaporation under high vacuum (<0.2 mm Hg) of those fractions found by TLC and HPLC to contain tiiis material. NMR (DMSO-dg, TMS): δ 1.41(s,9H); 1.99-2.10(q,2H); 2.40(s,3H); 2.40-2.48(t,2H); 2.50-2.59(t,2H); 2.77-2.87(t,2H); 2.90-3.01(t,2H); 3.68-3.79(t,lH); 3.94-4.03(d,lH); 4.13- 4.24(t,lH); 4.564.66(d,lH); 4.704.80(t,lH); 7.18(s,lH); 7.24(s,lH); 7.34-7.40(d,lH); 7.46- 7.53(d,lH); 7.56-7.67(m,3H); 7.70(s,lH); 7.85-7.92(m,2H); 8.00(s,lH); 8.13-8.20(d,lH); 8.20- 8.24(m,2H); 8.67(s,lH); 8.73(s,lH); 9.59(s,lH); 10.39(s,lH); 10.46(s,lH); 11.13(s,lH); 11.72(s,lH). HPLC: Vydac Protein-Peptide C 18 ; 1.5 ml/minute; 295 nm; eluted for 2 minutes wi 20% CH 3 CN - 80% 50 mM NEt3/HOAc (pH « 5.5), followed by a 5 minute gradient to 80% CH 3 CN - 20% 50 mM NEt3/HOAc, followed by 80% CH 3 CN - 20% 50 mM NEt3/HOAc. Retention time: 7.6 minutes. Example 24 Preparation of (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l ,2-b: 4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-(hydrazino)carbonyl]ethyl-2- benzofuran glutaric acid monoester mono amide of 7-amino-naphthalene-l, 3-disulfonic acid disodium salt (Cpd #24). A 20 mg (0.016 mmole) quantity of (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8- memylbenzo[l,2-b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2- [[(1, l-dimethylethyl)oxy]carbonyl]hydrazino]carbonyl]ethyl]-2-benzofuran glutaric acid monoester mono amide of 7-amino-naphthalene-l, 3-disulfonic acid disodium salt (Cpd #23) is treated widi 0.90 mL of trifluoroacetic acid at 25°C. After 2 min the mixture is evaporated under high vacuum (<02. mm Hg). The residue is immediately dissolved in 1 mL of DMF evaporated under high vacuum (<0.2 mm Hg) unto 0.5 g of Celite. The residue is added to die top of a 5 g C-18 reverse phase silica gel column and eluted witii 10 mL of (10-90) DMF-1 % sodium chloride in water, and subsequently with 10 mLs each of solvent changing from 10% -80% DMF in water in increaments of 10% . Fractions of 2 mL are collected. The desired (S)-[[[-2[[l-(chlorometiιyl)-l,6- dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5- v llamino]caτbon v !]-5-[2-(h v draziπo)carbonyI]ethvl-2-b'?nzo- !r!»η glutaric acid monoester mono amide of 7-amino-naphtiιalene-l,3-disulfonic acid disodium salt is obtained as a solid residue by evaporation under high vacuum (<0.2 mm Hg) of those fractions found by TLC and HPLC to contain this material. NMR (DMSO-dg, TMS): δ 1.98-2.12(q,2H); 2.40(s,3H); 2.34-2.46(t,2H); 2.52- 2.60(t,2H); 2.78-2.88(t,2H); 2.93-3.01(t,2H); 3.68-3.79(t,lH); 3.934.03(d,lH); 4.104.23(t,lH); 4.554.65(d,lH); 4.684.81(t,lH); 7.18(s,lH); 7.23(s,lH); 7.30-7.39(d,lH); 7.45-7.53 (d,lH); 7.57-7.67(m,3H); 7.70(s,lH); 7.83-7.93(m,2H); 8.01(s,lH); 8.10-8.19(d,lH); 8.19-8.24(m,2H); 8.67(s,lH); 8.98(s,lH); 10.39(s,lH); 10.45(s,lH); 11.13(s,lH); 11.72(s,lH). HPLC: Vydac Protein-Peptide C 18 ; 1.5 ml/minute; 295 nm; linear gradient over 3 minutes of 40% CH 3 CN - 60% 50 mM NEt3/HOAc at pH « 5.5 to 45% CH 3 CN - 55% 50 mM NEt3/HOAc. Retention time: 3.13 minutes. The starting compounds are known or can be readily prepared by known methods. See M.A. Warpehoski, Tet. Lett., 27, 4103 (1986); W. W. Wierenga, J. Am. Chem. Soc, 103, No. 18, 1981; D.G. Martin, J. Antibiotics 1985, 38, 746; and M.A. Warpehoski, I. Gebhard, R.C. Kelly, W.C. Krueger, L.H. Li, J.P. McGovren, M.D. Prairie, N. Wicnienski and W. Wierenga, J. Med. Chem., 1988, 31, pp. 590-603. The preparation of (S)-l-(chloromethyl)-l ,6-dihydro-5- hydroxy-8-methyl-benzo[ 1 ,2b :4,3- b']dipyrrole-3(2H)-carboxylic acid 1,1-dimethyl ester BOC(CPI) chlorophenyl HCl is described in R. C. Kelly, I. Gebhard, N. Wicnienski, P. A. Aristoff, P. D. Johnson, D. G. Martin, J. Am. Chem. Soc. 1987, 109 6837. The spirocyclopropylcyclohexadienyl compounds of Formula A and l-(halomemyl)-l,6- hydro-5-hydroxy-8-methyl-benzo[l ,2-b:4,3-b']dipyrrole-3(2H)-yl 5-ester or uretiianes (Formula B) can also be prepared by die procedures and methods disclosed in U.S. Patent Application Serial No. 894,314, filed August 7, 1986 (now abandoned), and PCT/87/03227 patent application filed December 11, 1987. Botii are incorporated herein by reference. See also EP Application 0 154 445 (published 9 November 1985). The compounds of Formula I and II are particularly useful as antitumor agents. Examples of compounds of Formula I and II demonstrate antitumor activity in P388 leukemic mice, and also show significant activity in the L1210 leukemia and B16 melanoma murine test systems. These murine test systems are predictive for clinically useful human antitumor agents (see, for example, A. Geldin et al, European J. Cancer, Vol. 17, pp 129-142, 1981; J.M Vendetti, Cancer Treatment Reports, Vol. 67, pp. 767-772, 1983; and J.M. Vendetti et al, Advances in Pharmacology and Chemotherapy, Vol. 20, pp. 1-20, 1984), and, tiierefore, die compounds of die subject invention (Formula I and II) will be useful in the control and treatment of susceptible neoplastic (cancer) diseases, including susceptible leukemics, in humans when given, for example, intravenously in dosεs of 0.0Q1 μg g to abont 10 mg/kg of body weight per day, die exact dose depending on die age, weight, and condition of die patient, and on me frequency of administration. The compounds of Formula I and II are effective when administered intravenously (IV) in fluid solutions by bolus injection or by infusion. The preferred doses are 0.01 microgram/kg to 1000 microgram/kg by bolus injection and 0.0002 to 20 microgram/kg/min by infusion. The exact dose will vary depending on die particular compound as well as die age, weight, route of ad- ministration, and physical condition of the patient, and on d e frequency of administration. Illustrative L1210 testing data on me compounds of Formula I are presented in Table I. In addition to die administration of the compounds of the subject invention directly, die compounds (Formula I and II) are preferably coupled to antibodies, either monoclonal (Mab) or polyclonal, directed at specific cancer cell antigens and tiius selectively eliminate those disease cells from the patient. The coupling of the compounds of this invention to antibodies can be done by methods well known in the art including tiiose of European Patent Application 85401776.1 (Publication No. 0175617) and 83400461.6 (Publication No. 0088695), herein incorporated by reference, as well as A.H. Blair, T.I. Ghose, J. Immunol. Methods, 59, 129 (1983), N. Endo, Y. Kato, Y. Takeda, M. Saito, N. Umemoto, K. Kishida, T. Hara, Cancer Res. 47, 1076 (1987), E. Hurwitz, R. Levy, R. Maron, M. Wilchek, R. Arnon, M. Sela, Cancer Res. 35, 1175 (1975), K. Ohkawa, Y. Tsukada, N. Hibi, N. Umemoto, T. Hara, Cancer Immunol. Immunother. 23, 81 (1986), B. Packard, M. Edidin, A. Komoriya, Biochemistry, 25, 3538 (1986), J.D. Rodwell, V.L. Alvarez, C. Lee, A.D. Lopes, J.W.F. Goers, H.D. King, H.J. Powsner, T.J. McKearn, Proc. Natl. Acad. Sci. USA, 83, 2632 (1986), Y. Tsukada, Y. Kato, N. Umemoto, Y. Takeda, T. Hara, H. Hirai, J. Nat. Cancer Inst. 73, 721 (1984), and N. Umemoto, Y. Kato, Y. Takeda, M. Saito, T. Hara, M. Seto, T. Takahashi, J. Appl. Biochem. 6, 297 (1984). Further, the compounds (Formula I and II) can be utilized to treat AIDS by preparing conjugates between die compounds and soluble human CD4 or a soluble human CD4 protein fragment capable of binding to the gpl20 envelope protein of die human immunodeficiency virus. The amino acid sequence of soluble human CD4 (or soluble human CD4 protein fragment capable of binding to the gpl20 envelope protein of the human immunodeficiency virus, i.e. biologically active CD4 fragments) can be the same as mature human CD4 protein or modified in such a manner mat me sequences are different from that of mature CD4 protein in that there can be 1) deletions) from, substitution^) in and/or additions to die amino acid sequence of human CD4 (see Maddon, P. J. et al., "The Isolation and Nucleotide Sequence of a cDNA Encoding d e T Cell Surface Protein T4: A New Member of the Immunoglobulin Gene Family", Cell, Vol. 24, pp. 93-104, August 1985, and Garlick, R. L., et al., "Eschericia coli expression, purification, and biological activity of a truncated soluble CD4", AIDS Research and Human Retroviruses, Vol. 6, No. 4, pp. 465479, 1990; 2) it is truncated (i.e., includes the same amino acid sequence); 3) it is truncated and d e truncated form or portion includes deletion(s) from, substitution(s) in and/or additions to the amino acid sequence which occurs in the corresponding portion or segment (see references cited above). Preferably biologically active, and/or modified soluble CD4 fragments include none (or at least less tiian six amino acids) of die hydrophobic transmembrane portion. Such biologically active (modified or unmodified) soluble CD4 fragments are long enough (ten amino acids or longer) to enable them to bind effectively to the gpl20 envelop protein of die HIV virus. Altiiough such fragments need not exhibit complete homology with human CD4 protein, tiiey will have about 75% homology in those regions to bind to gpl20. Illustrative CD4 fragments include tiiose disclosed in die patent and/or scientific literature, e.g. Nature, vol 337, p. 525-31 (1989) or US Patent Application Serial No. 333,516; filed 5 March 1989 (TUC's 183 fragment). The novel conjugates of die subject invention (compounds of Formula I or II and antibody/CD4) are effective when administered intravenously (IV) in fluid solutions by bolus injection or by infusion. The preferred doses are 0.01 microgram/kg to 1000 microgram/kg (in terms of compound I or II) by bolus injection and 0.0002 to 20 microgram/kg/min by infusion. The exact dose will vary depending on die particular compound as well as die age, weight, route of administration, and physical condition of die patient, and on die frequency of administration. Generic Example 1 Coupling of carboxy terminated Compounds I or II (eg. formulas A', B', C and the like) with active amine, guanidine, or hydrazide moiety of linker. See CHART 1. A 0.1 mMole quantity of the carboxy terminated CPI compound is dissolved in an aprotic solvent or mixmre of aprotic solvents such as DMF, DMA, THF, dioxane, etc. (preferably DMA or DMF) to give a concentration of 0.01 to 1.0 M. The resultant solution is stirred at -10° to 100°C (preferably at 20-25°C) and treated widi a peptide coupling agent such as emyl dimediylaminopropyl carbodiimide hydrochloride (EDC), dicyclohexylcarbodiimide (DCC) isobutyl chloroformate, or pivaloyl chloride, etc. (preferably EDC) either in the presence or absence of a coupling mediator such as N-hydroxy-benzotriazole or N-hyroxysuccinimide, etc. The resultant solution may be premixed with a suitable linker (eg. a protected hydrazine such as H 2 NNHBoc) so that botii die CPI and die linker start at die same molar concentration or the linker may be dissolved in the same or other aprotic solvent, as listed above, and die linker solution added to die CPI compound-peptide coupling agent mixmre (with or witiiout coupling mediator) until the same molar concentration of CPI carboxylate and linker are reached. The reaction is stirred at -10° to 100°C (preferably at 20-25°C) 1 min to 48 hr (preferably 24 hr). The reaction is then diluted widi water and die product eitiier collected by filtration or extracted widi a water immiscible solvent such as methylene chloride or emyl acetate. If extracted die extract is dried and evaporated. This product or mat collected by filtration is purified by crystallization or by chromatography using eitiier silica gel or otiier normal phase support or by reverse phase chromatography on C-2, C-8, or C-18 silica gel. Generic Example 2 Coupling of amino terminated Compounds I or π (eg. formulas D', E', F' and me like) widi active carboxyl moiety of linker. See CHART 2. A 0.1 mMole quantity of me carboxyl terminated linker is dissolved in an aprotic solvent or mixture of aprotic solvents such as DMF, DMA, THF, dioxane, etc. (preferably DMA or DMF) to give a concentration of 0.01 to 1.0 M. The resultant solution is stirred at -10° to 100°C (preferably at 20-25 °C) and treated widi a peptide coupling agent such as ethyl dimediylaminopropyl carbodiimide hydrochloride (EDC), dicyclohexylcarbodiimide (DCC) isobutyl chloroformate, or pivaloyl chloride, etc. (preferably EDC) eitiier in the presence or absence of a coupling mediator such as N-hydroxy-benzotriazole or N-hyroxysuccinimide, etc. The resultant solution may be premixed wim the amino or hydrazido terminated CPI compound so tiiat both the CPI and the linker start at die same molar concentration or the CPI compound may be dissolved in e same or other aprotic solvent, as listed above, and die CPI compound solution added to die linker-peptide coupling agent mixmre (with or widiout coupling mediator) until d e same molar concentration of CPI carboxylate and linker are reached. The reaction is stirred at -10° to 100°C (preferably at 20-25 °C) 1 min to 48 hr (preferably 24 hr). The reaction is then diluted widi water and die product eitiier collected by filtration or extracted widi a water immiscible solvent such as mediylene chloride or ediyl acetate. If extracted die extracted is dried and evaporated. This product or tiiat collected by filtration is purified by crystallization or by chromatography using either silica gel or other normal phase support or by reverse phase chromatography on C-2, C-8, or C-18 silica gel. Generic Example 3 Coupling of linker as ester prodrug to Compound I or II, (formulas G', H' or the like). See CHART 3. The CPI compound is dissolved at 0.01 to 3 M in an aprotic solvent such a pyridine, methylene chloride, THF, etc (preferably pyridine where no additional tertiary amine need be added) and die solution treated wim a tertiary amine such as triethylamine, pyridine, or ediyldisopropylamine and me solution stirred at -10° to 100°C. To this solution is added the linker acyl halide (preferably die acylchloride) and the resultant solution stirred at -10° to 100 C C (preferably at 20-25 °C) 1 min to 48 hr (preferably 24 hr). The reaction is then diluted with water. If a product precipitates as a solid it may be collected by filtration. Alternatively, die aqueous mixmre may be extracted wid a water immiscible solvent such as methylene chloride or ediyl acetate. The organic layer is washed widi 5% aqueous sodium bicarbonate, dried over magnesium sulfate or sodium sulfate, and concentrated in vacuo. The product obtained tiius from the extraction or as above by filtration may be further purified by normal phase chromatography on silica gel, alumina or other solid support or may be purified by reversed phase chromatography over C-2, C-8, or C-18 silica gel. Generic Example 4 Removal of N-Boc or t-butyl ester protecting group from linker attached to CPI compound. Deprotection of compounds of formulas such I', J' and die like. See CHART 4. The N-Boc or t-butyl ester protected linker attached to die CPI compound is dissolved at 0.01 to 2 M in a solvent such as ethyl acetate, dioxane, or methylene chloride and me solution stirred at -50° to 100°C (preferably at 20-25°C). This solution is treated with an acid known in die art for removal of N-Boc or t-Butyl ester groups such as HCl gas (1-3 M in e yl acetate) or trifluoroacetic acid for 1 min to 48 hr (preferably 2-4 hr). After die designated time me reaction is concentrated in vacuo. The product tiius obtained may be further purified by normal phase chromatography on silica gel, alumina or other solid support or may be purified by reversed phase chromatography over C-2, C-8, or C-18 silica gel. Generic Example 5 Removal of N-Cbz or benzyl ester protecting group from linker attached to CPI compound. Deprotection of compounds of formulae such as K\ L' and the like. See CHART 5. The N-Cbz (N-carbobenzyloxy or N-benzyloxycarbonyl) or benzyl ester protected linker attached to die CPI compound is dissolved at 0.01 to 2 M in a solvent or combination of solvents such as MeOH, MeOH-THF, MeOH-dioxane, etc. and the solution stirred at -50° to 100°C (preferably at 20-25°C). This solution is treated from 0.01 to 3 M equivalent of a hydrogenolysis catalyst such as palladium metal, 5% palladium on carbon, Raney nickel, etc. (preferably 5-10% palladium on carbon at 0.01-0.2 molar equivalents). The solution may be hydrogenated directly wim hydrogen at 1-5 times atmospheric pressure for 10 min to 48 hr (preferably 24 hr) or alternatively the solution of compound and catalyst may be treated widi ammonium formate, formic acid, cyclohexadiene or oflier phase transfer catalytic hydrogenation hydrogen donors (preferably ammonium formate) and e resultant mixmre stirred for 1 min to 48 hr (preferably 5 min to 3 hr). At the end of die designated time the reaction is filtered and the filtrate concentrated in vacuo. The product tiius obtained may be further purified by normal phase chromatography on silica gel, alumina or otiier solid support or may be purified by reversed phase chromatography over C-2, C-8, or C-18 silica gel. Generic Example 6 Coupling of linker as uremane prodrug to compounds II, eg. formulas M'. See CHART 6. The phenolic CPI compound is dissolved at 0.01 to 3 M in an aprotic solvent such a pyridine, methylene chloride, THF, etc (preferably pyridine where no additional tertiary amine need be added) and die solution treated widi a catalyst such as dibutyltinacetate or a tertiary amine such as triethylamine, pyridine, or ediyldisopropylamine and the solution stirred at -10° to 100°C. To this solution is added the linker isocyanate, chlorocarbamate or other activated aminocarbonyl derivative and the resultant solution stirred at -10° to 100°C (preferably at 20-25°C) 1 min to 48 hr (preferably 24 hr). The reaction is then diluted widi water. If a product precipitates as a solid it may be collected by filtration. Alternatively, me aqueous mixmre may be extracted widi a water immiscible solvent such as methylene chloride or ediyl acetate. The organic layer is washed widi 5% aqueous sodium bicarbonate, dried over magnesium sulfate or sodium sulfate, and concentrated in vacuo. The product obtained thus from the extraction or as above by filtration may be further purified by normal phase chromatography on silica gel, alumina or other solid support or may be purified by reversed phase chromatography over C-2, C-8, or C-18 silica gel. Generic Example 7 Coupling of carboxy terminated CPI-linker structures, eg. formulas P', Q', R' and die like with active amine, guanidine, or hydrazide moiety of monoclonal antibody (Mab) or CD4. See CHART 7. A 0.1 mMole quantity of the carboxy terminated CPI-linker compound is dissolved in an aprotic solvent or mixmre of aprotic solvents such as DMF, DMA, THF, dioxane, etc. (preferably DMA or DMF) to give a concentration of 0.01 to 1.0 M. The resultant solution is stirred at -10° to 100°C (preferably at 20-25°C) and treated widi a peptide coupling agent such as emyl dimediylaminopropyl carbodiimide hydrochloride (EDC), dicyclohexylcarbodiimide (DCC) isobutyl chloroformate, or pivaloyl chloride, etc. (preferably EDC) either in the presence or absence of a coupling mediator such as N-hydroxy-benzotriazole or N-hyroxysuccinimide, etc. The resultant solution is added to HN terminated Mab or CD4 protein dissolved in a polar solvent such as DMF, DMA, formamide, or water, buffered water at or near isotonic salt concentrations at pH 6.5-8.0 (preferably about 7.0-7.5), or a mixture of any of such solvents until the same molar concentration of CPI-linker carboxylate and protein are reached. The reaction is stirred at -10° to 100°C (preferably at 20-25°C) 1 min to 48 hr (preferably 24 hr). The reaction is then diluted widi water, a water salt mixture such as aqueous ammonium sulfate, an alcohol such as methanol or ethanol and d e product either collected by filtration or the product may dialyzed and the aqueous residue freeze dried. This product or tiiat collected by filtration is purified by salt precipitation procedures or by chromatographics such as size exclusion chromatography, affinity chromatography or reverse phase chromatography on C-18 silica gel. Generic Example 8 Coupling of amino, guanidino, or hydrazido terminated CPI-linker structures, eg. formulas T', U\ V or the like widi activated carboxyl of monoclonal antibody (Mab) or CD4 (see Chart A 0.1 mMole quantity of the carboxy Mab or CD4 is dissolved in water, buffered water at or near isotonic salt concentrations at pH 6.5-8.0 (preferably about 7.0-7.5), or a polar solvent such as DMF, DMA, or formamide or a mixmre of such polar solvents and water at 10-30°C. The solution of die -NH terminated CPI-linker compound is dissolved in an aprotic solvent or mixmre of aprotic solvents such as DMF, DMA, THF, dioxane, etc. (preferably DMA or DMF) to give a concentration of 0.01 to 1.0 M which is added to me carboxyl terminated protein solution. The resultant solution is stirred at 0° to 100°C (preferably at 20-25°C) and treated wim 0.8 to 5.0 molar equivalents (preferably one equivalent) of a peptide coupling agent such as emyl dimediylaminopropyl carbodiimide hydrochloride (EDC), dicyclohexylcarbodiimide (DCC) isobutyl chloroformate, or pivaloyl chloride, etc. (preferably EDC) eitiier in the presence or absence of a coupling mediator such as N-hydroxy-benzotriazole or N-hyroxysuccinimide, etc. The reaction is stirred at 0° to 100°C (preferably at 20-25 °C) 1 min to 48 hr (preferably 2-4 hr). The reaction is then diluted wid water, a water salt mixmre such as aqueous ammonium sulfate, an alcohol such as methanol or ethanol and the product eitiier collected by filtration or the product may dialyzed and the aqueous residue freeze dried. This product or that collected by filtration is purified by salt precipitation procedures or by chromatographics such as size exclusion chromatography, affinity chromatography or reverse phase chromatography on C-18 silica gel. Generic Example 9 Reduction of tiiiopyridyl terminated miol (i.e. pyridyl disulfide) CPI-linker structures, eg. formulas X' and Y * and the like to thiol. See CHART 9. A 0.1 mMole quantity of the thiopyridyl terminated thiol CPI-linker is dissolved in water or a polar solvent such as DMF, DMA, or formamide or a mixmre of such polar solvents and water at 10-50°C. To this is added an excess (2 to 50 fold excess, preferably 5 to 10 fold) of a reducing agent such as ditiiiotiireitol and die mixmre stirred for 5 min to 48 hr (preferably 30 min to 2 hr). The product thiol may then be isolated by precipitation widi water or a non polar solvent or by extraction in an oxygen free environment. The material from precipitation or extraction may be used directly in me next step or be further purified by crystallization, selective precipitation, or chromatography in an oxygen free environment. Suitable chromatographic procedures include size exclusion chromatography, affinity chromatography or reverse phase chromatography on C-18 silica gel. Generic Example 10 Coupling of thiol linker terminated CPI eg. structures AA' and AB', to thiol terminated Mab via disulfide linkage. See CHART 10. A 0.1 mMole quantity of die thiol terminated Mab is dissolved in water, aqueous buffer at pH 3 to 10 (preferably at pH 7 to 8) and at a salt concentration near isotonic, or in aqueous mixtures widi a polar solvent i'ch as DMF, DMA, or formamide or a mixmre of such polar solvents at 10-50°C. To this is added an excess (2 to 50 fold excess, preferably 5 to 10 fold) of a of the thiol linker terminated CPI compound and the mixture stirred while bubbling oxygen through for 5 min to 48 hr (preferably 30 min to 2 hr). The product Mab disulfide linked CPI compound may then be isolated by precipitation widi water, aqueous salt solutions such as 20% ammonium sulfate or saturated sodium sulfate, or a non polar solvent. Alternatively the product may be freed from low molecular weight impurities by dialysis. The material from precipitation or dialysis may be further purified by crystallization, selective precipitation, or chromatography. Suitable chromatographic procedures include size exclusion chromatography, affinity chromatography or reverse phase chromatography on C-18 silica gel. Generic Example 11 Coupling of tiiiopyridyl terminated tiiiol (i.e. pyridyl disulfide) CPI-linker structures, eg. formulas X', Y' and the like to thiol terminated Mab. See CHART 11. A 0.1 mMole quantity of the thiopyridyl terminated thiol CPI-linker is dissolved in water or a polar solvent such as DMF, DMA, or formamide or a mixture of such polar solvents and water at 10-50°C. To diis is added 0.5 to 3 equivalent (preferably 1 equivalent of tiiiol terminated antibody and die mixmre adjusted to pH 0 to 5 (preferably pH 3 to 4) widi an organic or inorganic acid or preferably widi a buffer of those acids. The mixmre is stirred for 5 min to 48 hr (preferably 30 min to 2 hr). The product disulfide may en be isolated and purified as in example 11 above. Generic Example 12 Coupling of N-maleimide terminated CPI-linker structures, eg. formulas AD', AE' and the like to thiol terminated Mab. See CHART 12. A 0.1 mMole quantity of the N-maleimide CPI-linker is dissolved in water or a polar solvent such as DMF, DMA, or formamide or a mixture of such polar solvents and water at 0- 50°C. To diis is added 0.5 to 3 equivalents (preferably 0.8 to 1.2 equivalents) of a thiol terminated Mab dissolved in water, an aqueous buffer of pH 3 to 10 (preferably pH 6 to 8) or a mixmre of the previous solvents widi polar solvents such as DMF, DMF or formamide and die mixmre allowed to stand at 0-50°C (preferably 5-20°C) for 5 min to 48 hr (preferably 30 min to 2 hr). The product may then be isolated by precipitation widi water, aqueous salt solutions such as 20% ammonium sulfate or samrated sodium sulfate, or a non polar solvent. Alternatively the product may be freed from low molecular weight impurities by dialysis. The material from precipitation or dialysis may be further purified by crystallization, selective precipitation, or chromatography. Suitable chromatographic procedures include size exclusion chromatography, affinity chromatography or reverse phase chromatography on C-18 silica gel. Generic Example 13 Coupling of hydrazido terminated CPI-linker structures, eg. formulas AG', AH' and die like to formyl terminated Mab. See CHART 13. A 0.1 mMole quantity of the hydrazido terminated CPI-linker is dissolved in water or a polar solvent such as DMF, DMA, or formamide or a mixture of such polar solvents and water at 0-50°C. To diis is added 0.5 to 3 equivalents (preferably 0.8 to 1.2 equivalents) of a formyl terminated Mab (prepared by cleavage of Mab glycosyl residue as in known in the art) dissolved in water, an aqueous buffer of pH 3 to 10 (preferably pH 4 to 6) or a mixmre of me previous solvents with polar solvents such as DMF, DMF or formamide and die mixmre allowed to stand at 0-50°C (preferably 5-20°C) for 5 min to 48 hr (preferably 30 min to 2 hr). The product hydrazone may then be isolated by precipitation widi water, aqueous salt solutions such as 20% ammonium sulfate or samrated sodium sulfate, or a non polar solvent. Alternatively die product may be freed from low molecular weight impurities by dialysis. The material from precipitation or dialysis may be further purified by crystallization, selective precipitation, or chromatography. Suitable chromatographic procedures include size exclusion chromatography, affinity chromatography or reverse phase chromatography on C-18 silica gel. Generic Example 14 Coupling of amino terminated CPI-linker structures, eg. formulas AJ', AK', and die like to formyl terminated Mab. See CHART 14. A 0.1 mMole quantity of the amino terminated CPI-linker is dissolved in water or a polar solvent such as DMF, DMA, or formamide or a mixmre of such polar solvents and water at 0- 50 °C. To this is added 0.5 to 3 equivalents (preferably 0.8 to 1.2 equivalents) of a formyl terminated Mab (prepared by cleavage of Mab glycosyl residue as in known in me art) dissolved in water, an aqueous buffer of pH 2 to 6 (preferably pH 3 to 5) or a mixmre of the previous solvents with polar solvents such as DMF, DMF or formamide and die mixmre treated with 1 to 100 equivalents of sodium cyanobofohydride (preferably 5 to 10 equivalents) and the mixmre stirred at 0-50 °C (preferably 5-20 °C) for 5 min to 48 hr (preferably 30 min to 2 hr). The product amine may then be isolated by precipitation witii water, aqueous salt solutions such as 20% ammonium sulfate or samrated sodium sulfate, or a non polar solvent. Alternatively me product may be freed from low molecular weight impurities by dialysis. The material from precipitation or dialysis may be further purified by crystallization, selective precipitation, or chromatography. Suitable chromatographic procedures include size exclusion chromatography, affinity chromatography or reverse phase chromatography on C-18 silica gel. Generic Example 15 Maleimide based coupling of monoclonal antibodies (Mab) or CD4 fragments wim compounds of Formula I or II, eg. Compounds of Formula AA', AC, AF' and die like. See CHART 15. Maleimide terminated proteins can be prepared as described for the preparation of peptide labeled carrier proteins suitable for elicitation of peptide specific antibody responses. References: J.A. Nicholas et al, J. Virology 62, 44654473 (1988); F.-T. Liu et al, Biochemistry 18, 690- 97 (1979). Succinimidyl 4-(N-maleimidomethyl)cyclohexane-l-carboxylate (0.540 equivalents, preferably 0.8-10 equivalents) or some other heterofunctional crosslinking reagent which contains an N-hydroxysuccinimidyl ester on one end and a maleimido group on d e opposite end is dissolved in water or a polar solvent such as DMF, DMA or formamide and die solution is added to a stirred solution of protein (0.1 mMol) dissolved in 0.01 N sodium phosphate, pH 7.0, (0.75 ml). This mixmre is stirred for 5 min - 4 hrs (preferably 20 min to 1 hr) at 0-50 °C (preferably 5-25 °C) and loaded directly onto a Sephadex 0-25 column previously equilibrated at 4°C widi 0.1 N sodium phosphate, pH 6.0. The column is run in the same buffer at 4°C. The first peak eluted contains the maleimide terminated protein which is suitable for direct coupling witii a thiol terminated CPI- linker. Coupling of thiol terminated CPI-linker structures R5 0 =SH) (cpds such as T, U', V) to maleimide terminated proteins such as Mab, biologically active soluble human CD4 fragments or truncated forms of soluble human CD4. A 0.1 mMole quantity of the maleimide terminated CD4 is prepared in water, aqueous buffer of pH 3-10 (preferably pH 6-8) or a mixmre of the previous solvents with polar solvents such as DMF, DMA, or formamide. To this is added 0.540 equivalents (preferably 0.8-10 equivalents) of a thiol terminated CPI-linker compound dissolved in water or a polar solvent such as DMF, DMA or formamide or a mixmre of such polar solvents and water at 0-50 °C and the mixmre allowed to stand at 0-50°C (preferably 5-25°C) for 5 min to 48 hr (preferably 30 min to 2 hr). The product may then be isolated by precipitation witii water, aqueous salt solutions such as 20% ammonium sulfate or samrated sodium sulfate, or a nonpolar solvent. Alternatively, the product may be freed from low molecular weight impurities by dialysis. The material from precipitation or dialysis may be further purified by crystallization, selective precipitation, or chromatography. Suitable chromatographic procedures include size exclusion chromatography, affinity chromatography or reverse phase chromatography on C-18 silica gel. The compounds of formula I and π are also useful as antibacterial agents. These compounds are useful to control me proliferation of susceptible microbes in various environments using standard microbiological techniques. Such environments include dental utensils contaminated witii ∑ . aureus. and die like, and laboratory benches in a microbiological laboratory which can be cleansed witii a formulation containing about 1-10% (w/v) of a compound of formula I or II. CHA T 1 O O H II II I Ar-(linker)-COH + H 2 NR → Ar-(linker)-C NR where Ar(linker)-C0 2 H ≡ ' ,B' ,C shown below and R linker moiety. For example: Q 0 Ar- (linker) -CNR = Ar(CH 2 ) CNNBoc H HH n = 0-5 B * CHART 2 R' R'O I Ar-(linker) -NH + H0 2 C - R → Ar-(linker) -N-C-R where Ar-(linker) -NH = D , ,E' and F' shown below and R is a linker moiety. CHART 3 R For example R = Boc CHART 4 Ar-( linker) -NH-Boc → Ar- (linker) -NH 2 where Ar-( linker) -NHBoc = 1' , 3' shown below. CHART 5 Ar- (linker) -C-OCH, -phenyl → Ar- (linker) -COH O Ar-( linker) -COCH, -phenyl ≡ K',L' shown below. K' CHART 6 M' N' CHART 7 O Ar-(Linker) -CO„H + NH, - Mab → Ar-(linker) -C-N-Mab H O Ar-(linker) -C0 2 H + NH 2 ~CD 4 → Ar-(linker) -CN-CD 4 H where Ar-(linker) -C0 2 H s P',Q/,R' shown below (CB 2 ) n -C0 2 H CHART 8 R O Ar-( linker) -NHR + HO_C-Mab Ar- (linker) -NH-C-Mab or H0 2 C-(CD 4 ) R- (linker) -NH-C-CD. II O where Ar- (linker) -NHR = T' ,U' ,V shown below. U' V CHART 9 Ar-( linker) -S-S-pyridine + HSCH 2 CHOHCHOHCH 2 SH → Ar-( linker) -SH where Ar- (linker) -SS-pyridine ≡ X',Y' shown below. CHART 10 inker) -SH + HS-Mab → Ar-linker-S-S-Mab where Ar- ( linker) -SH ≡ AA' , AB ' shown below. AA' AB * CHART 11 Ar-( linker) -S-S-pyridine + HS-Mab → Ar- (linker) -S-S-Mab where Ar- (linker) -S-S-pyridine ≡ X', Y' shown below. - .jl CHART 12 + BS-Uab-* where Ar-(linker)-N T| = AD', AE ' shown below. AD' AE' CHART 13 Ar- (linker)-CNHNH, OHC-Mab Ar-(linker)-CNHN=CH- Mab where Ar- (linker) -CNHNH 2 = AG' ,AH' shown below. AC AH' CHART 14 Ar- ( linker) -NH 2 1) OHC-Mab Ar- (linker) -NHCH 2 -Mab → 2) NaBH 3 CN where Ar-(linker) -NH 2 ≡ AJ', AK' shown below. AJ' AK' -€6- CHART 15 0 PROTEIN - NH C N II i Ar- (linke V 0 Ar- (linker) -S C-NH-PROTEIN where Ar- ( linker) -SH ≡ AA' , AC , AF ' shown below. AA' AC CHART 15 (cont'd.) CCB 2 D -CC ό0 CR 6 l)-SH AF' FORMULA CHART Compound 2 Compound 3 FORMULA CHART (continued. Compound 4 Compound 5 Compound 8 FORMULA CHART (continued. 10 Compound 10 20 Compound 11A 30 HCl Compound 11B FORMULA CHART (continued. Compound 12 Compound 13 • HCl Compound 14 FORMULA CHART (continued. Compound 16 Compound 17 35 FORMULA CHART (continued. Compound . 18 Compound 19 FORMULA CHART (continued. 20 Compound 21 35 FORMULA CHART (continued. Compound 22 15 Compound 23 FORMULA CHART (continued. 20 Compound 24 GENERAL FORMULAE CHART 15 GENERAL FORMULAE CHART (continued) 15 25 F GENERAL FORMULAE CHART (continued) 15 25 K GENERAL FORMULAE CHART (continued) 15 25 M GENERAL FORMULAE CHART (continued) N -*-o-c GENERAL FORMULAE CHART (continued) 15 U 25 GENERAL FORMULAE CHART (continued) 15 GENERAL FORMULAE CHART (continued) AA GENERAL FORMULAE CHART (continued) BB CC DD GENERAL FORMULAE CHART (continued) 0 0 II II -BuO — CHNBNC EE 0 0 II II t-BuO _ CBNHNC FF GG 0 o BE GENERAL FORMULAE CHART (continued) OB 10 <70 *71 20 GENERAL FORMULAE CHART (continued) (a) (b) xs GENERAL FORMULAE CHART (continued) (aa) GENERAL FORMULAE CHART (continued) dd 15 25 ddd dddd 35 GENERAL FORMULAE CHART (continued) ee 15 25 eee FORMULAE Ha FORMULAE (Cont'd) IB TABLE HI Linker Groups for Attachment of Therapeutic Agents (TA) to Antibody Molecules A. Linkers for Cleavage by Cl -lys- (a.a) n4 - -tyr- -phe- -arg- B. Tripeptide Sequences for Cleavage by C4,2 -leu-ala-arg- -leu-ala-lys- -leu-ala-tyr- -leu-leu-arg- -leu-leu-lys- -leu-leu-tyr- -leu-gly-arg- (a.a) n4 - -leu-gly-lys- -leu-gly-tyr- -leu-val-arg- -leu-cal-lys- -leu-val-tyr- -leu-ile-arg- -leu-ile-lys- -leu-ile-tyr- -ala-ala-arg- -ala-ala-lys- -ala-ala-tyr- -ala-leu-arg- -ala-leu-lys- -ala-leu-tyr- -ala-gly-arg- (a.a.) n4 - -ala-gly-lys- -ala-gly-tyr- -ala-val-arg- -ala-val-lys- ripeptide Sequences for Cleavage by C4,2 (cont'd) -ala-val-tyr- -ala-ile-arg- -ala-ile-Iys- -ala-ile-tyr- -gly-ala-arg- -gly-ala-lys- -gly-ala-tyr- -gly-leu-arg- -gly-leu-lys- -gly-gly-arg- -gly-gly-lys- -gly-gly-tyr- -gly-val-arg- -gly-val-lys- -gly-val-tyr- -gly-ile-arg- -gly-ile-lys- -gly-ile-tyr- -val-ala-arg- -val-ala-lys- -val-ala-tyr- -val-leu-arg- -val-leu-lys- -val-leu-tyr- -val-gly-arg- (a.a) n4 - -val-gly-lys- -val-gly-tyr- -val-val-arg- -val-val-lys- -val-val-tyr- -val-ile-arg- -val-ile-lys- -val-ile-tyr- -ile-ala-arg- iπ. B. Tripeptide Sequences for Cleavage by C4,2 (cont'd) -ile-ala-lys- -ile-ala-tyr- -ile-leu-arg- -ile-leu-lys- -ile-leu-tyr- -ile-gly-arg- (a.a) n4 - -ile-gly-lys- -ile-gly-tyr- -ile-val-arg- -ile-val-lys- -ile-val-tyr- -ile-ile-arg- -ile-ile-lys- -ile-ile-tyr- iπ. C. Peptide Sequences for Cleavage by C4, 2 -leu-gly- -leu-leu- -leu-ala- -leu-val- -leu-ile- -gly-gly- -gly-leu- -gly-ala- -gly-val- -ala-gly- -Tripeptide 2 -ala-leu- -ala-ala- -ala-val- -ala-ile- -val-elv- -val-leu- -val-ala- -val-val- -val-ile- -ile-gly- III. C. Peptide Sequences for Cleavage by C4, 2 (cont'd) -ile-leu- -ile-ala- -ile-val- -ile-ile- wherein (a.a) represents any naturally occurring amino acid (and can be the same or different) and ^ = 0-5.

Claims: CLAIMS 1. A compound of Formula I or II: wherein W is selected from C1-C5 alkyl, phenyl or hydrogen; wherein X is selected from azido, a halogen atom, cyanate, thiocyanate, isocyanate, thioisocyanate, phosphate diester (-PO OR)^, phosphonyl (-O-PO 2 R), thiophosphonyl (-O-PSOR), sulfinyl (-O-SOR) or sulfonyl (-O-SO 2 R); wherein D is R-^ or R'15; wherein Q is Y when D is R' 15 ; wherein Q is Y' when D is R^; wherein Y is selected from hydrogen, -C(O)R, -C(S)R, -C^OR j , -S(0) 2 R lf -C(O)NR 2 R 3> -C(S)NR 2 R 3 , -C(O)NHSO 2 R 4 , -CODJCH^OCH^H^O^-Cg alkyl) and n7 is 0-5, or -C(O)(CH 2 ) n8 C(O)Rj-, where n8 is 0-10 and R b is selected from -OH (or a metal or amine salt thereof), -OR c where R c is -CH 2 C(CH 2 OH) 3 or R 70 , and -N(R d ) R e where R d is hydrogen or C r C 4 alkyl, and R e is selected from -C(CH 2 OH) 3 , -CH 2 C(CH 2 OH) 3 , -CH 2 C(CH 2 NH2) 3 , R 70 , 1 or R 72 where R 70 is 0H where R 71 is *71 where R 72 is R 72 where n9 is 1 or 2 and nlO is 1-3; wherein Y' is selected from -C(O)R 10 , -C(S)R 10 , -C(O)OR 10 , -S(O) 2 R 10 , -C(O)NR 12 R 13 , -C(S)NR 12 R 13 , or -C(O)NHSO 2 R 14 ; wherein Z is selected from the group consisting of C1-C5 alkyl, phenyl or hydrogen; wherein R is selected from the group consisting of CJ-C^ Q alkyl; C-^-Cg alkenyl; C 2 -C 6 alkynyl; phenyl optionally substituted with one, 2 or 3 CJ- J alkyl, C!-C 3 alkoxy, halo, C j -C 3 alkylthio, trifluoromethyl, C^-Cg dialkylamino, or nitro; naphthyl optionally substituted with one or 2 C!-C alkyl, C1-C3 alkoxy, halo, trifluromethyl, ^-Cg dialkylamino, C j -C 3 alkylthio or nitro; wherein Ri is selected from CJ-C 2Q alkyl or phenyl optionally substituted with one. 2 or 3 C Γ C alkyl, C^C-** alkoxy, halo, C C 3 alkylthio, trifluoromethyl, C-^-Cg dialkylamino, or nitro; wherein R 2 and R 3 , being the same or different, are selected from hydrogen, C-f-C^o alkyl, or phenyl optionally substituted with one, 2 or 3 C1-C4 alkyl, CJ-C 3 alkoxy, halo, C C- alkyldiio, trifluoromethyl, ^-Cg dialkylamino, or nitro; with the proviso that both R 2 and R 3 cannot be phenyl or substituted phenyl; wherein R 4 is selected from CJ-C-^ Q alkyl; phenyl optionally substituted with one, 2 or 3 C j - j alkyl, C C^ alkoxy, halo, C C 3 alkylthio, trifluoromethyl, C^-Cg dialkylamino, or nitro; naphthyl optionally substituted with one or 2 ^-€4 alkyl, C j -C 3 alkoxy, halo, trifluromethyl, C* > - C 6 dialkylamino, C j -C 3 alkylthio or nitro; wherein R 10 , R j3 and R 1 , being the same or different, are selected from -(C j -C^ alkyl)(CH2) n R5o or -(phenyl optionally substituted with one or two C j -C alkyl, C j -C 3 alkoxy, halo, Cι*-C 3 alkylthio, trifluoromethyl, C^-Cg dialkylamino, or nitroXCH^R jQ ; wherein n is 0-10; wherein R 50 is selected from the group consisting of (i) -CO 2 H; (ii) -CH 2 NH 2 ; (iii) -SH; (iv) being the same or different, are C r C 4 alkyl or H; (v) wherein Rrø and Rg j are defined above and n j is O-5; (vi) -C(O)NHNH 2 (hydrazido); (vii) -NHNH 2 (hydrazino); (viii) -CH 2 OH (hydroxymethyl); (ix) -NHC(S)NH 2 (thioureido); (x) -CH 2 NHC(O)NH 2 ; (xi) -NHC(S)NHNH 2 ; (xii) -C(O)CH2X! (Xi is a halogen); (xiii) -CH 2 Xι (halomethyl) wherein X j is a halogen; (xiv) -CHO (aldehyde); ( xv) -C(0) (N-hydroxysuccimidyl) ; (xvi) -N II (maleimide) ; Y (xvii) -C(R 5 o)(R 61 )C(O)NHNH 2 wherein Rgg and R^, being the same or different, are C r C 4 alkyl or H; (xviii) -O(CH 2 )n 1 C(R 60 )(R 61 )C(O)NHNH 2 wherein R^, R^ , and n x are defined above; (xix) and Rg 2 are independently selected from C j -C 4 alkyl or H and n t = O-5; (xx) -O(CH 2 ) n2 C(R 60 )(R 61 )C(O)NHNH 2 (n 2 = 1-5); (xxi) -NHR 51 ; (xxii) -C(O)NHNHR 51 ; (xxiii) -NHNHR 51 ; wherein R 51 is an amine protecting group such as BOC (t-butoxycarbonyl), FMOC (9- fluorenylmethyloxycarbonyl), TFA (trifluoroacetate)amide), ALLOC (alloxycarbonyl), CBZ (benzoxycarbonyl), or TROC (trichloroethoxycarbonyl); (xxiv) -NHC(=NH)NH 2 (guanadinyl); or (xxv) -B-M-(CH )n 3 R 52 wherein n 3 = O-5; R 52 is the same as R^ above (groups (i) - (xxiv) only); wherein B is an ester [-OC(O)- or -C(O)O-] or amide [-NHC(O or -C(O)NH-] bond; wherein M is defined below as any compatible peptide, carbohydrate, or other organic moiety imparting to the embodiment of this invention specific properties (e.g. chemical, photochemical, or enzymatic cleavability; branching for multiple site attachment of additional therapeutic agents of the invention; optimal spacing between therapeutic agent and antibody); for cleavage of linkers by serum compliment M can be selected from: Linker Groups for Attachment of Therapeutic Agents (TA) to Antibody Molecules A. Linkers for Cleavage by Cl -lys- (a.a) n4 - -tyr- -phe- -arg- B. Tripeptide Sequences for Cleavage by C4,2 -leu-ala-arg- -l .p -ι -ι-a —la-1v ___. κ —- -leu-ala-tyr- -leu-leu-arg- -leu-leu-lys- -leu-leu-tyr- -leu-gly-arg- III. B. Tripeptide Sequences for Cleavage by C4,2 (cont'd) (a.a) n4 - -leu-gly-lys- -leu-gly-tyr- -leu-val-arg- -leu-cal-lys- -leu-val-tyr- -leu-ile-arg- -leu-ile-lys- -leu-ile-tyr- -ala-ala-arg- -ala-ala-Iys- -ala-ala-tyr- -ala-leu-arg- -ala-leu-lys- -ala-leu-tyr- -ala-gly-arg- (a.a.) n4 - -ala-gly-lys- -ala-gly-tyr- -ala-val-arg- -ala-val-lys- -ala-val-tyr- -ala-ile-arg- -ala-ile-lys- -ala-ile-tyr- -gly-ala-arg- -gly-ala-lys- -gly-ala-tyr- -gly-leu-arg- -gly-leu-lys- -gly-gly-arg- -gly-gly-lys- -gly-gly-tyr- -gly-val-arg- -gly-val-lys- -gly-val-tyr- iπ. B. Tripeptide Sequences for Cleavage by C4,2 (cont'd) -gly-ile-arg- -gly-ile-lys- -gly-ile-tyr- -val-ala-arg- -val-ala-lys- -val-ala-tyr- -val-leu-arg- -val-leu-lys- -val-leu-tyr- -val-gly-arg- (a.a) n4 - -val-gly-lys- -val-gly-tyr- -val-val-arg- -val-val-lys- -val-val-tyr- -val-ile-arg- -val-ile-lys- -val-ile-tyr- -ile-ala-arg- -ile-ala-lys- -ile-ala-tyr- -ile-leu-arg- -ile-leu-lys- -ile-leu-tyr- -ile-gly-arg- (a-a) n4 - -ile-gly-lys- -ile-gly-tyr- -ile-val-arg- -ile-val-lys- -ile-val-tyr- -ile-ile-arg- -ile-ile-lys- -ile-ile-tyr- H3. C. Peptide Sequences for Cleavage by C4, 2 -leu-gly- -leu-leu- -leu-ala- -leu-val- -leu-ile- -gly-gly- -gly-leu- -gly-ala- -gly-val- -ala-gly- -Tripeptide 2 -ala-leu- -ala-ala- -ala-val- -ala-ile- -val-gly- -val-leu- -val-ala- -val-val- -val-Ue- -ile-gly- -ile-leu- -ile-ala- -ile-val- -Ue-Ue- wherein (a.a) represents any naturally occurring amino acid (and can be the same or different), tripeptide is any peptide of Section III.B and n = 0-5; wherein R 12 is selected from hydrogen, CJ-C-JO alkyl, or phenyl optionally substituted with one, 2 or 3 C j -C alkyl, C j -^ alkoxy, halo, C j -C 3 alkylthio, trifluoromethyl, C 2 -C 6 dialkylamino, or nitro; wherein R j - is a carbonylaryl rou sftlerted from the group consisting of X5 wherein X g is -O-, -S-, -NH-; X 9 is -CH- or N; X 10 is -O-, -S-, -NH-; X n is -CH- or -N-; X 5 may be the same or different and is H, OCH 3 , NO 2 , NHC(O)CH 3 , OH, halo, C^ alkyl, C r C 3 alkoxy, C^-Cg dialkylamino, or NHC(O)C 6 H 5 ; and X 6 is H, OCH 3 , NO 2 , NHC(O)CH 3 , OH, halo, C r C 4 alkyl, C r C 3 alkoxy, C 2 -C 6 dialkylamino, or NHC(O)C 6 H 5 ; xs wherein X 5 , Xg, X 9 have the meanings defined above; (c) wherein X 5 , X 6 , Xg, X 9 have the meanings defined above; wherein R' 15 is a carbonylaryl group selected from the group consisting of (d) wherein 8 is -O-, -S-, -NH-; X 9 is -CH- or N; X 10 is -O-, -S-, -NH-; X n is -CH- or -N-; X 5 is the same or different and is H, OCH 3 , NO 2 , NHC(O)CH 3 , OH, halo, C r C 4 alkyl, C r C 3 alkoxy, C^-C dialkylamino, or NHC(O)C 6 H 5 ; Xg is H, OCH 3 , NO 2 , NHC(O)CH 3 , OH, halo, C C 4 alkyl, C!-C 3 alkoxy, ^-Cg dialkylamino, or NHC(O)C 6 H 5 ; n and R 50 have the meanings defined above; wherein X 8 is -O-, -S-, -NH-; X 9 is -CH- or N; X 10 is -O-, -S-, -NH-; X n is -CH- or -N-; X 5 is H, OCH 3 , NO 2 , NHC(O)CH 3 , OH, halo, C r -C 4 alkyl, C r C 3 alkoxy, C- j -Cg dialkylamino, or NHC(O)C 6 H 5 ; Xg is H, OCH 3 , NO 2 , NHC(O)CH 3 , OH, halo, C r C 4 alkyl, C r C 3 alkoxy, C 2 -C 6 dialkylamino, or NHC(O)CgH 5 ; n and R50 have the meanings defined above; wherein X 5 , X 8 , X 9 , n and R50 have the meanings defined above; wherein X 5 , Xg, Xg, X 9 , n and R 50 have the meanings defined above; wherein X 5 , Xg, Xg, X 9 n and R50 have the meanings defined above. 2. A compound of Formula I according to Claim 1 wherein W is methyl; Z is hydrogen; X is halogen; and Q is Y' and Y' is selected from -C(O)R 10 , -SO 2 R 10 , -C(O)NR 12 R 13 ; R 10 and R 13 are selected from -(phenyl optionally substituted one or two C j -^ alkyl, C j -C 3 alkoxy, halo, C j -C 3 alkylthio, trifluoromethyl, C 2 -C 6 dialkylamino, or nitro)(CH 2 ) n R 5 o wherein n is zero, one or two, and R 50 is -CO 2 H, -CH 2 NH 2 , -SH, -C(O)NHNH 2 , -CH 2 OH, -C(R 60 )(R 61 )C(O)NHNH 2 , -O(CH 2 )n 2 C(R 60 )(R 61 )C(O)NHNH 2 ; wherein n χ is i-3; n 2 is 0-2; R 60 , R 61 and Rg 2 , being the same or different, are H, methyl or ethyl; R 12 is hydrogen; and R 15 is (aa) wherein X 10 is -NH- or -O-; X 5 and Xg, being the same or different, are hydrogen, OH, NO2, NHC(O)CH 3 , halo, C^ alkyl, C^ alkoxy or C 2 -C 6 dialkylamino. 3. A compound of Formula I according to Claim 1 wherein W is methyl; Z is hydrogen; X is halogen; and Q is Y' and Y' is selected from -C(O)R 10 , -SO 2 R 10 , -C(O)NR 12 R 13 ; R 10 and R 13 are selected from -(phenyl optionally substituted one or two Ci*^ alkyl, C;ι-C 3 alkoxy, halo, C!-C 3 alkylthio, trifluoromethyl, C2*-C 6 dialkylamino, or nitroXCH^-^ wherein n is zero, one or two, and R50 -- N-hydroxysuccimidyl or maleimide; R 12 is hydrogen; and R 15 is (aa) wherein X 10 is -NH- or -O-; X5 and Xg, being the same or different, are hydrogen, OH, NC^, NHC(O)CH 3 , halo, C ] :-C 4 alkyl, C^ alkoxy or C^-Cg dialkylamino. 4. A compound of Formula I according to Claim 1 wherein W is methyl; Z is hydrogen; X is halogen; and Q is Y' and Y' is selected from -C(O)NR 12 R 13 , -C(O)R 10 , -SO 2 R 1Q , -C(O)NR 12 Rι 3 ; R j2 is hydrogen, R 10 and R 13 are selected from -(phenyl optionally substituted with one or two C j -C 4 alkyl, C j ^ alkoxy, halo, C-* ^ ^ alkylthio, trifluoromethyl, ^-C dialkylamino, or nitro)^^^^; n is zero or one; R50 is -B-M-(CH 2 )n 3 R 52 wherein R 52 is -NH- -CfWR or -55H and Jl.r is ( aa) wherein X 10 is -NH- or -O-; X 5 and Xg are independently H, NO 2 , NHC(O)CH 3 , halogen, C 1 -C 4 alkyl, C C 3 alkoxy, or C^-Cg dialkylamino. 5. A compound of Formula I according to Claim 1 wherein W is methyl; Z is hydrogen; X is halogen; and Q is Y and Y is selected from hydrogen, -C(O)R, -SO^, -C(O)NR 2 R 3 ; R 3 is hydrogen, R and R j and R 2 (being the same or different) are selected from phenyl optionally substituted with one to three C 1 -C alkyl, C j -C 3 alkoxy, halo, C-^-C^ alkylthio, trifluoromethyl, C^-Cg dialkylamino, or nitro; and R' 15 is selected from and n is 0-6; X 10 is -NH- or -O-; X 5 and Xg are independently H, OH, NO 2 , NHC(O)CH 3 , halo, C j -^ alkyl, C j ^ alkoxy or C^-Cg dialkylamino. 6. A compound according to Claim 5 wherein R50 is N-hydroxysuccimidyl or maleimidyl. 7. A compound according to Claim 5 wherein R50 is -B-M-(CH 2 )n 3 R 52 wherein R 52 is -NH 2 , -C(O)NHNH 2 , -CO 2 H, or -SH. 8. A compound according to Claim 5 wherein R^ is -CO 2 H, -CH 2 NH 2 , -SH, -C(Rg 0 )(R 61 )SH, -NHC(O)-(CH 2 ) nl -C(R6 0 )(R 61 )-SH, -C(O)NHNH 2 , -CH 2 OH, -C (R 60 ) (R 6 1 ) C(O)NHNH 2 , -N(R 62 ) (CH 2 ) n l C (R 6 o)(Rg 1 )C(O)-NH NH 2 , -O(CH 2 )n 2 C(Rg 0 )(R 61 )C(O)NHNH 2 ; wherein n j is 1-3; n 2 is 0-2; and R 60 , R 61 and Rg 2 , being the same or different, are H, methyl or ethyl. 9. A compound according to Claim 8 wherein X5 and Xg are both hydrogen. 10. A compound according to Claim 2 wherein X5 and Xg are both hydrogen. 11. A compound according to Claim 5 wherein X 5 and Xg are both hydrogen and R50 is -CO 2 H, -CH 2 NH 2 , -SH, -C^O^SH, -NHC(O)-(CH 2 ) nl -C(R 60 )(Rg 1 )-SH, -C(O)NHNH 2 , -CH 2 OH, -C(R 60 )(R 6 ι)C(O)NHNH 2 , -N(R 62 )(CH 2 ) nl C(R6o)(R6i)C(O)-NHNH 2 , -O(CH 2 )n 2 C(Rg 0 )(R 61 )C(O)NHNH 2 ; wherein n x is 1-3; n 2 is 0-2; and R 60 , R 61 and R 2 , being the same or different, are H, memyl or ethyl. 12. A compound according to Claim 5 wherein X5 and Xg are both hydrogen, and R'^ is 13. A compound according to Claim 12 wherein R50 is defined as in Claim 2. 14. A compound of Formula π according to Claim 1 wherein W is methyl; Z is hydrogen; and R' 15 is selected from and n is 0-6; X 10 is -NH- or -O-; and X 5 and X 6 are independently H, NO 2 , NHC(O)CH 3 , halogen, C 1 -C 4 alkyl, C j -C 3 alkoxy, or C^-Cg dialkylamino. 15. A compound of Formula π according to Claim 14 wherein R50 ιs -CO 2 H, -CH 2 NH 2 , -SH, -C(R6 0 )(R 61 )SH, -NHC(O)-(CH 2 ) nl -C(Rg 0 )(R6 1 )-SH, -C(O)NHNH 2 , -CH 2 OH, -C(R 6 o) (Rg ι)C(O)NHNH 2 , -N(Rg 2 ) (CH 2 ) n l C(R6 0 ) (R 6 1 )C (O)-NHNH 2 , -O(CH 2 )n 2 C(R cc )(R eι )C(O)NHNH 2 ; wherein n t is 1-3: n 2 is 0-2; R eo , R 61 and R 2 . being the same or different, are H, methyl or ethyl. 16. A compound of Formula π according to Claim 14 wherein X 5 and Xg are both hydrogen. 17. A compound of Formula II according to Claim 14 wherein X5 and Xg are both hydrogen and R50 is -CO 2 H, -CH 2 NH 2 , -SH, -C(R6o)(R 61 )SH, -NHC(O)-(CH 2 ) nl -C(R 60 )(R 61 )-SH, -C(O)NHNH 2> -CH 2 OH, -C(R 60 )(Rg 1 )C(O)NHNH 2 , -N(Rg 2 )(CH 2 ) nl C(Rg 0 )(R 61 )C(O)-NHNH 2 , -O(CH 2 )n 2 C(R 60 )(Rg 1 )C(O)NHNH 2 ; wherein n χ is 1-3; n 2 is 0-2; and R 60 , R 61 and Rg 2 , being the same or different, are H, methyl or ethyl. 18. A compound of Formula II according to Claim 14 wherein X 5 and Xg are both hydrogen, and R'15 is 19. A compound of Formula II according to Claim 17 wherein X 5 and Xg are both hydrogen. 20. A compound of Formula π according to Claim 14 wherein R50 is as defined in Claim 3. 21. A compound of Formula II according to Claim 14 wherein R50 is as defined in Claim 4. 22. A compound according to Claim 1 selected from the group consisting of: (S>2-[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-2-benzofuran-5-carboxylic acid phenylmethyl ester (Cpd #1); (S 2-[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-2-benzofuran-5-carboxylic acid (Cpd #2); (S 2-[[[2-[(4,5,8,8a-tetrahydro-7-methyl-4-oxocyclopropa-[c]pyrrol[3,2-e]indol-2(lH)-yl)- carbonyl]-lH-indol-5-yl]amino]carbonyl]-2-benzofuran-5-carboxylic acid (Cpd #3); (S)-2-[[[[2-[[l-(chloromethyl)-l ,6-dihydro-5-hydroxy-8-methylbenzo[ 1 ,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-lH-indol-5-yl]-carbamic acid, 1, 1-dimethyl¬ ethyl ester (Cpd #4); (S)-N-[2-t[l-(chloromethyl)-l,6-dihydro-8-methyl-5-[[[[4-[[[(l,l-dimethylethyl)cxy]- carbonyl]aminomethyl]phenyl]amino]car-bonyl]oxy]benzo[l,2-b:4,3-b']-dipyrrol-3(2H)- yl]carbonyl]-lH-indol-5-yl]-2-benzofurancarboxamide (Cpd #5); 5-[(2-mercaptopropionyl)amino]-N-[2-(4,5, 8, 8a-tetrahydro-7-methyl-4-oxocyclopropa [c-]pyrrolo[3,2-e]indol-2(lH)-yl)-lH-indol-5-yl]-lH-indole-2-carboxamide (Cpd #8); (S)-N-[2-[[ 1 -(chloromethyl)-l ,6-dihydro-8-methyl-5-[[[[4-[[(phenylmethyl)oxy]carbonyl] phenyl]amino]carbonyl]oxy]benzo[l,2-b:4,3-b']dipyrrol-3(2H)-2-yl]carbonyl]-lH-indol-5-yl]-2- benzofiirancarboxamide (Cpd #10); (S)-2-[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H yl]carbonyl]-lH-indol-5-yl]amino]carbonyl ]-5-[[2-[[(l , l-dimethylethyl)oxy]carbonyl]hydra- zino]carbonyl]-lH-indol (Cpd #11A); (S)-2-[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-(hydrazinocarbonyl)-lH-indol monohydrochloride (Cpd #11B); (S)-N-[2-[[l-(chloromethyl)-l ,6-dihydro-8-methyl-5-[[[[4-[[2-[[(l , l- dimethylethyl)oxy]carbonyl]hydrazino]carbonyl]phenyl]amino]carbonyl]oxy]benzo[l,2-b:4,3- b']dipyrrol-3(2H)-yl]carbonyl]-lH-indol-5-yl]-2-benzofurancarboxamide (Cpd #12); (S)-N-[2-[[l-(chloromethyl)-l,6-dihydro-8-methyl-5-[[[[4-[[[2-[[(l, 1-dimethylethyl) oxy]carbonyl]hydrazino]carbonyl]emyl]phenyl]amino]carbonyl]oxy]benzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]-2-benzofurancarboxamide (Cpd #13); (S ) -N - [2 - [ [ l - (chloro m ethyl)- l , 6-d ihydro-8 -methyl-5 - [[ [ [4- [2- [0ιydrazinocarbonyl)ethyl]phenyl]amino]carbonyl]oxy]benzo[l,2-b:4,3-b']dipyrrol-3(2H)- yl]carbonyl]-lH-indol-5-yl]-2-Benzofurancarboxamide, monohydrochloride (Cpd #14); (S)-[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3 (2 H ) -y l] c arb o nyl] - l H-indo l -5-yl] am ino] carbo nyl ] -5 - [2 - [ [2 - [ [ ( l , l - dimethylethyl)oxy]carbonyl]hydrazino]carbonyl]ethyl]-2-Benzofuran (Cpd #15); (S)-[[[2-[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl-5-[2-(hydrazinocarbonyl)ethyl]-2-benzofuran monohydrochloride (Cpd #16); (7bR)-N-[2-[[4,5,8,8a-tetrahydro-7-memyl-4-oxocy opropa[c]pyrrolo[3,2-e]indol-2(lH yl- carbonyl]-lH-indol-5-yl]aminocarbonyl]-5-[2-[[2-[(l,l-dimethylethyl)oxy]carbonyl] hydrazino]carbonyl]ethyl-2-benzofuran (Cpd #17); (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2-[[(l , 1-dimethylethyl) oxy]carbonyl]hydrazino]carbonyl]ethyl-2-benzofuran 3,6,9-trioxadecanoic acid ester (Cpd #18); (S)-[[[-2[[l-(ch1oromethyl)-1 7 6-dihydro-5-hy roxy-8-me ylbenzo[l,2-b:4,3-b']dipv!Tol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5 [2-(hydrazino)carrx)nyl]eΛyl-2-benzofiιran 3,6,9-trioxadecanoic acid ester (Cpd #19); (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2-[[(l, 1-dimethylethyl) oxy]carbonyl]hydrazino]carbonyl]ethyl]-2-benzofuran glutaric acid monoester (Cpd #20); (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2-[[(l, 1-dimethylethyl) oxy]carbonyl]hydrazino]carbonyl]ethyI]-2-benzofuran ester of N-[2-hydroxy-l,l- bis(hydroxymethyl)ethyl]glutaramic acid (Cpd #21); (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-(hydrazino)carbonyl]ethyl-2-benzofuran ester of N-[2-hydroxy-l,l-bis(hydroxymeuιyl)ethyl]glutaramic acid (Cpd #22); (S)-[[[-2[[ 1 -(chloromethyl)-l ,6-<lihydro-5-hydroxy-8-methylbenzo[l ,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-[[2-[[(l , 1-dimethylethyl) oxy]carbonyl]hydrazino]carbonyI]ethyl]-2-benzofuran glutaric acid monoester mono amide of 7- amino-naphthalene-1, 3-disulfonic acid disodium salt (Cpd #23); (S)-[[[-2[[l-(chloromethyl)-l,6-dihydro-5-hydroxy-8-methylbenzo[l,2-b:4,3-b']dipyrrol- 3(2H)-yl]carbonyl]-lH-indol-5-yl]amino]carbonyl]-5-[2-(hydrazino)carbonyl]ethyl-2-benzofuran glutaric acid monoester mono amide of 7-amino-naphthalene-l, 3-disulfonic acid disodium salt (Cpd #24); 23. A compound of Formula I according to Claim 1 wherein Y is selected from hydrogen, - C(O)R, -C(S)R, -C(O)OR j , -S(O) 2 Ri, -C(O)NR 2 R 3 , -C(S)NR 2 R 3 , -C(O)NHSO 2 R 4 , -C(O)CH 2 (OCH 2 CH 2 ) n7 O(C 1 -C 3 alkyl) and n7 is 0-5, or -C(O)(CH2) n8 C(O)R b where n8 is 0-iϋ and R b is selected from -OH (or a metal or amine salt thereof), -OR c where R c is -CH 2 C(CH 2 OH) 3 or R 70 , and -N(R d ) R e where R d is hydrogen or C r C 4 alkyl, and R g is selected from -C(CH 2 OH) 3 , -CH 2 C(CH 2 OH) 3 , -CH 2 C(CH 2 NH2)3> o * R 7l or R 72 where n9 is 1 or 2 and nlO is 1-3.

Inventors: ARISTOFF PAUL ADRIAN, KELLY ROBERT CHARLES, MITCHELL MARK ALLEN, ARISTOFF, PAUL, ADRIAN, KELLY, ROBERT, CHARLES, MITCHELL, MARK, ALLEN
Applicants: UPJOHN CO, THE UPJOHN COMPANY
Application year: 1991
Main classification: C07K5
IPC codes: A61K31, A61K38, A61K47, A61P31, A61P35, C07D487, C07F9, C07K1, C07K5, C07K16, C07K17